Professional Documents
Culture Documents
Standards of Care 2020
Standards of Care 2020
January 2020
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Standards of
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Medical Care
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in diabetes—2020
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Volume 43 | Supplement 1 | Pages s1–s212
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ISSN 0149-5992
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American Diabetes Association
Standards of
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Medical Care in
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Diabetesd2020
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© 2019 by the American Diabetes Association. Readers may use this work as long as the work is properly
cited, the use is educational and not for profit, and the work is not altered. Readers may link to the version of
record of this work on https://care.diabetesjournals.org, but ADA permission is required to post this work on
any third-party website or platform. Requests to reuse or repurpose; adapt or modify; or post, display, or
distribute this work may be sent to permissions@diabetes.org.
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January 2020 Volume 43, Supplement 1
[T]he simple word Care may suffice to express [the journal’s] philosophical
mission. The new journal is designed to promote better patient care by
serving the expanded needs of all health professionals committed to the care
of patients with diabetes. As such, the American Diabetes Association views
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Diabetes Care as a reaffirmation of Francis Weld Peabody’s contention that
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“the secret of the care of the patient is in caring for the patient.”
—Norbert Freinkel, Diabetes Care, January-February 1978
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EDITOR IN CHIEF
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Matthew C. Riddle, MD
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ASSOCIATE EDITORS EDITORIAL BOARD
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Lawrence Blonde, MD, FACP Linda A. Barbour, MD, MSPH John J.V. McMurray, MD, FRCP, FESC,
Andrew J.M. Boulton, MD Ananda Basu, MD, FRCP FACC, FAHA, FRSE, FMedSci
David D’Alessio, MD Roy W. Beck, MD, PhD Maureen Monaghan, PhD, CDE
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Linda A. DiMeglio, MA, MD, MPH Gianni Bellomo, MD Kristen J. Nadeau, MD, MS
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Linda Gonder-Frederick, PhD Geremia Bolli, MD Gregory A. Nichols, PhD, MBA
Korey K. Hood, PhD Sonia Caprio, MD Bruce A. Perkins, MD, MPH
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Frank B. Hu, MD, MPH, PhD Jessica R. Castle, MD Ravi Retnakaran, MD, MSc, FRCPC
Steven E. Kahn, MB, ChB J. Hans DeVries, MD, PhD Elizabeth Seaquist, MD
Sanjay Kaul, MD, FACC, FAHA Kathleen M. Dungan, MD, MPH Jonathan Shaw, MD, FRCP, FRACP,
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Julio Rosenstock, MD Reinhard W. Holl, MD, PhD Ram Weiss, MD, PhD
Judith Wylie-Rosett, EdD, RD Philip Home, DM, DPhil Deborah Wexler, MD, MSc
Byron J. Hoogwerf, MD, FACP, FACE Vincent C. Woo, MD, FRCPC
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Psychosocial Research, Epidemiology/Health Services Research, Emerging
Technologies and Therapeutics, Pathophysiology/Complications, and Cardiovascular
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and Metabolic Risk. The journal also publishes ADA statements, consensus reports,
clinically relevant review articles, letters to the editor, and health/medical news or points
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of view. Topics covered are of interest to clinically oriented physicians, researchers,
epidemiologists, psychologists, diabetes educators, and other health professionals.
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More information about the journal can be found online at care.diabetesjournals.org.
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Copyright © 2019 by the American Diabetes Association, Inc. All rights reserved. Printed in
the USA. Requests for permission to reuse content should be sent to Copyright Clearance
Center at www.copyright.com or 222 Rosewood Dr., Danvers, MA 01923; phone: (978)
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Permissions Editor, American Diabetes Association, at permissions@diabetes.org.
The American Diabetes Association reserves the right to reject any advertisement for
any reason, which need not be disclosed to the party submitting the advertisement.
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Commercial reprint orders should be directed to Sheridan Content Services,
(800) 635-7181, ext. 8065.
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Single issues of Diabetes Care can be ordered by calling toll-free (800) 232-3472, 8:30 A.M.
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to 5:00 P.M. EST, Monday through Friday. Outside the United States, call (703) 549-1500.
Rates: $75 in the United States, $95 in Canada and Mexico, and $125 for all other countries.
Diabetes Care is available online at care.diabetesjournals.org. Please call the
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numbers listed above, e-mail membership@diabetes.org, or visit the online journal for
more information about submitting manuscripts, publication charges, ordering reprints,
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PRINT ISSN 0149-5992 subscribing to the journal, becoming an ADA member, advertising, permission to reuse
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PRINTED IN THE USA Periodicals postage paid at Arlington, VA, and additional mailing offices.
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Lyn Reynolds
pnalbandian@diabetes.org
PRODUCTION COORDINATOR
(703) 549-1500, ext. 4806
PEER REVIEW MANAGER
Saleha Malik
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S3 Professional Practice Committee
Assessment
Summary of Revisions: Standards of Medical Care in
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S4 Diet, Physical Activity, and Behavioral Therapy
Diabetes—2020 Pharmacotherapy
Medical Devices for Weight Loss
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S7 1. Improving Care and Promoting Health in Metabolic Surgery
Populations 9. Pharmacologic Approaches to Glycemic
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S98
Diabetes and Population Health Treatment
Tailoring Treatment for Social Context
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Pharmacologic Therapy for Type 1 Diabetes
Surgical Treatment for Type 1 Diabetes
S14 2. Classification and Diagnosis of Diabetes Pharmacologic Therapy for Type 2 Diabetes
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Classification
S111 10. Cardiovascular Disease and Risk
Diagnostic Tests for Diabetes
Management
A1C
Type 1 Diabetes The Risk Calculator
Prediabetes and Type 2 Diabetes Hypertension/Blood Pressure Control
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Cystic Fibrosis–Related Diabetes Lipid Management
Posttransplantation Diabetes Mellitus Statin Changes
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Monogenic Diabetes Syndromes Antiplatelet Agents
Pancreatic Diabetes/Diabetes in the Cardiovascular Disease
Cardiac Testing
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Context of the Exocrine Pancreas
Gestational Diabetes Mellitus Screening Asymptomatic Patients
Lifestyle and Pharmacologic Interventions
Glucose-Lowering Therapies and Cardiovascular Outcomes
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Pharmacologic Interventions
Prevention of Cardiovascular Disease Diabetic Retinopathy
Diabetes Self-management Education and Support Neuropathy
Foot Care
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Hypoglycemia
Comprehensive Medical Evaluation Treatment Goals
Assessment of Comorbidities Lifestyle Management
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Pharmacologic Therapy
S48 5. Facilitating Behavior Change and Well-being to Special Considerations for Type 1 Diabetes
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Type 2 Diabetes
Transition From Pediatric to Adult Care
S66 6. Glycemic Targets
S183 14. Management of Diabetes in Pregnancy
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S193 15. Diabetes Care in the Hospital Transition From the Hospital to the Ambulatory Setting
Hospital Care Delivery Standards Preventing Admissions and Readmissions
Glycemic Targets in Hospitalized Patients
Bedside Blood Glucose Monitoring S203 16. Diabetes Advocacy
Glucose-Lowering Agents in Hospitalized Patients Advocacy Statements
Hypoglycemia
Medical Nutrition Therapy in the Hospital S205 Disclosures
Self-management in the Hospital
Standards for Special Situations S207 Index
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Diabetes Care Volume 43, Supplement 1, January 2020 S1
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Diabetes Care 2020;43(Suppl. 1):S1–S2 | https://doi.org/10.2337/dc20-SINT
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Diabetes is a complex, chronic illness re- The ADA strives to improve and update immediate inclusion. More information on
the “living Standards” can be found on the
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quiring continuous medical care with the Standards of Care to ensure that
multifactorial risk-reduction strategies clinicians, health plans, and policy mak- ADA’s professional website DiabetesPro at
beyond glycemic control. Ongoing dia- ers can continue to rely on it as the professional.diabetes.org/content-page/
betes self-management education and most authoritative source for current living-standards. The Standards of Care
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support are critical to preventing acute guidelines for diabetes care. supersedes all previous ADA position
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complications and reducing the risk of long- statementsdand the recommendations
ADA STANDARDS, STATEMENTS,
INTRODUCTION
term complications. Significant evidence thereindon clinical topics within the
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REPORTS, and REVIEWS purview of the Standards of Care; ADA
exists that supports a range of interven-
tions to improve diabetes outcomes. The ADA has been actively involved in position statements, while still contain-
The American Diabetes Association the development and dissemination of ing valuable analysis, should not be con-
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(ADA) “Standards of Medical Care in Di- diabetes care clinical practice recom- sidered the ADA’s current position. The
abetes,” referred to as the Standards of mendations and related documents for Standards of Care receives annual review
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30 years. The ADA’s Standards of Medical and approval by the ADA Board of Directors.
Care, is intended to provide clinicians,
Care is viewed as an important resource
patients, researchers, payers, and other ADA Statement
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dations are not intended to preclude supplement to Diabetes Care contains on advocacy, policy, economic, or
clinical judgment and must be applied official ADA position, is authored by medical issues related to diabetes.
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in the context of excellent clinical care, the ADA, and provides all of the ADA statements undergo a formal re-
with adjustments for individual prefer- ADA’s current clinical practice view process, including a review by the
ences, comorbidities, and other patient recommendations. appropriate ADA national committee,
factors. For more detailed information To update the Standards of Care, the ADA science and medicine staff, and
about the management of diabetes, please
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Type 2 Diabetes (2). with input from ADA staff and the med- A consensus report of a particular
The recommendations in the Stand- ical community at large. The PPC updates topic contains a comprehensive
ards of Care include screening, diagnos- the Standards of Care annually. However, examination and is authored by an
©
tic, and therapeutic actions that are known the Standards of Care is a “living” docu- expert panel (i.e., consensus panel)
or believed to favorably affect health out- ment, where important updates are pub- and represents the panel’s collective
comes of patients with diabetes. Many lished online should the PPC determine analysis, evaluation, and opinion.
of these interventions have also been that new evidence or regulatory changes The need for a consensus report arises
shown to be cost-effective (3). (e.g., drug approvals, label changes) merit when clinicians, scientists, regulators,
The “Standards of Medical Care in Diabetes” was originally approved in 1988. Most recent review/revision: December 2019.
© 2019 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
S2 Introduction Diabetes Care Volume 43, Supplement 1, January 2020
Table 1—ADA evidence-grading system for “Standards of Medical Care in Diabetes” the evidence in support of the recom-
Level of
mendation. Expert opinion E is a separate
evidence Description category for recommendations in which
there is no evidence from clinical trials,
A Clear evidence from well-conducted, generalizable randomized controlled trials that
are adequately powered, including
clinical trials may be impractical, or there
c Evidence from a well-conducted multicenter trial is conflicting evidence. Recommendations
c Evidence from a meta-analysis that incorporated quality ratings in the analysis with A level evidence are based on large
Compelling nonexperimental evidence, i.e., “all or none” rule developed by the Centre well-designed clinical trials or well-done
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for Evidence-Based Medicine at the University of Oxford meta-analyses. Generally, these recom-
Supportive evidence from well-conducted randomized controlled trials that are mendations have the best chance of im-
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adequately powered, including
proving outcomes when applied to the
c Evidence from a well-conducted trial at one or more institutions
c Evidence from a meta-analysis that incorporated quality ratings in the analysis
population for which they are appropriate.
a
B Supportive evidence from well-conducted cohort studies
Recommendations with lower levels of
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c Evidence from a well-conducted prospective cohort study or registry evidence may be equally important
c Evidence from a well-conducted meta-analysis of cohort studies but are not as well supported.
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Supportive evidence from a well-conducted case-control study Of course, evidence is only one com-
C Supportive evidence from poorly controlled or uncontrolled studies ponent of clinical decision-making. Clini-
c Evidence from randomized clinical trials with one or more major or three or more cians care for patients, not populations;
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minor methodological flaws that could invalidate the results guidelines must always be interpreted
c Evidence from observational studies with high potential for bias (such as case
with the individual patient in mind. In-
series with comparison with historical controls)
c Evidence from case series or case reports
dividual circumstances, such as comorbid
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Conflicting evidence with the weight of evidence supporting the recommendation and coexisting diseases, age, education,
E disability, and, above all, patients’ values
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Expert consensus or clinical experience
and preferences, must be considered and
may lead to different treatment targets
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and/or policy makers desire guidance Standards of Care. The category may also and strategies. Furthermore, conven-
and/or clarity on a medical or scientific include task force and expert committee tional evidence hierarchies, such as the
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issue related to diabetes for which the reports. one adapted by the ADA, may miss
evidence is contradictory, emerging, or nuances important in diabetes care.
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incomplete. Consensus reports may also GRADING OF SCIENTIFIC EVIDENCE For example, although there is excellent
highlight gaps in evidence and propose Since the ADA first began publishing evidence from clinical trials supporting
areas of future research to address clinical practice guidelines, there has the importance of achieving multiple risk
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these gaps. A consensus report is not been considerable evolution in the eval- factor control, the optimal way to achieve
an ADA position but represents expert uation of scientific evidence and in the this result is less clear. It is difficult to
assess each component of such a complex
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A consensus report may be developed af- classification system to grade the quality
ter an ADA Clinical Conference or Re- of scientific evidence supporting ADA rec- References
1. American Diabetes Association. Medical
Am
scientific or medical topic related having the majority of bulleted recom- Young LA, Eds. Alexandria, VA, American Diabetes
Association, 2012
to diabetes. mendations supported by A level or 3. Li R, Zhang P, Barker LE, Chowdhury FM, Zhang
A scientific review is not an ADA position B level evidence (4). A grading system
20
der the auspices of the ADA by invited clarify and codify the evidence that forms
dence level for the American Diabetes Associa-
experts. The scientific review may pro- the basis for the recommendations. ADA tion’s “Standards of Medical Care in Diabetes”
vide a scientific rationale for clini- recommendations are assigned ratings of from 2005 to 2014. Diabetes Care 2015;38:
cal practice recommendations in the A, B, or C, depending on the quality of 6–8
Diabetes Care Volume 43, Supplement 1, January 2020 S3
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Diabetes Care 2020;43(Suppl. 1):S3| https://doi.org/10.2337/dc20-SPPC
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The Professional Practice Committee (PPC) and published since 15 October 2018. Hsu, MD; Sally C. Hughes, BA; Scott
of the American Diabetes Association (ADA) Due to limitations associated with pro- Kahan, MD, MPH; Ka Hei Karen Lau,
is responsible for the “Standards of Medical duction timelines, evidence published in MS, RD, LDN, CDE; Jose Leon, MD; Ingrid
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Care in Diabetes,” referred to as the Stand- late 2019 was not incorporated into the Libman, MD, PhD; Sarah K. Lyons, MD;
s
diabetes educators, and others who have and Reduced Ejection Fraction [DAPA-HF], BS; Andrea Steck, MD; William S. Yancy,
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expertise in a range of areas, including, but Cardiovascular Outcome Study of Linaglip- MD, MHS; and Ann Zmuda, DPM.
not limited to, adult and pediatric endocri- tin Versus Glimepiride in Patients With Members of the PPC
nology, epidemiology, public health, cardio- Type 2 Diabetes [CAROLINA], etc.), but
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Joshua J. Neumiller, PharmD, CDE, FASCP
vascular risk management, microvascular salient new data will be incorporated in (Chair)
complications, preconception and preg- a living Standards update in early 2020 George Bakris, MD
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diabetes management. Appointment to the revised based on new evidence or, in some David D’Alessio, MD
PPCisbasedonexcellenceinclinicalpractice cases, to clarify the prior recommendation Jennifer Green, MD
and research. Although the primary role of or match the strength of the wording to the
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involved in ADA statements, reports, and evidence can be reviewed online at profes- Christine G. Lee, MD, MS
reviews. sional.diabetes.org/SOC. The Standards Nisa Maruthur, MD, MHS
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The ADA adheres to the National Acad- of Care is approved by the ADA’s Board Anne Peters, MD
emy of Medicine Standards for Developing of Directors, which includes health care Maria Jose Redondo, MD, PhD, MPH
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Trustworthy Clinical Practice Guidelines. All professionals, scientists, and lay people. Jane Reusch, MD
members of the PPC arerequired to disclose Feedback from the larger clinical com- Emily Weatherup, MS, RDN, CDE
potential conflicts of interest with industry munity was invaluable for the annual Jennifer Wyckoff, MD
and other relevant organizations. These 2019 revision of the Standards of Care. Deborah Young-Hyman, PhD, CDE
disclosures are discussed at the onset of Readers who wish to comment on the
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each Standards of Care revision meeting. 2020 Standards of Care are invited to do so American College of
Members of the committee, their employ- at professional.diabetes.org/SOC. CardiologydDesignated
ers, and their disclosed conflicts of interest The PPC thanks the following indi- Representatives (Section 10)
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are listed in “Disclosures: Standards of viduals who provided their expertise Sandeep Das, MD, MPH, FACC
Medical Care in Diabetesd2020” (https:// in reviewing and/or consulting with Mikhail Kosiborod, MD, FACC
©
doi.org/10.2337/dc20-SPPC). The ADA funds the committee: Nidhi Bansal, MD; Linda ADA Staff
development of the Standards of Care A. Barbour, MD, MSPH, FACP; Florence Mindy Saraco, MHA (corresponding author:
out of its general revenues and does not Brown, MD; Thomas Buchanan, MD; Linda msaraco@diabetes.org)
use industry support for this purpose. A. DiMeglio, MD; Alison B. Evert, MS, Malaika I. Hill, MA
For the current revision, PPC members RD, CDE; Hermes Flores, MD, PhD; Matthew P. Petersen
systematically searched MEDLINE for Thomas W. Gardner, MD, MS; Rose Shamera Robinson, MPH, RDN
human studies related to each section Gubitosi-Klug, MD, PhD; William C. Kenneth P. Moritsugu, MD, MPH, FACPM
© 2019 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
S4 Diabetes Care Volume 43, Supplement 1, January 2020
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Diabetes Care 2020;43(Suppl. 1):S4–S6 | https://doi.org/10.2337/dc20-SREV
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GENERAL CHANGES autoimmune diabetes in adults is now Centers for Disease Control (CDC) Diabetes
The field of diabetes care is rapidly chang- acknowledged. Prevention Impact Tool Kit. More infor-
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ing as new research, technology, and A new recommendation (2.8) was added mation was added on the risk reduction
treatments that can improve the health regarding testing for prediabetes and/or certain groups experienced with metformin
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and well-being of people with diabetes type 2 diabetes for women with over- use, based on 15-year follow-up data
continue to emerge. With annual up- weight or obesity and/or who have one from the Diabetes Prevention Program
dates since 1989, the American Diabetes or more additional risk factors for dia- Outcomes Study.
Association (ADA) has long been a leader betes who are planning a pregnancy.
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Additional considerations were added Section 4. Comprehensive Medical
in producing guidelines that capture the
SUMMARY OF REVISIONS
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most current state of the field.
Diabetes” (CFRD) regarding the use of Comorbidities
Although levels of evidence for several
(https://doi.org/10.2337/dc20-S004)
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recommendations have been updated, A1C tests to detect CFRD.
The 2020 Standards of Care includes The autoimmune diseases recommen-
these changes are not outlined below
a new section on “Pancreatic Diabetes or dation (4.12) was modified, and a new
where the clinical recommendation has
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form of diabetes and its diverse set of disease screening guidance differenti-
are not noted below. The 2020 Standards
etiologies. ated, and more information on the prev-
of Care contains, in addition to many
The “Gestational Diabetes Mellitus” alence of and screening for these diseases
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Type 2 Diabetes
(https://doi.org/10.2337/dc20-S001)
(https://doi.org/10.2337/dc20-S003) section was changed to “Sensory Impair-
Additional information was included on
On the basis of a new consensus report, ment,” and new information was added,
the rising cost of medications, particu-
“Nutrition Therapy for Adults With Di- including content on impairment of smell.
larly insulin.
abetes or Prediabetes: A Consensus Evidence was updated in the section
A new section “Migrant and Seasonal
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© 2019 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
care.diabetesjournals.org Summary of Revisions S5
Section 5. Facilitating Behavior 2 inhibitors or glucagon-like peptide 1 New evidence and a recommendation
Change and Well-being to Improve (GLP-1) receptor agonists in patients with (9.6) were added on early combination
Health Outcomes cardiovascular disease meeting A1C goals therapy for type 2 diabetes to extend the
(https://doi.org/10.2337/dc20-S005) for cardiovascular benefit. time to treatment failure based on find-
The title of this section was previously A new recommendation (6.11) on ings from the VERIFY trial.
“Lifestyle Management” and was changed screening patients who are taking med- FDA approval of oral semaglutide has
to more appropriately emphasize how ef- ication that can lead to hypoglycemia for been included in the discussion of com-
fective behavior management and psycho- hypoglycemia unawareness was introduced. bination therapies.
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logical well-being are foundational to Intranasal glucagon and glucagon so- Figure 9.1 has been revised to include
achieving treatment goals for people lution for subcutaneous injection were the latest trial findings on GLP-1 receptor
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with diabetes. included in the section “Hypoglycemia” agonists and SGLT2 inhibitors. It now
The section “Nutrition Therapy” was due to their recent approval by the U.S. suggests that these drugs should be con-
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updated to include guidance and evi- Food and Drug Administration (FDA). sidered for patients when atherosclerotic
dence presented in “Nutrition Therapy
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This section was modified to include a cardiovascular disease (ASCVD), heart
for Adults With Diabetes or Prediabetes: new discussion on the use of continuous failure, or chronic kidney disease pre-
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A Consensus Report” (https://doi.org/ glucose monitoring technology in hypo- dominates independent of A1C.
10.2337/dci19-0014), published in May glycemia prevention. Figure 9.2 has been simplified to more
2019. easily guide providers through intensifi-
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Because of the emerging evidence from Section 7. Diabetes Technology cation to injectable therapies.
the CDC on deaths related to e-cigarettes, (https://doi.org/10.2337/dc20-S007)
more information was added discourag- This section was reorganized into three Section 10. Cardiovascular Disease
ing their use. broad categories titled “Self-Monitoring of
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and Risk Management
Recommendations and supporting Blood Glucose,” “Continuous Glucose Mon- (https://doi.org/10.2337/dc20-S010)
evidence on anxiety disorders, depres-
sion, disordered eating behavior, and
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itors,” and “Insulin Delivery.” Within these
revised sections, emphasis has been made
This section is endorsed for the second
consecutive year by the American Col-
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serious mental illness previously found on how there is no “one-size-fits-all” lege of Cardiology.
at the end of Section 4 were moved to approach to technology use in people Blood pressure targets for pregnant
Section 5 and are included under “Psy- with diabetes. Due to the rapidly changing patients with pre-existing hypertension have
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chosocial Issues.” More information field of diabetes technology, the recom- been changed in the interest of reducing the
on psychosocial screening for social mendations in each category have been
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ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA
gets for Continuous Glucose Monitoring The body mass index (BMI) calculation Guideline on the Management of Blood
Data Interpretation: Recommendations recommendation (8.1) was modified to Cholesterol: Executive Summary: A Report
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From the International Consensus on Time recommend annual BMI calculations of the American College of Cardiology/
in Range” (https://doi.org/10.2337/dci19- rather than at every patient encounter. American Heart Association Task Force
0028) published in June 2019, new recom- More discussion was added on how on Clinical Practice Guidelines” (https://
mendations (6.4 and 6.5) were added on providers measure and record patient doi.org/10.1016/j.jacc.2018.11.002),
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use of the ambulatory glucose profile (AGP) weight, including recommendations on published in June 2019.
report and time in range (TIR) for assess- how to manage these encounters to Discussion of REDUCE-IT was added to
ment of glycemic management. A discus- maximize patient comfort and engage- the section “Treatment of Other Lipo-
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sion of AGP reports, time in range, and ment. Other considerationsdlike access protein Fractions or Targets,” and a new
glucose management indicators follow the to food and individual’s motivation recommendation (10.31) was included
new recommendations. An example of an leveldwere added to the section “Lifestyle on considering icosapent ethyl for re-
©
AGP report was also added (Fig. 6.1). Interventions.” ducing cardiovascular risk.
Table 6.1 was replaced with a simpli- Recommendations for treatment of
fied estimated average glucose table. Section 9. Pharmacologic Approaches cardiovascular disease (10.43a, 10.43b,
More discussion on the importance of to Glycemic Treatment 10.43c) are now individualized based on
reducing therapeutic inertia in the manage- (https://doi.org/10.2337/dc20-S009) patients’ existing ASCVD, risk of ASCVD,
ment of hyperglycemia and cardiovascular A discussion was added on access to diabetic kidney disease, or heart failure.
disease was included in the section “A1C analog insulins and how there are mul- Discussion of the trials CANVAS, CANVAS-
and Cardiovascular Disease Outcomes.” tiple approaches to insulin treatment, Renal, CREDENCE, DECLARE-TIMI 58,
Also new to “A1C and Cardiovascular with the goal of keeping patients safe REWIND, and CARMELINA were added
Disease Outcomes” is the strategy to and avoiding diabetic ketoacidosis and to the section “Glucose-Lowering Ther-
introduce sodium–glucose cotransporter significant hypo- or hyperglycemia. apies and Cardiovascular Outcomes.”
S6 Summary of Revisions Diabetes Care Volume 43, Supplement 1, January 2020
The cardiovascular outcomes trials of Section 12. Older Adults Section 14. Management of Diabetes
available antihyperglycemic medications (https://doi.org/10.2337/dc20-S012) in Pregnancy
completed after the issuance of FDA 2008 Within the section “Neurocognitive (https://doi.org/10.2337/dc20-S0014)
guidelines table (Table 10.3) has been Function,” more information was added Greater emphasis has been placed
divided into three tables by drug class on the importance of assessment for on preconception care for women
(Table 10.3A on DPP-4 Inhibitors; Table cognitive decline and impairment. with diabetes, and a recommendation
10.3B on GLP-1 receptor agonists; and A new recommendation (12.14) urg- (14.5) focusing on nutrition, diabetes
Table 10.3C on SGLT2 inhibitors). ing providers to consider cost of care education, and screening for diabetes
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and insurance coverage when prescrib- related complications was added. A
Section 11. Microvascular Complications ing medications to older adults to reduce new table (Table 14.1) was also added
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and Foot Care the risk of cost-related nonadherence on preconception education, medical
(https://doi.org/10.2337/dc20-S011) was added to the section “Pharmacologic assessment, and screening.
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The recommendation on screening for Therapy.” The GLP-1 receptor agonist Recommendations (14.9–14.12) on
chronic kidney disease (11.1) has been and SGLT2 inhibitor discussions were use of continuous glucose monitors
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modified toincludetwice-yearlyscreenings expanded in this section as well. and measuring glycemia in pregnancy
A new section titled “Special Con- were added to the section “Glycemic
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for certain patients. A treatment recom-
mendation (11.3) was modified to provide siderations for Older Adults With Targets in Pregnancy” to provide more
more detail on use of SGLT2 inhibitors and Type 1 Diabetes” was added to ad- information on their utility.
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GLP-1 receptor agonists in patients with dress the treatment of this growing Further discussion has been added
type 2 diabetes and diabetic kidney disease. population. regarding when insulin may not be
A new recommendation (11.5) was added an option for some women with GDM,
about avoiding discontinuation of RAS Section 13. Children and Adolescents and how oral agents may play a role in
s
blockade in response to minor increases (https://doi.org/10.2337/dc20-S013) treatment in certain circumstances.
in serum creatinine in the absence of
volume depletion.
te
To provide more detail for individual-
izing targets, new A1C goal recommen-
The section “Postpartum Care” was
expanded to include recommenda-
be
Additional information on acute kidney dations (13.21–13.24) were added to the tions (14.16–14.22) and supporting
injury was added to the section “Chronic section “Glycemic Control.” evidence on postpartum insulin re-
Kidney Disease,” with information on in- In the section “Management of Cardio- quirements, management of women
ia
creased serum creatinine levels. vascular Risk Factors,” the recommenda- with a history of GDM and risks of
More findings were added from the tions for screening and treatment of
D
ommendations (11.16 and 11.17) and vated blood pressure. The dyslipidemia Section 15. Diabetes Care in the
supportive text were revised to include testing recommendation (13.36) was Hospital
consideration of retinal photograph with also modified, and more evidence was (https://doi.org/10.2337/dc20-S0015)
ic
remote reading or use of a validated as- added to the dyslipidemia screening Discussion of new studies supporting
sessment tool as a way to improve screen- section. the use of closed-loop insulin delivery
er
ing access. The retinopathy screening recommen- with linked pump/sensor devices to
The section “Foot Care” was updated dation for type 1 diabetes (13.46) has been control blood glucose was added to
Am
with more evidence on therapeutic revised based on new evidence supporting the type 1 diabetes section “Transi-
footwear and evaluation for peripheral a lower frequency of eye examinations tioning Intravenous to Subcutaneous
arterial disease. than previously recommended. Insulin.”
Figure 11.1 was introduced (in place of A new recommendation (13.67) was New evidence was also added to
19
2019 Table 11.1dCKD Stages and Cor- added to the section “Pharmacologic Man- the section “Preventing Admissions and
responding Focus of Kidney-Related agement” for type 2 diabetes due to new Readmissions.”
Care) to show the risk of chronic kidney evidence and FDA approval of liraglutide in
20
disease progression, frequency of visits, children 10 years of age or older. Section 16. Diabetes Advocacy
and referral to nephrology according to A new recommendation (13.76) on (https://doi.org/10.2337/dc20-S016)
estimated glomerular filtration rate and pharmacologic treatment of hyperten- No changes have been made to this
©
n
of Medical Care in Diabetesd2020
tio
Diabetes Care 2020;43(Suppl. 1):S7–S13 | https://doi.org/10.2337/dc20-S001
a
ci
so
As
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
s
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-
SPPC), are responsible for updating the Standards of Care annually, or more
te
frequently as warranted. For a detailed description of ADA standards, statements,
be
and reports, as well as the evidence-grading system for ADA’s clinical practice
recommendations, please refer to the Standards of Care Introduction (https://doi
.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care
ia
Recommendations
1.1 Ensure treatment decisions are timely, rely on evidence-based guidelines, and
are made collaboratively with patients based on individual preferences,
ic
relevant data metrics to improve processes of care and health outcomes, with
simultaneous emphasis on care costs. B
20
including the distribution of health outcomes within the group”; these outcomes can
be measured in terms of health outcomes (mortality, morbidity, health, and functional
status), disease burden (incidence and prevalence), and behavioral and metabolic
factors (exercise, diet, A1C, etc.) (1). Clinical practice recommendations for health care Suggested citation: American Diabetes Association.
providers are tools that can ultimately improve health across populations; however, 1. Improving care and promoting health in pop-
for optimal outcomes, diabetes care must also be individualized for each patient. Thus, ulations: Standards of Medical Care in Diabetesd
efforts to improve population health will require a combination of system-level and 2020. Diabetes Care 2020;43(Suppl. 1):S7–S13
patient-level approaches. With such an integrated approach in mind, the American © 2019 by the American Diabetes Association.
Diabetes Association (ADA) highlights the importance of patient-centered care, Readers may use this article as long as the work
is properly cited, the use is educational and not
defined as care that considers individual patient comorbidities and prognoses; is for profit, and the work is not altered. More infor-
respectful of and responsive to patient preferences, needs, and values; and ensures mation is available at http://www.diabetesjournals
that patient values guide all clinical decisions (2). Clinical practice recommendations, .org/content/license.
S8 Improving Care and Promoting Health Diabetes Care Volume 43, Supplement 1, January 2020
whether based on evidence or expert Chronic Care Model diabetes care delivery, including oppor-
opinion, are intended to guide an overall Numerous interventions to improve ad- tunities and challenges (15).
approach to care. The science and art of herence to the recommended standards
Strategies for System-Level Improvement
medicine come together when the clinician have been implemented. However, a
major barrier to optimal care is a delivery Optimal diabetes management requires
is faced with making treatment recommen-
system that is often fragmented, lacks an organized, systematic approach and
dations for a patient who may not meet the
clinical information capabilities, dupli- the involvement of a coordinated team
eligibility criteria used in the studies on
cates services, and is poorly designed of dedicated health care professionals
which guidelines are based. Recognizing
working in an environment where
n
that one size does not fit all, the standards for the coordinated delivery of chronic
care. The Chronic Care Model (CCM) patient-centered high-quality care is a
presented here provide guidance for when
tio
takes these factors into consideration priority (6,16,17). While many diabetes
and how to adapt recommendations for an
and is an effective framework for im- processes of care have improved nation-
individual.
ally in the past decade, the overall quality
a
proving the quality of diabetes care (8).
of care for patients with diabetes remains
ci
Care Delivery Systems Six Core Elements. The CCM includes six suboptimal (3). Efforts to increase the
The proportion of patients with diabetes core elements to optimize the care of quality of diabetes care include provid-
so
who achieve recommended A1C, blood patients with chronic disease: ing care that is concordant with evidence-
pressure, and LDL cholesterol levels has
based guidelines (18); expanding the
remained stagnant in recent years (3). In 1. Delivery system design (moving from a
As
role of teams to implement more in-
2013–2016, 64% of adults with diag- reactive to a proactive care delivery tensive disease management strategies
nosed diabetes met individualized A1C system where planned visits are coordi- (6,19,20); tracking medication-taking be-
target levels, 70% achieved recommen- nated through a team-based approach) havior at a systems level (21); redesigning
s
ded blood pressure control, 57% met the 2. Self-management support the organization of the care process
LDL cholesterol target level, and 85%
te
3. Decision support (basing care on (22); implementing electronic health record
were nonsmokers (3). Only 23% met evidence-based, effective care guide- tools (23,24); empowering and educating
targets for glycemic, blood pressure, lines)
be
patients (25,26); removing financial bar-
and cholesterol measures while also 4. Clinical information systems (using reg- riers and reducing patient out-of-pocket
avoiding smoking (3). The mean A1C istries that can provide patient-specific costs for diabetes education, eye exams,
ia
nationally among people with diabetes and population-based support to the diabetes technology, and necessary med-
increased slightly from 7.3% in 2005– care team) ications (6); assessing and addressing psy-
D
2008 to 7.5% in 2013–2016 based on the 5. Community resources and policies chosocial issues (27,28); and identifying,
National Health and Nutrition Examina- (identifying or developing resources developing, and engaging community re-
tion Survey (NHANES), with younger to support healthy lifestyles)
an
in 53,436 primary care patients with design and implement more effective
other social hardships, and/or limited type 2 diabetes suggested that the use health care delivery systems for those
English proficiency, face particular chal-
Am
tice settings indicates that substantial lar disease (CVD) risk by 56.6%, micro- and prioritize timely and appropriate
system-level improvements are still vascular complications by 11.9%, and intensification of lifestyle and/or phar-
needed. mortality by 66.1% (9). The same study macologic therapy for patients who have
20
Diabetes poses a significant financial suggested that health care utilization was not achieved the recommended meta-
burden to individuals and society. It is lower in the CCM group, resulting in bolic targets (30–32). Strategies shown to
©
estimated that the annual cost of diag- health care savings of $7,294 per indi- improve care team behavior and thereby
nosed diabetes in 2017 was $327 billion, vidual over the study period (10). catalyze reductions in A1C, blood pres-
including $237 billion in direct medical Redefining the roles of the health care sure, and/or LDL cholesterol include en-
costs and $90 billion in reduced produc- delivery team and empowering patient gaging in explicit and collaborative goal
tivity. After adjusting for inflation, eco- self-management are fundamental to the setting with patients (33,34); identifying
nomic costs of diabetes increased by 26% successful implementation of the CCM (11). and addressing language, numeracy, or
from 2012 to 2017 (7). This is attributed to Collaborative, multidisciplinary teams are cultural barriers to care (35–37); inte-
the increased prevalence of diabetes and best suited to provide care for people with grating evidence-based guidelines and
the increased cost per person with di- chronic conditions such as diabetes and clinical information tools into the process
abetes. Ongoing population health strat- to facilitate patients’ self-management of care (18,38,39); soliciting performance
egies are needed in order to reduce costs (12–14). There are references to guide feedback, setting reminders, and provid-
and provide optimized care. the implementation of the CCM into ing structured care (e.g., guidelines,
care.diabetesjournals.org Improving Care and Promoting Health S9
formal case management, and patient patients who are prescribed insulin report and the use of accurate, reliable data
education resources) (6); and incorporat- cost-related insulin underuse (47). The cost metrics that include sociodemographic
ing care management teams including of insulin has continued to increase in variables to examine health equity within
nurses, dietitians, pharmacists, and other recent years for reasons that are not and across populations (59).
providers (19,40). Initiatives such as the entirely clear. There are recommenda- In addition to quality improvement
Patient-Centered Medical Home show tions from the ADA Insulin Access efforts, other strategies that simulta-
promise for improving health outcomes and Affordability Working Group for ap- neously improve the quality of care and
by fostering comprehensive primary care proaches to this issue from a systems potentially reduce costs are gaining mo-
n
and offering new opportunities for team- level. Recommendations including concepts mentum and include reimbursement
based chronic disease management (41). such as cost-sharing for insured people structures that, in contrast to visit-based
tio
with diabetes should be based on the billing, reward the provision of appropriate
Telemedicine
lowest price available, list price for insulins and high-quality care to achieve metabolic
Telemedicine is a growing field that may
a
that closely reflect net price, and health goals (60) and incentives that accommo-
increase access to care for patients with
ci
plans that ensure that people with di- date personalized care goals (6,61).
diabetes. Telemedicine is defined as the abetes can access insulin without undue
use of telecommunications to facilitate
so
administrative burden or excessive cost
remote delivery of health-related serv- (48). TAILORING TREATMENT FOR
ices and clinical information (42). A grow- SOCIAL CONTEXT
As
ing body of evidence suggests that Access to Care and Quality Improvement
Recommendations
various telemedicine modalities may The Affordable Care Act has resulted in
1.5 Providers should assess social con-
be effective at reducing A1C in patients increased access to care for many indi-
text, including potential food in-
with type 2 diabetes compared with viduals with diabetes with an emphasis
s
security, housing stability, and
usual care or in addition to usual care on the protection of people with preex-
financial barriers, and apply that
te
(43). For rural populations or those with isting conditions, health promotion, and
information to treatment deci-
limited physical access to health care, disease prevention (49). In fact, health
sions. A
be
telemedicine has a growing body of insurance coverage increased from 84.7%
1.6 Refer patients to local commu-
evidence for its effectiveness, particu- in 2009 to 90.1% in 2016 for adults with
nity resources when available. B
larly with regard to glycemic control as diabetes aged 18–64 years. Coverage for 1.7 Provide patients with self-
ia
measured by A1C (44–46). Interactive those $65 years remained near universal management support from lay
strategies that facilitate communication (50). Patients who have either private or
D
messaging and those that incorporate (51). As mandated by the Affordable Care
medication adjustment, appear more Act,theAgencyfor Healthcare Research and Health inequities related to diabetes and
effective. There is limited data avail- Quality developed a National Quality Strat- its complications are well documented
ic
able on the cost-effectiveness of these egy based on the triple aims that include and are heavily influenced by social de-
strategies. improving the health of a population,
er
experience, as well as cost, in assessing the and environmental factors and the pre-
been shown to improve patient self-
quality of diabetes care (54,55). Informa- vention and treatment of diabetes and
management, satisfaction, and glucose
tion and guidance specific to quality im- has issued a call for research that seeks to
20
ioral strategies (goal setting, problem the relationships between these varia-
solving), and engagement with psycho- formation website and the National In- bles might be modified for the preven-
social concerns (28). For more informa- stitute of Diabetes and Digestive and tion and management of diabetes (68).
tion on DSMES, see Section 5 “Facilitating Kidney Diseases report on diabetes care While a comprehensive strategy to re-
Behavior Change and Well-being to Im- and quality (56,57). Using patient registries duce diabetes-related health inequities
prove Health Outcomes” (https://doi and electronic health records, health sys- in populations has not been formally stud-
.org/10.2337/dc20-S005). tems can evaluate the quality of diabetes ied, general recommendations from other
care being delivered and perform inter- chronic disease models can be drawn upon
Cost Considerations vention cycles as part of quality improve- to inform systems-level strategies in di-
The cost of diabetes medications, partic- ment strategies (58). Critical to these abetes. For example, the National Academy
ularly insulin, is an ongoing barrier to efforts is provider adherence to clinical of Medicine has published a framework for
achieving glycemic goals. Up to 25% of practice recommendations (see Table 4.1) educating health care professionals on the
S10 Improving Care and Promoting Health Diabetes Care Volume 43, Supplement 1, January 2020
importance of social determinants of health with low adherence to taking medica- are homeless need secure places to keep
(69). Furthermore, there are resources tions appropriately and recommended their diabetes supplies, as well as re-
available for the inclusion of standardized self-care behaviors, depression, diabetes frigerator access to properly store their
sociodemographic variables in electronic distress, and worse glycemic control insulin and take it on a regular schedule.
medical records to facilitate the measure- when compared with individuals who Risk for homelessness can be ascertained
ment of health inequities as well as the are food secure (78,79). Older adults using a brief risk assessment tool de-
impact of interventions designed to re- with food insecurity are more likely to veloped and validated for use among
duce those inequities (70–72). have emergency department visits and veterans (85). Given the potential chal-
n
Social determinants of health are not hospitalizations compared with older lenges, providers who care for homeless
individuals should be familiar with re-
tio
always recognized and often go undis- adults who do not report food insecurity
cussed in the clinical encounter (65). A (80). Risk for food insecurity can be sources or have access to social workers
studyby Piette et al. (73) found that among assessed with a validated two-item that can facilitate temporary housing for
a
patients with chronic illnesses, two-thirds screening tool (81) that includes the their patients as a way to improve di-
statements: 1) “Within the past12 months
ci
of those who reported not taking medi- abetes care.
cations as prescribed due to cost never we worried whether our food would run
so
shared this with their physician. In a study out before we got money to buy more” Migrant and Seasonal Agricultural
using data from the National Health In- and 2) “Within the past 12 months the Workers
terview Survey (NHIS), Patel et al. (65) food we bought just didn’t last and we Migrant and seasonal agricultural workers
As
found that one-half of adults with diabetes didn’t have money to get more.” An may have a higher risk of type 2 diabetes
reported financial stress and one-fifth affirmative response to either statement than the overall population. While mi-
reported food insecurity. One population had a sensitivity of 97% and specificity of grant farmworker-specific data are lack-
s
in which such issues must be considered is 83%. ing, most agricultural workers in the U.S.
are Latino, a population with a high rate of
te
older adults, where social difficulties may
Treatment Considerations type 2 diabetes. Living in severe poverty
impair the quality of life and increase the
In those with diabetes and food insecu- brings with it food insecurity, high chronic
be
risk of functional dependency (74) (see
rity, the priority is mitigating the increased stress, and increased risk of diabetes;
Section 12 “Older Adults,” https://doi.org/
risk for uncontrolled hyperglycemia and there is also an association between
10.2337/dc20-S012, for a detailed discus-
severe hypoglycemia. Reasons for the
ia
sion of social considerations in older the use of certain pesticides and the
increased risk of hyperglycemia include incidence of diabetes (85a).
adults). Creating systems-level mecha-
the steady consumption of inexpensive
D
nisms to screen for social determinants Data from the Department of Labor
carbohydrate-rich processed foods, binge indicates that there are 2.5–3 million
of health may help overcome structural
eating, financial constraints to filling di- agricultural workers in the U.S., and these
barriers and communication gaps be-
an
around factors that significantly impact data, 174 health centers across the U.S.
following the administration of sulfony- reported that they provided health care
treatment during the clinical encounter.
lureas or insulin. See Table 9.1 for drug- services to 579,806 adult agricultural
Am
Food Insecurity should consider these factors when mak- ceiving care. Migration, which may occur
Food insecurity is the unreliable avail- ing treatment decisions in people with as frequently as every few weeks for
ability of nutritious food and the inability food insecurity and seek local resources farmworkers, disrupts care. Cultural
20
to consistently obtain food without re- that might help patients with diabetes and and linguistic barriers, lack of transpor-
sorting to socially unacceptable practi- their family members to more regularly tation and money, lack of available work
ces. Over 18% of the U.S. population obtain nutritious food (82).
©
workers and community resources, as Intern Med. 12 August 2019 [Epub ahead of print] a large-scale hypertension program. JAMA 2013;
available, to assist with removing barriers DOI: 10.1001/jamainternmed.2019.2396 310:699–705
4. Kerr EA, Heisler M, Krein SL, et al. Beyond 20. Peikes D, Chen A, Schore J, Brown R. Effects
to care.
comorbidity counts: how do comorbidity type of care coordination on hospitalization, quality of
and severity influence diabetes patients’ treat- care, and health care expenditures among Medi-
Language Barriers ment priorities and self-management? J Gen care beneficiaries: 15 randomized trials. JAMA
Providers who care for non-English speakers Intern Med 2007;22:1635–1640 2009;301:603–618
should develop or offer educational pro- 5. Fernandez A, Schillinger D, Warton EM, et al. 21. Raebel MA, Schmittdiel J, Karter AJ,
grams and materials in multiple languages Language barriers, physician-patient language Konieczny JL, Steiner JF. Standardizing terminol-
concordance, and glycemic control among in- ogy and definitions of medication adherence and
n
with the specific goals of preventing di-
sured Latinos with diabetes: the Diabetes Study persistence in research employing electronic
abetes and building diabetes awareness in
tio
of Northern California (DISTANCE). J Gen Intern databases. Med Care 2013;51(Suppl. 3):S11–S21
people who cannot easily read or write in Med 2011;26:170–176 22. Feifer C, Nemeth L, Nietert PJ, et al. Different
English. The National Standards for Cultur- 6. TRIAD Study Group. Health systems, patients paths to high-quality care: three archetypes of
a
ally and Linguistically Appropriate Services factors, and quality of care for diabetes: a syn- top-performing practice sites. Ann Fam Med
in Health and Health Care (National CLAS thesis of findings from the TRIAD study. Diabetes 2007;5:233–241
ci
Care 2010;33:940–947 23. Reed M, Huang J, Graetz I, et al. Outpatient
Standards) provide guidance on how health electronic health records and the clinical care and
7. American Diabetes Association. Economic
so
care providers can reduce language barriers costs of diabetes in the U.S. in 2017. Diabetes outcomes of patients with diabetes mellitus. Ann
by improving their cultural competency, Care 2018;41:917–928 Intern Med 2012;157:482–489
addressing health literacy, and ensuring 8. Stellefson M, Dipnarine K, Stopka C. The 24. Cebul RD, Love TE, Jain AK, Hebert CJ.
As
communication with language assistance chronic care model and diabetes management Electronic health records and quality of diabetes
in US primary care settings: a systematic review. care. N Engl J Med 2011;365:825–833
(87). The National CLAS Standards website
Prev Chronic Dis 2013;10:E26 25. Battersby M, Von Korff M, Schaefer J, et al.
offers a number of resources and ma- 9. Wan EYF, Fung CSC, Jiao FF, et al. Five-year Twelve evidence-based principles for implement-
terials that can be used to improve the
s
effectiveness of the multidisciplinary Risk Assess- ing self-management support in primary care. Jt
quality of care delivery to non-English- ment and Management Programme-Diabetes Comm J Qual Patient Saf 2010;36:561–570
speaking patients (87).
te
Mellitus (RAMP-DM) on diabetes-related compli-
cations and health service uses-a population-based
26. Grant RW, Wald JS, Schnipper JL, et al. Practice-
linked online personal health records for type 2
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Community Support and propensity-matched cohort study. Diabetes diabetes mellitus: a randomized controlled trial.
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Identification or development of com-
10. Jiao FF, Fung CSC, Wan EYF, et al. Five-year 27. Young-Hyman D, de Groot M, Hill-Briggs F,
munity resources to support healthy life- Gonzalez JS, Hood K, Peyrot M. Psychosocial care
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Agency for Healthcare Research and millennium. Health Aff (Millwood) 2009;28:75–85 standards for diabetes self-management education
Quality, and others as a means of pro- 12. Piatt GA, Anderson RM, Brooks MM, et al. 3- and support. Diabetes Care 2017;40:1409–1419
moting translation of clinical recommen- Year follow-up of clinical and behavioral im- 29. Pullen-Smith B, Carter-Edwards L, Leathers
ic
dations for lifestyle modification in provements following a multifaceted diabetes KH. Community health ambassadors: a model for
real-world settings (88). Community health care intervention: results of a randomized con- engaging community leaders to promote better
er
trolled trial. Diabetes Educ 2010;36:301–309 health in North Carolina. J Public Health Manag
workers (CHWs) (89), peer supporters
13. Katon WJ, Lin EHB, Von Korff M, et al. Col- Pract 2008;14(Suppl.):S73–S81
(90–92), and lay leaders (93) may assist laborative care for patients with depression and 30. Davidson MB. How our current medical care
Am
in the delivery of DSMES services (70,94), chronic illnesses. N Engl J Med 2010;363:2611– system fails people with diabetes: lack of timely,
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and the delivery of care consistent with the ment intensification and risk factor control: to-
19
health worker who is a trusted member of chronic care model in primary care settings: ward more clinically relevant quality measures.
and/or has an unusually close understand- a STARNet study. Med Care 2007;45:1129–1134 Med Care 2009;47:395–402
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20
can be part of a cost-effective, evidence- management services for complex diabetes man- Intensification of antihyperglycemic therapy
based strategy to improve the manage- agement: a practical overview. Curr Diab Rep among patients with incident diabetes: a Surveil-
2018;18:135 lance Prevention and Management of Diabetes
ment of diabetes and cardiovascular risk
©
16. Tricco AC, Ivers NM, Grimshaw JM, et al. Mellitus (SUPREME-DM) study. Pharmacoepide-
factors in underserved communities and Effectiveness of quality improvement strategies miol Drug Saf 2014;23:699–710
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2010;33:478–484 Pages/resourcedetail.aspx. Accessed 25 October to reduce racial and ethnic disparities in
41. Bojadzievski T, Gabbay RA. Patient-centered 2019 health care. J Gen Intern Med 2012;27:
medical home and diabetes. Diabetes Care 2011; 57. Diabetes Care and Quality: Past, Present, 992–1000
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34:1047–1053 and Future [Internet], 2017. Available from: 72. National Quality Forum. National Voluntary
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42. American Telemedicine Association. About https://www.niddk.nih.gov/health-information/ Consensus Standards for Ambulatory Cared
Telehealth [Internet], 2018.. Available from: health-communication-programs/ndep/health- Measuring Healthcare Disparities [Internet], 2008.
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about-telemedicine/telemedicine-faqs. Accessed quality-care/diabetes-care-quality/Pages/default Publications/2008/03/National_Voluntary_Consensus_
25 October 2019 .aspx. Accessed 25 October 2019 Standards_for_Ambulatory_Care%E2%80%
43. Lee SWH, Chan CKY, Chua SS, Chaiyakunapruk 58. O’Connor PJ, Sperl-Hillen JM, Fazio CJ, Averbeck 94Measuring_Healthcare_Disparities.aspx.
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N. Comparative effectiveness of telemedicine BM, Rank BH, Margolis KL. Outpatient diabetes Accessed 25 October 2019
strategies on type 2 diabetes management: a sys- clinical decision support: current status and future 73. Piette JD, Heisler M, Wagner TH. Cost-
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tematic reviewand networkmeta-analysis. Sci Rep directions. Diabet Med 2016;33:734–741 related medication underuse among chronically
2017;7:12680 59. Centers for Medicare & Medicaid Services.. ill adults: the treatments people forgo, how
44. Faruque LI, Wiebe N, Ehteshami-Afshar A, CMS Equity Plan for Medicare [Internet], 2017. often, and who is at risk. Am J Public Health
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et al.; Alberta Kidney Disease Network. Effect of Available from: https://www.cms.gov/About- 2004;94:1782–1787
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a systematic review and meta-analysis of ran- equity-plan.html. Accessed 25 October 2019 Correlates of quality of life in older adults
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domized trials. CMAJ 2017;189:E341–E364 60. Rosenthal MB, Cutler DM, Feder J. The ACO with diabetes: the Diabetes & Aging Study. Di-
45. Marcolino MS, Maia JX, Alkmim MBM, rules–striking the balance between participation abetes Care 2011;34:1749–1753
Boersma E, Ribeiro AL. Telemedicine applica- and transformative potential. N Engl J Med 2011; 75. O’Gurek DT, Henke C. A practical approach to
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tion in the care of diabetes patients: systematic 365:e6 screening for social determinants of health. Fam
review and meta-analysis. PLoS One 2013;8: 61. Washington AE, Lipstein SH. The Patient- Pract Manag 2018;25:7–12
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e79246 Centered Outcomes Research Institutedpromoting 76. Walker RJ, Grusnick J, Garacci E, Mendez C,
46. Heitkemper EM, Mamykina L, Travers J, better information, decisions, and health. N Engl J Egede LE. Trends in food insecurity in the USA for
Smaldone A. Do health information technology Med 2011;365:e31 individuals with prediabetes, undiagnosed di-
self-management interventions improve glycemic 62. Hutchinson RN, Shin S. Systematic review of abetes, and diagnosed diabetes. J Gen Intern
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abetes? A systematic review and meta-analysis. J associated factors among American Indian and 77. Berkowitz SA, Karter AJ, Corbie-Smith G, et al.
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Am Med Inform Assoc 2017;24:1024–1035 Alaska Native populations. PLoS One 2014;9: Food insecurity, food “deserts,” and glycemic
47. Herkert D, Vijayakumar P, Luo J, et al. Cost- e80973 control in patients with diabetes: a longitudinal
related insulin underuse among patients with di- 63. Borschuk AP, Everhart RS. Health disparities analysis. Diabetes Care 2018;41:1188–1195
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abetes. JAMA Intern Med 2019;179:112–114 among youth with type 1 diabetes: a systematic 78. Heerman WJ, Wallston KA, Osborn CY, et al.
48. Cefalu WT, Dawes DE, Gavlak G, et al.; Insulin review of the current literature. Fam Syst Health Food insecurity is associated with diabetes self-
Access and Affordability Working Group. Insulin 2015;33:297–313 care behaviours and glycaemic control. Diabet
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Access and Affordability Working Group: Conclu- 64. Walker RJ, Strom Williams J, Egede LE. In- Med 2016;33:844–850
sions and recommendations. Diabetes Care 2018; fluence of race, ethnicity and social determinants 79. Silverman J, Krieger J, Kiefer M, Hebert P,
41:1299–1311 of health on diabetes outcomes. Am J Med Sci Robinson J, Nelson K. The relationship between
49. Myerson R, Laiteerapong N. The Affordable 2016;351:366–373 food insecurity and depression, diabetes distress
Care Act and diabetes diagnosis and care:exploring 65. Patel MR, Piette JD, Resnicow K, Kowalski- and medication adherence among low-income
the potential impacts. Curr Diab Rep 2016;16:27 Dobson T, Heisler M. Social determinants of patients with poorly-controlled diabetes. J Gen
50. Casagrande SS, McEwen LN, Herman WH. health, cost-related nonadherence, and cost- Intern Med 2015;30:1476–1480
Changes in health insurance coverage under the reducing behaviors among adults with diabetes: 80. Schroeder EB, Zeng C, Sterrett AT, Kimpo TK,
Affordable Care Act: a national sample of U.S. findings from the National Health Interview Paolino AR, Steiner JF. The longitudinal relation-
adults with diabetes, 2009 and 2016. Diabetes Survey. Med Care 2016;54:796–803 ship between food insecurity in older adults with
Care 2018;41:956–962 66. Steve SL, Tung EL, Schlichtman JJ, Peek ME. diabetes and emergency department visits, hos-
51. Insurance coverage and diabetes quality Social disorder in adults with type 2 diabetes: pitalizations, hemoglobin A1c, and medication
indicators among patients in NHANES. Am J building on race, place, and poverty. Curr Diab adherence. J Diabetes Complications 2019;33:
Manag Care 2016;22:484-90 Rep 2016;16:72 289–295
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81. Hager ER, Quigg AM, Black MM, et al. De- q5tall&year52018&state5&fd5mh. Accessed 93. Foster G, Taylor SJC, Eldridge SE, Ramsay J,
velopment and validity of a 2-item screen to 25 October 2019 Griffiths CJ. Self-management education pro-
identify families at risk for food insecurity. Pe- 87. U.S. Department of Health & Human Serv- grammes by lay leaders for people with chronic
diatrics 2010;126:e26–e32 ices. Think Cultural Health [Internet], 2017. Avail- conditions. Cochrane Database Syst Rev 2007 (4):
82. Seligman HK, Schillinger D. Hunger and able from: https://www.thinkculturalhealth.hhs CD005108
socioeconomic disparities in chronic disease. .gov/. Accessed 25 October 2019 94. Piatt GA, Rodgers EA, Xue L, Zgibor JC.
N Engl J Med 2010;363:6–9 88. U.S. Department of Health & Human Serv-
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homelessness: an integrated review. Curr Diab Available from: http://www.ahrq.gov/professionals/ from Project SEED (Support, Education, and
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84. Bernstein RS, Meurer LN, Plumb EJ, Jackson .html. Accessed 25 October 2019
JL. Diabetes and hypertension prevalence in 89. Egbujie BA, Delobelle PA, Levitt N, Puoane T, 95. Understanding Scope and Competencies:
homeless adults in the United States: a system- Sanders D, van Wyk B. Role of community health A Contemporary Look at the United States
atic review and meta-analysis. Am J Public Health workersintype2diabetesmellitusself-management: Community Health Worker Field: Progress Re-
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2015;105:e46–e60 a scoping review. PLoSOne 2018;13:e0198424 port of the Community Health Worker (CHW)
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85. Montgomery AE, Fargo JD, Kane V, Culhane 90. Heisler M, Vijan S, Makki F, Piette JD. Di- Core Consensus (C3) Project: Building National
DP. Development and validation of an instru- abetes control with reciprocal peer support Consensus on CHW Core Roles, Skills, and Qual-
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ment to assess imminent risk of homelessness versus nurse care management: a randomized ities [Internet], 2016. Available from: http://files
among veterans. Public Health Rep 2014;129: trial. Ann Intern Med 2010;153:507–515 .ctctcdn.com/a907c850501/1c1289f0-88cc-
428–436 91. Long JA, Jahnle EC, Richardson DM, Loewenstein 49c3-a238-66def942c147.pdf. Accessed 25 Oc-
85a. Evangelou E, Ntritsos G, Chondrogiorgi M, G, Volpp KG. Peer mentoring and financial incentives
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Kavvoura FK, Hernández AF, Ntzani EE, Tzoulaki, I. to improve glucose control in African American
96. Community Health WorkersHelp PatientsMan-
Exposure to pesticides and diabetes: a systematic veterans: a randomized trial. Ann Intern Med 2012;
review and meta-analysis. Environment Interna- 156:416–424 age Diabetes [Internet], 2017. The Guide to Com-
tional 2016;91:60–68 92. Fisher EB, Boothroyd RI, Elstad EA, et al. Peer munity Preventive Services (The Community Guide).
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86. U.S. Department of Health & Human Services, support of complex health behaviors in prevention Available from: https://www.thecommunityguide.
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Health Resources & Services Administration. and disease management with special reference to
2018 Health Center Data [Internet], 2018. Available diabetes: systematic reviews. Clin Diabetes Endo- patients-manage-diabetes. Accessed 25 October
from: https://bphc.hrsa.gov/uds/datacenter.aspx? crinol 2017;3:4 2019
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S14 Diabetes Care Volume 43, Supplement 1, January 2020
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Care in Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S14–S31 | https://doi.org/10.2337/dc20-S002
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2. CLASSIFICATION AND DIAGNOSIS OF DIABETES
s
the components of diabetes care, general treatment goals and guidelines, and tools
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to evaluate quality of care. Members of the ADA Professional Practice Committee
(https://doi.org/10.2337/dc20-SPPC), a multidisciplinary expert committee, are
be
responsible for updating the Standards of Care annually, or more frequently as warranted.
For a detailed description of ADA standards, statements, and reports, as well as the
evidence-grading system for ADA’s clinical practice recommendations, please refer to the
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CLASSIFICATION
Diabetes can be classified into the following general categories:
ic
insulin deficiency)
2. Type 2 diabetes (due to a progressive loss of adequate b-cell insulin secretion
frequently on the background of insulin resistance)
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the exocrine pancreas (such as cystic fibrosis and pancreatitis), and drug- or
chemical-induced diabetes (such as with glucocorticoid use, in the treatment of
HIV/AIDS, or after organ transplantation)
20
This section reviews most common forms of diabetes but is not comprehensive. For
©
n
c 2-h PG 140–199 mg/dL (7.8–11.0 mmol/L)
c A1C 5.7–6.4% (39–47 mmol/mol) or $10%
tio
increase in A1C
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symptoms seen in children and may expe- serve as a framework for future research mainly been demonstrated among indi-
rience temporary remission from the need and regulatory decision-making (8,9). There viduals who have impaired glucose tol-
so
for insulin (3–5). Occasionally, patients is debate as to whether slowly progressive erance (IGT) with or without elevated
with type 2 diabetes may present with autoimmune diabetes with an adult onset fasting glucose, not for individuals with
DKA (6), particularly ethnic minorities (7). should be termed latent autoimmune di- isolated impaired fasting glucose (IFG)
As
It is important for the provider to realize abetes in adults (LADA) or whether the or for those with prediabetes defined
that classification of diabetes type is not clinical priority is awareness that slow auto- by A1C criteria.
always straightforward at presentation and immune b-cell destruction means there may The same tests may be used to screen
s
that misdiagnosis is common (e.g., adults be long duration of marginal insulin secre- for and diagnose diabetes and to detect
with type 1 diabetes misdiagnosed as hav- tory capacity. For the purpose of this clas- individuals with prediabetes (Table 2.2
ing type 2 diabetes; individuals with matu-
rity-onset diabetes of the young [MODY] te
sification, all forms of diabetes mediated by
autoimmune b-cell destruction are included
and Table 2.5). Diabetes may be identi-
fied anywhere along the spectrum of
be
misdiagnosed as having type 1 diabetes, under the rubric of type 1 diabetes. clinical scenariosdin seemingly low-
etc.). Although difficulties in distinguish- The paths to b-cell demise and dys- risk individuals who happen to have glu-
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ing diabetes type may occur in all age- function are less well defined in type 2 cose testing, in individuals tested based on
groups at onset, the diagnosis becomes diabetes, but deficient b-cell insulin se- diabetes risk assessment, and in symp-
D
more obvious over time. cretion, frequently in the setting of in- tomatic patients.
In both type 1 and type 2 diabetes, sulin resistance, appears to be the
various genetic and environmental fac- common denominator. Characterization Fasting and 2-Hour Plasma Glucose
an
tors can result in the progressive loss of of subtypes of this heterogeneous dis- The FPG and 2-h PG may be used to
b-cell mass and/or function that mani- order have been developed and vali- diagnose diabetes (Table 2.2). The con-
fests clinically as hyperglycemia. Once dated in Scandinavian and Northern
ic
forms of diabetes are at risk for devel- been confirmed in other ethnic and ra- dance between A1C and either glucose-
oping the same chronic complications, cial groups. Type 2 diabetes is associated based test. Compared with FPG and
although rates of progression may differ. with insulin secretory defects related
Am
persistent presence of two or more islet plasma glucose criteria, either the fast-
dardized to the Diabetes Control
autoantibodies is an almost certain pre- ing plasma glucose (FPG) value or the
and Complications Trial (DCCT)
dictor of clinical hyperglycemia and diabe- 2-h plasma glucose (2-h PG) value during
assay. B
tes. The rate of progression is dependent on a 75-g oral glucose tolerance test (OGTT),
2.2 Marked discordance between
the age at first detection of autoantibody, or A1C criteria (12) (Table 2.2).
measured A1C and plasma glu-
number ofautoantibodies, autoantibody Generally, FPG, 2-h PG during 75-g
cose levels should raise the pos-
specificity, and autoantibody titer. Glu- OGTT, and A1C are equally appropriate
sibility of A1C assay interference
cose and A1C levels rise well before the for diagnostic screening. It should be
due to hemoglobin variants (i.e.,
clinical onset of diabetes, making diag- noted that the tests do not necessarily
hemoglobinopathies) and con-
nosis feasible well before the onset of detect diabetes in the same individuals.
sideration of using an assay with-
DKA. Three distinct stages of type 1 di- The efficacy of interventions for primary
out interference or plasma blood
abetes can be identified (Table 2.1) and prevention of type 2 diabetes (13,14) has
S16 Classification and Diagnosis of Diabetes Diabetes Care Volume 43, Supplement 1, January 2020
cut point, greater cost, limited availabil- between measured A1C and plasma glu-
glucose criteria to diagnose di-
ity of A1C testing in certain regions of cose levels should prompt consideration
abetes. B
the developing world, and the imperfect that the A1C assay may not be reliable for
2.3 In conditions associated with an
correlation between A1C and average that individual. For patients with a hemo-
altered relationship between A1C
glucose in certain individuals. The A1C globin variant but normal red blood cell
and glycemia, such as sickle cell
test, with a diagnostic threshold of turnover, such as those with the sickle cell
disease, pregnancy (second and
$6.5% (48 mmol/mol), diagnoses only trait, an A1C assay without interference
third trimesters and the postpar-
30% of the diabetes cases identified col- from hemoglobin variants should be used.
tum period), glucose-6-phosphate
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lectively using A1C, FPG, or 2-h PG, ac- An updated list of A1C assays with inter-
dehydrogenase deficiency, HIV,
cording to National Health and Nutrition ferences is available at www.ngsp.org/
tio
hemodialysis, recent blood loss
Examination Survey (NHANES) data (16). interf.asp.
or transfusion, or erythropoietin
When using A1C to diagnose diabetes, African Americans heterozygous for
therapy, only plasma blood glu-
a
it is important to recognize that A1C is the common hemoglobin variant HbS
cose criteria should be used to
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an indirect measure of average blood may have, for any given level of mean
diagnose diabetes. B
glucose levels and to take other factors glycemia, lower A1C by about 0.3% than
so
into consideration that may impact he- those without the trait (20). Another ge-
The A1C test should be performed using
moglobin glycation independently of netic variant, X-linked glucose-6-phosphate
a method that is certified by the NGSP
glycemia, such as hemodialysis, preg- dehydrogenase G202A, carried by 11% of
As
(www.ngsp.org) and standardized or
nancy, HIV treatment (17,18), age, race/ African Americans, was associated with a
traceable to the Diabetes Control and
ethnicity, pregnancy status, genetic back- decrease in A1C of about 0.8% in homo-
Complications Trial (DCCT) reference as-
ground, and anemia/hemoglobinopathies. zygous men and 0.7% in homozygous
say. Although point-of-care A1C assays
s
(See OTHER CONDITIONS ALTERING THE RELATION- women compared with those without
may be NGSP certified or U.S. Food and SHIP OF A1C AND GLYCEMIA below for more the variant (21).
Drug Administration approved for diag-
nosis, proficiency testing is not always
information.)
te Even in the absence of hemoglobin
variants, A1C levels may vary with race/
be
mandated for performing the test. There- Age
ethnicity independently of glycemia
fore, point-of-care assays approved for The epidemiological studies that formed
(22–24). For example, African Americans
diagnostic purposes should only be con- the basis for recommending A1C to
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pared with FPG and OGTT, including lower levels of 1,5-anhydroglucitol, sug-
greater convenience (fasting not re- Race/Ethnicity/Hemoglobinopathies gesting that their glycemic burden (par-
quired), greater preanalytical stability, ticularly postprandially) may be higher
Am
Table 2.2—Criteria for the diagnosis of diabetes Other Conditions Altering the Relationship
FPG $126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* of A1C and Glycemia
20
by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose cell disease, pregnancy (second and
dissolved in water.* third trimesters), glucose-6-phosphate
OR dehydrogenase deficiency (31,32), he-
A1C $6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that modialysis, recent blood loss or trans-
is NGSP certified and standardized to the DCCT assay.* fusion, or erythropoietin therapy, only
OR plasma blood glucose criteria should be
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma used to diagnose diabetes (33). A1C is
glucose $200 mg/dL (11.1 mmol/L). less reliable than blood glucose mea-
DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; OGTT, oral glucose surement in other conditions such as
tolerance test; WHO, World Health Organization; 2-h PG, 2-h plasma glucose. *In the absence of the postpartum state (34–36), HIV
unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or treated with certain drugs (17), and
in two separate test samples.
iron-deficient anemia (37).
care.diabetesjournals.org Classification and Diagnosis of Diabetes S17
Confirming the Diagnosis knowing the plasma glucose level is modest fasting hyperglycemia that can
Unless there is a clear clinical diagnosis critical because, in addition to confirm- rapidly change to severe hyperglycemia
(e.g., patient in a hyperglycemic crisis or ing that symptoms are due to diabetes, and/or DKA with infection or other stress.
with classic symptoms of hyperglycemia it will inform management decisions. Adults may retain sufficient b-cell func-
and a random plasma glucose $200 Some providers may also want to know tion to prevent DKA for many years; such
mg/dL [11.1 mmol/L]), diagnosis requires the A1C to determine how long a patient individuals may have remission or de-
two abnormal test results from the same has had hyperglycemia. The criteria to creased insulin needs for months or years
sample (38) or in two separate test diagnose diabetes are listed in Table 2.2. and eventually become dependent on
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samples. If using two separate test sam- insulin for survival and are at risk for DKA
ples, it is recommended that the second TYPE 1 DIABETES (3–5,39,40). At this latter stage of the
tio
test, which may either be a repeat of the disease, there is little or no insulin se-
Recommendations
initial test or a different test, be per- cretion, as manifested by low or undetect-
2.4 Screening for type 1 diabetes risk
a
formed without delay. For example, if the able levels of plasma C-peptide. Immune-
with a panel of islet autoanti-
A1C is 7.0% (53 mmol/mol) and a repeat
ci
mediated diabetes is the most common
bodies is currently recommended
result is 6.8% (51 mmol/mol), the di- form of diabetes in childhood and ado-
in the setting of a research trial or
so
agnosis of diabetes is confirmed. If two lescence, but it can occur at any age, even
can be offered as an option for
different tests (such as A1C and FPG) are in the 8th and 9th decades of life.
first-degree family members of a
both above the diagnostic threshold Autoimmune destruction of b-cells
proband with type 1 diabetes. B
As
when analyzed from the same sample has multiple genetic predispositions
2.5 Persistence of autoantibodies is
or in two different test samples, this also and is also related to environmental
a risk factor for clinical diabetes
confirms the diagnosis. On the other factors that are still poorly defined. Al-
and may serve as an indication for
hand, if a patient has discordant results
s
though patients are not typically obese
intervention in the setting of
from two different tests, then the test when they present with type 1 diabetes,
te
a clinical trial. B
result that is above the diagnostic cut obesity is increasingly common in the
point should be repeated, with consid- general population and there is evidence
be
eration of the possibility of A1C assay Immune-Mediated Diabetes that it may also be a risk factor for type 1
interference. The diagnosis is made on This form, previously called “insulin- diabetes. As such, obesity should not
the basis of the confirmed test. For dependent diabetes” or “juvenile-onset
ia
nevertheless be considered to have islet cell autoantibodies and autoanti- immune hepatitis, myasthenia gravis,
diabetes. bodies to GAD (GAD65), insulin, the and pernicious anemia (see Section
All the tests have preanalytic and tyrosine phosphatases IA-2 and IA-2b, 4 “Comprehensive Medical Evaluation
ic
analytic variability, so it is possible and zinc transporter 8 (ZnT8). Numer- and Assessment of Comorbidities,”
that an abnormal result (i.e., above
er
the diagnostic cut point. This scenario of islet autoimmunity (www.clinicaltrials Some forms of type 1 diabetes have no
is likely for FPG and 2-h PG if the glucose .gov). Stage 1 of type 1 diabetes is defined known etiologies. These patients have per-
samples remain at room temperature by the presence of two or more of these manent insulinopenia and are prone to DKA
and are not centrifuged promptly. Be- autoimmune markers. The disease has but have no evidence of b-cell autoimmu-
19
cause of the potential for preanalytic strong HLA associations, with linkage to nity. However, only a minority of patients
variability, it is critical that samples for the DQA and DQB genes. These HLA-DR/ with type 1 diabetes fall into this category.
plasma glucose be spun and separated DQ alleles can be either predisposing or Individuals with autoantibody-negative
20
immediately after they are drawn. If protective (Table 2.1). There are important type 1 diabetes of African or Asian ancestry
patients have test results near the mar- genetic considerations, as most of the mu- may suffer from episodic DKA and exhibit
gins of the diagnostic threshold, the
©
tations that cause diabetes are dominantly varying degrees of insulin deficiency be-
health care professional should discuss inherited. The importance of genetic testing tween episodes. This form of diabetes is
signs and symptoms with the patient and is in the genetic counseling that follows. strongly inherited and is not HLA associated.
repeat the test in 3–6 months. Some mutations are associated with other An absolute requirement for insulin re-
conditions, which then may prompt addi- placement therapy in affected patients
Diagnosis tional screenings. may be intermittent. Future research is
In a patient with classic symptoms, The rate of b-cell destruction is quite needed to determine the cause of b-cell
measurement of plasma glucose is suf- variable, being rapid in some individuals destruction in this rare clinical scenario.
ficient to diagnose diabetes (symptoms (mainly infants and children) and slow in
of hyperglycemia or hyperglycemic crisis others (mainly adults). Children and ado- Screening for Type 1 Diabetes Risk
plus a random plasma glucose $200 lescents may present with DKA as the first The incidence and prevalence of type 1
mg/dL [11.1 mmol/L]). In these cases, manifestation of the disease. Others have diabetes is increasing (41). Patients with
S18 Classification and Diagnosis of Diabetes Diabetes Care Volume 43, Supplement 1, January 2020
n
of those with type 1 diabetes or indi- 2.7 Testing for prediabetes and/or centile) and who have one or
viduals from the general population
tio
type 2 diabetes in asymptomatic more risk factor for diabetes.
with type 1 diabetes–associated genetic people should be considered in (See Table 2.4 for evidence grad-
factors) identifies individuals who may adults of any age with over- ing of risk factors.)
a
develop type 1 diabetes (9). Such testing, weight or obesity (BMI $25
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coupled with education about diabetes kg/m2 or $23 kg/m2 in Asian
symptoms and close follow-up, may en- Prediabetes
Americans) and who have one or “Prediabetes” is the term used for indi-
so
able earlier identification of type 1 di- more additional risk factors for
abetes onset. A study reported the risk of viduals whose glucose levels do not meet
diabetes (Table 2.3). B the criteria for diabetes but are too high
progression to type 1 diabetes from the 2.8 Testing for prediabetes and/or
As
time of seroconversion to autoantibody to be considered normal (29,30). Patients
type 2 diabetes should be con- with prediabetes are defined by the
positivity in three pediatric cohorts from sidered in women planning
Finland, Germany, and the U.S. Of the presence of IFG and/or IGT and/or A1C
pregnancy with overweight or 5.7–6.4% (39–47 mmol/mol) (Table 2.5).
s
585 children who developed more than obesity and/or who have one or
two autoantibodies, nearly 70% devel- Prediabetes should not be viewed as a
te
more additional risk factor for clinical entity in its own right but rather
oped type 1 diabetes within 10 years and diabetes (Table 2.3). C
84% within 15 years (42). These findings as an increased risk for diabetes and
2.9 For all people, testing should
be
are highly significant because while the cardiovascular disease (CVD). Criteria
begin at age 45 years. B for testing for diabetes or prediabetes
German group was recruited from off- 2.10 If tests are normal, repeat testing in asymptomatic adults is outlined in
ia
recruited from the general population. 2.11 To test for prediabetes and type
Remarkably, the findings in all three visceral obesity), dyslipidemia with high
2 diabetes, fasting plasma glu- triglycerides and/or low HDL choles-
groups were the same, suggesting that
an
of relevant autoantibodies detected in- type 2 diabetes, identify and 6.9 mmol/L) (47,56) and IGT as 2-h PG
creases (43–45). In The Environmental De- treat other cardiovascular dis- during 75-g OGTT levels between 140
terminants of Diabetes in the Young and 199 mg/dL (between 7.8 and 11.0
Am
accepted screening programs, one should Americans) adults who have one or more of the following risk factors:
c First-degree relative with diabetes
consider referring relatives of those with
c High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American,
type 1 diabetes for islet autoantibody
20
Pacific Islander)
testing for risk assessment in the set- c History of CVD
ting of a clinical research study (see www c Hypertension ($140/90 mmHg or on therapy for hypertension)
c HDL cholesterol level ,35 mg/dL (0.90 mmol/L) and/or a triglyceride level .250 mg/dL
©
Table 2.4—Risk-based screening for type 2 diabetes or prediabetes in asymptomatic (Fig. 2.1) (diabetes.org/socrisktest). For
children and adolescents in a clinical setting (163) additional background regarding risk fac-
Testing should be considered in youth* who have overweight ($85th percentile) or obesity
tors and screening for prediabetes, see
($95th percentile) A and who have one or more additional risk factors based on the strength SCREENING AND TESTING FOR PREDIABETES AND
of their association with diabetes: TYPE 2 DIABETES IN ASYMPTOMATIC ADULTS and
c Maternal history of diabetes or GDM during the child’s gestation A also SCREENING AND TESTING FOR PREDIABETES
AND TYPE 2 DIABETES IN CHILDREN AND ADOLESCENTS
c Family history of type 2 diabetes in first- or second-degree relative A
below.
c Race/ethnicity (Native American, African American, Latino, Asian American, Pacific
n
Islander) A
tio
Type 2 Diabetes
c Signsof insulin resistance or conditions associated with insulin resistance (acanthosis
nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small-for-gestational-
Type 2 diabetes, previously referred to
age birth weight) B as “noninsulin-dependent diabetes” or
a
“adult-onset diabetes,” accounts for 90–
GDM, gestational diabetes mellitus. *After the onset of puberty or after 10 years of age, whichever
ci
occurs earlier. If tests are normal, repeat testing at a minimum of 3-year intervals, or more 95% of all diabetes. This form encom-
frequently if BMI is increasing, is recommended. Reports of type 2 diabetes before age 10 years passes individuals who have relative
so
exist, and this can be considered with numerous risk factors. (rather than absolute) insulin deficiency
and have peripheral insulin resistance. At
least initially, and often throughout their
As
World Health Organization (WHO) and the high-risk participants in the Diabetes
lifetime, these individuals may not need
numerous other diabetes organizations Prevention Program (DPP) (51), and A1C
insulin treatment to survive.
define the IFG cutoff at 110 mg/dL at baseline was a strong predictor of
There are various causes of type 2
(6.1 mmol/L). the development of glucose-defined di-
s
diabetes. Although the specific etiologies
As with the glucose measures, several abetes during the DPP and its follow-up
are not known, autoimmune destruction
te
prospective studies that used A1C to (52). Hence, it is reasonable to consider
of b-cells does not occur and patients do
predict the progression to diabetes as an A1C range of 5.7–6.4% (39–47 mmol/
not have any of the other known causes
be
defined by A1C criteria demonstrated a mol) as identifying individuals with pre-
of diabetes. Most but not all patients with
strong, continuous association between diabetes. Similar to those with IFG and/or
type 2 diabetes have overweight or obe-
A1C and subsequent diabetes. In a sys- IGT, individuals with A1C of 5.7–6.4%
ia
25%). Those with an A1C range of 6.0– the continuum of risk is curvilinear, so as
type 2 diabetes; when seen, it usually
6.5% (42–48 mmol/mol) had a 5-year A1C rises, the diabetes risk rises dispro-
er
higher compared with A1C of 5.0% pursued for those considered at very
steroids, atypical antipsychotics, and
(31 mmol/mol) (49). In a community- high risk (e.g., those with A1C .6.0%
sodium–glucose cotransporter 2 in-
based study of African American and [42 mmol/mol]).
hibitors) (53,54). Type 2 diabetes fre-
non-Hispanic white adults without dia- Table 2.5 summarizes the categories
quently goes undiagnosed for many
of prediabetes and Table 2.3 the cri-
19
(50). Other analyses suggest that A1C of tion for assessment to determine the
notice the classic diabetes symptoms.
5.7% (39 mmol/mol) or higher is associated appropriateness of testing for diabetes
Nevertheless, even undiagnosed pa-
with a diabetes risk similar to that of or prediabetes in asymptomatic adults.
©
may improve with weight reduction diabetes are undiagnosed (47,56). Al- BMI and Ethnicity
and/or pharmacologic treatment of hy- though screening of asymptomatic indi- In general, BMI $25 kg/m2 is a risk factor
perglycemia but is seldom restored to viduals to identify those with prediabetes for diabetes. However, data suggest that
normal. or diabetes might seem reasonable, rig- the BMI cut point should be lower for the
The risk of developing type 2 diabetes orous clinical trials to prove the effective- Asian American population (60,61). The
increases with age, obesity, and lack of ness of such screening have not been BMI cut points fall consistently between
physical activity. It occurs more fre- conducted and are unlikely to occur. 23 and 24 kg/m2 (sensitivity of 80%) for
quently in women with prior gestational Based on a population estimate, diabe- nearly all Asian American subgroups
n
diabetes mellitus (GDM), in those with tes in women of childbearing age is (with levels slightly lower for Japanese
hypertension or dyslipidemia, and in underdiagnosed. Employing a probabi- Americans). This makes a rounded cut
tio
certain racial/ethnic subgroups (African listic model, Peterson et al. (57) dem- point of 23 kg/m2 practical. An argument
American, American Indian, Hispanic/ onstrated cost and health benefits of can be made to push the BMI cut point to
a
Latino, and Asian American). It is often preconception screening. lower than 23 kg/m2 in favor of increased
sensitivity; however, this would lead to
ci
associated with a strong genetic predis- A large European randomized con-
position or family history in first-degree trolled trial compared the impact of an unacceptably low specificity (13.1%).
so
relatives, more so than type 1 diabetes. screening for diabetes and intensive Data from the WHO also suggests that a
However, the genetics of type 2 diabetes multifactorial intervention with that of BMI of $23 kg/m2 should be used to
is poorly understood. In adults without screening and routine care (55). General define increased risk in Asian Americans
As
traditional risk factors for type 2 diabetes practice patients between the ages of (62). The finding that one-third to one-
and/or younger age, consider islet auto- 40 and 69 years were screened for di- half of diabetes in Asian Americans is
antibody testing (e.g., GAD65 autoanti- abetes and randomly assigned by prac- undiagnosed suggests that testing is
not occurring at lower BMI thresholds
s
bodies) to exclude the diagnosis of tice to intensive treatment of multiple
type 1 diabetes. risk factors or routine diabetes care. (63,64).
Medications
socrisktest), is recommended to guide screened control arm limited the au-
providers on whether performing a di- thors’ ability to determine whether Certain medications, such as glucocor-
agnostic test (Table 2.2) is appropriate. screening and early treatment im- ticoids, thiazide diuretics, some HIV
ic
Prediabetes and type 2 diabetes meet proved outcomes compared with no medications, and atypical antipsy-
chotics (66), are known to increase
er
criteria for conditions in which early screening and later treatment after
detection is appropriate. Both conditions clinical diagnoses. Computer simula- the risk of diabetes and should be
are common and impose significant clin- tion modeling studies suggest that considered when deciding whether
Am
ical and public health burdens. There is major benefits are likely to accrue to screen.
often a long presymptomatic phase be- from the early diagnosis and treat- Testing Interval
fore the diagnosis of type 2 diabetes. ment of hyperglycemia and cardiovas- The appropriate interval between
Simple tests to detect preclinical disease cular risk factors in type 2 diabetes screening tests is not known (67). The
19
are readily available. The duration of (58); moreover, screening, beginning at rationale for the 3-year interval is
glycemic burden is a strong predictor age 30 or 45 years and independent of that with this interval, the number of
of adverse outcomes. There are effec- risk factors, may be cost-effective
20
n
a tio
ci
so
As
s
te
be
ia
D
an
ic
er
Am
19
20
©
appropriate follow-up testing and care. diabetes in children with cystic fibrosis or however, recent publications suggest
However, in specific situations where symptoms suggestive of acute onset of that an A1C cut point lower than 5.4%
an adequate referral system is estab- type 1 diabetes and only A1C assays (5.8% in a second study) would detect
lished beforehand for positive tests, without interference are appropriate more than 90% of cases and reduce
community screening may be consid- for children with hemoglobinopathies, patient screening burden (77,78). On-
ered. Community testing may also be the ADA continues to recommend A1C going studies are underway to validate
poorly targeted; i.e., it may fail to for diagnosis of type 2 diabetes in this this approach. Regardless of age, weight
reach the groups most at risk and in- cohort (74,75). loss or failure of expected weight gain
n
appropriately test those at very low risk is a risk for CFRD and should prompt
or even those who have already been screening (77,78). Continuous glucose
tio
CYSTIC FIBROSIS–RELATED
diagnosed (68). DIABETES monitoring or HOMA of b-cell function
(79) may be more sensitive than OGTT to
Screening in Dental Practices
a
Recommendations
detect risk for progression to CFRD;
Because periodontal disease is associated 2.14 Annual screening for cystic
ci
however, evidence linking these results
with diabetes, the utility of screening in a fibrosis–related diabetes (CFRD)
to long-term outcomes is lacking, and
dental setting and referral to primary care with an oral glucose tolerance
so
these tests are not recommended for
as a means to improve the diagnosis of test should begin by age 10 years
screening (80).
prediabetes and diabetes has been in all patients with cystic fibrosis
CFRD mortality has significantly de-
As
explored (69–71), with one study es- not previously diagnosed with
creased over time, and the gap in mor-
timating that 30% of patients $30 CFRD. B
tality between cystic fibrosis patients
years of age seen in general dental 2.15 A1C is not recommended as a
with and without diabetes has consid-
practices had dysglycemia (71). Further screening test for cystic fibrosis–
s
erably narrowed (81). There are limited
research is needed to demonstrate the related diabetes. B
clinical trial data on therapy for CFRD.
te
feasibility, effectiveness, and cost-effec- 2.16 Patients with cystic fibrosis–
The largest study compared three regi-
tiveness of screening in this setting. related diabetes should be
mens: premeal insulin aspart, repagli-
be
treated with insulin to attain
Screening and Testing for Prediabetes nide, or oral placebo in cystic fibrosis
individualized glycemic goals. A
and Type 2 Diabetes in Children and patients with diabetes or abnormal glu-
2.17 Beginning 5 years after the di-
ia
prediabetes in asymptomatic children people with cystic fibrosis, occurring in placebo group continued to lose weight
er
and adolescents in a clinical setting about 20% of adolescents and 40–50% of (81). Insulin remains the most widely
(19). See Table 2.2 and Table 2.5 for adults (76). Diabetes in this population, used therapy for CFRD (82).
the criteria for the diagnosis of diabetes compared with individuals with type 1 or Additional resources for the clinical
Am
and prediabetes, respectively, which type 2 diabetes, is associated with worse management of CFRD can be found in
apply to children, adolescents, and nutritional status, more severe inflam- the position statement “Clinical Care
adults. See Section 13 “Children and matory lung disease, and greater mor- Guidelines for Cystic Fibrosis–Related
Adolescents” (https://doi.org/10.2337/ tality. Insulin insufficiency is the primary Diabetes: A Position Statement of the
19
dc20-S013) for additional information defect in CFRD. Genetically determined American Diabetes Association and a
on type 2 diabetes in children and b-cell function and insulin resistance Clinical Practice Guideline of the Cystic
adolescents. associated with infection and inflamma- Fibrosis Foundation, Endorsed by the
20
Some studies question the validity of tion may also contribute to the devel- Pediatric Endocrine Society” (83) and
A1C in the pediatric population, espe- opment of CFRD. Milder abnormalities in the International Society for Pedi-
©
cially among certain ethnicities, and sug- of glucose tolerance are even more com- atric and Adolescent Diabetes’s 2014
gest OGTT or FPG as more suitable mon and occur at earlier ages than CFRD. clinical practice consensus guidelines
diagnostic tests (72). However, many Whether individuals with IGT should be (84).
of these studies do not recognize that treated with insulin replacement has not
diabetes diagnostic criteria are based on currently been determined. Although POSTTRANSPLANTATION
long-term health outcomes, and valida- screening for diabetes before the age DIABETES MELLITUS
tions are not currently available in the of 10 years can identify risk for progres- Recommendations
pediatric population (73). The ADA ac- sion to CFRD in those with abnormal 2.18 Patients should be screened af-
knowledges the limited data supporting glucose tolerance, no benefit has been ter organ transplantation for
A1C for diagnosing type 2 diabetes in established with respect to weight, hyperglycemia, with a formal
children and adolescents. Although A1C height, BMI, or lung function. OGTT diagnosis of posttransplantation
is not recommended for diagnosis of is the recommended screening test;
care.diabetesjournals.org Classification and Diagnosis of Diabetes S23
n
Few randomized controlled studies
tion diabetes mellitus. B 2.22 Children and those diagnosed
have reported on the short- and long-
tio
2.20 Immunosuppressive regimens in early adulthood who have
term use of antihyperglycemic agents in
shown to provide the best out- diabetes not characteristic of
the setting of PTDM (91,94,95). Most
comes for patient and graft type 1 or type 2 diabetes that
a
studies have reported that transplant
survival should be used, irre- occurs in successive generations
ci
patients with hyperglycemia and PTDM
spective of posttransplantation (suggestive of an autosomal
after transplantation have higher rates of
diabetes mellitus risk. E dominant pattern of inheri-
so
rejection, infection, and rehospitalization
tance) should have genetic test-
(89,91,96).
ing for maturity-onset diabetes
Several terms are used in the literature Insulin therapy is the agent of choice
of the young. A
As
to describe the presence of diabetes for the management of hyperglycemia,
2.23 In both instances, consultation
following organ transplantation (85). PTDM, and preexisting diabetes and di-
with a center specializing in di-
“New-onset diabetes after transplanta- abetes in the hospital setting. After dis-
abetes genetics is recommen-
s
tion” (NODAT) is one such designation charge, patients with preexisting diabetes
ded to understand the significance
that describes individuals who develop could go back on their pretransplant reg-
te
of these mutations and how best
new-onset diabetes following trans- imen if they were in good control before
to approach further evaluation,
plant. NODAT excludes patients with transplantation. Those with previously poor
be
treatment, and genetic counsel-
pretransplant diabetes that was undi- control or with persistent hyperglycemia
ing. E
agnosed as well as posttransplant hy- should continue insulin with frequent
ia
transplantation diabetes mellitus” (PTDM) tions may be needed and when it dysfunction, such as neonatal diabetes
(86,87), describes the presence of di- may be appropriate to switch to non- and MODY, represent a small fraction
abetes in the posttransplant setting insulin agents. of patients with diabetes (,5%). Ta-
an
irrespective of the timing of diabetes No studies to date have established ble 2.6 describes the most common
onset. which noninsulin agents are safest or causes of monogenic diabetes. For a com-
Hyperglycemia is very common during most efficacious in PTDM. The choice
ic
most cases, such stress- or steroid- dose adjustments may be required be- Diabetes occurring under 6 months of
induced hyperglycemia resolves by the cause of decreases in the glomerular age is termed “neonatal” or “congeni-
time of discharge (89,90). Although filtration rate, a relatively common com- tal” diabetes, and about 80–85% of
the use of immunosuppressive therapies plication in transplant patients. A small cases can be found to have an under-
19
is a major contributor to the develop- short-term pilot study reported that lying monogenic cause (103). Neonatal
ment of PTDM, the risks of transplant metformin was safe to use in renal trans- diabetes occurs much less often after
rejection outweigh the risks of PTDM and plant recipients (97), but its safety has 6 months of age, whereas autoimmune
20
the role of the diabetes care provider not been determined in other types of type 1 diabetes rarely occurs before
is to treat hyperglycemia appropriately organ transplant. Thiazolidinediones 6 months of age. Neonatal diabetes
©
regardless of the type of immunosup- have been used successfully in patients can either be transient or permanent.
pression (86). Risk factors for PTDM in- with liver and kidney transplants, but side Transient diabetes is most often due to
clude both general diabetes risks (such as effects include fluid retention, heart fail- overexpression of genes on chromo-
age, family history of diabetes, etc.) as ure, and osteopenia (98,99). Dipeptidyl some 6q24, is recurrent in about half
well as transplant-specific factors, such peptidase 4 inhibitors do not interact of cases, and may be treatable with
as use of immunosuppressant agents with immunosuppressant drugs and have medications other than insulin. Perma-
(91). Whereas posttransplantation hy- demonstrated safety in small clinical trials nent neonatal diabetes is most commonly
perglycemia is an important risk factor (100,101). Well-designed intervention due to autosomal dominant mutations in
for subsequent PTDM, a formal diagnosis trials examining the efficacy and safety the genes encoding the Kir6.2 subunit
of PTDM is optimally made once the of these and other antihyperglycemic (KCNJ11) and SUR1 subunit (ABCC8) of
patient is stable on maintenance immu- agents in patients with PTDM are the b-cell KATP channel. Correct diagnosis
nosuppression and in the absence of needed. has critical implications because most
S24 Classification and Diagnosis of Diabetes Diabetes Care Volume 43, Supplement 1, January 2020
n
(.90 mg/dL [5 mmol/L]); sensitive to sulfonylureas
tio
HNF4A AD HNF4A-MODY: progressive insulin secretory defect with presentation in adolescence or early
adulthood; may have large birth weight and transient neonatal hypoglycemia; sensitive to
sulfonylureas
a
HNF1B AD HNF1B-MODY: developmental renal disease (typically cystic); genitourinary abnormalities;
atrophy of the pancreas; hyperuricemia; gout
ci
Neonatal
diabetes
so
KCNJ11 AD Permanent or transient: IUGR; possible developmental delay and seizures; responsive to
sulfonylureas
INS AD Permanent: IUGR; insulin requiring
As
ABCC8 AD Permanent or transient: IUGR; rarely developmental delay; responsive to sulfonylureas
6q24 (PLAGL1, AD for paternal Transient: IUGR; macroglossia; umbilical hernia; mechanisms include UPD6, paternal
HYMA1) duplications duplication or maternal methylation defect; may be treatable with medications other than
s
insulin
GATA6 AD Permanent: pancreatic hypoplasia; cardiac malformations; pancreatic exocrine insufficiency;
EIF2AK3 AR
insulin requiring
te
Permanent: Wolcott-Rallison syndrome: epiphyseal dysplasia; pancreatic exocrine
be
insufficiency; insulin requiring
FOXP3 X-linked Permanent: immunodysregulation, polyendocrinopathy, enteropathy X-linked (IPEX)
syndrome: autoimmune diabetes; autoimmune thyroid disease; exfoliative dermatitis;
ia
insulin requiring
AD, autosomal dominant; AR, autosomal recessive; IUGR, intrauterine growth restriction; OGTT, oral glucose tolerance test; 2-h PG, 2-h plasma
D
glucose.
an
patients with KATP-related neonatal di- MODY (MODY3), and HNF4A-MODY HNF4A-MODY). Additionally, diagnosis can
abetes will exhibit improved glycemic (MODY1). lead to identification of other affected
ic
control when treated with high-dose For individuals with MODY, the treat- family members. Genetic screening is in-
oral sulfonylureas instead of insulin. ment implications are considerable and creasingly available and cost-effective
er
Insulin gene (INS) mutations are the warrant genetic testing (104,105). Clin- (104,105).
second most common cause of perma- ically, patients with GCK-MODY exhibit A diagnosis of MODY should be con-
Am
nent neonatal diabetes, and, while mild, stable, fasting hyperglycemia and sidered in individuals who have atypical
intensive insulin management is cur- do not require antihyperglycemic ther- diabetes and multiple family members
rently the preferred treatment strategy, apy except sometimes during pregnancy. with diabetes not characteristic of type
there are important genetic counseling Patients with HNF1A- or HNF4A-MODY 1 or type 2 diabetes, although admit-
considerations, as most of the mutations usually respond well to low doses of tedly “atypical diabetes” is becoming
19
that cause diabetes are dominantly in- sulfonylureas, which are considered increasingly difficult to precisely define
herited. first-line therapy. Mutations or deletions in the absence of a definitive set of tests
20
in HNF1B are associated with renal cysts for either type of diabetes (104–110). In
Maturity-Onset Diabetes of the Young and uterine malformations (renal cysts
MODY is frequently characterized by most cases, the presence of autoantibodies
and diabetes [RCAD] syndrome). Other for type 1 diabetes precludes further
©
onset of hyperglycemia at an early age extremely rare forms of MODY have been
(classically before age 25 years, although testing for monogenic diabetes, but
reported to involve other transcription
diagnosis may occur at older ages). the presence of autoantibodies in pa-
factor genes including PDX1 (IPF1) and
MODY is characterized by impaired in- tients with monogenic diabetes has been
NEUROD1.
sulin secretion with minimal or no de- reported (111). Individuals in whom
fects in insulin action (in the absence of Diagnosis of Monogenic Diabetes monogenic diabetes is suspected should
coexistent obesity). It is inherited in A diagnosis of one of the three most be referred to a specialist for further
an autosomal dominant pattern with common forms of MODY, including GCK- evaluation if available, and consultation
abnormalities in at least 13 genes on MODY, HNF1A-MODY, and HNF4A-MODY, is available from several centers. Readily
different chromosomes identified to allows for more cost-effective therapy available commercial genetic testing fol-
date. The most commonly reported (no therapy for GCK-MODY; sulfonylureas lowing the criteria listed below now
forms are GCK-MODY (MODY2), HNF1A- as first-line therapy for HNF1A-MODY and enables a cost-effective (112), often
care.diabetesjournals.org Classification and Diagnosis of Diabetes S25
cost-saving, genetic diagnosis that is in- pancreoprivic diabetes (1). The diverse Definition
creasingly supported by health insur- set of etiologies includes pancreatitis For many years, GDM was defined as
ance. A biomarker screening pathway (acute and chronic), trauma or pancre- any degree of glucose intolerance that
such as the combination of urinary atectomy, neoplasia, cystic fibrosis (ad- was first recognized during preg-
C-peptide/creatinine ratio and antibody nancy (49), regardless of the degree
dressed elsewhere in this chapter),
screening may aid in determining who of hyperglycemia. This definition facili-
hemochromatosis, fibrocalculous pan-
should get genetic testing for MODY tated a uniform strategy for detection
creatopathy, rare genetic disorders
(113). It is critical to correctly diagnose and classification of GDM, but this defi-
(117), and idiopathic forms (1). A distin-
n
one of the monogenic forms of diabetes nition has serious limitations (126). First,
because these patients may be incor- guishing feature is concurrent pancreatic the best available evidence reveals that
tio
rectly diagnosed with type 1 or type 2 exocrine insufficiency (according to the many, perhaps most, cases of GDM rep-
diabetes, leading to suboptimal, even monoclonal fecal elastase 1 test or direct resent preexisting hyperglycemia that is
a
potentially harmful, treatment regimens function tests), pathological pancreatic detected by routine screening in preg-
imaging (endoscopic ultrasound, MRI, nancy, as routine screening is not widely
ci
and delays in diagnosing other family
members (114). The correct diagnosis is computed tomography) and absence of performed in nonpregnant women of
so
especially critical for those with GCK- type 1 diabetes–associated autoimmu- reproductive age. It is the severity of
MODY mutations where multiple studies nity (118–122). There is loss of both hyperglycemia that is clinically important
have shown that no complications ensue insulin and glucagon secretion and often with regard to both short- and long-term
As
in the absence of glucose-lowering ther- maternal and fetal risks. Universal pre-
higher-than-expected insulin require-
apy (115). Genetic counseling is recom- conception and/or first trimester screen-
ments. Risk for microvascular complica-
mended to ensure that affected ing is hampered by lack of data and
tions is similar to other forms of diabetes. In
s
individuals understand the patterns of consensus regarding both appropriate
the context of pancreatectomy, islet auto-
inheritance and the importance of a diagnostic thresholds and outcomes. A
te
transplantation can be done to retain insulin
correct diagnosis. compelling argument for further work in
secretion (123,124). In some cases, this can
The diagnosis of monogenic diabetes this area is the fact that hyperglycemia
be
lead to insulin independence. In others,
should be considered in children and that would be diagnostic of diabetes
it may decrease insulin requirements
adults diagnosed with diabetes in outside of pregnancy and is present at
(125).
the time of conception is associated with
ia
presenting later, mostly INS and diabetes has led to more type 2 diabetes
betes and diabetes at the first
ABCC8 mutations) (103,116) in women of reproductive age, with an
prenatal visit in those with risk
c Diabetes without typical features of increase in the number of pregnant
ic
diagnostic criteria for the 75-g OGTT as well normal for pregnancy. For most compli- study population. This one-step strategy
as the GDM screening and diagnostic cri- cations, there was no threshold for risk. was anticipated to significantly increase
teria used in the two-step approach were These results have led to careful recon- the incidence of GDM (from 5–6% to 15–
not derived from data in the first half of sideration of the diagnostic criteria for 20%), primarily because only one abnor-
pregnancy, so the diagnosis of GDM in GDM. mal value, not two, became sufficient to
early pregnancy by either FPG or OGTT GDM diagnosis (Table 2.7) can be ac- make the diagnosis (142). Many regional
values is not evidence based (134) and complished with either of two strate- studies have investigated the impact of
further work is needed. gies: adopting IADPSG criteria on prevalence
n
GDM is often indicative of underly- and have seen a roughly one- to threefold
ing b-cell dysfunction (135), which 1. The “one-step” 75-g OGTT derived increase (143). The anticipated increase
tio
confers marked increased risk for later from the IADPSG criteria or in the incidence of GDM could have a
development of diabetes, generally but 2. The older “two-step” approach with a substantial impact on costs and medical
a
not always type 2 diabetes, in the mother 50-g (nonfasting) screen followed by infrastructure needs and has the poten-
a 100-g OGTT for those who screen tial to “medicalize” pregnancies previ-
ci
after delivery (136,137). As effective pre-
vention interventions are available positive, based on the work of Car- ously categorized as normal. A recent
so
(138,139), women diagnosed with GDM penter and Coustan’s interpretation follow-up study of women participating
should receive lifelong screening for pre- of the older O’Sullivan (141a) criteria. in a blinded study of pregnancy OGTTs
diabetes to allow interventions to reduce found that 11 years after their pregnan-
As
diabetes risk and for type 2 diabetes to Different diagnostic criteria will iden- cies, women who would have been di-
allow treatment at the earliest pos- tify different degrees of maternal hyper- agnosed with GDM by the one-step
sible time (140). glycemia and maternal/fetal risk, leading approach, as compared with those
s
some experts to debate, and disagree on, without, were at 3.4-fold higher risk
Diagnosis optimal strategies for the diagnosis of of developing prediabetes and type 2
GDM carries risks for the mother, fetus,
and neonate. The Hyperglycemia and
GDM.
te diabetes and had children with a higher
risk of obesity and increased body fat,
be
One-Step Strategy
Adverse Pregnancy Outcome (HAPO) suggesting that the larger group of
The IADPSG defined diagnostic cut points
study (141), a large-scale multinational women identified by the one-step ap-
for GDM as the average fasting, 1-h, and 2-h
ia
cohort study completed by more than proach would benefit from increased
23,000 pregnant women, demonstrated PG values during a 75-g OGTT in women at screening for diabetes and prediabetes
24–28 weeks of gestation who participated
D
that risk of adverse maternal, fetal, and that would accompany a history of GDM
neonatal outcomes continuously in- in the HAPO study at which odds for ad- (144). The ADA recommends the IADPSG
creased as a function of maternal glyce- verse outcomes reached 1.75 times the diagnostic criteria with the intent of
an
mia at 24–28 weeks of gestation, even estimated odds of these outcomes at the optimizing gestational outcomes be-
within ranges previously considered mean fasting, 1-h, and 2-h PG levels of the cause these criteria were the only
ones based on pregnancy outcomes
ic
One-step strategy
of subsequent maternal diabetes.
Perform a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 The expected benefits of using IADPSG to
the offspring are inferred from intervention
Am
and 2 h, at 24–28 weeks of gestation in women not previously diagnosed with diabetes.
The OGTT should be performed in the morning after an overnight fast of at least 8 h. trials that focused on women with lower
The diagnosis of GDM is made when any of the following plasma glucose values are met or levels of hyperglycemia than identified
exceeded: using older GDM diagnostic criteria. Those
c Fasting: 92 mg/dL (5.1 mmol/L) trials found modest benefits including re-
19
Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 24– being treated for mild GDM in these two
28 weeks of gestation in women not previously diagnosed with diabetes. randomized controlled trials could be man-
If the plasma glucose level measured 1 h after the load is $130, 135, or 140 mg/dL (7.2, 7.5, or
©
Data are also lacking on how the treat- of neonatal macrosomia, large-for- approaches have been inconsistent to
ment of lower levels of hyperglycemia gestational-age births (153), and shoulder date (159,160). In addition, pregnancies
affects a mother’s future risk for the dystocia, without increasing small-for- complicated by GDM per the IADPSG
development of type 2 diabetes and her gestational-age births. ACOG currently criteria, but not recognized as such,
offspring’s risk for obesity, diabetes, supports the two-step approach but have outcomes comparable to preg-
and other metabolic disorders. Addi- notes that one elevated value, as op- nancies with diagnosed GDM by the
tional well-designed clinical studies are posed to two, may be used for the di- more stringent two-step criteria (161,162).
needed to determine the optimal in- agnosis of GDM (150). If this approach There remains strong consensus that
n
tensity of monitoring and treatment of is implemented, the incidence of GDM establishing a uniform approach to di-
agnosing GDM will benefit patients,
tio
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gestational diabetes mellitus on pregnancy out- mellitus: systematic review and meta-analysis. Group criteria is suitable for gestational diabetes
comes. N Engl J Med 2005;352:2477–2486 BMJ 2010;340:c1395 mellitus diagnosis: further evidence from China.
147. Tam WH, Ma RCW, Ozaki R, et al. In utero 154. Carpenter MW, Coustan DR. Criteria for Chin Med J (Engl) 2014;127:3553–3556
screening tests for gestational diabetes. Am J
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exposure to maternal hyperglycemia increases 160. Feldman RK, Tieu RS, Yasumura L. Gesta-
childhood cardiometabolic risk in offspring. Di- Obstet Gynecol 1982;144:768–773 tional diabetes screening: the International As-
tio
abetes Care 2017;40:679–686 155. National Diabetes Data Group. Classifica- sociation of the Diabetes and Pregnancy Study
148. Landon MB, Rice MM, Varner MW, et al.; tion and diagnosis of diabetes mellitus and other Groups compared with Carpenter-Coustan screen-
Eunice Kennedy Shriver National Institute of Child categories of glucose intolerance. Diabetes 1979;
ing. Obstet Gynecol 2016;127:10–17
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Health and Human Development Maternal-Fetal 28:1039–1057 161. Ethridge JK Jr, Catalano PM, Waters
156. Harper LM, Mele L, Landon MB, et al.;
Medicine Units (MFMU) Network. Mild gesta- TP. Perinatal outcomes associated with the di-
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Eunice Kennedy Shriver National Institute of Child
tional diabetes mellitus and long-term child agnosis of gestational diabetes made by the in-
Health and Human Development (NICHD)
health. Diabetes Care 2015;38:445–452 ternational association of the diabetes and
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Maternal-Fetal Medicine Units (MFMU) Network.
149. Vandorsten JP, Dodson WC, Espeland MA, pregnancy study groups criteria. Obstet Gynecol
Carpenter-Coustan compared with National Di-
et al. NIH consensus development conference: abetes Data Group criteria for diagnosing 2014;124:571–578
diagnosing gestational diabetes mellitus. NIH 162. Mayo K, Melamed N, Vandenberghe H,
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gestational diabetes. Obstet Gynecol 2016;
Consens State Sci Statements 2013;29:1–31 127:893–898 Berger H. The impact of adoption of the
150. Committee on Practice BulletinsdObstetrics. 157. Werner EF, Pettker CM, Zuckerwise L, et al. international association of diabetes in preg-
Practice Bulletin No. 190: gestational diabetes Screening for gestational diabetes mellitus: are nancy study group criteria for the screening and
mellitus. Obstet Gynecol 2018;131:e49–e64 the criteria proposed by the International Association diagnosis of gestational diabetes. Am J Obstet
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151. Donovan L, Hartling L, Muise M, Guthrie A, of the Diabetes and Pregnancy Study Groups cost- Gynecol 2015;212:224.e1–224.e9
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Vandermeer B, Dryden DM. Screening tests for effective? Diabetes Care 2012;35:529–535 163. Hutchins J, Barajas RA, Hale D, Escaname E,
gestational diabetes: a systematic review for the 158. Duran A, Sáenz S, Torrejón MJ, et al. In- Lynch J. Type 2 diabetes in a 5-year-old and single
U.S. Preventive Services Task Force. Ann Intern troduction of IADPSG criteria for the screening center experience of type 2 diabetes in youth
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Med 2013;159:115–122 and diagnosis of gestational diabetes mellitus under 10. Pediatr Diabetes 2017;18:674–677
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S32 Diabetes Care Volume 43, Supplement 1, January 2020
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Care in Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S32–S36 | https://doi.org/10.2337/dc20-S003
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so
As
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
3. PREVENTION OR DELAY OF TYPE 2 DIABETES
includes the ADA’s current clinical practice recommendations and is intended to provide
the components of diabetes care, general treatment goals and guidelines, and tools
to evaluate quality of care. Members of the ADA Professional Practice Committee, a
s
multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are re-
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sponsible for updating the Standards of Care annually, or more frequently as
warranted. For a detailed description of ADA standards, statements, and reports, as
be
well as the evidence-grading system for ADA’s clinical practice recommendations,
please refer to the Standards of Care Introduction (https://doi.org/10.2337/
ia
dc20-SINT). Readers who wish to comment on the Standards of Care are invited to
do so at professional.diabetes.org/SOC.
D
For guidelines related to screening for increased risk for type 2 diabetes (prediabetes),
please refer to Section 2 “Classification and Diagnosis of Diabetes” (https://doi.org/10
an
.2337/dc20-S002).
Recommendation
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3.1 At least annual monitoring for the development of type 2 diabetes in those
with prediabetes is suggested. E
er
Screening for prediabetes and type 2 diabetes risk through an informal assessment of
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risk factors (Table 2.3) or with an assessment tool, such as the American Diabetes
Association risk test (Fig. 2.1), is recommended to guide providers on whether
performing a diagnostic test for prediabetes (Table 2.5) and previously undiagnosed
type 2 diabetes (Table 2.2) is appropriate (see Section 2 “Classification and Diagnosis
19
candidates for diabetes prevention efforts. Using A1C to screen for prediabetes may
be problematic in the presence of certain hemoglobinopathies or conditions that
affect red blood cell turnover. See Section 2 “Classification and Diagnosis of
©
n
of diabetes observed at about 7–10% changes alone can be difficult to maintain
3.5 Given the cost-effectiveness of
weight loss (9). The recommended pace long term (6), people being treated with
tio
diabetes prevention, such inter-
of weight loss was 1–2 lb/week. Calorie weight loss therapy should have access
vention programs should be cov-
goals were calculated by estimating the to ongoing support and additional ther-
ered by third-party payers. B
a
daily calories needed to maintain the apeutic options (such as pharmacother-
apy) if needed. Based on intervention
ci
participant’s initial weight and subtracting
The Diabetes Prevention Program 500–1,000 calories/day (depending on trials, a variety of eating patterns may
so
Several major randomized controlled initial body weight). The initial focus be appropriate for patients with pre-
trials, including the Diabetes Prevention was on reducing total dietary fat. After diabetes (10), including Mediterranean
Program (DPP) (1), the Finnish Diabetes several weeks, the concept of calorie (11–13) and low-calorie, low-fat eating
As
Prevention Study (DPS) (2), and the Da Qing balance and the need to restrict calories patterns (8). An eating pattern repre-
Diabetes Prevention Study (Da Qing study) as well as fat was introduced (8). sents the totality of all foods and
(3), demonstrate that lifestyle/behavioral The goal for physical activity was se- beverages consumed (14). In addition,
evidence suggests that the overall
s
therapy featuring an individualized re- lected to approximate at least 700
duced calorie meal plan is highly effective kcal/week expenditure from physical ac- quality of food consumed (as mea-
in preventing type 2 diabetes and im-
proving other cardiometabolic markers te
tivity. For ease of translation, this goal was
described as at least 150 min of moderate-
sured by the Healthy Eating Index,
Alternative Healthy Eating Index, and
be
(such as blood pressure, lipids, and in- intensity physical activity per week Dietary Approaches to Stop Hyperten-
flammation) (4). The strongest evidence similar in intensity to brisk walking. Par- sion [DASH] score), with an emphasis
on whole grains, legumes, nuts, fruits
ia
for diabetes prevention in the U.S. comes ticipants were encouraged to distribute
from the DPP trial (1). The DPP demon- their activity throughout the week with a and vegetables and minimal refined
and processed foods, is also important
D
strated that an intensive lifestyle inter- minimum frequency of three times per
vention could reduce the incidence of week and at least 10 min per session. A (15–18).
type 2 diabetes by 58% over 3 years. maximum of 75 min of strength training As is the case for those with di-
an
Follow-up of three large studies of lifestyle could be applied toward the total abetes, individualized medical nutri-
intervention for diabetes prevention has 150 min/week physical activity goal (8). tion therapy (see Section 5 “Facilitating
shown sustained reduction in the rate of To implement the weight loss and Behavior Change and Well-being to
ic
conversion to type 2 diabetes: 39% re- physical activity goals, the DPP used Improve Health Outcomes,” https://
doi.org/10.2337/dc20-S005, for more
er
duction at 30 years in the Da Qing study (5), an individual model of treatment rather
43% reduction at 7 years in the Finnish DPS than a group-based approach. This choice detailed information) is effective in
(2), and 34% reduction at 10 years (6) and was based on a desire to intervene lowering A1C in individuals diagnosed
Am
27% reduction at 15 years (7) in the U.S. before participants had the possibility with prediabetes (19).
Diabetes Prevention Program Outcomes of developing diabetes or losing inter-
Study (DPPOS). Notably, in the 30-year est in the program. The individual ap- Physical Activity
follow-up for the Da Qing study, reduc- proach also allowed for tailoring of Just as 150 min/week of moderate-
19
tions in all-cause mortality, cardiovascular interventions to reflect the diversity of intensity physical activity, such as brisk
disease–related mortality, and microvascu- the population (8). walking, showed beneficial effects in
lar complications were observed for the The DPP intervention was adminis- those with prediabetes (1), moderate-
20
lifestyle intervention groups compared tered as a structured core curriculum intensity physical activity has been
with the control group (5). followed by a more flexible mainte- shown to improve insulin sensitivity
and reduce abdominal fat in children
©
The two major goals of the DPP in- nance program of individual sessions,
tensive, behavioral lifestyle intervention group classes, motivational campaigns, and young adults (20,21). On the basis
were to achieve and maintain a minimum and restart opportunities. The 16-session of these findings, providers are encour-
of 7% weight loss and 150 min of physical core curriculum was completed within aged to promote a DPP-style program,
activity similar in intensity to brisk walk- the first 24 weeks of the program and including its focus on physical activity, to
ing per week. The DPP lifestyle interven- included sections on lowering calories, all individuals who have been identified
tion was a goal-based intervention: all increasing physical activity, self-monitor- to be at an increased risk of type 2
participants were given the same weight ing, maintaining healthy lifestyle be- diabetes. In addition to aerobic activity,
loss and physical activity goals, but in- haviors, and psychological, social, and an exercise regimen designed to prevent
dividualization was permitted in the motivational challenges. For further de- diabetes may include resistance training
specific methods used to achieve the tails on the core curriculum sessions, (8,22,23). Breaking up prolonged sed-
goals (8). refer to ref. 8. entary time may also be encouraged,
S34 Prevention or Delay of Type 2 Diabetes Diabetes Care Volume 43, Supplement 1, January 2020
as it is associated with moderately producing weight loss and diabetes risk PHARMACOLOGIC
lower postprandial glucose levels reduction (39–42). The use of community INTERVENTIONS
(24,25). The preventive effects of health workers to support DPP efforts Recommendations
exercise appear to extend to the pre- has been shown to be effective with 3.6 Metformin therapy for preven-
vention of gestational diabetes mellitus cost savings (43,44) (see Section 1 “Im- tion of type 2 diabetes should be
(GDM) (26). proving Care and Promoting Health considered in those with predia-
in Populations,” https://doi.org/10 betes, especially for those with
Tobacco Use .2337/dc20-S001, for more informa- BMI $35 kg/m2, those aged ,60
n
Smoking may increase the risk of type 2 tion). Given the cost-effectiveness of years, and women with prior
diabetes (27); therefore, evaluation for diabetes prevention, such intervention
tio
gestational diabetes mellitus. A
tobacco use and referral for tobacco programs should be covered by third- 3.7 Long-term use of metformin may
cessation, if indicated, should be part party payers. be associated with biochemical
a
of routine care for those at risk for The CDC coordinates the National Di- vitamin B12 deficiency, and pe-
ci
diabetes. Of note, the years immedi- abetes Prevention Program (National DPP), riodic measurement of vitamin
ately following smoking cessation may a resource designed to bring evidence- B12 levels should be considered
so
represent a time of increased risk for based lifestyle change programs for pre- in metformin-treated patients,
diabetes (27–29) and patients should venting type 2 diabetes to communities especially in those with anemia
be monitored for diabetes develop- (www.cdc.gov/diabetes/prevention/index or peripheral neuropathy. B
As
ment and receive evidence-based inter- .htm). This online resource includes loca-
ventions for diabetes prevention as tions of CDC-recognized diabetes preven-
described in this section. See Section tion lifestyle change programs (available Pharmacologic agents including met-
5 “Facilitating Behavior Change and formin, a-glucosidase inhibitors, glu-
s
at nccd.cdc.gov/DDT_DPRP/Programs
Well-being to Improve Health Outcomes” .aspx). To be eligible for this program, cagon-like peptide 1 receptor agonists,
(https://doi.org/10.2337/dc20-S005) for
more detailed information. te
patients must have a BMI in the over-
weight range and be at risk for diabetes
thiazolidinediones, and several agents
approved for weight loss have been
be
based on laboratory testing or a posi- shown in research studies to decrease
Technology-Assisted Interventions to tive risk test (available at www.cdc.gov/ the incidence of diabetes to various
ia
Deliver Lifestyle Interventions prediabetes/takethetest/). Results from degrees in those with prediabetes
Technology-assisted interventions may the CDC’s National DPP during the first (1,47–53), though none are approved
D
effectively deliver the DPP lifestyle 4 years of implementation are promis- by the U.S. Food and Drug Administra-
intervention, reducing weight and, ing (45). The CDC has also developed tion specifically for diabetes preven-
therefore, diabetes risk (30–35). Such the Diabetes Prevention Impact Tool tion. The risk versus benefit of each
an
technology-assisted interventions may Kit (available at nccd.cdc.gov/toolkit/ medication must be weighed. Metfor-
deliver content through smartphone diabetesimpact) to help organizations min has the strongest evidence base
and web-based applications and tele- assess the economics of providing or (54) and demonstrated long-term
ic
health (30). The Centers for Disease covering the National DPP lifestyle safety as pharmacologic therapy for
er
Control and Prevention (CDC) Diabetes change program (46). diabetes prevention (52). For other
Prevention Recognition Program (DPRP) drugs, cost, side effects, and durable
(www.cdc.gov/diabetes/prevention/ National Policy efficacy require consideration.
Am
requirements-recognition.htm) certifies In an effort to expand preventive services Metformin was overall less effective
technology-assisted modalities as ef- using a cost-effective model that began than lifestyle modification in the DPP,
fective vehicles for DPP-based inter- in April 2018, the Centers for Medicare though group differences declined over
ventions; such programs must use an & Medicaid Services expanded Medi- time in the DPPOS (7), and metformin
19
approved curriculum, include interac- care reimbursement coverage for the may be cost-saving over a 10-year
tion with a coach, and attain the DPRP National DPP lifestyle intervention to period (38). During initial follow up
outcomes of participation, physical organizations recognized by the CDC in the DPP, metformin was as effective
20
activity reporting, and weight loss. that become Medicare suppliers for this as lifestyle modification in participants
The selection of an in-person or virtual service (online at innovation.cms.gov/ with BMI $35 kg/m2 but not signifi-
©
program should be based on patient initiatives/medicare-diabetes-prevention- cantly better than placebo in those over
preference. program/). The locations of Medicare 60 years of age (1). In the DPP, for
DPPs are available online at innovation women with a history of GDM, met-
Cost-effectiveness .cms.gov/initiatives/medicare-diabetes- formin and intensive lifestyle modifi-
A cost-effectiveness model suggested prevention-program/mdpp-map.html. cation led to an equivalent 50%
that the lifestyle intervention used in To qualify for Medicare coverage, patients reduction in diabetes risk (55), and
the DPP was cost-effective (36,37). Ac- must have a BMI in the overweight both interventions remained highly ef-
tual cost data from the DPP and DPPOS range and laboratory testing consistent fective during a 10-year follow-up pe-
confirmed this (38). Group delivery of with prediabetes in the last year. Med- riod (56). By the time of the 15-year
DPP content in community or primary icaid coverage of the DPP lifestyle follow-up (DPPOS), exploratory analy-
care settings has the potential to re- intervention is also expanding on a ses demonstrated that participants
duce overall program costs while still state-by-state basis. with a higher baseline fasting glucose
care.diabetesjournals.org Prevention or Delay of Type 2 Diabetes S35
($110 mg/dL vs. 95–109 mg/dL) and Change and Well-being to Improve 9. Hamman RF, Wing RR, Edelstein SL, et al.
women with a history of GDM (vs. Health Outcomes,” https://doi.org/10 Effect of weight loss with lifestyle intervention
on risk of diabetes. Diabetes Care 2006;29:2102–
women without a history of GDM) ex- .2337/dc20-S005) can also apply to people 2107
perienced higher risk reductions with with prediabetes. Currently, there are sig- 10. Evert AB, Dennison M, Gardner CD, et al.
metformin (compared with the placebo nificant barriers to the provision of educa- Nutrition therapy for adults with diabetes or
arm) (57). In the Indian Diabetes Pre- tion and support to those with prediabetes. prediabetes: a consensus report. Diabetes Care
vention Program (IDPP-1), metformin and However, the strategies for supporting 2019;42:731–754
11. Salas-Salvadó J, Guasch-Ferré M, Lee C-H,
the lifestyle intervention reduced diabetes successful behavior change and the
Estruch R, Clish CB, Ros E. Protective effects of
n
risk similarly at 30 months; of note, the healthy behaviors recommended for the Mediterranean diet on type 2 diabetes and
lifestyle intervention in IDPP-1 was less people with prediabetes are compara-
tio
metabolic syndrome. J Nutr 2016;146:920S–
intensive than that in the DPP (58). Based ble to those for people with diabetes. 927S
on findings from the DPP, metformin should Although reimbursement remains a bar- 12. Bloomfield HE, Koeller E, Greer N, MacDonald
a
R, Kane R, Wilt TJ. Effects on health outcomes of a
be recommended as an option for high-risk rier, studies show that providers of di- Mediterranean diet with no restriction on fat
ci
individuals (e.g., those with a history of abetes self-management education and intake: a systematic review and meta-analysis.
GDM or those with BMI $35 kg/m2). support are particularly well equipped to Ann Intern Med 2016;165:491–500
so
Consider monitoring vitamin B12 levels assist people with prediabetes in develop- 13. Estruch R, Ros E, Salas-Salvadó J, et al.;
in those taking metformin chronically to ing and maintaining behaviors that can PREDIMED Study Investigators. Primary pre-
vention of cardiovascular disease with a Med-
check for possible deficiency (56) (see Sec- prevent or delay the development of di-
As
iterranean diet supplemented with extra-virgin
tion 9 “Pharmacologic Approaches to Gly- abetes (19,63). olive oil or nuts. N Engl J Med 2018;378:e34
cemic Treatment,” https://doi.org/10 14. Department of Health and Human Services
.2337/dc20-S009, for more details). and Department of Agriculture. Dietary Guide-
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6:e93 in obese subjects (XENDOS) study: a randomized attack: a systematic review and meta-analysis.
36. Herman WH, Hoerger TJ, Brandle M, et al.; study of orlistat as an adjunct to lifestyle changes J Stroke Cerebrovasc Dis 2019;28:683–692
Diabetes Prevention Program Research Group. for the prevention of type 2 diabetes in obese 61. Huang Y, Cai X, Mai W, Li M, Hu Y. Association
20
The cost-effectiveness of lifestyle modification patients. Diabetes Care 2004;27:155–161 between prediabetes and risk of cardiovascular
or metformin in preventing type 2 diabetes in 49. le Roux CW, Astrup A, Fujioka K, et al.; SCALE disease and all cause mortality: systematic re-
adults with impaired glucose tolerance. Ann Obesity Prediabetes NN8022-1839 Study view and meta-analysis. BMJ 2016;355:i5953
Intern Med 2005;142:323–332 Group. 3 years of liraglutide versus placebo 62. Bress AP, King JB, Kreider KE, et al.; SPRINT
©
37. Chen F, Su W, Becker SH, et al. Clinical and for type 2 diabetes risk reduction and weight Research Group. Effect of intensive versus stan-
economic impact of a digital, remotely-delivered management in individuals with prediabetes: dard blood pressure treatment according to
intensive behavioral counseling program on a randomised, double-blind trial. Lancet 2017; baseline prediabetes status: a post hoc analysis
Medicare beneficiaries at risk for diabetes and 389:1399–1409 of a randomized trial. Diabetes Care 2017;40:
cardiovascular disease. PLoS One 2016;11: 50. Gerstein HC, Yusuf S, Bosch J, et al.; DREAM 1401–1408
e0163627 (Diabetes REduction Assessment with ramipril and 63. Butcher MK, Vanderwood KK, Hall TO,
38. Diabetes Prevention Program Research rosiglitazone Medication) Trial Investigators. Ef- Gohdes D, Helgerson SD, Harwell TS. Capacity
Group. The 10-year cost-effectiveness of lifestyle fect of rosiglitazone on the frequency of diabetes of diabetes education programs to provide both
intervention or metformin for diabetes preven- in patients with impaired glucose tolerance or diabetes self-management education and to
tion: an intent-to-treat analysis of the DPP/ impaired fasting glucose: a randomised controlled implement diabetes prevention services. J Public
DPPOS [published correction appears in Diabetes trial. Lancet 2006;368:1096–1105 Health Manag Pract 2011;17:242–247
Diabetes Care Volume 43, Supplement 1, January 2020 S37
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Comorbidities: Standards of
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Medical Care in Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S37–S47 | https://doi.org/10.2337/dc20-S004
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the components of diabetes care, general treatment goals and guidelines, and tools to
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evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible
be
for updating the Standards of Care annually, or more frequently as warranted. For a
detailed description of ADA standards, statements, and reports, as well as the evidence-
ia
grading system for ADA’s clinical practice recommendations, please refer to the Standards
of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment
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Recommendations
4.1 A patient-centered communication style that uses person-centered and
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Figure 4.1—Decision cycle for patient-centered glycemic management in type 2 diabetes. Reprinted from Davies et al. (99).
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on their individual preferences, values, and “nonadherence” when the outcomes language in diabetes care and education
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goals. The management plan should take of self-management are not optimal (8). can help to inform and motivate people,
into account the patient’s age, cognitive The familiar terms “noncompliance” and yet language that shames and judges may
abilities, school/work schedule and con- “nonadherence” denote a passive, obe- undermine this effort. The American Diabe-
ic
ditions, health beliefs, support systems, dient role for a person with diabetes in tes Association (ADA) and the American
“following doctor’s orders” that is at odds
er
literacy), diabetes complications and du- making, planning, monitoring, evaluation, expert opinion regarding the use of language
ration of disease, comorbidities, health and problem-solving involved in diabetes by health care professionals when speaking
priorities, other medical conditions, pref- self-management. Using a nonjudgmental or writing about diabetes for people with
erences for care, and life expectancy. Var- approach that normalizes periodic lapses diabetes or for professional audiences (14).
19
ious strategies and techniques should be in self-management may help minimize Although further research is needed to ad-
used to support patients’ self-management patients’ resistance to reporting problems dress the impact of language on diabetes
efforts, including providing education with self-management. Empathizing and outcomes, the report includes five key
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on problem-solving skills for all aspects using active listening techniques, such as consensus recommendations for lan-
of diabetes management. open-ended questions, reflective state- guage use:
Provider communication with patients ments, and summarizing what the patient
©
and families should acknowledge that said, can help facilitate communication. c Use language that is neutral, nonjudg-
multiple factors impact glycemic manage- Patients’ perceptions about their own mental, and based on facts, actions, or
ment but also emphasize that collabo- ability, or self-efficacy, to self-manage physiology/biology.
ratively developed treatment plans and diabetes are one important psychosocial c Use language free from stigma.
a healthy lifestyle can significantly im- factor related to improved diabetes self- c Use language that is strength based, respect-
prove disease outcomes and well-being management and treatment outcomes in ful, and inclusive and that imparts hope.
(4–7). Thus, the goal of provider-patient diabetes (9–13) and should be a target of c Use language that fosters collabora-
communication is to establish a collaborative ongoing assessment, patient education, tion between patients and providers.
relationship and to assess and address and treatment planning. c Use language that is person centered
self-management barriers without blam- Language has a strong impact on percep- (e.g., “person with diabetes” is pre-
ing patients for “noncompliance” or tions and behavior. The use of empowering ferred over “diabetic”).
care.diabetesjournals.org Comprehensive Medical Evaluation and Assessment of Comorbidities S39
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give guidance on routine immunizations.
c Evaluate for diabetes complica- people $6 months of age, es-
The assessment of sleep pattern and
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tions and potential comorbid pecially those with diabetes. C
duration should be considered; a recent
conditions. B 4.9 Vaccination against pneumo-
meta-analysis found that poor sleep
c Review previous treatment and coccal disease, including pneu-
a
quality, short sleep, and long sleep
risk factor control in patients with mococcal pneumonia, with
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were associated with higher A1C in
established diabetes. B 13-valent pneumococcal conju-
people with type 2 diabetes (15). In-
c Begin patient engagement in the gate vaccine (PCV13) is recom-
so
terval follow-up visits should occur at
formulation of a care manage- mended for children before age
least every 3–6 months, individualized
ment plan. B 2 years. People with diabetes
to the patient, and then annually.
c Develop a plan for continuing care. B
As
ages 2 through 64 years should
Lifestyle management and psychoso-
4.4 A follow-up visit should include also receive 23-valent pneumo-
cial care are the cornerstones of diabetes
most components of the initial coccal polysaccharide vaccine
management. Patients should be re-
comprehensive medical evalua- (PPSV23). At age $65 years,
s
ferred for diabetes self-management ed-
tion, including interval medical his- regardless of vaccination his-
ucation and support, medical nutrition
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tory, assessment of medication- tory, additional PPSV23 vacci-
therapy, and assessment of psychosocial/
taking behavior and intolerance/ nation is necessary. C
emotional health concerns if indicated.
be
side effects, physical examination, 4.10 Administer a 2- or 3-dose series
Patients should receive recommended
laboratory evaluation as appro- of hepatitis B vaccine, depend-
preventive care services (e.g., immuniza-
priate to assess attainment of ing on the vaccine, to unvacci-
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4.5 Ongoing management should Children and adults with diabetes should
disease and heart failure (Section 10
be guided by the assessment receive vaccinations according to age-
“Cardiovascular Disease and Risk Man-
er
and sex-specific Pooled Cohort Equa- People with diabetes are at higher risk
should be used to individualize targets
tionstobetter stratifyatherosclerotic
for glycemia (Section 6 “Glycemic Targets,” for hepatitis B infection and are more
cardiovascular disease risk. B likely to develop complications from in-
https://doi.org/10.2337/dc20-S006), blood
20
pressure, and lipids and to select specific fluenza and pneumococcal disease. The
The comprehensive medical evalua-
glucose-lowering medication (Section CDC Advisory Committee on Immunization
tion includes the initial and follow-up
9 “Pharmacologic ApproachestoGlycemic
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Continued on p. S41
care.diabetesjournals.org Comprehensive Medical Evaluation and Assessment of Comorbidities S41
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mortality and morbidity in vulnerable with a mortality rate as high as 50% (19). be due to contact with infected blood or
populations, including youth, older The ADA endorses recommendations from through improper equipment use (glucose
adults, and people with chronic dis- the CDC ACIP that adults age $65 years, monitoring devices or infected needles).
©
eases. Influenza vaccination in people who are at higher risk for pneumococcal Because of the higher likelihood of trans-
with diabetes has been found to sig- disease, receive an additional 23-valent mission, hepatitis B vaccine is recommen-
nificantly reduce influenza and diabe- pneumococcal polysaccharide vaccine ded for adults with diabetes age ,60 years.
tes-related hospital admissions (18). (PPSV23), regardless of prior pneumococcal Foradultsage$60years, hepatitisBvaccine
vaccination history. See detailed recom- may be administered at the discretion of the
Pneumococcal Pneumonia
mendations at www.cdc.gov/vaccines/hcp/ treating clinician based on the patient’s
Like influenza, pneumococcal pneumo-
acip-recs/vacc-specific/pneumo.html. likelihood of acquiring hepatitis B infection.
nia is a common, preventable disease.
People with diabetes are at increased risk Hepatitis B
for the bacteremic form of pneumococ- Compared with the general population, ASSESSMENT OF COMORBIDITIES
cal infection and have been reported to people with type 1 or type 2 diabetes Besides assessing diabetes-related com-
have a high risk of nosocomial bacteremia, have higher rates of hepatitis B. This may plications, clinicians and their patients
S42 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 43, Supplement 1, January 2020
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c If hypertension is present, establish blood pressure target evidence for these links is scarce. Patients
c Diabetes self-management goals with diabetes should be encouraged to
tio
Therapeutic treatment plans undergo recommended age- and sex-
c Lifestyle management
appropriate cancer screenings and to
c Pharmacologic therapy: glucose lowering
a
c Pharmacologic therapy: cardiovascular disease risk factors and renal
reduce their modifiable cancer risk fac-
ci
c Use of glucose monitoring and insulin delivery devices
tors (obesity, physical inactivity, and
c Referral to diabetes education and medical specialists (as needed) smoking). New onset of atypical diabetes
so
ASCVD, atherosclerotic cardiovascular disease. *Assessment and treatment planning are essential
(lean body habitus, negative family his-
components of initial and all follow-up visits. tory) in a middle-aged or older patient
may precede the diagnosis of pancreatic
As
adenocarcinoma (35). However, in the
need to be aware of common comorbid- diseases, with thyroid disease, celiac dis- absence of other symptoms (e.g., weight
ities that affect people with diabetes and ease, and pernicious anemia (vitamin B12 loss, abdominal pain), routine screen-
s
may complicate management (20–24). deficiency) being among the most common ing of all such patients is not currently
Diabetes comorbidities are conditions (25). Other associated conditions include recommended.
that affect people with diabetes more
often than age-matched people without te
autoimmune hepatitis, primary adrenal in-
sufficiency (Addison disease), dermatomyo- Cognitive Impairment/Dementia
be
diabetes. This section discusses many of sitis, and myasthenia gravis (26–29). Type 1 Recommendation
the common comorbidities observed in diabetes may also occur with other auto- 4.14 In the presence of cognitive im-
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patients with diabetes but is not neces- immune diseases in the context of specific pairment, diabetes treatment regi-
sarily inclusive of all the conditions that genetic disorders or polyglandular autoim- mens should be simplified as much
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have been reported. mune syndromes (30). Given the high prev- as possible and tailored to min-
alence, nonspecific symptoms, and imize the risk of hypoglycemia. B
Autoimmune Diseases insidious onset of primary hypothyroidism,
an
abetes should be screened for ficiency anemia) (31,32). Measurement of creased risk of all types of dementia,
celiac disease in the presence of vitamin B12 levels should be considered for 56% increased risk of Alzheimer demen-
gastrointestinal symptoms, signs, patients with type 1 diabetes and peripheral tia, and 127% increased risk of vascular
or laboratory manifestations sug- neuropathy or unexplained anemia. dementia compared with individuals
19
creased risk for other autoimmune risk of cancers of the liver, pancreas, abetes than people without Alzheimer
dementia. In a 15-year prospective
©
Table 4.4—Referrals for initial care management mediated, at least in part, by weight loss
c Eye care professional for annual dilated eye exam (53–55).
c Family planning for women of reproductive age
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infection. HCV may impair glucose me-
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related to dementia. More rapid cog- low reporting rate for cognitive-related tabolism by several mechanisms, in-
nitive decline is associated with both adverse events, including cognitive dys- cluding directly via viral proteins and
increased A1C and longer duration of function or dementia, with statin ther- indirectly by altering proinflammatory
a
diabetes (38). The Action to Control apy, similar to rates seen with other cytokine levels (56). The use of newer
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Cardiovascular Risk in Diabetes (ACCORD) commonly prescribed cardiovascular direct-acting antiviral drugs produces a
study found that each 1% higher A1C medications (46). Therefore, fear of sustained virological response (cure) in
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level was associated with lower cog- cognitive decline should not be a bar- nearly all cases and has been reported
nitive function in individuals with rier to statin use in individuals with to improve glucose metabolism in in-
As
type 2 diabetes (40). However, the diabetes and a high risk for cardiovas- dividuals with diabetes (57). A meta-
ACCORD study found no difference cular disease. analysis of mostly observational stud-
in cognitive outcomes in participants ies found a mean reduction in A1C
randomly assigned to intensive and Nonalcoholic Fatty Liver Disease levels of 0.45% (95% CI 20.60 to
s
standard glycemic control, supporting 20.30) and reduced requirement for
Recommendation
te
the recommendation that intensive glucose-lowering medication use fol-
4.15 Patients with type 2 diabetes or lowing successful eradication of HCV
glucose control should not be advised prediabetes and elevated liver
be
for the improvement of cognitive func- infection (58).
enzymes (ALT) or fatty liver on
tion in individuals with type 2 diabetes ultrasound should be evaluated Pancreatitis
(41).
ia
In type 2 diabetes, severe hypoglycemia Diabetes is associated with the develop- be considered for patients re-
is associated with reduced cognitive ment of nonalcoholic fatty liver disease, quiring total pancreatectomy
an
function, and those with poor cognitive including its more severe manifesta- for medically refractory chronic
function have more severe hypoglyce- tions of nonalcoholic steatohepatitis, pancreatitis to prevent postsur-
mia. In a long-term study of older pa- liver fibrosis, cirrhosis, and hepatocel- gical diabetes. C
ic
tients with type 2 diabetes, individuals lular carcinoma (47). Elevations of he-
with one or more recorded episodes of
er
the ACCORD trial found that as cognitive lower HDL cholesterol levels. Noninva- ture or physiology of the pancreas, often
function decreased, the risk of severe sive tests, such as elastography or fibrosis resulting in both exocrine and endocrine
hypoglycemia increased (43). Tailoring biomarkers, may be used to assess risk of dysfunction. Up to half of patients with
glycemic therapy may help to prevent fibrosis, but referral to a liver specialist diabetes may have some degree of im-
19
hypoglycemia in individuals with cogni- and liver biopsy may be required for paired exocrine pancreas function (59).
tive dysfunction. definitive diagnosis (48). Interventions People with diabetes are at an approx-
that improve metabolic abnormalities imately twofold higher risk of developing
20
Nutrition
In one study, adherence to the Mediter- in patients with diabetes (weight loss, acute pancreatitis (60).
ranean diet correlated with improved glycemic control, and treatment with Conversely, prediabetes and/or diabe-
©
cognitive function (44). However, a re- specific drugs for hyperglycemia or dyslip- tes has been found to develop in approx-
cent Cochrane review found insufficient idemia) are also beneficial for fatty liver imately one-third of patients after an
evidence to recommend any dietary disease (49,50). Pioglitazone and vitamin E episode of acute pancreatitis (61); thus,
change for the prevention or treatment treatment of biopsy-proven nonalcoholic the relationship is likely bidirectional.
of cognitive dysfunction (45). steatohepatitis have been shown to im- Postpancreatitis diabetes may include
prove liver histology, but effects on longer- either new-onset disease or previously
Statins term clinical outcomes are not known unrecognized diabetes (62). Studies of
A systematic review has reported that data (51,52). Treatment with liraglutide and patients treated with incretin-based ther-
do not support an adverse effect of statins with sodium–glucose cotransporter 2 in- apies for diabetes have also reported that
on cognition (46). The U.S. Food and Drug hibitors (dapagliflozin and empagliflozin) pancreatitis may occur more frequently
Administration postmarketing surveil- has also shown some promise in prelim- with these medications, but results have
lance databases have also revealed a inary studies, although benefits may be been mixed (63,64).
S44 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 43, Supplement 1, January 2020
Islet autotransplantation should be twice as prevalent in people with diabetes diabetes. Among patients with HIV
considered for patients requiring total compared with those without, after and diabetes, preventive health care
pancreatectomy for medically refractory adjusting for age and other risk factors using an approach similar to that used
chronic pancreatitis to prevent postsur- for hearing impairment (75). Low HDL, in patients without HIV is critical to
gical diabetes. Approximately one-third coronary heart disease, peripheral neu- reduce the risks of microvascular and
of patients undergoing total pancreatec- ropathy, and general poor health have macrovascular complications.
tomy with islet autotransplantation are been reported as risk factors for hearing For patients with HIV and ARV-associated
insulin free 1 year postoperatively, and impairment for people with diabetes, hyperglycemia, it may be appropriate to
n
observational studies from different cen- but an association of hearing loss with consider discontinuing the problematic
ters have demonstrated islet graft func- ARV agents if safe and effective alter-
tio
blood glucose levels has not been
tion up to a decade after the surgery in consistently observed (76). In the Di- natives are available (82). Before making
some patients (65–69). Both patient and abetes Control and Complications Trial/ ARV substitutions, carefully consider
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disease factors should be carefully con- Epidemiology of Diabetes Interventions the possible effect on HIV virological
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sidered when deciding the indications and Complications (DCCT/EDIC) cohort, control and the potential adverse ef-
and timing of this surgery. Surgeries time-weighted mean A1C was associated fects of new ARV agents. In some cases,
so
should be performed in skilled facilities with increased risk of hearing impairment antihyperglycemic agents may still be
that have demonstrated expertise in islet when tested after long-term (.20 years) necessary.
autotransplantation. follow-up (77). Impairment in smell, but
As
not taste, has also been reported in in- Low Testosterone in Men
Fractures
dividuals with diabetes (78).
Recommendation
Age-specific hip fracture risk is signifi- 4.18 In men with diabetes who have
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cantly increased in both people with HIV symptoms or signs of hypogo-
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type 1 diabetes (relative risk 6.3) and Recommendation nadism, such as decreased sex-
those with type 2 diabetes (relative risk 4.17 Patients with HIV should be ual desire (libido) or activity, or
be
1.7) in both sexes (70). Type 1 diabetes is screened for diabetes and pre- erectile dysfunction, consider
associated with osteoporosis, but in type 2 diabetes with a fasting glucose screening with a morning se-
diabetes, an increased risk of hip fracture test before starting antiretroviral rum testosterone level. B
ia
is seen despite higher bone mineral den- therapy, at the time of switching
sity (BMD) (71). In three large observa-
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Organization Fracture Risk Assessment tial screening results are normal, obesity is a major confounder (83,84).
Tool (FRAX) score were associated with fasting glucose should be checked Treatment in asymptomatic men is con-
hip and nonspine fractures. Fracture annually. E troversial. Testosterone replacement in
ic
should assess fracture history and risk New-onset diabetes is estimated to men with diabetes who have symp-
factors in older patients with diabetes occur in more than 5% of patients toms or signs of low testosterone
and recommend measurement of BMD infected with HIV on PIs, whereas (hypogonadism), a morning total testos-
if appropriate for the patient’s age and more than 15% may have prediabetes terone level should be measured using
19
sex. Fracture prevention strategies for (79). PIs are associated with insulin an accurate and reliable assay. In men
people with diabetes are the same resistance and may also lead to apo- who have total testosterone levels close
as for the general population and in- ptosis of pancreatic b-cells. NRTIs also to the lower limit, it is reasonable to check
20
Obstructive Sleep Apnea treatment and risk of complications in patients 18. Goeijenbier M, van Sloten TT, Slobbe L, et al.
Age-adjusted rates of obstructive sleep with type 2 diabetes (UKPDS 33). Lancet 1998; Benefits of flu vaccination for persons with di-
apnea, a risk factor for cardiovascular 352:837–853 abetes mellitus: a review. Vaccine 2017;35:
5. Nathan DM, Genuth S, Lachin J, et al.; Diabetes 5095–5101
disease, are significantly higher (4- to Control and Complications Trial Research Group. 19. Smith SA, Poland GA. Use of influenza and
10-fold) with obesity, especially with The effect of intensive treatment of diabetes on pneumococcal vaccines in people with diabetes.
central obesity (88). The prevalence of the development and progression of long-term Diabetes Care 2000;23:95–108
obstructive sleep apnea in the popula- complications in insulin-dependent diabetes 20. Selvin E, Coresh J, Brancati FL. The burden
tion with type 2 diabetes may be as high mellitus. N Engl J Med 1993;329:977–986 and treatment of diabetes in elderly individuals
6. Lachin JM, Genuth S, Nathan DM, Zinman B, in the U.S. Diabetes Care 2006;29:2415–2419
n
as 23%, and the prevalence of any sleep- Rutledge BN; DCCT/EDIC Research Group. Effect 21. Grant RW, Ashburner JM, Hong CS, Chang Y,
disordered breathing may be as high as
tio
of glycemic exposure on the risk of microvascular Barry MJ, Atlas SJ. Defining patient complexity
58% (89,90). In obese participants en- complications in the Diabetes Control and Com- from the primary care physician’s perspective:
rolled in the Action for Health in Diabetes plications Trialdrevisited. Diabetes 2008;57: a cohort study [published correction appears in
a
(Look AHEAD) trial, it exceeded 80% (91). 995–1001 Ann Intern Med 2012;157:152]. Ann Intern Med
7. White NH, Cleary PA, Dahms W, Goldstein D, 2011;155:797–804
Patients with symptoms suggestive of
ci
Malone J, Tamborlane WV; Diabetes Control and 22. Tinetti ME, Fried TR, Boyd CM. Designing
obstructive sleep apnea (e.g., excessive Complications Trial (DCCT)/Epidemiology of Di- health care for the most common chronic con-
so
daytime sleepiness, snoring, witnessed abetes Interventions and Complications (EDIC) ditiondmultimorbidity. JAMA 2012;307:2493–
apnea) should be considered for screen- Research Group. Beneficial effects of intensive 2494
ing (92). Sleep apnea treatment (lifestyle therapy of diabetes during adolescence: out- 23. Sudore RL, Karter AJ, Huang ES, et al. Symp-
As
comes after the conclusion of the Diabetes tom burden of adults with type 2 diabetes across
modification, continuous positive airway Control and Complications Trial (DCCT). J Pediatr the disease course: diabetes & aging study.
pressure, oral appliances, and surgery) 2001;139:804–812 J Gen Intern Med 2012;27:1674–1681
significantly improves quality of life and 8. Anderson RM, Funnell MM. Compliance and 24. Borgnakke WS, Ylöstalo PV, Taylor GW,
blood pressure control. The evidence adherence are dysfunctional concepts in diabe- Genco RJ. Effect of periodontal disease on di-
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for a treatment effect on glycemic con- tes care. Diabetes Educ 2000;26:597–604 abetes: systematic review of epidemiologic
te
9. Sarkar U, Fisher L, Schillinger D. Is self-efficacy observational evidence. J Periodontol 2013;
trol is mixed (93). associated with diabetes self-management 84(Suppl.):S135–S152
across race/ethnicity and health literacy? Dia- 25. Nederstigt C, Uitbeijerse BS, Janssen LGM,
be
Periodontal Disease betes Care 2006;29:823–829 Corssmit EPM, de Koning EJP, Dekkers OM.
Periodontal disease is more severe, and 10. King DK, Glasgow RE, Toobert DJ, et al. Self- Associated auto-immune disease in type 1 di-
may be more prevalent, in patients with efficacy, problem solving, and social-environmental abetes patients: a systematic review and meta-
ia
support are associated with diabetes self- analysis. Eur J Endocrinol 2019;180:135–144
diabetes than in those without and has management behaviors. Diabetes Care 2010;33: 26. De Block CE, De Leeuw IH, Van Gaal LF. High
been associated with higher A1C levels
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have higher rates of incident diabetes. role of self-efficacy and illness representations gian Diabetes Registry. J Clin Endocrinol Metab
in relation to dietary self-care and diabetes 1999;84:4062–4067
Current evidence suggests that peri- distress in adolescents with type 1 diabetes. 27. Triolo TM, Armstrong TK, McFann K, et al.
odontal disease adversely affects diabe-
ic
(24,97). In a randomized clinical trial, diabetes. Diabetes Spectr 2013;26:172–178 28. Hughes JW, Riddlesworth TD, DiMeglio LA,
13. Iannotti RJ, Schneider S, Nansel TR, et al. Self- Miller KM, Rickels MR, McGill JB; T1D Exchange
intensive periodontal treatment was
Am
efficacy, outcome expectations, and diabetes Clinic Network. Autoimmune diseases in children
associated with better glycemic control self-management in adolescents with type 1 and adults with type 1 diabetes from the T1D
(A1C 8.3% vs. 7.8% in control subjects diabetes. J Dev Behav Pediatr 2006;27:98–105 Exchange Clinic Registry. J Clin Endocrinol Metab
and the intensive-treatment group, re- 14. Dickinson JK, Guzman SJ, Maryniuk MD, et al. 2016;101:4931–4937
spectively) and reduction in inflam- The use of language in diabetes care and edu- 29. Kahaly GJ, Hansen MP. Type 1 diabetes
cation. Diabetes Care 2017;40:1790–1799 associated autoimmunity. Autoimmun Rev 2016;
19
matory markers after 12 months of 15. Lee SWH, Ng KY, Chin WK. The impact of 15:644–648
follow-up (98). sleep amount and sleep quality on glycemic 30. Eisenbarth GS, Gottlieb PA. Autoimmune
control in type 2 diabetes: a systematic review polyendocrine syndromes. N Engl J Med 2004;
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in US primary care settings: a systematic review. C; Advisory Committee on Immunization Prac- terology. ACG clinical guidelines: diagnosis and
Prev Chronic Dis 2013;10:E26 tices (ACIP) Child/Adolescent Immunization management of celiac disease. Am J Gastro-
2. Coleman K, Austin BT, Brach C, Wagner EH. Work Group. Advisory Committee on Immuni- enterol 2013;108:656–676; quiz 677
Evidence on the Chronic Care Model in the new zation Practices recommended immunization 32. Husby S, Murray JA, Katzka DA. AGA clinical
millennium. Health Aff (Millwood) 2009;28:75– schedule for children and adolescents aged practice update on diagnosis and monitoring of
85 18 years or younger – United States, 2017. celiac diseasedchanging utility of serology and
3. Gabbay RA, Bailit MH, Mauger DT, Wagner EH, MMWR Morb Mortal Wkly Rep 2017;66:134– histologic measures: expert review. Gastroen-
Siminerio L. Multipayer patient-centered med- 135 terology 2019;156:885–889
ical home implementation guided by the chronic 17. Kim DK, Riley LE, Harriman KH, Hunter P, 33. Suh S, Kim K-W. Diabetes and cancer: is
care model. Jt Comm J Qual Patient Saf 2011;37: Bridges CB. Advisory Committee on Immuniza- diabetes causally related to cancer? Diabetes
265–273 tion Practices recommended immunization Metab J 2011;35:193–198
4. UK Prospective Diabetes Study (UKPDS) Group. schedule for adults aged 19 years or older – 34. Giovannucci E, Harlan DM, Archer MC, et al.
Intensive blood-glucose control with sulphonylur- United States, 2017. MMWR Morb Mortal Wkly Diabetes and cancer: a consensus report. CA
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35. Aggarwal G, Kamada P, Chari ST. Prevalence steatohepatitis and prediabetes or type 2 diabetes summary of an NIDDK workshop. Ann Surg
of diabetes mellitus in pancreatic cancer com- mellitus: a randomized trial. Ann Intern Med 2016; 2015;261:21–29
pared to common cancers. Pancreas 2013;42: 165:305–315 66. Sutherland DER, Radosevich DM, Bellin MD,
198–201 51. Belfort R, Harrison SA, Brown K, et al. A et al. Total pancreatectomy and islet autotrans-
36. Cukierman T, Gerstein HC, Williamson JD. placebo-controlled trial of pioglitazone in sub- plantation for chronic pancreatitis. J Am Coll Surg
Cognitive decline and dementia in diabetesd jects with nonalcoholic steatohepatitis. N Engl J 2012;214:409–424; discussion 424–426
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tional studies. Diabetologia 2005;48:2460–2469 52. Sanyal AJ, Chalasani N, Kowdley KV, et al.; predictors of insulin independence after total
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a systematic review. Lancet Neurol 2006;5:64–74 362:1675–1685 68. Webb MA, Illouz SC, Pollard CA, et al. Islet
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Diabetes mellitus and risk of dementia: a meta- LEAN trial team. Liraglutide safety and efficacy in tomy: a long-term assessment of graft function.
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community: the Hisayama study. Neurology 54. Shimizu M, Suzuki K, Kato K, et al. Evaluation pancreatitis patients. Endocr J 2015;62:227–234
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Diabetes-Memory in Diabetes (ACCORD-MIND) tients with type 2 diabetes and non-alcoholic Epidemiol 2007;166:495–505
Investigators. Relationship between baseline fatty liver disease. Diabetes Obes Metab 2019; 71. Vestergaard P. Discrepancies in bone min-
glycemic control and cognitive function in indi- 21:285–292 eral density and fracture risk in patients with
viduals with type 2 diabetes and other cardio- 55. Sattar N, Fitchett D, Hantel S, George JT, type 1 and type 2 diabetesda meta-analysis.
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abetes (ACCORD-MIND) trial. Diabetes Care reductions in liver fat: results from randomised Study of Osteoporotic Fractures (SOF) Research
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42. Whitmer RA, Karter AJ, Yaffe K, Quesenberry 57. Hum J, Jou JH, Green PK, et al. Improvement Outcome Progression Trial (ADOPT) Study Group.
CP Jr, Selby JV. Hypoglycemic episodes and risk of in glycemic control of type 2 diabetes after Rosiglitazone-associated fractures in type 2 di-
dementia in older patients with type 2 diabetes successful treatment of hepatitis C virus. Di- abetes: an analysis from A Diabetes Outcome
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43. Punthakee Z, Miller ME, Launer LJ, et al.; 58. Carnovale C, Pozzi M, Dassano A, et al. The 845–851
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epidemiologic analysis of the ACCORD trial. Di- Acta Diabetol 2019;56:341–354 75. Bainbridge KE, Hoffman HJ, Cowie CC. Di-
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abetes Care 2012;35:787–793 59. Piciucchi M, Capurso G, Archibugi L, Delle abetes and hearing impairment in the United
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81. Kim PS, Woods C, Georgoff P, et al. A1C diabetes. Thorax 2006;61:945–950 CD004714
underestimates glycemia in HIV infection. Di- 90. Resnick HE, Redline S, Shahar E, et al.; Sleep 98. D’Aiuto F, Gkranias N, Bhowruth D, et al.;
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tion and its therapy. Clin Infect Dis 2006;43: Sleep AHEAD Research Group. Obstructive sleep 99. Davies MJ, D’Alessio DA, Fradkin J, et al.
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Testosterone treatment and coronary artery A, Batayha WQ. Periodontal status of diabetics JE, Sinclair AJ. Hypoglycemia in older people - a
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Mohler ER III. Testosterone and cardiovascular abetes and periodontal disease: a two-way re- macroalbuminuria predicts severe hypoglycemia
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status in men and women: National Health and 2009-2014. J Am Dent Assoc 2018;149:576–588.e6 for prevention. Drugs Aging 2004;21:511–530
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S48 Diabetes Care Volume 43, Supplement 1, January 2020
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Outcomes: Standards of Medical
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Care in Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S48–S65 | https://doi.org/10.2337/dc20-S005
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so
As
5. FACILITATING BEHAVIOR CHANGE AND WELL-BEING
s
The American Diabetes Association (ADA) “Standards of Medical Care in Diabe-
te
tes” includes the ADA’s current clinical practice recommendations and is intended
to provide the components of diabetes care, general treatment goals and guide-
be
lines, and tools to evaluate quality of care. Members of the ADA Professional
Practice Committee, a multidisciplinary expert committee (https://doi.org/10
ia
dards, statements, and reports, as well as the evidence-grading system for ADA’s
clinical practice recommendations, please refer to the Standards of Care In-
troduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to com-
an
these goals are diabetes self-management education and support (DSMES), med-
ical nutrition therapy (MNT), routine physical activity, smoking cessation counsel-
ing when needed, and psychosocial care. Following an initial comprehensive medical
evaluation (see Section 4, “Comprehensive Medical Evaluation and Assessment of
Comorbidities,” https://doi.org/10.2337/dc20-S004), patients and providers are
19
regimen and lifestyle (7). Re-evaluation during routine care should include not only
assessment of medical health but also behavioral and mental health outcomes,
©
judgmental words with increased feelings lower A1C (14,16–18), lower self-reported
implementation, medical nutri-
of shame and guilt, providers are encour- weight (19,20), improved quality of life
tion therapy, and well-being: at
aged to consider the impact that language (17,21), reduced all-cause mortality risk
diagnosis, annually, when com-
has on building therapeutic relationships (22), healthy coping (5,23), and reduced
plicating factors arise, and when
and to choose positive, strength-based health care costs (24–26). Better out-
transitions in care occur. E
words and phrases that put people first comes were reported for DSMES inter-
5.3 Clinical outcomes, health status,
(4,10). Patient performance of self-man- ventions that were over 10 h in total
and well-being are key goals of
agement behaviors, as well as psychosocial duration (18), included ongoing support
diabetes self-management edu-
n
factors with the potential to impact the (12,27), were culturally (28,29) and age
cation and support that should
person’s self-management, should be appropriate (30,31), were tailored to
tio
be measured as part of routine
monitored. Please see Section 4 “Compre- individual needs and preferences, and
care. C
hensive Medical Evaluation and Assess- addressed psychosocial issues and incor-
5.4 Diabetes self-management edu-
a
ment of Comorbidities”(https://doi.org/ porated behavioral strategies (13,23,32,33).
cation and support should be pa-
ci
10.2337/dc20-S004) for more on use of Individual and group approaches are
tient centered, may be given in
language. effective (20,34,35), with a slight ben-
group or individual settings and/
so
DSMES and the current national stan- efit realized by those who engage in
or use technology, and should be
dards guiding it (2,11) are based on evi- both (18).
communicated with the entire
dence of benefit. Specifically, DSMES Emerging evidence demonstrates the
diabetes care team. A
As
helps people with diabetes to identify benefit of internet-based DSMES services
5.5 Because diabetes self-management
and implement effective self-management for diabetes prevention and the man-
educationandsupportcanimprove
strategies and cope with diabetes at four agement of type 2 diabetes (36–38).
outcomes and reduce costs B,
s
critical time points (see below) (2). On- Technology-enabled diabetes self-man-
reimbursement by third-party
going DSMES helps people with diabetes agement solutions improve A1C most
te
payers is recommended. C
to maintain effective self-management effectively when there is two-way com-
throughout a lifetime of diabetes as they munication between the patient and the
be
Diabetes self-management education face new challenges and as advances in health care team, individualized feed-
and support (DSMES) services facilitate treatment become available (12). back, use of patient-generated health
ia
the knowledge, decision-making, and Four critical time points have been data, and education (38). Current re-
skills mastery necessary for optimal dia- defined when the need for DSMES is to search supports nurses, dietitians, and
D
betes self-care and incorporate the be evaluated by the medical care pro- pharmacists as providers of DSMES who
needs, goals, and life experiences of vider and/or multidisciplinary team, may also tailor curriculum to the person’s
the person with diabetes. The overall with referrals made as needed (2): needs (39–41). Members of the DSMES
an
objectives of DSMES are to support in- team should have specialized clinical
formed decision-making, self-care be- 1. At diagnosis knowledge in diabetes and behavior
havior, problem-solving, and active 2. Annually for assessment of education, change principles. Certification as a diabetes
ic
collaboration with the health care nutrition, and emotional needs educator (see www.ncbde.org) and/or
er
team to improve clinical outcomes, 3. When new complicating factors (health board certification in advanced diabetes
health status, and well-being in a cost- conditions, physical limitations, emo- management (see www.diabeteseducator
effective manner (2). Providers are en- tional factors, or basic living needs) .org/education/certification/bc_adm) dem-
Am
couraged to consider the burden of arise that influence self-management onstrates an individual’s specialized training
treatment and the patient’s level of 4. When transitions in care occur in and understanding of diabetes manage-
confidence/self-efficacy for management ment and support. (11). Additionally, there
behaviors as well as the level of social and DSMES focuses on supporting patient is growing evidence for the role of com-
19
family support when providing DSMES. empowerment by providing people munity health workers (42,43), as well as
Patient performance of self-manage- with diabetes the tools to make informed peer (42–46) and lay leaders (47), in pro-
ment behaviors, including its effect on self-management decisions (13). Diabe- viding ongoing support.
20
clinical outcomes, health status, and tes care has shifted to an approach that DSMES is associated with an increased
quality of life, as well as the psychosocial places the person with diabetes and his use of primary care and preventive ser-
or her family/support system at the center
©
factors impacting the person’s ability vices (24,48,49) and less frequent use of
to self-manage should be monitored as of the care model, working in collaboration acute care and inpatient hospital services
part of routine clinical care. A randomized with health care professionals. Patient- (19). Patients who participate in DSMES
controlled trial testing a decision-making centered care is respectful of and respon- are more likely to follow best practice
education and skill-building program (8) sive to individual patient preferences, treatment recommendations, particu-
showed that addressing these targets needs, and values. It ensures that patient larly among the Medicare population,
improved health outcomes in a popu- values guide all decision-making (14). and have lower Medicare and insurance
lation in need of health care resources. claim costs (25,48). Despite these bene-
Furthermore, following a DSMES cur- Evidence for the Benefits fits, reports indicate that only 5–7%
riculum improves quality of care (9). Studies have found that DSMES is of individuals eligible for DSMES through
In addition, in response to the grow- associated with improved diabetes Medicare or a private insurance plan
ing literature that associates potentially knowledge and self-care behaviors (14,15), actually receive it (50,51). This low
S50 Facilitating Behavior Change and Well-being to Improve Health Outcomes Diabetes Care Volume 43, Supplement 1, January 2020
participation may be due to lack of with A1C decreases of 1.0–1.9% for peo- team be knowledgeable about nutrition
referral or other identified barriers ple with type 1 diabetes (57) and 0.3– therapy principles for people with all
such as logistical issues (accessibility, 2.0% for people with type 2 diabetes (57). types of diabetes and be supportive of
timing, costs) and the lack of a perceived See Table 5.1 for specific nutrition rec- their implementation. Members of the
benefit (52). Thus, in addition to educat- ommendations. Because of the progres- health care team should complement
ing referring providers about the benefits sive nature of type 2 diabetes, behavior MNT by providing evidence-based guid-
of DSMES and the critical times to refer modification alone may not be adequate ance that helps people with diabetes
(2), alternative and innovative models to maintain euglycemia over time. How- make healthy food choices that meet
n
of DSMES delivery need to be explored ever, after medication is initiated, nu- their individualized needs and improve
and evaluated. trition therapy continues to be an overall health. A variety of eating pat-
tio
important component and should be terns are acceptable for the management
Reimbursement integrated with the overall treatment of diabetes (41,58,60). Until the evidence
a
Medicare reimburses DSMES when that plan (55). surrounding comparative benefits of dif-
service meets the national standards
ci
ferent eating patterns in specific individ-
(2,11) and is recognized by the Ameri- Goals of Nutrition Therapy for Adults uals strengthens, health care providers
so
can Diabetes Association (ADA) or other With Diabetes should focus on the key factors that are
approval bodies. DSMES is also covered 1. To promote and support healthful common among the patterns: 1) empha-
by most health insurance plans. Ongoing eating patterns, emphasizing a variety size nonstarchy vegetables, 2) minimize
As
support has been shown to be instru- of nutrient-dense foods in appropri- added sugars and refined grains, and 3)
mental for improving outcomes when ate portion sizes, to improve overall choose whole foods over highly pro-
it is implemented after the completion health and: cessed foods to the extent possible
of education services. DSMES is fre-
s
c achieve and maintain body weight (41). An individualized eating pattern
quently reimbursed when performed goals also considers the individual’s health
in person. However, although DSMES
can also be provided via phone calls
te
c attain individualized glycemic, blood
pressure, and lipid goals
status, skills, resources, food preferen-
ces, and health goals. Referral to an RD/
be
and telehealth, these remote versions c delay or prevent the complications RDN is essential to assess the overall
may not always be reimbursed. Changes of diabetes nutrition status of, and to work collab-
in reimbursement policies that increase
ia
erences, health literacy and numeracy, nates and aligns with the overall treat-
clinical outcomes, quality of life, health access to healthful foods, willingness ment plan, including physical activity
care utilization, and costs (53,54). and ability to make behavioral changes, and medication use. The Mediterranean-
an
“Nutrition Therapy for Adults With Di- about food choices while limiting of healthful eating patterns that have
er
abetes or Prediabetes: A Consensus Re- food choices only when indicated shown positive results in research, but
port” for more information on nutrition by scientific evidence individualized meal planning should fo-
therapy (41). For many individuals with 4. To provide an individual with diabe- cus on personal preferences, needs, and
Am
diabetes, the most challenging part of tes the practical tools for developing goals. Reducing overall carbohydrate in-
the treatment plan is determining what healthy eating patterns rather than take for individuals with diabetes has
to eat. There is not a “one-size-fits-all” focusing on individual macronutrients, demonstrated the most evidence for
eating pattern for individuals with diabe- micronutrients, or single foods improving glycemia and may be applied
19
tes, and meal planning should be individ- in a variety of eating patterns that meet
ualized. Nutrition therapy plays an Eating Patterns, Macronutrient individual needs and preferences. For
integral role in overall diabetes manage- Distribution, and Meal Planning individuals with type 2 diabetes not
20
ment, and each person with diabetes Evidence suggests that there is not an meeting glycemic targets or for whom
should be actively engaged in education, ideal percentage of calories from carbo- reducing glucose-lowering drugs is a
©
self-management, and treatment plan- hydrate, protein, and fat for people with priority, reducing overall carbohydrate
ning with his or her health care team, diabetes. Therefore, macronutrient dis- intake with a low- or very-low-carbohy-
including the collaborative development tribution should be based on an individ- drate eating pattern is a viable option
of an individualized eating plan (41,55). ualized assessment of current eating (63–65). As research studies on some
All individuals with diabetes should be patterns, preferences, and metabolic low-carbohydrate eating plans generally
referred for individualized MNT provided goals. Consider personal preferences indicate challenges with long-term sus-
by a registered dietitian nutritionist (RD/ (e.g., tradition, culture, religion, health tainability, it is important to reassess and
RDN) who is knowledgeable and skilled beliefs and goals, economics) as well as individualize meal plan guidance regu-
in providing diabetes-specific MNT (56) metabolic goals when working with in- larly for those interested in this ap-
at diagnosis and as needed throughout dividuals to determine the best eating proach. This eating pattern is not
the life span, similar to DSMES. MNT pattern for them (41,58,59). It is impor- recommended at this time for women
delivered by an RD/RDN is associated tant that each member of the health care who are pregnant or lactating, people
care.diabetesjournals.org Facilitating Behavior Change and Well-being to Improve Health Outcomes S51
n
therapy should be adequately reimbursed by insurance and other payers. E
Energy balance 5.8 For all patients with overweight or obesity, lifestyle modification to achieve and maintain A
tio
a minimum weight loss of 5% is recommended for all patients with diabetes and prediabetes.
Eating patterns and 5.9 There is no single ideal dietary distribution of calories among carbohydrates, fats, and proteins E
a
macronutrient for people with diabetes; therefore, meal plans should be individualized while keeping total
distribution calorie and metabolic goals in mind.
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5.10 A variety of eating patterns are acceptable for the management of type 2 diabetes and B
prediabetes.
so
Carbohydrates 5.11 Carbohydrate intake should emphasize nutrient-dense carbohydrate sources that are B
high in fiber and minimally processed. Eating plans should emphasize nonstarchy vegetables,
minimal added sugars, fruits, whole grains, as well as dairy products.
As
5.12 Reducing overall carbohydrate intake for individuals with diabetes has demonstrated the B
most evidence for improving glycemia and may be applied in a variety of eating patterns
that meet individual needs and preferences.
5.13 For people with diabetes who are prescribed a flexible insulin therapy program, education A, B
s
on how to use carbohydrate counting A and on dosing for fat and protein content B should
te
be used to determine mealtime insulin dosing.
5.14 For adults using fixed insulin doses, consistent pattern of carbohydrate intake with respect to B
time and amount, while considering the insulin action time, can result in improved glycemia
be
and reduce the risk for hypoglycemia.
5.15 People with diabetes and those at risk are advised to replace sugar-sweetened beverages B, A
(including fruit juices) with water as much as possible in order to control glycemia and weight
ia
and reduce their risk for cardiovascular disease and fatty liver B and should minimize the
consumption of foods with added sugar that have the capacity to displace healthier, more
D
Micronutrients and 5.19 There is no clear evidence that dietary supplementation with vitamins, minerals (such as C
herbal supplements chromium and vitamin D), herbs, or spices (such as cinnamon or aloe vera) can improve
outcomes in people with diabetes who do not have underlying deficiencies, and they are
not generally recommended for glycemic control.
Alcohol 5.20 Adults with diabetes who drink alcohol should do so in moderation (no more than one drink C
19
per day for adult women and no more than two drinks per day for adult men).
5.21 Educating people with diabetes about the signs, symptoms, and self-management of delayed B
hypoglycemia after drinking alcohol, especially when using insulin or insulin secretagogues,
20
with or at risk for disordered eating, or involving both aerobic and resistance importance of providing guidance on
people who have renal disease, and it exercise (73,76,77) and a healthy eating an individualized meal plan containing
should be used with caution in patients plan, such as a Mediterranean-style eating nutrient-dense foods, such as vegeta-
taking sodium–glucose cotransporter pattern (78). bles, fruits, legumes, dairy, lean sources
2 inhibitors due to the potential risk For many individuals with overweight of protein (including plant-based sources
of ketoacidosis (68,69). There is inade- and obesity with type 2 diabetes, 5% as well as lean meats, fish, and poultry),
quate research in type 1 diabetes to weight loss is needed to achieve bene- nuts, seeds, and whole grains, cannot be
support one eating pattern over another ficial outcomes in glycemic control, lipids, overemphasized (92), as well as guidance
n
at this time. and blood pressure (79). It should be on achieving the desired energy deficit
The diabetes plate method is com- noted, however, that the clinical benefits (93–96). Any approach to meal planning
tio
monly used for providing basic meal of weight loss are progressive, and more should be individualized considering the
planning guidance (70) and provides a intensive weight loss goals (i.e., 15%) may health status, personal preferences, and
a
visual guide showing how to portion be appropriate to maximize benefit de- ability of the person with diabetes to
ci
calories (featuring a 9-inch plate) and pending on need, feasibility, and safety sustain the recommendations in the plan.
carbohydrates (by limiting them to what (80,81). In select individuals with type 2
so
fits in one-quarter of the plate) and places diabetes, an overall healthy eating plan Carbohydrates
an emphasis on low-carbohydrate (or non- that results in energy deficit in conjunc- Studies examining the ideal amount
starchy) vegetables. Providing a visual/ tion with weight loss medications and/or of carbohydrate intake for people with
As
small graphic of the diabetes plate method metabolic surgery should be considered diabetes are inconclusive, although mon-
is preferred, as descriptions of the concept to help achieve weight loss and mainte- itoring carbohydrate intake and con-
can be confusing when unfamiliar. nance goals, lower A1C, and reduce CVD sidering the blood glucose response to
s
risk (82–84). Overweight and obesity dietary carbohydrate are key for improv-
Weight Management are also increasingly prevalent in people ing postprandial glucose management
Management and reduction of weight
is important for people with type 1 di- te
with type 1 diabetes and present clinical
challenges regarding diabetes treatment
(97,98). The literature concerning gly-
cemic index and glycemic load in in-
be
abetes, type 2 diabetes, or prediabetes and CVD risk factors (85,86). Sustaining dividuals with diabetes is complex, often
and overweight or obesity. To support weight loss can be challenging (79,87) but yielding mixed results, though in some
ia
weight loss and improve A1C, cardio- has long-term benefits; maintaining studies lowering the glycemic load of
vascular disease (CVD) risk factors, and weight loss for 5 years is associated consumed carbohydrates has demon-
D
well-being in adults with overweight/ with sustained improvements in A1C and strated A1C reductions of 0.2% to 0.5%
obesity and prediabetes or diabetes, lipid levels (88). MNT guidance from an (99,100). Studies longer than 12 weeks
MNT and DSMES services should include RD/RDN with expertise in diabetes and report no significant influence of glycemic
an
an individualized eating plan in a format weight management, throughout the index or glycemic load independent of
that results in an energy deficit in com- course of a structured weight loss plan, weight loss on A1C; however, mixed
bination with enhanced physical activ- is strongly recommended. results have been reported for fasting
ic
ity (41). Lifestyle intervention programs People with diabetes and prediabetes glucose levels and endogenous insulin
er
should be intensive and have frequent should be screened and evaluated during levels.
follow-up to achieve significant reduc- DSMES and MNT encounters for disor- Reducing overall carbohydrate intake
tions in excess body weight and improve dered eating, and nutrition therapy for individuals with diabetes has dem-
Am
clinical indicators. There is strong and should be individualized to accommo- onstrated evidence for improving gly-
consistent evidence that modest persis- date disorders (41). Disordered eating cemia and may be applied in a variety
tent weight loss can delay the progres- can make following an eating plan chal- of eating patterns that meet individ-
sion from prediabetes to type 2 diabetes lenging, and individuals should be re- ual needs and preferences (41). For
19
(58,71,72) (see Section 3 “Prevention or ferred to a mental health professional as people with type 2 diabetes or predia-
Delay of Type 2 Diabetes,” https://doi needed. Studies have demonstrated that betes, low-carbohydrate eating plans
.org/10.2337/dc20-S003) and is benefi- a variety of eating plans, varying in mac- show potential to improve glycemia
20
cial to the management of type 2 diabe- ronutrient composition, can be used and lipid outcomes for up to 1 year
tes (see Section 8 “Obesity Management effectively and safely in the short term (63,65,90,101–104). Part of the chal-
©
for the Treatment of Type 2 Diabetes,” (1–2 years) to achieve weight loss in lenge in interpreting low-carbohydrate
https://doi.org/10.2337/dc20-S008). people with diabetes. This includes struc- research has been due to the wide range
In prediabetes, the weight loss goal tured low-calorie meal plans with meal of definitions for a low-carbohydrate
is 7–10% for preventing progression to replacements (80,88,89) and the Medit- eating plan (65,100). As research stud-
type 2 diabetes (73). In conjunction erranean-style eating pattern (78), as well ies on low-carbohydrate eating plans
with lifestyle therapy, medication-assisted as low-carbohydrate meal plans (90). generally indicate challenges with long-
weight loss can be considered for peo- However, no single approach has been term sustainability, it is important to
ple at risk for type 2 diabetes when proven to be consistently superior reassess and individualize meal plan
needed to achieve and sustain 7–10% (41,91,92), and more data are needed guidance regularly for those interested
weight loss (74,75). People with predia- to identify and validate those meal plans in this approach. Providers should main-
betes at a healthy weight should also that are optimal with respect to long-term tain consistent medical oversight and
be considered for lifestyle intervention outcomes and patient acceptability. The recognize that certain groups are not
care.diabetesjournals.org Facilitating Behavior Change and Well-being to Improve Health Outcomes S53
appropriate for low-carbohydrate eating and/or high-protein mixed meals is is not an ideal percentage of calories
plans, including women who are preg- recommended to address delayed hy- from fat for people with or at risk for
nant or lactating, children, and people perglycemia that may occur 3 h or more diabetes and that macronutrient distri-
who have renal disease or disordered after eating (41). Checking glucose 3 h bution should be individualized accord-
eating behavior, and these plans should after eating may help to determine if ing to the patient’s eating patterns,
be used with caution in those taking additional insulin adjustments are required preferences, and metabolic goals (41).
sodium–glucose cotransporter 2 inhibitors (112,113). Continuous glucose monitoring The type of fats consumed is more im-
because of the potential risk of ketoacidosis or self-monitoring of blood glucose portant than total amount of fat when
n
(68,69). There is inadequate research should guide decision making for admin- looking at metabolic goals and CVD
about dietary patterns for type 1 diabe- istration of additional insulin. For indi- risk, and it is recommended that the
tio
tes to support one eating plan over viduals on a fixed daily insulin schedule, percentage of total calories from satu-
another at this time. meal planning should emphasize a rel- rated fats should be limited (78,105,
a
Most individuals with diabetes re- atively fixed carbohydrate consump- 119–121). Multiple randomized con-
ci
port a moderate intake of carbohydrate tion pattern with respect to both time trolled trials including patients with
(44–46% of total calories) (58). Efforts and amount, while considering insulin type 2 diabetes have reported that a
so
to modify habitual eating patterns are action time (41). Mediterranean-style eating pattern (78,
often unsuccessful in the long term; 122–127), rich in polyunsaturated and
people generally go back to their usual Protein monounsaturated fats, can improve both
As
macronutrient distribution (58). Thus, There is no evidence that adjusting the glycemic management and blood lipids.
the recommended approach is to indi- daily level of protein intake (typically 1– However, supplements do not seem to
vidualize meal plans to meet caloric goals 1.5 g/kg body wt/day or 15–20% total have the same effects as their whole-
calories) will improve health in individ-
s
with a macronutrient distribution that is food counterparts. A systematic review
more consistent with the individual’s uals without diabetic kidney disease, and concluded that dietary supplements
usual intake to increase the likelihood
for long-term maintenance. te
research is inconclusive regarding the
ideal amount of dietary protein to opti-
with n-3 fatty acids did not improve
glycemic management in individuals
be
As for all individuals in developed mize either glycemic management or with type 2 diabetes (99). Randomized
countries, both children and adults CVD risk (99,114). Therefore, protein controlled trials also do not support
intake goals should be individualized
ia
with diabetes are encouraged to mini- recommending n-3 supplements for pri-
mize intake of refined carbohydrates and based on current eating patterns. mary or secondary prevention of CVD
Some research has found successful
D
added sugars and instead focus on carbo- (128–132). People with diabetes should
hydrates from vegetables, legumes, fruits, management of type 2 diabetes with be advised to follow the guidelines for
dairy (milk and yogurt), and whole grains. meal plans including slightly higher levels the general population for the recom-
an
The consumption of sugar-sweetened of protein (20–30%), which may contrib- mended intakes of saturated fat, die-
beverages (including fruit juices) and pro- ute to increased satiety (115). tary cholesterol, and trans fat (105). In
cessed food products with high amounts Those with diabetic kidney disease general, trans fats should be avoided.
ic
of refined grains and added sugars is (with albuminuria and/or reduced esti- In addition, as saturated fats are progres-
mated glomerular filtration rate) should
er
be offered intensive and ongoing edu- body wt/day. Reducing the amount of
cation on the need to couple insulin dietary protein below the recommended Sodium
administration with carbohydrate intake. daily allowance is not recommended be- As for the general population, people
For people whose meal schedule or car- cause it does not alter glycemic meas- with diabetes are advised to limit their
19
bohydrate consumption is variable, reg- ures, cardiovascular risk measures, or the sodium consumption to ,2,300 mg/day
ular counseling to help them understand rate at which glomerular filtration rate (41). Restriction below 1,500 mg, even
the complex relationship between car- declines (116,117). for those with hypertension, is generally
20
bohydrate intake and insulin needs In individuals with type 2 diabetes, not recommended (133–135). Sodium
is important. In addition, education on protein intake may enhance or increase intake recommendations should take
the insulin response to dietary carbohy-
©
per a report from the Diabetes Preven- reduce overall calorie and carbohydrate
be interrupted every 30 min for
tion Program Outcomes Study (DPPOS), intake (58). Most systematic reviews and
blood glucose benefits. C
suggesting that periodic testing of vita- meta-analyses show benefits for nonnu-
5.28 Flexibility training and balance
min B12 levels should be considered tritive sweetener use in weight loss
training are recommended 2–3
in patients taking metformin, particularly (142,143); however, some research sug-
times/week for older adults with
in those with anemia or peripheral gests an association with weight gain
diabetes. Yoga and tai chi may
neuropathy (137). Routine supplemen- (144). When use of sugar substitutes
be included based on individual
tation with antioxidants, such as vita- is meant to reduce overall caloric and
preferences to increase flexibil-
n
mins E and C and carotene, is not advised carbohydrate intake, people should be
ity, muscular strength, and bal-
due to lack of evidence of efficacy and counseled to avoid compensating with
tio
ance. C
concern related to long-term safety. In intake of additional calories from other
addition, there is insufficient evidence to food sources (41). Regulatory agencies
a
support the routine use of herbal supple- set acceptable daily intake levels for each Physical activity is a general term that
ci
ments and micronutrients, such as cin- nonnutritive sweetener, defined as the includes all movement that increases
namon (138), curcumin, vitamin D (139), amount that can be safely consumed energy use and is an important part of
so
aloe vera, or chromium, to improve gly- over a person’s lifetime (41,145). For the diabetes management plan. Exercise
cemia in people with diabetes (41,140). those who consume sugar-sweetened is a more specific form of physical activ-
However, for special populations, in- beverages regularly, a low-calorie or ity that is structured and designed to
As
cluding pregnant or lactating women, nonnutritive-sweetened beverage may improve physical fitness. Both physical
older adults, vegetarians, and people serve as a short-term replacement strat- activity and exercise are important. Ex-
following very low-calorie or low-carbo- egy, but overall, people are encour- ercise has been shown to improve blood
s
hydrate diets, a multivitamin may be aged to decrease both sweetened and glucose control, reduce cardiovascu-
necessary. nonnutritive-sweetened beverages and lar risk factors, contribute to weight
cohol consumption include hypogly- 5.24 Children and adolescents with is not as clear as it is for those with type 2
cemia and/or delayed hypoglycemia type 1 or type 2 diabetes or diabetes. A recent study suggested that
(particularly for those using insulin or the percentage of people with diabetes
an
about these risks and encouraged to ening activities at least 3 days/ 65.1% of whites, African Americans, and
monitor blood glucose frequently after week. C Hispanics, respectively, met the thresh-
drinking alcohol to minimize such risks. old (148). It is important for diabetes care
Am
men, no more than two drinks per day is least 3 days/week, with no more improve goal achievement.
recommended (one drink is equal to a than 2 consecutive days without Moderate to high volumes of aerobic
12-oz beer, a 5-oz glass of wine, or 1.5 oz activity are associated with substantially
20
Nonnutritive Sweeteners be sufficient for younger and (149). A recent prospective observational
For some people with diabetes who more physically fit individuals. study of adults with type 1 diabetes
are accustomed to sugar-sweetened 5.26 Adults with type 1 C and type 2 B suggested that higher amounts of phys-
products, nonnutritive sweeteners (con- diabetes should engage in 2–3 ical activity led to reduced cardiovascular
taining few or no calories) may be an sessions/week of resistance ex- mortality after a mean follow-up time of
acceptable substitute for nutritive sweet- ercise on nonconsecutive days. 11.4 years for patients with and without
eners (those containing calories, such 5.27 All adults, and particularly those chronic kidney disease (150). Addition-
as sugar, honey, and agave syrup) when with type 2 diabetes, should ally, structured exercise interventions of
consumed in moderation. While use decrease the amount of time at least 8 weeks’ duration have been
of nonnutritive sweeteners does not spent in daily sedentary behav- shown to lower A1C by an average of
appear to have a significant effect on ior. B Prolonged sitting should 0.66% in people with type 2 diabetes,
glycemic management (141), they can even without a significant change in BMI
care.diabetesjournals.org Facilitating Behavior Change and Well-being to Improve Health Outcomes S55
(151). There are also considerable data more than 2 days to elapse between resistance training in older adults with
for the health benefits (e.g., increased exercise sessions, is recommended to type 2 diabetes (169) and for an additive
cardiovascular fitness, greater muscle decrease insulin resistance, regardless benefit of combined aerobic and resis-
strength, improved insulin sensitivity, of diabetes type (161,162). Over time, tance exercise in adults with type 2 di-
etc.) of regular exercise for those with activities should progress in intensity, abetes (170). If not contraindicated,
type 1 diabetes (152). A recent study frequency, and/or duration to at least patients with type 2 diabetes should
suggested that exercise training in type 1 150 min/week of moderate-intensity ex- be encouraged to do at least two weekly
diabetes may also improve several im- ercise. Adults able to run at 6 miles/h sessions of resistance exercise (exercise
n
portant markers such as triglyceride (9.7 km/h) for at least 25 min can benefit with free weights or weight machines),
level, LDL, waist circumference, and sufficiently from shorter-intensity activ- with each session consisting of at least
tio
body mass (153). Higher levels of exercise ity (75 min/week) (156). Many adults, one set (group of consecutive repetitive
intensity are associated with greater including most with type 2 diabetes, exercise motions) of five or more differ-
a
improvements in A1C and in fitness would be unable or unwilling to partic- ent resistance exercises involving the
ci
(154). Other benefits include slowing ipate in such intense exercise and should large muscle groups (169).
the decline in mobility among over- engage in moderate exercise for the For type 1 diabetes, although exercise
so
weight patients with diabetes (155). recommended duration. Adults with di- in general is associated with improve-
The ADA position statement “Physical abetes should engage in 2–3 sessions/ ment in disease status, care needs to be
Activity/Exercise and Diabetes” reviews week of resistance exercise on noncon- taken in titrating exercise with respect
As
the evidence for the benefits of exercise secutive days (163). Although heavier to glycemic management. Each individ-
in people with type 1 and type 2 diabetes resistance training with free weights ual with type 1 diabetes has a variable
and offers specific recommendation (156). and weight machines may improve glycemic response to exercise. This var-
s
Physical activity and exercise should be glycemic control and strength (164), iability should be taken into consider-
recommended and prescribed to all indi- resistance training of any intensity is ation when recommending the type
viduals with diabetes as part of manage-
ment of glycemia and overall health. te
recommended to improve strength,
balance, and the ability to engage in
and duration of exercise for a given in-
dividual (171).
be
Specific recommendations and precau- activities of daily living throughout the Women with preexisting diabetes,
tions will vary by the type of diabetes, life span. Providers and staff should help particularly type 2 diabetes, and those
ia
age, activity done, and presence of di- patients set stepwise goals toward meet- at risk for or presenting with gestational
abetes-related health complications. ing the recommended exercise targets. diabetes mellitus should be advised to
D
Recommendations should be tailored As persons intensify their exercise pro- engage in regular moderate physical
to meet the specific needs of each in- gram, medical monitoring may be indi- activity prior to and during their preg-
dividual (156). cated to ensure safety and evaluate the nancies as tolerated (156).
an
couraged to engage in regular physical dividuals, including those with diabetes, agement” (https://doi.org/10.2337/
activity. Children should engage in at should be encouraged to reduce the dc20-S010), the best protocol for as-
amount of time spent being sedentary sessing asymptomatic patients with
Am
being physically active, and an active light physical activities (165,166). Avoid- that routine testing is not recommended.
lifestyle should be recommended to ing extended sedentary periods may help However, providers should perform a
prevent type 2 diabetes for those at risk careful history, assess cardiovascular
20
and health-related quality of life (159, A wide range of activities, including in patients with diabetes. Certainly, high-
160). yoga, tai chi, and other types, can have risk patients should be encouraged to
significant impacts on A1C, flexibility, start with short periods of low-intensity
Frequency and Type of Physical muscle strength, and balance (147, exercise and slowly increase the inten-
Activity 167,168). Flexibility and balance exercises sity and duration as tolerated. Providers
People with diabetes should perform may be particularly important in older should assess patients for conditions
aerobic and resistance exercise regularly adults with diabetes to maintain range that might contraindicate certain types
(156). Aerobic activity bouts should ide- of motion, strength, and balance (156). of exercise or predispose to injury, such as
ally last at least 10 min, with the goal of uncontrolled hypertension, untreated
;30 min/day or more, most days of the Physical Activity and Glycemic Control proliferative retinopathy, autonomic
week for adults with type 2 diabetes. Clinical trials have provided strong evi- neuropathy, peripheral neuropathy, and
Daily exercise, or at least not allowing dence for the A1C-lowering value of a history of foot ulcers or Charcot foot. The
S56 Facilitating Behavior Change and Well-being to Improve Health Outcomes Diabetes Care Volume 43, Supplement 1, January 2020
patient’s age and previous physical activity an ophthalmologist prior to engaging SMOKING CESSATION: TOBACCO
level should be considered. The provider in an intense exercise regimen may be AND E-CIGARETTES
should customize the exercise regimen appropriate. Recommendations
to the individual’s needs. Those with 5.29 Advise all patients not to use
Peripheral Neuropathy
complications may require a more thorough cigarettes and other tobacco
Decreased pain sensation and a higher
evaluation prior to beginning an exer- products A or e-cigarettes. A
pain threshold in the extremities can
cise program (171). 5.30 After identification of tobacco or
result in an increased risk of skin break-
e-cigarette use, include smoking
n
down, infection, and Charcot joint de-
Hypoglycemia struction with some forms of exercise. cessation counseling and other
tio
In individuals taking insulin and/or insulin forms of treatment as a routine
Therefore, a thorough assessment
secretagogues, physical activity may component of diabetes care. A
should be done to ensure that neurop-
cause hypoglycemia if the medication
a
athy does not alter kinesthetic or pro-
dose or carbohydrate consumption is Results from epidemiological, case-
prioceptive sensation during physical
ci
not altered. Individuals on these thera- control, and cohort studies provide con-
pies may need to ingest some added activity, particularly in those with more vincing evidence to support the causal
so
carbohydrate if pre-exercise glucose lev- severe neuropathy. Studies have shown link between cigarette smoking and
els are ,90 mg/dL (5.0 mmol/L), depend- that moderate-intensity walking may health risks (178). Recent data show
ing on whether they are able to lower not lead to an increased risk of foot
As
tobacco use is higher among adults
insulin doses during the workout (such ulcers or reulceration in those with with chronic conditions (179) as well as
as with an insulin pump or reduced pre- peripheral neuropathy who use proper in adolescents and young adults with
exercise insulin dosage), the time of day footwear (174). In addition, 150 min/week diabetes (180). Smokers with diabetes
s
exercise is done, and the intensity and of moderate exercise was reported to (and people with diabetes exposed to
te
duration of the activity (156,171). In improve outcomes in patients with pre- second-hand smoke) have a height-
some patients, hypoglycemia after diabetic neuropathy (175). All individuals ened risk of CVD, premature death,
be
exercise may occur and last for several with peripheral neuropathy should wear microvascular complications, and worse
hours due to increased insulin sensitivity. glycemic control when compared with
proper footwear and examine their feet
Hypoglycemia is less common in patients nonsmokers (181–183). Smoking may
daily to detect lesions early. Anyone
ia
with diabetes who are not treated with have a role in the development of type 2
with a foot injury or open sore should
insulin or insulin secretagogues, and no diabetes (184–187).
D
glucose levels are elevated (152). Be- verse events through decreased cardiac effectiveness of brief counseling in
cause of the variation in glycemic re- responsiveness to exercise, postural hy- smoking cessation, including the use of
er
sponse to exercise bouts, patients need potension, impaired thermoregulation, telephone quit lines, in reducing tobacco
to be educated to check blood glucose impaired night vision due to impaired use. Pharmacologic therapy to assist with
Am
levels before and after periods of ex- papillary reaction, and greater suscepti- smoking cessation in people with diabe-
ercise and about the potential pro- bility to hypoglycemia (176). Cardiovas- tes has been shown to be effective (188),
longed effects (depending on intensity and for the patient motivated to quit, the
cular autonomic neuropathy is also an
and duration) (see the section DIABETES addition of pharmacologic therapy to
independent risk factor for cardiovascu-
19
cations and Foot Care” (https://doi.org/ that to which they are accustomed.
gain weight in the period shortly after
10.2337/dc20-S011) for more informa- Diabetic Kidney Disease
smoking cessation (191), recent research
tion on these long-term complications. Physical activity can acutely increase has demonstrated that this weight gain
urinary albumin excretion. However, does not diminish the substantial CVD
Retinopathy
If proliferative diabetic retinopathy or there is no evidence that vigorous- benefit realized from smoking cessation
severe nonproliferative diabetic retinop- intensity exercise accelerates the rate (192). One study in smokers with newly
athy is present, then vigorous-intensity of progression of diabetic kidney disease, diagnosed type 2 diabetes found that
aerobic or resistance exercise may be and there appears to be no need for smoking cessation was associated with
contraindicated because of the risk of specific exercise restrictions for people amelioration of metabolic parameters
triggering vitreous hemorrhage or ret- with diabetic kidney disease in general and reduced blood pressure and albu-
inal detachment (173). Consultation with (173). minuria at 1 year (193).
care.diabetesjournals.org Facilitating Behavior Change and Well-being to Improve Health Outcomes S57
In recent years e-cigarettes have multifaceted issues when integrating as feeling overwhelmed or stressed by
gained public awareness and popularity diabetes care into daily life (11). having diabetes (see the section DIABETES
because of perceptions that e-cigarette Emotional well-being is an important DISTRESS below), changes in finances, or
use is less harmful than regular cigarette part of diabetes care and self-management. competing medical demands (e.g., the
smoking (194,195). However, in light of Psychological and social problems can diagnosis of a comorbid condition). In
recent Centers for Disease Control and impair the individual’s (11,197–201) or circumstances where persons other
Prevention evidence (196) of deaths re- family’s (200) ability to carry out di- than the patient are significantly in-
lated to e-cigarette use, no persons abetes care tasks and therefore poten- volved in diabetes management, these
n
should be advised to use e-cigarettes, tially compromise health status. There issues should be explored with non-
either as a way to stop smoking tobacco medical care providers (205). Standard-
tio
are opportunities for the clinician to
or as a recreational drug. routinely assess psychosocial status ized and validated tools for psychosocial
in a timely and efficient manner for monitoring and assessment can also be
PSYCHOSOCIAL ISSUES
a
referral to appropriate services (202, used by providers (1), with positive
findings leading to referral to a mental
ci
Recommendations 203). A systematic review and meta-
5.31 Psychosocial care should be in- analysis showed that psychosocial in- health provider specializing in diabetes
so
tegrated with a collaborative, terventions modestly but significantly for comprehensive evaluation, diagno-
patient-centered approach and improved A1C (standardized mean dif- sis, and treatment.
provided to all people with di- ference –0.29%) and mental health out-
As
Diabetes Distress
abetes, with the goals of opti- comes (204). However, there was a
mizing health outcomes and limited association between the effects Recommendation
health-related quality of life. A on A1C and mental health, and no in- 5.35 Routinely monitor people with
5.32 Psychosocial screening and
s
tervention characteristics predicted ben- diabetes for diabetes distress,
follow-up may include, but are efit on both outcomes. particularly when treatment
not limited to, attitudes about
diabetes, expectations for med- Screening
te targets are not met and/or at
the onset of diabetes complica-
be
ical management and outcomes, Key opportunities for psychosocial screen- tions. B
affect or mood, general and ing occur at diabetes diagnosis, during
regularly scheduled management visits,
ia
social, and emotional), and psy- ders (207–209). Diabetes distress refers
chiatric history. E sitions in care such as from pediatric to to significant negative psychological re-
5.33 Providers should consider assess- adult care teams (205), or when prob- actions related to emotional burdens and
an
ment for symptoms of diabetes lems with achieving A1C goals, quality of worries specific to an individual’s expe-
distress, depression, anxiety, dis- life, or self-management are identified rience in having to manage a severe,
ordered eating, and cognitive (2). Patients are likely to exhibit psycho- complicated, and demanding chronic
ic
capacities using appropriate logical vulnerability at diagnosis, when disease such as diabetes (208–210).
their medical status changes (e.g., end
er
change in disease, treatment, or ident, and when complications are dis- eating patterns, and physical activity) of
life circumstance. Including care- covered. Significant changes in life diabetes self-management and the po-
givers and family members in this circumstances, often called social deter- tential or actuality of disease progression
assessment is recommended. B minants of health, are known to con- are directly associated with reports of
19
5.34 Consider screening older adults siderably affect a person’s ability to diabetes distress (208). The prevalence
(aged $65 years) with diabetes self-manage their illness. Thus, screen- of diabetes distress is reported to be 18–
for cognitive impairment and ing for social determinants of health 45% with an incidence of 38–48% over
20
depression. B (e.g., loss of employment, birth of a child, 18 months in persons with type 2 di-
or other family-based stresses) should abetes (210). In the second Diabetes
also be incorporated into routine care
©
Please refer to the ADA position state- Attitudes, Wishes and Needs (DAWN2)
ment “Psychosocial Care for People With (206). study, significant diabetes distress was
Diabetes” for a list of assessment tools Providers can start with informal ver- reported by 45% of the participants, but
and additional details (1). bal inquires, for example, by asking only 24% reported that their health care
Complex environmental, social, be- whether there have been persistent teams asked them how diabetes affected
havioral, and emotional factors, known changes in mood during the past 2 weeks their lives (207). High levels of diabetes
as psychosocial factors, influence living or since the patient’s last visit and distress significantly impact medication-
with diabetes, both type 1 and type 2, whether the person can identify a trig- taking behaviors and are linked to higher
and achieving satisfactory medical out- gering event or change in circumstan- A1C, lower self-efficacy, and poorer
comes and psychological well-being. ces. Providers should also ask whether dietary and exercise behaviors (5,208,210).
Thus, individuals with diabetes and their there are new or different barriers to DSMES has been shown to reduce diabe-
families are challenged with complex, treatment and self-management, such tes distress (5). It may be helpful to
S58 Facilitating Behavior Change and Well-being to Improve Health Outcomes Diabetes Care Volume 43, Supplement 1, January 2020
provide counseling regarding expected ADA Mental Health Provider Directory measures is provided in the ADA position
diabetes-related versus generalized psy- (professional.diabetes.org/mhp_listing). statement “Psychosocial Care for People
chological distress, at diagnosis and when Ideally, psychosocial care providers with Diabetes” (1).
disease state or treatment changes (211). should be embedded in diabetes care
Diabetes distress should be routinely settings. Although the clinician may not Anxiety Disorders
monitored (212) using person-based feel qualified to treat psychological prob- Recommendations
diabetes-specific validated measures (1). lems (214), optimizing the patient-pro- 5.36 Consider screening for anxiety
If diabetes distress is identified, the person vider relationship as a foundation may in people exhibiting anxiety
n
should be referred for specific diabetes increase the likelihood of the patient or worries regarding diabetes
education to address areas of diabetes accepting referral for other services.
tio
complications, insulin admin-
self-care causing the patient distress Collaborative care interventions and a istration, and taking medications,
and impacting clinical management. team approach have demonstrated ef- as well as fear of hypoglyce-
a
People whose self-care remains im- ficacy in diabetes self-management, out- mia and/or hypoglycemia un-
ci
paired after tailored diabetes education comes of depression, and psychosocial awareness that interferes with
should be referred by their care team to a functioning (5,6). self-management behaviors, and
so
behavioral health provider for evaluation in those who express fear,
and treatment. Psychosocial/Emotional Distress dread, or irrational thoughts
Other psychosocial issues known to Clinically significant psychopathologic di- and/or show anxiety symp-
As
affect self-management and health out- agnoses are considerably more preva- toms such as avoidance be-
comes include attitudes about the illness, lent in people with diabetes than in haviors, excessive repetitive
expectations for medical management those without (215,216). Symptoms, behaviors, or social withdrawal.
s
and outcomes, available resources (fi- both clinical and subclinical, that inter- Refer for treatment if anxiety is
nancial, social, and emotional) (213), and fere with the person’s ability to carry out present. B
psychiatric history.
te
daily diabetes self-management tasks
must be addressed. In addition to im-
5.37 People with hypoglycemia un-
awareness, which can co-occur
be
Referral to a Mental Health Specialist pacting a person’s ability to carry out with fear of hypoglycemia, should
Indications for referral to a mental health self-management, and the association of be treated using blood glucose
ia
specialist familiar with diabetes manage- mental health diagnosis and poorer awareness training (or other ev-
ment may include positive screening for short-term glycemic stability, symptoms idence-based intervention) to
D
overall stress related to work-life bal- of emotional distress are associated with help re-establish awareness of
ance, diabetes distress, diabetes man- mortality risk (215). Providers should symptoms of hypoglycemia and
agement difficulties, depression, anxiety, consider an assessment of symptoms reduce fear of hypoglycemia. A
an
care rather than waiting for a specific patient distress is suspected, and when compulsive disorder, specific phobias,
problem or deterioration in metabolic or there is a change in health, treatment, or and posttraumatic stress disorder) are
common in people with diabetes (217).
Am
of diabetes, to whom they can refer pa- state is very common and expected and type 2 diabetes (218). Common diabetes-
tients. The ADA provides a list of mental is distinct from the psychological dis- specific concerns include fears related to
health providers who have received orders discussed below (1). A list of age- hypoglycemia (219,220), not meeting
20
additional education in diabetes at the appropriate screening and evaluation blood glucose targets (217), and insulin
©
Table 5.2—Situations that warrant referral of a person with diabetes to a mental health provider for evaluation and treatment
c If self-care remains impaired in a person with diabetes distress after tailored diabetes education
c If a person has a positive screen on a validated screening tool for depressive symptoms
c In the presence of symptoms or suspicions of disordered eating behavior, an eating disorder, or disrupted patterns of eating
c If intentional omission of insulin or oral medication to cause weight loss is identified
c If a person has a positive screen for anxiety or fear of hypoglycemia
c If a serious mental illness is suspected
c In youth and families with behavioral self-care difficulties, repeated hospitalizations for diabetic ketoacidosis, or significant distress
c If a person screens positive for cognitive impairment
c Declining or impaired ability to perform diabetes self-care behaviors
c Before undergoing bariatric or metabolic surgery and after surgery if assessment reveals an ongoing need for adjustment support
care.diabetesjournals.org Facilitating Behavior Change and Well-being to Improve Health Outcomes S59
n
toms of obsessive compulsive disorder
of type 2 diabetes, especially if the in- self-reported behaviors related
(222).
tio
dividual has other risk factors such as to medication dosing, meal plan,
General anxiety is a predictor of in- obesity and family history of type 2 di- and physical activity. In addi-
jection-related anxiety and associated abetes (228–230). Elevated depressive tion, a review of the medical
a
with fear of hypoglycemia (220,223). symptoms and depressive disorders af- regimen is recommended to iden-
ci
Fear of hypoglycemia and hypoglyce- fect one in four patients with type 1 or tify potential treatment-related
mia unawareness often co-occur. In- type 2 diabetes (199). Thus, routine effects on hunger/caloric intake. B
so
terventions aimed at treating one often screening for depressive symptoms is
benefit both (224). Fear of hypoglycemia indicated in this high-risk population in- Estimated prevalence of disordered
may explain avoidance of behaviors as-
As
cluding people with type 1 or type 2 eating behavior and diagnosable eat-
sociated with lowering glucose such as diabetes, gestational diabetes mellitus, ing disorders in people with diabetes
increasing insulin doses or frequency of and postpartum diabetes. Regardless varies (234–236). For people with
monitoring. If fear of hypoglycemia is of diabetes type, women have signifi- type 1 diabetes, insulin omission causing
s
identified and a person does not have cantly higher rates of depression than glycosuria in order to lose weight is the
symptoms of hypoglycemia, a structured
te
men (231). most commonly reported disordered eat-
program of blood glucose awareness Routine monitoring with appropriate ing behavior (237,238); in people with
training delivered in routine clinical prac-
be
validated measures (1) can help to identify type 2 diabetes, bingeing (excessive food
tice can improve A1C, reduce the rate if referral is warranted. Adult patients intake with an accompanying sense of loss
of severe hypoglycemia, and restore with a history of depressive symptoms of control) is most commonly reported.
ia
hypoglycemia awareness (225,226). If or disorder need ongoing monitoring of For people with type 2 diabetes treated
not available within the practice setting, depression recurrence within the context with insulin, intentional omission is also
D
a structured program targeting both of routine care (228). Integrating mental frequently reported (239). People with
fear of hypoglycemia and unawareness and physical health care can improve diabetes and diagnosable eating disorders
should be sought out and implemented
an
into the diabetes treatment team (232). rates of diabetes distress and fear of
Depression
As with DSMES, person-centered collab- hypoglycemia (241).
er
nual screening of all patients and medical outcomes (233). dered or disrupted eating (when the
with diabetes, especially those Various randomized controlled trials individual exhibits eating behavior that
with a self-reported history of have shown improvements in diabetes is nonvolitional and maladaptive) in
depression, for depressive symp- and depression health outcomes when people with diabetes, etiology and
toms with age-appropriate de- depression is treated (233). It is impor- motivation for the behavior should be
19
pression screening measures, tant to note that medical regimen should considered (236,242). Adjunctive med-
recognizing that further evalu- also be monitored in response to re- ication such as glucagon-like peptide 1
receptor agonists (243) may help indi-
20
5.39 Beginning at diagnosis of com- to follow recommended treatment be- food intake, thus having the potential to
plications or when there are haviors), which may include increased reduce uncontrollable hunger and bu-
significant changes in medical physical activity and intensification of limic symptoms.
status, consider assessment for regimen behaviors and monitoring, result-
depression. B Serious Mental Illness
ing in changed glucose profiles.
5.40 Referrals for treatment of de- Recommendations
Disordered Eating Behavior
pression should be made to 5.43 Incorporate active monitoring
mental health providers with Recommendations of diabetes self-care activities
experience using cognitive be- 5.41 Providers should consider reeval- into treatment goals for people
havioral therapy, interpersonal uating the treatment regimen of with diabetes and serious men-
therapy, or other evidence-based people with diabetes who present tal illness. B
S60 Facilitating Behavior Change and Well-being to Improve Health Outcomes Diabetes Care Volume 43, Supplement 1, January 2020
American Association of Diabetes Educators, of the effect on glycemic control. Patient Educ
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prescribed atypical antipsychotic Diabetes Care 2015;38:1372–1382 19. Steinsbekk A, Rygg LØ, Lisulo M, Rise MB,
medications for prediabetes or 3. Rutten GEHM, Alzaid A. Person-centred type 2 Fretheim A. Group based diabetes self-management
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5.45 If a second-generation antipsy-
4. Dickinson JK, Guzman SJ, Maryniuk MD, et al. atic review with meta-analysis. BMC Health Serv
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for adolescents or adults with cation. Diabetes Care 2017;40:1790–1799 20. Deakin T, McShane CE, Cade JE, Williams
diabetes, changes in weight, 5. Fisher L, Hessler D, Glasgow RE, et al. REDEEM: RDRR. Group based training for self-manage-
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S66 Diabetes Care Volume 43, Supplement 1, January 2020
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Diabetes Care 2020;43(Suppl. 1):S66–S76 | https://doi.org/10.2337/dc20-S006
a tio
ci
so
As
The American Diabetes Association (ADA) “Standards of Medical Care in Diabe-
tes” includes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guidelines,
and tools to evaluate quality of care. Members of the ADA Professional Practice
s
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-
te
6. GLYCEMIC TARGETS
SPPC), are responsible for updating the Standards of Care annually, or more
frequently as warranted. For a detailed description of ADA standards, statements,
be
and reports, as well as the evidence-grading system for ADA’s clinical practice
recommendations, please refer to the Standards of Care Introduction (https://doi
.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care
ia
control. Patient self-monitoring of blood glucose (SMBG) may help with self-
management and medication adjustment, particularly in individuals taking insulin.
er
Continuous glucose monitoring (CGM) also has an important role in assessing the
effectiveness and safety of treatment in many patients with type 1 diabetes, and
Am
limited data suggest it may also be helpful in selected patients with type 2 diabetes,
such as those on intensive insulin regimens (1).
A1C Testing
19
Recommendations
6.1 Perform the A1C test at least two times a year in patients who are meeting
treatment goals (and who have stable glycemic control). E
20
6.2 Perform the A1C test quarterly in patients whose therapy has changed or
who are not meeting glycemic goals. E
6.3 Point-of-care testing for A1C provides the opportunity for more timely
©
treatment changes. E
A1C reflects average glycemia over approximately 3 months. The performance of Suggested citation: American Diabetes Associa-
the test is generally excellent for National Glycohemoglobin Standardization tion. 6. Glycemic targets: Standards of Medical
Program (NGSP)-certified assays (see www.ngsp.org). The test is the major tool Care in Diabetesd2020. Diabetes Care 2020;
for assessing glycemic control and has strong predictive value for diabetes 43(Suppl. 1):S66–S76
complications (1–3). Thus, A1C testing should be performed routinely in all patients © 2019 by the American Diabetes Association.
with diabetesdat initial assessment and as part of continuing care. Measurement Readers may use this article as long as the work
is properly cited, the use is educational and not
approximately every 3 months determines whether patients’ glycemic targets have for profit, and the work is not altered. More infor-
been reached and maintained. The frequency of A1C testing should depend on mation is available at http://www.diabetesjournals
the clinical situation, the treatment regimen, and the clinician’s judgment. The .org/content/license.
care.diabetesjournals.org Glycemic Targets S67
use of point-of-care A1C testing may also inform the accuracy of the patient’s ethnic groups in the regression lines
provide an opportunity for more timely meter (or the patient’s reported SMBG between A1C and mean glucose, al-
treatment changes during encounters results) and the adequacy of the SMBG though the study was underpowered
between patients and providers. Pa- testing schedule. to detect a difference and there was a
tients with type 2 diabetes with stable trend toward a difference between the
glycemia well within target may do well Correlation Between SMBG and A1C African/African American and non-Hispanic
with A1C testing only twice per year. Table 6.1 shows the correlation between white cohorts, with higher A1C values
Unstable or intensively managed pa- A1C levels and mean glucose levels based observed in Africans/African Americans
n
tients or people not at goal with treat- on the international A1C-Derived Average compared with non-Hispanic whites
ment adjustments may require testing for a given mean glucose. Other studies
tio
Glucose (ADAG) study, which assessed the
more frequently (every 3 months) (4). correlation between A1C and frequent have also demonstrated higher A1C levels
SMBG and CGM in 507 adults (83% non- in African Americans than in whites
a
A1C Limitations Hispanic whites) with type 1, type 2, and at a given mean glucose concentration
ci
The A1C test is an indirect measure of no diabetes (6), and an empirical study of (8,9).
average glycemia and, as such, is sub- the average blood glucose levels at pre- A1C assays are available that do not
so
ject to limitations. As with any labo- meal, postmeal, and bedtime associated demonstrate a statistically significant
ratory test, there is variability in the with specified A1C levels using data from difference in individuals with hemoglo-
measurement of A1C. Although such the ADAG trial (7). The American Diabe- bin variants. Other assays have statisti-
As
variability is less on an intraindividual tes Association (ADA) and the American cally significant interference, but the
basis than that of blood glucose measure- Association for Clinical Chemistry have difference is not clinically significant.
ments, clinicians should exercise judg- determined that the correlation (r 5 Use of an assay with such statistically
s
ment when using A1C as the sole basis 0.92) in the ADAG trial is strong enough significant interference may explain a
for assessing glycemic control, particu- to justify reporting both the A1C result report that for any level of mean glyce-
larly if the result is close to the threshold
that might prompt a change in medica- te
and the estimated average glucose (eAG)
result when a clinician orders the A1C
mia, African Americans heterozygous for
the common hemoglobin variant HbS
be
tion therapy. Conditions that affect red test. Clinicians should note that the had lower A1C by about 0.3 percentage
blood cell turnover (hemolytic and other mean plasma glucose numbers in Table points when compared with those with-
6.1 are based on ;2,700 readings per A1C
ia
fusion, use of drugs that stimulate glucose measured with CGM versus cen- dehydrogenase G202A, carried by 11%
erythropoesis, end-stage kidney disease, tral laboratory–measured A1C in 387 of African Americans, was associated
and pregnancy) may result in discrep- participants in three randomized trials with a decrease in A1C of about 0.8%
an
ancies between the A1C result and the demonstrated that A1C may underesti- in hemizygous men and 0.7% in homo-
patient’s true mean glycemia. Hemoglo- mate or overestimate mean glucose (5). zygous women compared with those
bin variants must be considered, partic- Thus, as suggested, a patient’s CGM pro- without the trait (12).
ic
ularly when the A1C result does not file has considerable potential for opti- A small study comparing A1C to CGM
er
correlate with the patient’s SMBG levels. mizing his or her glycemic management data in children with type 1 diabetes
However, most assays in use in the U.S. (5). found a highly statistically significant
are accurate in individuals heterozy- correlation between A1C and mean
Am
gous for the most common variants A1C Differences in Ethnic Populations blood glucose, although the correlation
(see www.ngsp.org/interf.asp). Other and Children (r 5 0.7) was significantly lower than in
measures of average glycemia such as In the ADAG study, there were no sig- the ADAG trial (13). Whether there are
fructosamine and 1,5-anhydroglucitol nificant differences among racial and clinically meaningful differences in how
19
A1C relates to average glucose in children response to therapy and assess whether providers. Reports can be generated
or in different ethnicities is an area for glycemic targets are being safely achieved. from CGM that will allow the provider
further study (8,14,15). Until further The international consensus on time in to determine time in range (TIR) and to
evidence is available, it seems prudent range provides guidance on standardized assess hypoglycemia, hyperglycemia, and
to establish A1C goals in these popula- CGM metrics (see Table 6.2) and consid- glycemic variability. As discussed in a re-
tions with consideration of both individ- erations for clinical interpretation and cent consensus document, a report for-
ualized SMBG and A1C results. care (17). To make these metrics more matted as shown in Fig. 6.1 can be
actionable, standardized reports with generated (17). Published data sug-
n
Glucose Assessment visual cues such as the Ambulatory Glu- gest a strong correlation between TIR
cose Profile (see Fig. 6.1) are recommended and A1C, with a goal of 70% TIR aligning
tio
Recommendations
(17) and may help the patient and the with an A1C of ;7% in two prospective
6.4 Standardized, single-page glu-
provider interpret the data and use it to studies (18,19).
cose reports with visual cues
a
guide treatment decisions. Integrating
such as the Ambulatory Glucose A1C GOALS
ci
SMBG and CGM results into diabetes
Profile (AGP) should be consid-
management can be useful for guiding For glycemic goals in older adults, please
ered as a standard printout for
so
all CGM devices. E
medical nutrition therapy and physical refer to Section 12 “Older Adults” (https://
activity, preventing hypoglycemia, and doi.org/10.2337/dc20-S012). For glycemic
6.5 Time in range (TIR) is associated
adjusting medications. As recently re- goals in children, please refer to Section
As
with the risk of microvascular
viewed, while A1C is currently the primary 13 “Children and Adolescents” (https://
complications and should be an
measure guiding glucose management doi.org/10.2337/dc20-S013). For glycemic
acceptable end point for clinical
and a valuable marker of the risk of goals in pregnant women, please refer to
trials and can be used for assess-
Section 14 “Management of Diabetes in
s
developing diabetes complications, the
ment of glycemic control. Addi-
Glucose Management Indicator (GMI) along Pregnancy” (https://doi.org/10.2337/dc20-
te
tionally, time below target (,70
with the other CGM metrics are suggested S014).
and ,54 mg/dL [3.9 and 3.0
to provide for a much more personalized
be
mmol/L]) and time above target
diabetes management plan. The incorpo- Recommendations
(.180 mg/dL [10.0 mmol/L]) are
ration of these metrics into clinical prac- 6.6 An A1C goal for many nonpreg-
useful parameters for reevaluation
ia
tient and provider needs. The patient’s 6.7 On the basis of provider judge-
For many people with diabetes, glucose specific needs and goals should dictate ment and patient preference,
monitoring is key for the achievement of SMBG frequency and timing or the con-
an
Table 6.2—Standardized continuous glucose monitoring (CGM) metrics for clinical care
1. Number of days CGM device is worn (recommend 14 days)
©
2. Percentage of time CGM device is active (recommend 70% of data from 14 days)
3. Mean glucose
4. Glucose management indicator (GMI)
5. Glycemic variability (%CV) target #36%*
6. Time above range (TAR): % of readings and time .250 mg/dL (.13.9 mmol/L) Level 2
7. Time above range (TAR): % of readings and time 181–250 mg/dL (10.1–13.9 mmol/L) Level 1
8. Time in range (TIR): % of readings and time 70–180 mg/dL (3.9–10.0 mmol/L) In range
9. Time below range (TBR): % of readings and time 54–69 mg/dL (3.0–3.8 mmol/L) Level 1
10. Time below range (TBR): % of readings and time ,54 mg/dL (,3.0 mmol/L) Level 2
CGM, continuous glucose monitoring; CV, coefficient of variation. *Some studies suggest that lower %CV targets (,33%) provide additional protection
against hypoglycemia for those receiving insulin or sulfonylureas. Adapted from Battelino et al. (17).
care.diabetesjournals.org Glycemic Targets S69
n
a tio
ci
so
As
s
Figure 6.1—Sample Ambulatory Glucose Profile (AGP) report. Adapted from Battelino et al. (17).
te
glycemic separation between the treat- low hypoglycemia risk with a long life
be
complications, extensive comorbid
ment groups diminished and disappeared expectancy.
conditions, or long-standing dia-
during follow-up. Given the substantially increased risk
betes in whom the goal is difficult
The Kumamoto Study (22) and UK of hypoglycemia in type 1 diabetes and
ia
B tients with short-duration type 2 diabe- mark trials (Action to Control Cardiovas-
6.9 Reassess glycemic targets over tes. Long-term follow-up of the UKPDS cular Risk in Diabetes [ACCORD], Action
cohorts showed enduring effects of early in Diabetes and Vascular Disease: Pre-
ic
A1C and Microvascular Complications to reduce microvascular complications of blood glucose on cardiovascular out-
Hyperglycemia defines diabetes, and gly- of type 1 and type 2 diabetes when comes in individuals with long-standing
cemic control is fundamental to diabetes instituted early in the course of disease type 2 diabetes and either known car-
management. The Diabetes Control and (26). Epidemiologic analyses of the DCCT diovascular disease (CVD) or high cardio-
19
Complications Trial (DCCT) (16), a pro- (16) and UKPDS (27) demonstrate a cur- vascular risk. These trials showed that
spective randomized controlled trial of lower A1C levels were associated with
vilinear relationship between A1C and
intensive (mean A1C about 7% [53 reduced onset or progression of some
20
in patients with type 1 diabetes, showed the ACCORD trial (31), discussed below,
will be averted by taking patients from
definitively that better glycemic control and the relatively intense efforts re-
is associated with 50–76% reductions very poor control to fair/good control. quired to achieve near euglycemia should
in rates of development and progres- These analyses also suggest that further also be considered when setting glycemic
sion of microvascular (retinopathy, neu- loweringofA1Cfrom7%to6%[53mmol/mol targets for individuals with long-standing
ropathy, and diabetic kidney disease) to 42 mmol/mol] is associated with fur- diabetes such as those studied in ACCORD,
complications. Follow-up of the DCCT ther reduction in the risk of microvascular ADVANCE, and VADT. Findings from these
cohorts in the Epidemiology of Diabetes complications, although the absolute risk studies suggest caution is needed in
Interventions and Complications (EDIC) reductions become much smaller. The im- treating diabetes aggressively to near-
study (20,21) demonstrated persistence plication of these findings is that there is no normal A1C goals in people with long-
of these microvascular benefits over need to deintensify therapy for an individ- standing type 2 diabetes with or at
two decades despite the fact that the ual with an A1C between 6% and 7% and significant risk of CVD. However, on the
S70 Glycemic Targets Diabetes Care Volume 43, Supplement 1, January 2020
basis of physician judgment and patient years of observational follow-up, those targets, therapeutic approaches, and
preferences, select patients, especially originally randomized to intensive glyce- population characteristics (41).
those with little comorbidity and long mic control had significant long-term Mortality findings in ACCORD (31) and
life expectancy, may benefit from adopt- reductions in MI (15% with sulfonylurea subgroup analyses of VADT (42) suggest
ing more intensive glycemic targets if or insulin as initial pharmacotherapy, that the potential risks of intensive gly-
they can achieve it safely without hy- 33% with metformin as initial pharma- cemic control may outweigh its benefits
poglycemia or significant therapeutic cotherapy) and in all-cause mortality in higher-risk patients. In all three trials,
burden. (13% and 27%, respectively) (25). severe hypoglycemia was significantly
n
ACCORD, ADVANCE, and VADT sug- more likely in participants who were
A1C and Cardiovascular Disease gested no significant reduction in CVD randomly assigned to the intensive gly-
tio
Outcomes outcomes with intensive glycemic con- cemic control arm. Those patients with
Cardiovascular Disease and Type 1 Diabetes trol in participants followed for shorter long duration of diabetes, a known history
a
CVD is a more common cause of death durations (3.5–5.6 years) and who had of hypoglycemia, advanced atherosclero-
than microvascular complications in pop-
ci
more advanced type 2 diabetes than sis, or advanced age/frailty may benefit
ulations with diabetes. There is evidence UKPDS participants. All three trials from less aggressive targets (43,44).
for a cardiovascular benefit of intensive
so
were conducted in relatively older par- As discussed further below, severe
glycemic control after long-term follow-up ticipants with longer known duration of hypoglycemia is a potent marker of
of cohorts treated early in the course of diabetes (mean duration 8–11 years) and high absolute risk of cardiovascular
As
type 1 diabetes. In the DCCT, there was a either CVD or multiple cardiovascular risk events and mortality (45). Providers
trend toward lower risk of CVD events factors. The target A1C among intensive- should be vigilant in preventing hypo-
with intensive control. In the 9-year control subjects was ,6% (42 mmol/mol) glycemia and should not aggressively
post-DCCT follow-up of the EDIC cohort, in ACCORD, ,6.5% (48 mmol/mol) in
s
attempt to achieve near-normal A1C
participants previously randomized to ADVANCE, and a 1.5% reduction in A1C levels in patients in whom such tar-
the intensive arm had a significant 57%
reduction in the risk of nonfatal myo-
te
compared with control subjects in VADT,
with achieved A1C of 6.4% vs. 7.5%
gets cannot be safely and reasonably
achieved. As discussed in Section 9 “Phar-
be
cardial infarction (MI), stroke, or car- (46 mmol/mol vs. 58 mmol/mol) in macologic Approaches to Glycemic Treat-
diovascular death compared with those ACCORD, 6.5% vs. 7.3% (48 mmol/mol ment” (https://doi.org/10.2337/dc20-S009),
previously randomized to the standard
ia
in VADT. Details of these studies are gon-like peptide 1 receptor agonists (GLP-1
diabetes has been shown to persist for reviewed extensively in “Intensive Gly- RA) that have demonstrated CVD benefit
several decades (33) and to be associ- cemic Control and the Prevention of are recommended for use in patients with
an
ated with a modest reduction in all- Cardiovascular Events: Implications of established CVD or indicators of high risk.
cause mortality (34). the ACCORD, ADVANCE, and VA Diabetes As outlined in more detail in Section 9
Cardiovascular Disease and Type 2 Diabetes Trials” (38). “Pharmacologic Approaches to Glycemic
ic
In type 2 diabetes, there is evidence The glycemic control comparison in Treatment” (https://doi.org/10.2337/dc20-
S009) and Section 10 “Cardiovascular Dis-
er
that more intensive treatment of glyce- ACCORD was halted early due to an
mia in newly diagnosed patients may increased mortality rate in the intensive ease and Risk Management” (https://doi
reduce long-term CVD rates. In addi- compared with the standard treatment .org/10.2337/dc20-S010), the cardiovas-
Am
tion, data from the Swedish National arm (1.41% vs. 1.14% per year; hazard cular benefits of SGLT2i or GLP-1 RA are
Diabetes Registry and Joint Asia Diabetes ratio 1.22 [95% CI 1.01–1.46]), with a not dependent upon A1C lowering, so
Evaluation (JADE) demonstrate greater similar increase in cardiovascular deaths. initiation can be considered in people with
proportions of people with diabetes be- Analysis of the ACCORD data did not type 2 diabetes and CVD independent of
19
ing diagnosed at ,40 years of age and a identify a clear explanation for the ex- the current A1C or A1C goal. Based on
demonstrably increased burden of heart cess mortality in the intensive treat- these considerations, the following two
disease and years of life lost in people ment arm (31). strategies are offered (46):
20
cular and macrovascular complications harm in the ADVANCE trial (39). The
of diabetes, there is a major call to end-stage renal disease rate was lower on an SGLT2i or GLP-1 RA, consider
overcome therapeutic inertia and treat in the intensive treatment group over switching to one of these agents with
to target for an individual patient (37). follow-up. However, 10-year follow-up of proven cardiovascular benefit.
During the UKPDS, there was a 16% the VADT cohort (40) showed a reduction 2. Introduce SGLT2i or GLP-1 RA in pa-
reduction in CVD events (combined fa- in the risk of cardiovascular events (52.7 tients with CVD at A1C goal for car-
tal or nonfatal MI and sudden death) [control group] vs. 44.1 [intervention diovascular benefit.
in the intensive glycemic control arm group] events per 1,000 person-years) Setting and Modifying A1C Goals
that did not reach statistical signifi- with no benefit in cardiovascular or over- Numerous factors must be considered
cance (P 5 0.052), and there was no all mortality. Heterogeneity of mortal- when setting glycemic targets. The ADA
suggestion of benefit on other CVD out- ity effects across studies was noted, proposes general targets appropriate
comes (e.g., stroke). However, after 10 which may reflect differences in glycemic for many patients but emphasizes the
care.diabetesjournals.org Glycemic Targets S71
n
The issue of preprandial versus post-
prandial SMBG targets is complex (48).
tio
Elevated postchallenge (2-h oral glucose
tolerance test) glucose values have been
a
associated with increased cardiovascu-
ci
lar risk independent of fasting plasma
glucose in some epidemiologic studies,
so
but intervention trials have not shown
postprandial glucose to be a cardiovas-
cular risk factor independent of A1C. In
As
subjects with diabetes, surrogate meas-
ures of vascular pathology, such as
endothelial dysfunction, are negatively
s
affected by postprandial hyperglycemia.
It is clear that postprandial hypergly-
gets must be individualized in the context that might be appropriate for an indi- prandial SMBG. Additionally, a random-
of shared decision-making to address the vidual early in the course of the disease ized controlled trial in patients with
needs and preferences of each patient may change over time. Newly diag- known CVD found no CVD benefit of
ic
and the individual characteristics that nosed patients and/or those without insulin regimens targeting postprandial
er
influence risks and benefits of therapy comorbidities that limit life expectancy glucose compared with those targeting
for each patient. may benefit from intensive control proven preprandial glucose (49). Therefore, it is
The factors to consider in individual- to prevent microvascular complications. reasonable for postprandial testing to be
Am
izing goals are depicted in Fig. 6.2. Figure Both DCCT/EDIC and UKPDS demon- recommended for individuals who have
6.2 is not designed to be applied rigidly strated metabolic memory, or a legacy premeal glucose values within target but
but to be used as a broad construct to effect, in which a finite period of intensive have A1C values above target. Measuring
guide clinical decision-making (47) and control yielded benefits that extended for postprandial plasma glucose 1–2 h after
19
engage in shared decision-making in both decades after that control ended. Thus, the start of a meal and using treatments
type 1 and type 2 diabetes. More strin- a finite period of intensive control to near- aimed at reducing postprandial plasma
normal A1C may yield enduring benefits glucosevaluesto,180mg/dL(10.0mmol/L)
20
but did not affect the definition of hy- Table 6.3—Summary of glycemic recommendations for many nonpregnant adults
poglycemia. with diabetes
A1C ,7.0% (53 mmol/mol)*
HYPOGLYCEMIA Preprandial capillary plasma glucose 80–130 mg/dL* (4.4–7.2 mmol/L)
Recommendations Peak postprandial capillary plasma glucose† ,180 mg/dL* (10.0 mmol/L)
6.10 Individuals at risk for hypogly- *More or less stringent glycemic goals may be appropriate for individual patients. Goals should be
cemia should be asked about individualized based on duration of diabetes, age/life expectancy, comorbid conditions, known
CVD or advanced microvascular complications, hypoglycemia unawareness, and individual patient
symptomatic and asymptom-
n
considerations. †Postprandial glucose may be targeted if A1C goals are not met despite reaching
atic hypoglycemia at each en- preprandial glucose goals. Postprandial glucose measurements should be made 1–2 h after the
tio
counter. C beginning of the meal, generally peak levels in patients with diabetes.
6.11 In patients taking medication
that can lead to hypoglycemia,
a
investigate, screen, and assess If a patient has level 2 hypoglycemia
at least several weeks in order to
ci
risk for or occurrence of un- without adrenergic or neuroglycopenic
partially reverse hypoglycemia
recognized hypoglycemia, con- symptoms, they likely have hypoglycemia
so
unawareness and reduce risk of
sidering that patients may unawareness (discussed further below).
future episodes. A
have hypoglycemia unaware- This clinical scenario warrants investiga-
6.16 Ongoing assessment of cogni-
ness. C
As
tion and review of the medical regimen.
tive function is suggested with
6.12 Glucose (15–20 g) is the preferred Lastly, level 3 hypoglycemia is defined as a
increased vigilance for hypogly-
treatment for the conscious in- severe event characterized by altered
cemia by the clinician, patient,
dividual with blood glucose ,70 mental and/or physical functioning
and caregivers if low cognition
s
mg/dL [3.9 mmol/L]), although that requires assistance from another
or declining cognition is found. B
te
any form of carbohydrate that person for recovery.
contains glucose may be used. Symptoms of hypoglycemia include,
be
Fifteen minutes after treatment, Hypoglycemia is the major limiting but are not limited to, shakiness, irrita-
if SMBG shows continued hypo- factor in the glycemic management of bility, confusion, tachycardia, and hun-
glycemia,thetreatmentshouldbe type 1 and type 2 diabetes. Recommen- ger. Hypoglycemia may be inconvenient
ia
repeated. Once SMBG returns to dations regarding the classification of or frightening to patients with diabetes.
normal, the individual should con- hypoglycemia are outlined in Table 6.4 Level 3 hypoglycemia may be recognized
D
sume a meal or snack to prevent (51–56). Level 1 hypoglycemia is defined or unrecognized and can progress to
recurrence of hypoglycemia. B as a measurable glucose concentration loss of consciousness, seizure, coma,
6.13 Glucagon should be prescribed ,70 mg/dL (3.9 mmol/L) but $54 mg/dL
an
as blood glucose ,54 mg/dL been recognized as a threshold for neu- person with diabetes or others, espe-
(3.0 mmol/L), so it is available roendocrine responses to falling glucose cially if it causes falls, motor vehicle
er
should it be needed. Caregivers, in people without diabetes. Because accidents, or other injury. Recurrent
school personnel, or family mem- many people with diabetes demonstrate level 2 hypoglycemia and/or level 3 hy-
Am
bers of these individuals should impaired counterregulatory responses poglycemia is an urgent medical issue
know where it is and when and to hypoglycemia and/or experience hy- and requires intervention with medical
how to administer it. Glucagon poglycemia unawareness, a measured regimen adjustment, behavioral inter-
administration is not limited to glucose level ,70 mg/dL (3.9 mmol/L) is vention, and, in some cases, use of
health care professionals, partic- considered clinically important, inde- technology to assist with hypoglycemia
19
ularly with the availability of intra- pendent of the severity of acute hypo- prevention and identification (52,57–60).
nasal and stable soluble glucagon glycemic symptoms. Level 2 hypoglycemia A large cohort study suggested that
available in autoinjector pens. E
20
(defined as a blood glucose concentration among older adults with type 2 diabetes,
6.14 Hypoglycemia unawareness or ,54 mg/dL [3.0 mmol/L]) is the thresh- a history of level 3 hypoglycemia was
one or more episodes of level old at which neuroglycopenic symp- associated with greater risk of dementia
©
3 hypoglycemia should trigger toms begin to occur and requires immediate (61). Conversely, in a substudy of the
hypoglycemia avoidance edu- action to resolve the hypoglycemic event. ACCORD trial, cognitive impairment at
cation and reevaluation of the
treatment regimen. E
Table 6.4—Classification of hypoglycemia
6.15 Insulin-treated patients with hy-
Glycemic criteria/description
poglycemia unawareness, one
level 3 hypoglycemic event, or Level 1 Glucose ,70 mg/dL (3.9 mmol/L) and $54 mg/dL (3.0 mmol/L)
a pattern of unexplained level 2 Level 2 Glucose ,54 mg/dL (3.0 mmol/L)
hypoglycemia should be advised Level 3 A severe event characterized by altered mental and/or physical status requiring
to raise their glycemic targets to assistance for treatment of hypoglycemia
strictly avoid hypoglycemia for Reprinted from Agiostratidou et al. (51).
care.diabetesjournals.org Glycemic Targets S73
baseline or decline in cognitive function and hypoglycemia unawareness that per- use of glucagon, including where
during the trial was significantly associ- sists despite medical treatment, human the glucagon product is kept and
ated with subsequent episodes of level islet transplantation may be an option, when and how to administer. An in-
3 hypoglycemia (62). Evidence from but the approach remains experimental dividual does not need to be a health
DCCT/EDIC, which involved adolescents (72,73). care professional to safely administer
and younger adults with type 1 diabetes, In 2015, the ADA changed its prepran- glucagon. In addition to traditional glu-
found no association between fre- dial glycemic target from 70–130 mg/dL cagon injection powder that requires
quency of level 3 hypoglycemia and (3.9–7.2 mmol/L) to 80–130 mg/dL (4.4– reconstitution prior to injection, intra-
n
cognitive decline (63), as discussed in 7.2 mmol/L). This change reflects the nasal glucagon and glucagon solution
Section 13 “Children and Adolescents” results of the ADAG study, which dem- for subcutaneous injection recently re-
tio
(https://doi.org/10.2337/dc20-S013). onstrated that higher glycemic targets ceived U.S. Food and Drug Administra-
Studies of rates of level 3 hypoglycemia corresponded to A1C goals (7). An addi- tion approval. Care should be taken to
a
that rely on claims data for hospitaliza- tional goal of raising the lower range of ensure that glucagon products are not
ci
tion, emergency department visits, and the glycemic target was to limit over- expired.
ambulance use substantially underesti- treatment and provide a safety margin
so
mate rates of level 3 hypoglycemia (64) in patients titrating glucose-lowering Hypoglycemia Prevention
yet find high burden of hypoglycemia in drugs such as insulin to glycemic targets. Hypoglycemia prevention is a critical
adults over 60 years of age in the com- component of diabetes management.
As
munity (65). African Americans are at Hypoglycemia Treatment SMBG and, for some patients, CGM
substantially increased risk of level 3 hy- Providers should continue to counsel are essential tools to assess therapy
poglycemia (65,66). In addition to age patients to treat hypoglycemia with and detect incipient hypoglycemia. Pa-
fast-acting carbohydrates at the hypo- tients should understand situations that
s
and race, other important risk factors
found in a community-based epidemi- glycemia alert value of 70 mg/dL increase their risk of hypoglycemia, such
ologic cohort of older black and white
adults with type 2 diabetes include insulin te
(3.9 mmol/L) or less. This should be
reviewed at each patient visit. Hypogly-
as when fasting for tests or procedures,
when meals are delayed, during and after
be
use, poor or moderate versus good gly- cemia treatment requires ingestion of the consumption of alcohol, during and
cemic control, albuminuria, and poor glucose- or carbohydrate-containing foods after intense exercise, and during sleep.
(74–76). The acute glycemic response Hypoglycemia may increase the risk of
ia
tween hypoglycemia, achieved A1C, and carbohydrate that contains glucose will these strategies are not always sufficient
treatment intensity were not straightfor- raise blood glucose. Added fat may retard for prevention.
ward. An association of level 3 hypo- and then prolong the acute glycemic In type 1 diabetes and severely insulin
ic
glycemia with mortality was also found response. In type 2 diabetes, ingested deficient type 2 diabetes, hypoglycemia
protein may increase insulin response unawareness (or hypoglycemia-associated
er
reported in clinical practice (68) drate sources high in protein should not quality of life. This syndrome is char-
Young children with type 1 diabetes be used to treat or prevent hypogly- acterized by deficient counterregu-
and the elderly, including those with cemia. Ongoing insulin activity or latory hormone release, especially in
type 1 and type 2 diabetes (61,69), insulin secretagogues may lead to older adults, and a diminished auto-
19
are noted as particularly vulnerable to recurrent hypoglycemia unless more nomic response, which are both risk
hypoglycemia because of their reduced food is ingested after recovery. Once factors for, and caused by, hypoglyce-
ability to recognize hypoglycemic symp- the glucose returns to normal, the in- mia. A corollary to this “vicious cycle” is
20
toms and effectively communicate their dividual should be counseled to eat a that several weeks of avoidance of
needs. Individualized glucose targets, meal or snack to prevent recurrent hypoglycemia has been demonstrated
hypoglycemia. to improve counterregulation and hy-
©
promise of alarm-based prevention of hyperglycemia requires temporary ad- 11. Rohlfing C, Hanson S, Little RR. Measure-
hypoglycemia (80,81). To date, there justment of the treatment regimen ment of hemoglobin A1c in patients with sickle
cell trait. JAMA 2017;317:2237
have been six randomized controlled and immediate interaction with the di- 12. Wheeler E, Leong A, Liu C-T, et al.; EPIC-CVD
trials in adults with type 1 diabetes abetes care team. The patient treated Consortium; EPIC-InterAct Consortium; Lifelines
and seven in adults and children with with noninsulin therapies or medical Cohort Study. Impact of common genetic deter-
type 1 diabetes using real-time CGM. nutrition therapy alone may require in- minants of Hemoglobin A1c on type 2 diabetes
These studies had differing A1C at entry sulin. Adequate fluid and caloric intake risk and diagnosis in ancestrally diverse popu-
lations: A transethnic genome-wide meta-
and differing primary end points and thus must be ensured. Infection or dehydra- analysis. PLoS Med 2017;14:e1002383
n
must be interpreted carefully. Real-time tion is more likely to necessitate hospi- 13. Wilson DM, Kollman; Diabetes Research in
CGM studies can be divided into studies talization of the person with diabetes
tio
Children Network (DirecNet) Study Group. Re-
with elevated A1C with the primary end than the person without diabetes. lationship of A1C to glucose concentrations in
point of A1C reduction and studies with A physician with expertise in diabe- children with type 1 diabetes: assessments by
a
high-frequency glucose determinations by sen-
A1C near target with the primary end tes management should treat the hos- sors. Diabetes Care 2008;31:381–385
ci
point of reduction in hypoglycemia pitalized patient. For further information 14. Buse JB, Kaufman FR, Linder B, Hirst K, El
(81–97). In people with type 1 and on the management of diabetic keto- Ghormli L, Willi S; HEALTHY Study Group. Di-
so
type 2 diabetes with A1C above target, acidosis and the nonketotic hyperglyce- abetes screening with hemoglobin A1c versus
CGM improved A1C between 0.3% and mic hyperosmolar state, please refer to fasting plasma glucose in a multiethnic middle-
school cohort. Diabetes Care 2013;36:429–435
0.6%. For studies targeting hypoglyce- the ADA consensus report “Hyperglyce-
As
15. Kamps JL, Hempe JM, Chalew SA. Racial
mia, most studies demonstrated a sig- mic Crises in Adult Patients With Diabe- disparity in A1C independent of mean blood
nificant reduction in time spent between tes” (105). glucose in children with type 1 diabetes. Diabetes
54 and 70 mg/dL. No study to date has Care 2010;33:1025–1027
References 16. Diabetes Control and Complications Trial
s
reported a decrease in level 3 hypogly-
1. Laiteerapong N, Ham SA, Gao Y, et al. The Research Group. The effect of intensive treat-
cemia. In a single study using intermit-
te
legacy effect in type 2 diabetes: impact of early ment of diabetes on the development and
tently scanned CGM, adults with type 1 progression of long-term complications in
glycemic control on future complications (the
diabetes with A1C near goal and im- insulin-dependent diabetes mellitus. N Engl J
be
Diabetes & Aging Study). Diabetes Care 2019;42:
paired awareness of hypoglycemia demon- 416–426 Med 1993;329:977–986
strated no change in A1C and decreased 2. Stratton IM, Adler AI, Neil HAW, et al. Asso- 17. Battelino T, Danne T, Bergenstal RM, et al.
ciation of glycaemia with macrovascular and Clinical targets for continuous glucose monitor-
ia
level 2 hypoglycemia (88). For people ing data interpretation: recommendations from
microvascular complications of type 2 diabetes
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©
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2009;169:1307–1316 tes, 2015: a patient-centered approach: update ucation (BUD1E) study survey. Diabet Med 2018;
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68. McCoy RG, Van Houten HK, Ziegenfuss JY, Shah 84. Sequeira PA, Montoya L, Ruelas V, et al. 111:933–938
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Diabetes Care Volume 43, Supplement 1, January 2020 S77
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Diabetes Care 2020;43(Suppl. 1):S77–S88 | https://doi.org/10.2337/dc20-S007
a tio
ci
so
As
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
includes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guidelines,
and tools to evaluate quality of care. Members of the ADA Professional Practice
7. DIABETES TECHNOLOGY
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC),
te
are responsible for updating the Standards of Care annually, or more frequently as
warranted. For a detailed description of ADA standards, statements, and reports, as well
be
as the evidence-grading system for ADA’s clinical practice recommendations, please refer
to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who
ia
Diabetes technology is the term used to describe the hardware, devices, and software
that people with diabetes use to help manage their condition, from lifestyle to blood
an
glucose levels. Historically, diabetes technology has been divided into two main
categories: insulin administered by syringe, pen, or pump, and blood glucose
monitoring as assessed by meter or continuous glucose monitor. More recently,
ic
diabetes technology has expanded to include hybrid devices that both monitor
glucose and deliver insulin, some automatically, as well as software that serves as a
er
people with diabetes; however, the complexity and rapid change of the diabetes
technology landscape can also be a barrier to patient and provider implementation.
OVERALL STATEMENT
19
Recommendation
7.1 Use of technology should be individualized based on a patient’s needs,
desires, skill level, and availability of devices. Nonprofit websites can offer advice
20
use in people with diabetes. Insurance coverage can lag behind device availability,
patient interest in devices and willingness to change can vary, and providers may have
trouble keeping up with newly released technology. Not-for-profit websites such as
DiabetesWise.org (1) and others can help providers and patients make decisions as Suggested citation: American Diabetes Associa-
tion. 7. Diabetes Technology: Standards of Med-
to the initial choice of devices. Other sources, including health care providers and
ical Care in Diabetesd2020. Diabetes Care
device manufacturers, can help people troubleshoot when difficulties arise. 2020;43(Suppl. 1):S77–S88
© 2019 by the American Diabetes Association.
SELF-MONITORING OF BLOOD GLUCOSE
Readers may use this article as long as the work is
Recommendations properly cited, the use is educational and not
for profit, and the work is not altered. More infor-
7.2 Most patients using intensive insulin regimens (multiple daily injections or
mation is available at http://www.diabetesjournals
insulin pump therapy) should be encouraged to assess glucose levels using .org/content/license.
S78 Diabetes Technology Diabetes Care Volume 43, Supplement 1, January 2020
glucose monitoring (CGM) has emerged almost 27,000 children and adolescents
self-monitoring of blood glucose
as a method for the assessment of glu- with type 1 diabetes showed that, after
(and/or continuous glucose mon-
cose levels (discussed below). Glucose adjustment for multiple confounders,
itoring) prior to meals and
monitoring allows patients to evaluate increased daily frequency of SMBG was
snacks, at bedtime, prior to ex-
their individual response to therapy and significantly associated with lower A1C
ercise, when they suspect low
assess whether glycemic targets are (–0.2% per additional test per day) and
blood glucose, after treating
being safely achieved. Integrating with fewer acute complications (7).
low blood glucose until they
results into diabetes management can
are normoglycemic, and prior
n
be a useful tool for guiding medical Patients Using Basal Insulin and/or
to and while performing critical
nutrition therapy and physical activity,
tio
Oral Agents
tasks such as driving. B
preventing hypoglycemia, and adjusting The evidence is insufficient regarding
7.3 When prescribed as part of a
medications (particularly prandial insulin when to prescribe SMBG and how often
diabetes self-management edu-
a
doses). The patient’s specific needs and testing is needed for insulin-treated pa-
cation and support program, self-
ci
goals should dictate SMBG frequency tients who do not use intensive insulin
monitoring of blood glucose may
and timing or the consideration of regimens, such as those with type 2
help to guide treatment decisions
so
CGM use. diabetes using basal insulin with or with-
and/or self-management for pa-
out oral agents. However, for patients
tients taking less-frequent insulin Optimizing SMBG Monitor Use using basal insulin, assessing fasting glu-
injections. B
As
SMBG accuracy is dependent on the cose with SMBG to inform dose adjust-
7.4 Although self-monitoring of blood instrument and user, so it is important ments to achieve blood glucose targets
glucose in patients on noninsulin to evaluate each patient’s monitoring results in lower A1C (8,9).
therapies has not shown clinically technique, both initially and at regular
s
In people with type 2 diabetes not
significant reductions in A1C, it intervals thereafter. Optimal use of using insulin, routine glucose monitoring
te
may be helpful when altering SMBG requires proper review and in- may be of limited additional clinical
diet, physical activity, and/or terpretation of the data, by both the benefit. By itself, even when combined
be
medications (particularly medica- patient and the provider, to ensure that with education, it has showed limited
tions that can cause hypoglyce- data are used in an effective and timely improvement in outcomes (10–13). How-
mia) inconjunctionwithatreatment manner. In patients with type 1 diabetes,
ia
and regular evaluation of techni- taking no action when results are high or useful in assessing hypoglycemia, glu-
que, results, and their ability to use low (4). Patients should be taught how cose levels during intercurrent illness,
data from self-monitoring of blood to use SMBG data to adjust food or discrepancies between measured
ic
glucose to adjust therapy. E intake, exercise, or pharmacologic ther- A1C and glucose levels when there is con-
7.6 Health care providers should be apy to achieve specific goals. The ongoing
er
min C and hypoxemia, that can avoid overuse, particularly if SMBG is not ment program. In a year-long study of
interfere with glucose meter being used effectively for self-management insulin-naive patients with suboptimal
accuracy and provide clinical (4–6). initial glycemic stability, a group trained
management as indicated. E
Patients on Intensive Insulin Regimens in structured SMBG (a paper tool was
7.7 Providers should be aware of the
19
SMBG is especially important for insulin- used at least quarterly to collect and
differences in accuracy among
treated patients to monitor for and pre- interpret seven-point SMBG profiles
glucose metersdonly U.S. Food
vent hypoglycemia and hyperglycemia. taken on 3 consecutive days) reduced
20
n
ganization for Standardization (ISO) (ISO
under a variety of circumstances, pro- awareness, and/or have episodes
15197:2013) and the FDA. The current
tio
viders and people with diabetes need to
ISO and FDA standards are compared in of hypoglycemia. A
be aware of factors that can impair meter
Table 7.2. In Europe, currently marketed 7.10 When used properly, intermit-
accuracy. A meter reading that seems tently scanned continuous glucose
a
monitors must meet current ISO stand-
discordant with clinical reality needs to monitors in conjunction with in-
ards. In the U.S., currently marketed
ci
be retested or tested in a laboratory. sulin therapy are useful tools to
monitors must meet the standard under
Providers in intensive care unit settings lower A1C levels and/or reduce
so
which they were approved, which may
need to be particularly aware of the hypoglycemia in adults with type
not be the current standard. Moreover,
potential for abnormal meter readings, 1 diabetes who are not meeting
the monitoring of current accuracy is
and laboratory-based values should be
As
left to the manufacturer and not rou- glycemic targets, have hypogly-
used if there is any doubt. Some meters cemia unawareness, and/or have
tinely checked by an independent
give error messages if meter readings
source. episodes of hypoglycemia. C
are likely to be false (18).
Patients assume their glucose monitor 7.11 When used properly, real-time
s
Oxygen. Currently available glucose mon- and intermittently scanned con-
is accurate because it is FDA cleared, but
te
itors utilize an enzymatic reaction linked to tinuous glucose monitors in con-
an electrochemical reaction, either glucose often that is not the case. There is sub-
stantial variation in the accuracy of junction with insulin therapy are
be
oxidase or glucose dehydrogenase (19). useful tools to lower A1C and/or
Glucose oxidase monitors are sensitive widely used blood glucose monitoring
systems (20). The Diabetes Technology reduce hypoglycemia in adults
to the oxygen available and should only with type 2 diabetes who are
Society Blood Glucose Monitoring Sys-
ia
program found that only 6 of the top 1 diabetes, whether using injec-
(i.e., highaltitude, hypoxia, or venousblood tions or continuous subcutaneous
readings) may lead to false high glucose 18 glucose meters met the accuracy
standard (21). insulin infusion, as an additional
ic
Table 7.2—Comparison of ISO 15197:2013 and FDA blood glucose meter accuracy standards
Setting FDA (154,155) ISO 15197:2013 (156)
Home use 95% within 15% for all BG in the usable BG range† 95% within 15% for BG $100 mg/dL
99% within 20% for all BG in the usable BG range† 95% within 15 mg/dL for BG ,100 mg/dL
99% in A or B region of consensus error grid‡
Hospital use 95% within 12% for BG $75 mg/dL
95% within 12 mg/dL for BG ,75 mg/dL
98% within 15% for BG $75 mg/dL
98% within 15 mg/dL for BG ,75 mg/dL
n
BG, blood glucose; FDA, U.S. Food and Drug Administration; ISO, International Organization for Standardization. To convert mg/dL to mmol/L, see
tio
endmemo.com/medical/unitconvert/Glucose.php. †The range of blood glucose values for which the meter has been proven accurate and will provide
readings (other than low, high, or error). ‡Values outside of the “clinically acceptable” A and B regions are considered “outlier” readings and may be
dangerous to use for therapeutic decisions (157).
a
ci
Some real-time systems require calibra- Real-time CGM Device Use in Adults
7.16 People who have been using
so
tion by the user, which varies in frequency With Type 1 Diabetes
continuous glucose monitors
depending on the device. Additionally, for Data exist to support the use of real-time
should have continued access
CGM in adults, both those on multiple
As
some CGM systems, the FDA suggests
across third-party payers. E
SMBG for making treatment decisions. daily injections (MDI) and continuous
Devices that require SMBG confirmation subcutaneons insulin infusion (CSII). In
CGM measures interstitial glucose
(which correlates well with plasma glu- are called “adjunctive,” while those that terms of RCTs in people with type 1
s
do not are called “nonadjunctive.” An RCT diabetes, there are four studies in adults
cose). There are two basic types of CGM
te
of 226 adults suggested that a CGM device with A1C as the primary outcome
devices: those that provide unblinded data
could be used safely and effectively with- (28–32), three studies in adults with
to the user and those that are blinded with
be
out regular confirmatory SMBG in patients hypoglycemia as the primary outcome
data available to the patient and their (33–35), four studies in adults and chil-
health care provider for retrospective anal- with well-controlled type 1 diabetes at
low risk of severe hypoglycemia (23). Two dren with A1C as the primary outcome
ysis. Table 7.3 provides the definitions
ia
CGM offers opportunities to analyze pa- In general, A1C reduction was shown in
using real-time CGM devices that have studies where the baseline A1C was higher.
tient data more granularly than was pre-
alarms and alerts. It is difficult to deter- In two larger studies in adults with type 1
viously possible, providing additional
ic
mine how much impact having these information to aid in achieving glycemic diabetes that assessed the benefit of real-
notices makes in terms of reacting to targets. A variety of metrics have been pro- time CGM in patients on MDI, there were
er
glucose levels. There is one small study posed (26) and are discussed in Section significant reductions in A1C: –0.6% in one
in patients at risk for hypoglycemia that 6, “Glycemic Targets” (https://doi.org/10 (28,29) and –0.43% in the other (30). No
Am
compares real-time CGM with intermit- .21337/dc20-S006). CGM is essential for reduction in A1C was seen in a small study
tently scanned CGM (isCGM) (22). The creating the ambulatory glucose profile performed in underserved, less well-
study showed improvement in time spent (AGP) and providing data on time in educated adults with type 1 diabetes
in hypoglycemia with real-time CGM com- range, percentage of time spent above (31). In the adult subset of the JDRF CGM
19
pared with isCGM. and below range, and variability (27). study, there was a significant reduction in
A1C of –0.53% (43) in patients who were
primarily treated with insulin pump ther-
20
n
hypoglycemia (36–38). in people with type 2 diabetes on MDI did children aged 4–9 years did not demon-
not show a reduction in hypoglycemia strate improvements in glycemic control
tio
Intermittently Scanned CGM Device (50), although it did show a reduction in following 6 months of real-time CGM use
Use in Adults With Type 1 Diabetes A1C. Studies in individuals with type 2 (53). However, observational feasibility
a
isCGM does not currently provide alarms diabetes on oral agents with or without studies of toddlers demonstrated a high
ci
and alerts but is an option used by many insulin did not show reductions in rates of degree of parental satisfaction and sus-
patients. There is relatively little RCT data hypoglycemia (48,49). tained use of the devices despite the in-
so
proving benefit in people with type 1 In one study of isCGM in people with ability to change the degree of glycemic
diabetes. One study, designed to show a type 2 diabetes on a variety of insulin control attained (56).
reduction in episodes of hypoglycemia in regimens and an initial A1C of ;8.8%, no Registry data has also shown an asso-
As
patients at higher risk for hypoglycemia, reduction in A1C was seen; however, the ciation between real-time CGM use and
showed a significant benefit in terms of time spent in a hypoglycemic range was lower A1C levels (43,57), even when lim-
time spent in a hypoglycemic range (P , reduced by 43% (51). In a study of isCGM iting assessment of real-time CGM use to
s
0.0001) (33). Additional observational in individuals with type 2 diabetes on participants on injection therapy (57).
studies have shown benefit in terms MDI, the A1C was reduced by 0.82% in
te
Impact on Hypoglycemia
of A1C reduction (44). the intervention group and 0.33% in the There are no studies solely including pedi-
There are several published reviews control group (P 5 0.005) with no change
be
atric patients that assess rates of hypogly-
of data available on isCGM (45–47). The in rates of hypoglycemia (52). cemia as the primary outcome. Some of the
Norwegian Institute of Public Health con- studies where pediatric and adult patients
ia
ducted an assessment of isCGM clini- Real-time CGM Device Use in Children were combined together did show potential
cal effectiveness, cost-effectiveness, and and Adolescents With Type 1 Diabetes reductions in hypoglycemia (10,62,63).
D
cluded that, although there were few of data collected by registries. Seven RCTs Type 1 Diabetes
quality data available at the time of the have included both adult and pediatric par- Data on use of isCGM in children come from
report, isCGM may increase treatment
ic
ticipants (36–42), while others have only observational studies. In these reports,
satisfaction, increase time in range, and included pediatric participants (53) or limited isCGM is favorably adopted and is associated
er
reduce frequency of nocturnal hypoglyce- the analysis of larger studies to just the with improvements in outcomes (64–67).
mia, without differences in A1C or quality pediatric participants (36). Given the feasi-
of life or serious adverse events. The
Am
isfaction and quality of life and concluded by the observational nature, registry data quency of sensor use (36). In this study,
that the system could replace SMBG, provide some evidence of real-world use overall use was highest in those aged
particularly in patients who require $25 years (who had the most improvement
20
affordable alternative to real-time CGM When data from adult and pediatric par- Real-time CGM Device Use in
systems for individuals with diabetes who ticipants are analyzed together, real-time Pregnancy
are on intensive insulin therapy. CGM use in RCTs has been associated with One well-designed RCT showed a reduc-
reduction in A1C levels (37–39). Yet in the tion in A1C levels in adult women with
Real-time and Intermittently Scanned JDRF CGM trial, when youth were ana- type 1 diabetes on MDI or CSII who were
CGM Device Use in Adults With Type 2 lyzed by age-group (8- to 14-year-olds and pregnant (68). Neonatal outcomes were
Diabetes 15- to 24-year-olds), no change in A1C was better when the mother used CGM dur-
Studies in people with type 2 diabetes are seen, likely due to poor real-time CGM ing pregnancy (28). Two studies employ-
heterogeneous in designdin two, par- adherence (36). Indeed, in a secondary ing intermittent use of real-time CGM
ticipants were using basal insulin with analysis of that RCT’s data in both pediatric showed no difference in neonatal out-
oral agents or oral agents alone (48,49); cohorts, those who used the sensor $6 comes in women with type 1 diabetes
in one, individuals were on MDI alone days/week had an improvement in their (69) or gestational diabetes mellitus (70).
S82 Diabetes Technology Diabetes Care Volume 43, Supplement 1, January 2020
n
evaluate patients when either real- to dosing increment and minimal dose,
setting when proper supervi-
time or isCGM is not available to the which can range from half-unit doses to
tio
sion is available. E
patient or the patient prefers a blinded 2-unit dose increments.
analysis. It can be particularly useful to Needle thickness (gauge) and length
a
evaluate periods of hypoglycemia in Injecting insulin with a syringe or pen is is another consideration. Needle gauges
patients on agents that can cause hy-
ci
the insulin delivery method used by most range from 22 to 33, with higher gauge
poglycemia for making medication dose people with diabetes (76,77), although indicating a thinner needle. A thicker
so
adjustments. It can also be useful to inhaled insulin is also available. Others needle can give a dose of insulin more
evaluate for periods of hyperglycemia. Use use insulin pumps or automated insulin quickly, while a thinner needle may cause
of blinded CGM should always be cou- delivery devices (see sections on those less pain. Needle length ranges from 4 to
As
pled with analysis and interpretation for topics below). For patients with diabetes 12.7 mm, with some evidence suggesting
the patient, along with education as who use insulin, insulin syringes and pens shorter needles may lower the risk of
needed to adjust medication and change are both able to deliver insulin safely and intramuscular injection. When reused, nee-
lifestyle behaviors.
s
effectively for the achievement of glyce- dles may be duller and thus injection more
mic targets. When choosing among de- painful. Proper insulin technique is a req-
Side Effects of CGM Devices
Contact dermatitis has been reported with
te
livery systems, patient preferences, cost,
insulin type and dosing regimen, and self-
uisite to obtain the full benefits of insulin
injection therapy, and concerns with tech-
be
all devices that attach to the skin (71). In management capabilities should be con- nique and using the proper technique are
some cases this has been linked to the sidered. It is important to note that while outlined in Section 9 “Pharmacologic Ap-
presence of isobornyl acrylate, which is a
ia
many insulin types are available for pur- proaches to Glycemic Treatment” (https://
skin sensitizer and can cause an additional chase as either pens or vials, others may doi.org/10.2337/dc20-S009).
spreading allergic reaction (72–74). Patch
D
only be available in one form or the other Another insulin delivery option is a
testing can be done to identify the cause and there may be significant cost differ- disposable patch-like device, which pro-
of the contact dermatitis (75). ences between pens and vials (see Table vides a continuous, subcutaneous infu-
an
9.3 for a list of insulin product costs with sion of rapid-acting insulin (basal), as
INSULIN DELIVERY dosage forms). Insulin pens may allow well as 2 unit increments of bolus insulin
Insulin Syringes and Pens people with vision impairment or dex- at the press of a button (82).
ic
terity issues to dose insulin accurately Bolus calculators have been developed
Recommendations
er
(78–80), while insulin injection aids are to aid in dosing decisions (83–87). These
7.17 For people with diabetes who
also available to help with these issues. are subject to FDA approval to ensure
require insulin, insulin syringes
(For a helpful list of injection aids, see safety in terms of dosing recommenda-
Am
The most common syringe sizes are for setting the initial dosing calculations
7.18 Insulin pens or insulin injection
1 mL, 0.5 mL, and 0.3 mL, allowing doses with ongoing follow-up for adjustments
aids may be considered for pa-
of up to 100 units, 50 units, and 30 units as needed.
20
CSII or insulin pumps have been available must be recognized and managed early diabetes, there is insufficient evidence to
in the U.S. for 40 years. These devices (97); lipohypertrophy or, less frequently, make recommendations.
deliver rapid-acting insulin throughout the lipoatrophy (98,99); and pump site in- Commonbarrierstopumptherapyadop-
day to help manage blood glucose levels. fection (100). Discontinuation of pump tion in children and adolescents are con-
Most insulin pumps use tubing to deliver therapy is relatively uncommon today; cerns regarding the physical interference of
insulin through a cannula, while a few the frequency has decreased over the the device, discomfort with idea of having a
attach directly to the skin, without tubing. past few decades, and its causes have device on the body, therapeutic effective-
Most studies comparing MDI with CSII changed (100,101). Current reasons for ness, and financial burden (107,117).
n
have been relatively small and of short attrition are problems with cost, wear-
duration. However, a recent systematic ability, disliking the pump, suboptimal Insulin Pumps in Patients With Type 2
tio
review and meta-analysis concluded that glycemic control, or mood disorders and Other Types of Diabetes
pump therapy has modest advantages (e.g., anxiety or depression) (102). Certain patients with insulin deficiency,
a
for lowering A1C (20.30% [95% CI 20.58 for instance those with long standing
to 20.02]) and for reducing severe hypo- type 2 diabetes, those who have had a
ci
Insulin Pumps in Pediatric Patients
glycemia rates in children and adults (88). The safety of insulin pumps in youth has pancreatectomy, and/or individuals with
cystic fibrosis may benefit from insulin
so
There is no consensus to guide choosing been established for over 15 years (103).
which form of insulin administration is best Studying the effectiveness of CSII in pump therapy. This is an individual de-
for a given patient, and research to guide lowering A1C has been challenging be- cision and must be tailored to fit patient
As
this decision-making is needed (89). Thus, cause of the potential selection bias of needs and preferences.
the choice of MDI or an insulin pump is observational studies. Participants on
often based upon the individual character- CSII may have a higher socioeconomic Insulin Pumps in Older Adults
Older individuals with type 1 diabetes
s
istics of the patient and which is most likely status that may facilitate better glycemic
to benefit him or her. Newer systems, such control (104) versus MDI. In addition, the benefit from ongoing insulin pump ther-
as sensor-augmented pumps and auto-
matic insulin delivery systems, are dis- te
fast pace of development of new insulins
and technologies quickly renders com-
apy. There is no data to suggest that
measurement of C-peptide levels or
be
cussed elsewhere in this section. parisons obsolete. However, RCTs com- antibodies predicts success with insulin
Adoption of pump therapy in the U.S. paring CSII and MDI with insulin analogs pump therapy (118,119). Additionally,
frequency of follow-up does not influ-
ia
socioeconomic status as reflected by participants on CSII (107–109). Although Combined Insulin Pump and Sensor
race/ethnicity, private health insurance, hypoglycemia was a major adverse effect Systems
family income, and education (91,92). of intensified insulin regimen in the Di-
ic
Recommendations
Given the additional barriers to optimal abetes Control and Complications Trial 7.25 Sensor-augmented pump ther-
er
diabetes care observed in disadvantaged (DCCT) (110), data suggest that CSII may apy with automatic low glucose
groups (93), addressing the differences reduce the rates of severe hypoglycemia suspend may be considered for
in access to insulin pumps and other compared with MDI (109,111–113).
Am
Practical aspects of pump therapy initia- compared with MDI (62). Finally, treat- and adults with type 1 diabetes
tion include assessment of patient and ment satisfaction and quality-of-life to improve glycemic control. A
family readiness (although there is no measures improved on CSII compared 7.27 Individual patients may be using
20
consensus on which factors to consider with MDI (115,116). Therefore, CSII can systems not approved by the U.S.
in adults [96] or pediatric patients), se- be used safely and effectively in youth Food and Drug Administration
©
lection of pump type and initial pump with type 1 diabetes to assist with achiev- such as do-it-yourself closed
settings, patient/family education of po- ing targeted glycemic control while re- loop systems and others; providers
tential pump complications (e.g., diabetic ducing the risk of hypoglycemia and DKA, cannot prescribe these systems
ketoacidosis [DKA] with infusion set fail- improving quality of life and preventing but can provide safety informa-
ure), transition from MDI, and introduction long-term complications. Based on pa- tion/troubleshooting/backup
of advanced pump settings (e.g., tem- tient–provider shared decision-making, advice for the individual devices
porary basal rates, extended/square/ insulin pumps may be considered in all to enhance patient safety. E
dual wave bolus). pediatric patients. In particular, pump
Complications of the pump can be therapy may be the preferred mode of
caused by issues with infusion sets (dis- insulin delivery for children under 7 years Sensor-Augmented Pumps
lodgement, occlusion), which place pa- of age (63). Because of a paucity of data Sensor-augmented pumps that suspend
tients at risk for ketosis and DKA and thus in adolescents and youth with type 2 insulin when glucose is low or predicted
S84 Diabetes Technology Diabetes Care Volume 43, Supplement 1, January 2020
to go low within the next 30 min have delivery (139–141). These systems are or less information, such as being part of
been approved by the FDA. The Auto- not approved by the FDA, although there a registry or data repository or not).
mation to Simulate Pancreatic Insulin are efforts underway to obtain regula- There are many online programs that
Response (ASPIRE) trial of 247 patients tory approval for them. The information offer lifestyle counseling to aid with
with type 1 diabetes and documented on how to set up and manage these weight loss and increase physical activity
nocturnal hypoglycemia showed that systems is freely available on the inter- (144). Many of these include a health
sensor-augmented insulin pump therapy net, and there are internet groups where coach and can create small groups of
with a low glucose suspend function people inform each other as to how to set similar patients in social networks. There
n
significantly reduced nocturnal hypogly- up and use them. Although not pre- are programs that aim to treat predia-
cemia over 3 months without increasing scribed by providers, it is important to betes and prevent progression to diabe-
tio
A1C levels (39). In a different sensor- keep patients who are using these meth- tes, often following the model of the
augmented pump, predictive low glu- ods for automated insulin delivery safe. Diabetes Prevention Program (145,146).
a
cose suspend reduced time spent with Part of this entails making sure people Others assist in improving diabetes out-
glucose ,70 mg/dL from 3.6% at baseline have a “backup plan” in case of pump
ci
comes by remotely monitoring patient
to 2.6% (3.2% with sensor-augmented failure. Additionally, in most DIY systems, clinical data (for instance, wireless mon-
so
pump therapy without predictive low insulin doses are adjusted based on the itoring of glucose levels, weight, or blood
glucose suspend) without rebound hyper- pump settings for basal rates, carbohy- pressure) and providing feedback and
glycemia during a 6-week randomized drate ratios, correction doses, and insulin coaching (147–149). There are text mes-
As
crossover trial (120). These devices may activity. Therefore, these settings can be saging approaches that tie into a variety
offer the opportunity to reduce hypogly- evaluated and changed based on the of different types of lifestyle and treat-
cemia for those with a history of nocturnal patient’s insulin requirements. ment programs, which vary in terms of
s
hypoglycemia. Additional studies have their effectiveness (150,151). For many of
been performed, in adults and children, Digital Health Technology these interventions, there are limited RCT
showing the benefits of this technology
(121,122). te
Increasingly, people are turning to the
internet for advice, coaching, connec-
data and long-term follow-up is lacking.
But for an individual patient, opting into
be
Automated insulin delivery systems tion, and health care. Diabetes, in part one of these programs can be helpful and,
increase and decrease insulin delivery because it is both common and numeric, for many, is an attractive option.
ia
based on sensor derived glucose level to lends itself to the development of apps
begin to approximate physiologic insulin and online programs. The FDA approves Inpatient Care
D
delivery. These systems consist of three and monitors clinically validated, digital, Patients who are comfortable using their
components: an insulin pump, a contin- usually online, health technologies diabetes devices, such as insulin pumps
uous glucose sensor, and an algorithm intended to treat a medical or psycho- and sensors, should be given the chance
an
that determines insulin delivery. With logical conditiondthese are known as to use them in an inpatient setting if they
these systems, insulin delivery can not digital therapeutics or “digiceuticals” are competent to do so (152,153). Pa-
only be suspended but also increased or (142). Other applications, such as those tients who are familiar with treating their
ic
decreased based on sensor glucose val- that assist in displaying or storing data, own glucose levels can often adjust in-
er
ues. Emerging evidence suggests such encourage a healthy lifestyle or provide sulin doses more knowledgably than in-
systems may lower the risk of exercise- limited clinical data support. Therefore, it patient staff who do not personally know
related hypoglycemia (123) and may is possible to find apps that have been the patient or their management style.
Am
have psychosocial benefits (124–127). fully reviewed and approved and others However, this should occur based on the
While eventually insulin delivery in designed and promoted by people with hospital’s policies for diabetes manage-
closed-loop systems may be truly auto- relatively little skill or knowledge in the ment, and there should be supervision to
mated, currently meals must be an- clinical treatment of diabetes. be sure that the individual can adjust their
19
nounced. A so-called hybrid approach, An area of particular importance is that insulin doses in a hospitalized setting
hybrid closed-loop, has been adopted in of online privacy and security. There are where factors such as infection, certain
first-generation closed-loop systems and established cloud-based data collection medications, immobility, changes in diet,
20
requires users to bolus for meals and programs, such as Tidepool, Glooko, and and other factors can impact insulin sen-
snacks. Multiple studies, utilizing a vari- others, that have been developed with sitivity and the response to insulin.
©
ety of systems with varying algorithms, appropriate data security features and
pump, and sensors have been performed are HIPAA (U.S. Health Insurance Porta- The Future
in adults and children (128–138). Use of bility and Accountability Act of 1996) The pace of development in diabetes
these systems depends on patient pref- compliant. These programs can be useful technology is extremely rapid. New ap-
erence and selection of patients (and/or for monitoring patients, both by the proaches and tools are available each
caregivers) who are capable of safely and patients themselves as well as their year. It is hard for research to keep up
effectively using the devices. health care team (143). Consumers should with these advances because by the
Some people with type 1 diabetes read the policy regarding data privacy time a study is completed, newer ver-
have been using “do-it-yourself” (DIY) and sharing before providing data into sions of the devices are already on the
systems that combine a pump and a real- an application and learn how they can market. The most important component
time CGM with a controller and an control how their data will be used (some in all of these systems is the patient.
algorithm designed to automate insulin programs offer the ability to share more Technology selection must be appropriate
care.diabetesjournals.org Diabetes Technology S85
for the individual. Simply having a device 12. Simon J, Gray A, Clarke P, Wade A, Neil A, 1 November 2019. Available from https://www.fda
or application does not change outcomes Farmer A; Diabetes Glycaemic Education and .gov/NewsEvents/Newsroom/PressAnnouncements/
Monitoring Trial Group. Cost effectiveness of self ucm577890.htm
unless the human being engages with it monitoring of blood glucose in patients with non- 26. Danne T, Nimri R, Battelino T, et al. In-
to create positive health benefits. This insulin treated type 2 diabetes: economic eval- ternational consensus on use of continuous
underscores the need for the health care uation of data from the DiGEM trial. BMJ 2008; glucose monitoring. Diabetes Care 2017;40:
provider to assist the patient in device/ 336:1177–1180 1631–1640
program selection and to support its use 13. Young LA, Buse JB, Weaver MA, et al.; 27. Battelino T, Danne T, Bergenstal RM, et al.
Monitor Trial Group. Glucose self-monitoring Clinical targets for continuous glucose monitor-
through ongoing education and training. in non-insulin-treated patients with type 2 di- ing data interpretation: recommendations from
n
Expectations must be tempered by realityd abetes in primary care settings: a randomized the international consensus on time in range.
we do not yet have technology that com-
tio
trial. JAMA Intern Med 2017;177:920–929 Diabetes Care 2019;42:1593–1603
pletely eliminates the self-care tasks neces- 14. Polonsky WH, Fisher L, Schikman CH, et al. 28. Beck RW, Riddlesworth T, Ruedy K, et al.;
sary for treating diabetes, but the tools Structured self-monitoring of blood glucose sig- DIAMOND Study Group. Effect of continuous
nificantly reduces A1C levels in poorly controlled, glucose monitoring on glycemic control in adults
a
described in this section can make it easier noninsulin-treated type 2 diabetes: results from with type 1 diabetes using insulin injections: the
ci
to manage. the Structured Testing Program study. Diabetes DIAMOND randomized clinical trial. JAMA 2017;
Care 2011;34:262–267 317:371–378
References
so
15. Malanda UL, Welschen LMC, Riphagen II, 29. Riddlesworth T, Price D, Cohen N, Beck RW.
1. DiabetesWise.org. Accessed 24 September Dekker JM, Nijpels G, Bot SDM. Self-monitoring Hypoglycemic event frequency and the effect of
2019. Available from https://www.diabeteswise of blood glucose in patients with type 2 diabetes continuous glucose monitoring in adults with
.org mellitus who are not using insulin. Cochrane type 1 diabetes using multiple daily insulin
As
2. Nathan DM, Genuth S, Lachin J, et al.; Diabetes Database Syst Rev 2012;1:CD005060 injections. Diabetes Ther 2017;8:947–951
Control and Complications Trial Research Group. 16. Willett LR. ACP Journal Club. Meta-analysis: 30. Lind M, Polonsky W, Hirsch IB, et al. Con-
The effect of intensive treatment of diabetes on self-monitoring in non-insulin-treated type 2 di- tinuous glucose monitoring vs conventional ther-
the development and progression of long-term abetes improved HbA1c by 0.25%. Ann Intern apy for glycemic control in adults with type 1
s
complications in insulin-dependent diabetes Med 2012;156:JC6–JC12 diabetes treated with multiple daily insulin in-
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mellitus. N Engl J Med 1993;329:977–986 17. Mannucci E, Antenore A, Giorgino F, Scavini jections: the GOLD randomized clinical trial
3. Miller KM, Beck RW, Bergenstal RM, et al.; M. Effects of structured versus unstructured self- [published correction appears in JAMA 2017;
T1D Exchange Clinic Network. Evidence of a monitoring of blood glucose on glucose control in 317:1912]. JAMA 2017;317:379–387
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strong association between frequency of self- patients with non-insulin-treated type 2 diabe- 31. Sequeira PA, Montoya L, Ruelas V, et al. Con-
monitoring of blood glucose and hemoglobin A1c tes: a meta-analysis of randomized controlled tinuous glucose monitoring pilot in low-income
levels in T1D Exchange clinic registry participants. trials. J Diabetes Sci Technol 2018;12:183–189 type 1 diabetes patients. Diabetes Technol Ther
ia
who self-monitor blood glucose and their unused POCT devices, showing drastic high values, low of real-time continuous glucose monitoring on
testing results. Am J Manag Care 2015;21:e119–e129 values, or error messages. J Diabetes Sci Technol glycaemic control and glucose variability in
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APCam11 Consortium. Closed-loop insulin de- 10.2337/dci19-0062 Glucose Monitoring Test Systems for Prescrip-
livery in suboptimally controlled type 1 diabetes: 143. Wong JC, Izadi Z, Schroeder S, et al. A pilot tion Point-of-Care Use: Guidance for Industry and
Am
a multicentre, 12-week randomised trial. Lancet study of use of a software platform for the Food and Drug Administration Staff [Internet],
2018;392:1321–1329 collection, integration, and visualization of di- 2016. Accessed 1 November 2019. Available from
131. Ekhlaspour L, Forlenza GP, Chernavvsky D, abetes device data by health care providers in a http://www.fda.gov/downloads/medicaldevices/
et al. Closed loop control in adolescents and multidisciplinary pediatric setting. Diabetes deviceregulationandguidance/guidancedocuments/
children during winter sports: use of the Tandem Technol Ther 2018;20:806–816 ucm380325.pdf
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Control-IQ AP system. Pediatr Diabetes 2019;20: 144. Chao DY, Lin TM, Ma W-Y. Enhanced self- 156. International Standards Organization. ISO
759–768 efficacy and behavioral changes among patients 15197:2013. In vitro diagnostic test systems –
132. Buckingham BA, Christiansen MP, Forlenza with diabetes: cloud-based mobile health plat- requirements for blood glucose monitoring
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GP, et al. Performance of the Omnipod person- form and mobile app service. JMIR Diabetes systems for self-testing in managing diabetes
alized model predictive control algorithm with 2019;4:e11017 mellitus. Accessed 24 September 2019. Avail-
meal bolus challenges in adults with type 1 145. Sepah SC, Jiang L, Peters AL. Translating the able from http://www.iso.org/cms/render/live/en/
diabetes. Diabetes Technol Ther 2018;20:585– Diabetes Prevention Program into an online sites/isoorg/contents/data/standard/05/49/54976
©
n
Standards of Medical Care in
tio
Diabetesd2020
a
Diabetes Care 2020;43(Suppl. 1):S89–S97 | https://doi.org/10.2337/dc20-S008
ci
so
As
te
includes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guidelines, and
be
tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsi-
ia
ble for updating the Standards of Care annually, or more frequently as warranted. For a
detailed description of ADA standards, statements, and reports, as well as the evidence-
D
grading system for ADA’s clinical practice recommendations, please refer to the Standards
of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment
on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
an
There is strong and consistent evidence that obesity management can delay the
ic
overweight or obesity, modest and sustained weight loss has been shown to improve
glycemic control and to reduce the need for glucose-lowering medications (6–8). Small
Am
studies have demonstrated that in patients with type 2 diabetes and obesity, more
extreme dietary energy restriction with very low-calorie diets can reduce A1C
to ,6.5% (48 mmol/mol) and fasting glucose to ,126 mg/dL (7.0 mmol/L) in
the absence of pharmacologic therapy or ongoing procedures (10,18,19). The goal of
19
ASSESSMENT
©
Recommendations
8.1 Measure height and weight and calculate BMI at annual visits or more
frequently. E Suggested citation: American Diabetes Associa-
8.2 Based on clinical considerations, such as the presence of comorbid heart tion. 8. Obesity management for the treatment
failure or significant unexplained weight gain or loss, weight may need to be of type 2 diabetes: Standards of Medical Care in
Diabetesd2020. Diabetes Care 2020;43(Suppl. 1):
monitored and evaluated more frequently. B If deterioration of medical status S89–S97 (https://doi.org/10.2337/dc20-s008)
is associated with significant weight gain or loss, inpatient evaluation should
© 2019 by the American Diabetes Association.
be considered, specifically focused on the association between medication Readers may use this article as long as the work
use, food intake, and glycemic status. E is properly cited, the use is educational and not
8.3 For patients with a high level of weight-related distress, special accommo- for profit, and the work is not altered. More infor-
dations should be made to ensure privacy during weighing. E mation is available at http://www.diabetesjournals
.org/content/license.
S90 Obesity Management for the Treatment of Type 2 Diabetes Diabetes Care Volume 43, Supplement 1, January 2020
n
Clinical considerations, such as the
who have overweight or obesity monitoring. To maintain weight
presence of comorbid heart failure
tio
and are ready to achieve weight loss, such programs must incor-
or unexplained weight change, may
loss. Greater benefits in control porate long-term comprehensive
warrant more frequent weight mea-
weight-maintenance counseling. B
a
surement and evaluation (21,22). of diabetes and cardiovascular
risk factors may be gained from
ci
When weighing is questioned or re-
even greater weight loss. B Among patients with both type 2 diabe-
fused, the practitioner should query
8.5 Such interventions should be tes and overweight or obesity who also
so
for concerns, and the need for weight
high intensity ($16 sessions in 6 have inadequate glycemic, blood pres-
monitoring should be explained as a
months) and focus on dietary sure, and lipid control and/or other
part of the medical evaluation process
As
changes, physical activity, and be- obesity-related medical conditions, life-
that helps to inform treatment deci-
havioral strategies to achieve a style changes that result in modest and
sions (23,24). If patients report or
500–750 kcal/day energy deficit. A sustained weight loss produce clinically
exhibit a high level of weight-related
8.6 Individual’smotivation,lifecircum- meaningful reductions in blood glucose,
s
distress, special accommodations should
stances, and willingness to make A1C, and triglycerides (6–8). Greater
be made to ensure privacy during weigh-
te
weight loss produces even greater ben-
ing. Once calculated, BMI should be clas- lifestyle changes to achieve weight
efits, including reductions in blood pres-
sified to determine the presence of loss should be assessed along with
be
sure, improvements in LDL and HDL
overweight or obesity, discussed with medical status when weight loss
cholesterol, and reductions in the need
the patient, and documented in the interventions are undertaken. C
for medications to control blood glucose,
8.7 As all energy-deficit food intake
ia
and quality of life outcomes. Providers dietary patterns. C .org/10.2337/dc20-S005). For a detailed
should assess each patient’s readi- 8.9 For patients who achieve short- discussion of nutrition interventions
ness to engage in behavioral changes
Am
physical activity, behavioral therapy, tact, as well as encourage ongo- Look AHEAD Trial
pharmacologic therapy, and metabolic ing monitoring of body weight Although the Action for Health in Di-
surgery (Table 8.1). The latter two abetes (Look AHEAD) trial did not show
20
diet, physical activity, and behavioral in adults with type 2 diabetes and over-
activity (200–300 min/week). A
therapy. weight or obesity (31), it did show the
feasibility of achieving and maintaining practitioners, with close patient moni- PHARMACOTHERAPY
long-term weight loss in patients with toring, can be beneficial. Within the in-
Recommendations
type 2 diabetes. In the Look AHEAD tensive lifestyle intervention group of the
8.11 When choosing glucose-lowering
intensive lifestyle intervention group, Look AHEAD trial, for example, use of a
medications for patients with
mean weight loss was 4.7% at 8 years partial meal replacement plan was as-
type 2 diabetes and overweight
(32). Approximately 50% of intensive sociated with improvements in diet
or obesity, consider a medica-
lifestyle intervention participants lost quality (38). The diet choice should be
tion’s effect on weight. B
and maintained $5% of their initial based on the patient’s health status and
8.12 Whenever possible, minimize
n
body weight, and 27% lost and main- preferences, including a determination
medications for comorbid con-
tained $10% of their initial body weight of food availability and other cultural
tio
ditions that are associated with
at 8 years (32). Participants randomly circumstances that could affect dietary
weight gain. E
assigned to the intensive lifestyle group patterns (39).
8.13 Weight-loss medications are ef-
a
achieved equivalent risk factor con- Intensive behavioral lifestyle interven-
fective as adjuncts to diet, phys-
tions should include $16 sessions in
ci
trol but required fewer glucose-, blood
ical activity, and behavioral
pressure–, and lipid-lowering medica- 6 months and focus on dietary changes,
counseling for selected patients
so
tions than those randomly assigned physical activity, and behavioral strate-
with type 2 diabetes and
to standard care. Secondary analyses gies to achieve an ;500–750 kcal/day
BMI $27 kg/m2. Potential ben-
of the Look AHEAD trial and other large energy deficit. Interventions should be
As
efits must be weighed against
cardiovascular outcome studies docu- provided by trained interventionists in
potential risks of medications. A
ment other benefits of weight loss in either individual or group sessions (34).
8.14 If a patient’s response to weight-
patients with type 2 diabetes, includ- Assessing an individual’s motivation level,
loss medications is ,5% weight
s
ing improvements in mobility, physical life circumstances, and willingness to im-
loss after 3 months or if there
and sexual function, and health-related plement lifestyle changes to achieve weight
te
are significant safety or tolera-
quality of life (23). A post hoc analysis loss should be considered along with med-
bility issues at any time, the
of the Look AHEAD study suggests ical status when weight-loss interventions
be
medication should be discon-
that heterogeneous treatment effects are recommended and initiated (27).
tinued and alternative medica-
may have been present. Participants Patients with type 2 diabetes and
tions or treatment approaches
ia
who had moderately or poorly controlled overweight or obesity who have lost
should be considered. A
diabetes (A1C $6.8% [51 mmol/mol]) weight during a 6-month intensive be-
D
found to have significantly reduced grams that provide at least monthly of weight loss include metformin,
cardiovascular events with inten- contact with a trained interventionist a-glucosidase inhibitors, sodium–glucose
sive lifestyle intervention during and focus on ongoing monitoring of cotransporter 2 inhibitors, glucagon-like
ic
follow-up (33). body weight (weekly or more frequently) peptide 1 receptor agonists, and amylin
er
with lifestyle programs that achieve a diet; and participation in high levels of nediones, and insulin often cause weight
500–750 kcal/day energy deficit, which in physical activity (200–300 min/week) gain (see Section 9 “Pharmacologic Ap-
most cases is approximately 1,200–1,500 (40). Some commercial and proprietary proaches to Glycemic Treatment,” https://
kcal/day for women and 1,500–1,800 weight-loss programs have shown doi.org/10.2337/dc20-s009).
19
kcal/day for men, adjusted for the indi- promising weight-loss results (41). A meta-analysis of 227 randomized
vidual’s baseline body weight. Weight When provided by trained practi- controlled trials of glucose-lowering
loss of 3–5% is the minimum necessary tioners in medical care settings with treatments in type 2 diabetes found
20
for clinical benefit (20,34). However, close medical monitoring, short-term that A1C changes were not associated
weight-loss benefits are progressive; (3-month) interventions that use very with baseline BMI, indicating that pa-
low-calorie diets (defined as #800
©
more intensive weight-loss goals (.5%, tients with obesity can benefit from the
.7%, .15%, etc.) may be pursued if kcal/day) and total meal replacements same types of treatments for diabetes as
needed to achieve a healthy weight may achieve greater short-term weight normal-weight patients (44).
and/or if the patient is more motivated loss (10–15%) than intensive behav-
and more intensive goals can be feasibly ioral lifestyle interventions that typically Concomitant Medications
and safely attained. achieve 5% weight loss. However, weight Providers should carefully review the
Dietary interventions may differ in the regain following the cessation of very patient’s concomitant medications
types of foods they restrict (such as high- low-calorie diets is greater than regain and, whenever possible, minimize or
fat or high-carbohydrate foods) but are following intensive behavioral lifestyle provide alternatives for medications
effective if they create the necessary interventions unless a long-term com- that promote weight gain. Examples of
energy deficit (20,35–37). Use of meal prehensive weight-loss maintenance medications associated with weight gain
replacement plans prescribed by trained program is provided (42,43). include antipsychotics (e.g., clozapine,
S92 Obesity Management for the Treatment of Type 2 Diabetes Diabetes Care Volume 43, Supplement 1, January 2020
n
in people with diabetes at this time, ices to help with the adjustment
tio
Approved Weight-Loss Medications medical devices for weight loss are cur- to medical and psychosocial
The U.S. Food and Drug Administration rently not considered to be the standard changes after surgery. C
(FDA) has approved medications for both of care for obesity management in peo-
a
short-term and long-term weight man- ple with type 2 diabetes. Several gastrointestinal (GI) operations
ci
agement as adjuncts to diet, exercise, including partial gastrectomies and bari-
and behavioral therapy. Nearly all FDA- METABOLIC SURGERY atric procedures (40) promote dramatic
so
approved medications for weight loss and durable weight loss and improvement
have been shown to improve glycemic Recommendations
of type 2 diabetes in many patients. Given
control in patients with type 2 diabetes 8.15 Metabolic surgery should be
As
the magnitude and rapidity of the effect of
and delay progression to type 2 diabetes recommended as an option to GI surgery on hyperglycemia and exper-
in patients at risk (46). Phentermine and treat type 2 diabetes in imental evidence that rearrangements of
other older adrenergic agents are indi- screened surgical candidates GI anatomy similar to those in some
with BMI $40 kg/m2 (BMI
s
cated as short-term (#12 weeks) treat- metabolic procedures directly affect glu-
$37.5 kg/m2 in Asian Americans)
te
ment (47). Five weight-loss medications cose homeostasis (41), GI interventions
are FDA approved for long-term use and in adults with BMI 35.0– have been suggested as treatments for
39.9 kg/m2 (32.5–37.4 kg/m2 in
be
(more than a few weeks) by patients type 2 diabetes, and in that context they
with BMI $27 kg/m2 with one or more Asian Americans) who do not are termed “metabolic surgery.”
obesity-associated comorbid condition achieve durable weight loss
A substantial body of evidence has now
ia
and their key advantages and disadvan- cemic control and reduction of cardiovas-
tages are summarized in Table 8.2. The with type 2 diabetes and BMI
cular risk factors in patients with type 2
rationale for weight-loss medication use 30.0–34.9 kg/m2 (27.5–32.4
diabetes and obesity compared with var-
kg/m2 in Asian Americans) who
ic
label and should balance the potential cemia) with tested efficacious
only in nonrandomized observational
benefits of successful weight loss against nonsurgical methods. A
studies (50–61). Cohort studies attempt-
the potential risks of the medication for 8.17 Metabolic surgery should be
ing to match surgical and nonsurgical sub-
each patient. These medications are con- performed in high-volume cen-
jects suggest that the procedure may
ters with multidisciplinary teams
19
All medications are contraindicated in women who are or may become pregnant. Women of reproductive potential must be counseled regarding the use of reliable methods of contraception. Select
safety and side effect information is provided; for a comprehensive discussion of safety considerations, please refer to the prescribing information for each agent. b.i.d., twice daily; BP, blood pressure;
ci
ER, extended release; MEN 2, multiple endocrine neoplasia syndrome type 2; MTC, medullary thyroid carcinoma; OTC, over the counter; PBO, placebo; q.d., daily; Rx, prescription; t.i.d., three times
a
daily; XR, extended release. *Use lowest effective dose; maximum appropriate dose is 37.5 mg. †Duration of treatment was 28 weeks in a general obese adult population. **Agent has demonstrated cardiovascular
safety in a dedicated cardiovascular outcome trial (118,119). ‡Enrolled participants had normal (79%) or impaired (21%) glucose tolerance. §Maximum dose, depending on response, is 15 mg/92 mg q.d.
| Approximately 68% of enrolled participants had type 2 diabetes or impaired glucose tolerance.
tio
n
S93
S94 Obesity Management for the Treatment of Type 2 Diabetes Diabetes Care Volume 43, Supplement 1, January 2020
degrees and lengths of remission compared of minimally invasive approaches (lapa- or other mental health conditions should
with other bariatric surgeries (17,70). Avail- roscopic surgery), enhanced training and therefore first be assessed by a mental
able data suggest an erosion of diabetes credentialing, and involvement of multi- health professional with expertise in
remission over time (71): 35–50% or disciplinary teams. Mortality rates with obesity management prior to consider-
more of patients who initially achieve metabolic operations are typically 0.1– ation for surgery (107). Surgery should
remission of diabetes eventually experi- 0.5%, similar to cholecystectomy or hys- be postponed in patients with alcohol
ence recurrence. However, the median terectomy (87–91). Morbidity has also or substance abuse disorders, significant
disease-free period among such individ- dramatically declined with laparoscopic depression, suicidal ideation, or other men-
n
uals following RYGB is 8.3 years (72,73). approaches. Major complications rates tal health conditions until these condi-
With or without diabetes relapse, the (e.g., venous thromboembolism, need tions have been fully addressed. Individuals
tio
majority of patients who undergo sur- for operative reintervention) are 2–6%, with preoperative psychopathology should
gery maintain substantial improvement with other minor complications in up to be assessed regularly following metabolic
a
of glycemic control from baseline for 15% (87–96), rates which compare favor- surgery to optimize mental health man-
ci
at least 5 years (74,75) to 15 years ably with those for other commonly per- agement and to ensure that psychiatric
(51,52,73,76–78). formed elective operations (91). Empirical symptoms do not interfere with weight loss
so
Exceedingly few presurgical predic- data suggest that proficiency of the and lifestyle changes.
tors of success have been identified, operating surgeon is an important
but younger age, shorter duration of factor for determining mortality, com-
As
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American Heart Association Task Force on Prac- 37. Johnston BC, Kanters S, Bandayrel K, et al. subjects. N Engl J Med 2007;357:741–752
tice Guidelines. J Am Coll Cardiol 2013;62:e147– Comparison of weight loss among named diet 54. Sjöström L, Gummesson A, Sjöström CD,
e239 programs in overweight and obese adults: a et al.; Swedish Obese Subjects Study. Effects
©
22. Bosch X, Monclús E, Escoda O, et al. Un- meta-analysis. JAMA 2014;312:923–933 of bariatric surgery on cancer incidence in obese
intentional weight loss: clinical characteristics 38. Raynor HA, Anderson AM, Miller GD, et al.; patients in Sweden (Swedish Obese Subjects
and outcomes in a prospective cohort of 2677 pa- Look AHEAD Research Group. Partial meal re- Study): a prospective, controlled intervention
tients. PLoS One 2017;12:e0175125 placement plan and quality of the diet at 1 year: trial. Lancet Oncol 2009;10:653–662
23. Wilding JPH. The importance of weight Action for Health in Diabetes (Look AHEAD) trial. 55. Sjöström L, Peltonen M, Jacobson P, et al.
management in type 2 diabetes mellitus. Int J J Acad Nutr Diet 2015;115:731–742 Bariatric surgery and long-term cardiovascular
Clin Pract 2014;68:682–691 39. Leung CW, Epel ES, Ritchie LD, Crawford PB, events. JAMA 2012;307:56–65
24. Van Gaal L, Scheen A. Weight management Laraia BA. Food insecurity is inversely associated 56. Adams TD, Gress RE, Smith SC, et al. Long-
in type 2 diabetes: current and emerging ap- with diet quality of lower-income adults. J Acad term mortality after gastric bypass surgery. N
proaches to treatment. Diabetes Care 2015;38: Nutr Diet 2014;114:1943–1953.e2 Engl J Med 2007;357:753–761
1161–1172 40. Donnelly JE, Blair SN, Jakicic JM, Manore 57. Arterburn DE, Olsen MK, Smith VA, et al.
25. WHO Expert Consultation. Appropriate MM, Rankin JW, Smith BK; American College of Association between bariatric surgery and long-
body-mass index for Asian populations and its Sports Medicine. Appropriate physical activity term survival. JAMA 2015;313:62–70
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58. Adams TD, Arterburn DE, Nathan DM, Eckel Subjects (SOS) study. Diabetologia 2015;58: 87. Flum DR, Belle SH, King WC, et al.; Longi-
RH. Clinical outcomes of metabolic surgery: 1448–1453 tudinal Assessment of Bariatric Surgery (LABS)
microvascular and macrovascular complications. 73. Arterburn DE, Bogart A, Sherwood NE, Consortium. Perioperative safety in the longitu-
Diabetes Care 2016;39:912–923 et al. A multisite study of long-term remission dinal assessment of bariatric surgery. N Engl J
59. Sheng B, Truong K, Spitler H, Zhang L, Tong X, and relapse of type 2 diabetes mellitus fol- Med 2009;361:445–454
Chen L. The long-term effects of bariatric sur- lowing gastric bypass. Obes Surg 2013;23:93– 88. Courcoulas AP, Christian NJ, Belle SH, et al.;
gery on type 2 diabetes remission, micro- 102 Longitudinal Assessment of Bariatric Surgery
vascular and macrovascular complications, and 74. Mingrone G, Panunzi S, De Gaetano A, et al. (LABS) Consortium. Weight change and health
mortality: a systematic review and meta-analysis. Bariatric-metabolic surgery versus conventional outcomes at 3 years after bariatric surgery
Obes Surg 2017;27:2724–2732 medical treatment in obese patients with type 2 among individuals with severe obesity. JAMA
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60. Fisher DP, Johnson E, Haneuse S, et al. diabetes: 5 year follow-up of an open-label, 2013;310:2416–2425
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Association between bariatric surgery and mac- single-centre, randomised controlled trial. Lan- 89. Arterburn DE, Courcoulas AP. Bariatric sur-
rovascular disease outcomes in patients with cet 2015;386:964–973 gery for obesity and metabolic conditions in
type 2 diabetes and severe obesity. JAMA 2018; 75. Schauer PR, Bhatt DL, Kirwan JP, et al.; adults. BMJ 2014;349:g3961
320:1570–1582 STAMPEDE Investigators. Bariatric surgery ver- 90. Young MT, Gebhart A, Phelan MJ, Nguyen
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61. Billeter AT, Scheurlen KM, Probst P, et al. sus intensive medical therapy for diabetesd5- NT. Use and outcomes of laparoscopic sleeve
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Meta-analysis of metabolic surgery versus med- year outcomes. N Engl J Med 2017;376:641–651 gastrectomy vs laparoscopic gastric bypass: anal-
ical treatment for microvascular complications 76. Cohen RV, Pinheiro JC, Schiavon CA, Salles JE, ysis of the American College of Surgeons NSQIP.
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in patients with type 2 diabetes mellitus. Br J Surg Wajchenberg BL, Cummings DE. Effects of gastric J Am Coll Surg 2015;220:880–885
2018;105:168–181 bypass surgery in patients with type 2 diabetes 91. Aminian A, Brethauer SA, Kirwan JP, Kashyap
62. Rubino F, Kaplan LM, Schauer PR, Cummings and only mild obesity. Diabetes Care 2012;35: SR, Burguera B, Schauer PR. How safe is meta-
DE; Diabetes Surgery Summit Delegates. The 1420–1428 bolic/diabetes surgery? Diabetes Obes Metab
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Diabetes Surgery Summit consensus conference: 77. Brethauer SA, Aminian A, Romero-Talamás 2015;17:198–201
recommendations for the evaluation and use of H, et al. Can diabetes be surgically cured? Long- 92. Birkmeyer NJO, Dimick JB, Share D, et al.;
gastrointestinal surgery to treat type 2 diabetes term metabolic effects of bariatric surgery in Michigan Bariatric Surgery Collaborative. Hospi-
mellitus. Ann Surg 2010;251:399–405 obese patients with type 2 diabetes mellitus. Ann tal complication rates with bariatric surgery in
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63. Cummings DE, Cohen RV. Beyond BMI: the Surg 2013;258:628–636; discussion 636–637 Michigan. JAMA 2010;304:435–442
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need for new guidelines governing the use of 78. Hsu C-C, Almulaifi A, Chen J-C, et al. Effect of 93. Altieri MS, Yang J, Telem DA, et al. Lap band
bariatric and metabolic surgery. Lancet Diabetes bariatric surgery vs medical treatment on type 2 outcomes from 19,221 patients across centers
Endocrinol 2014;2:175–181 diabetes in patients with body mass index lower and over a decade within the state of New York.
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64. Zimmet P, Alberti KGMM, Rubino F, Dixon JB. than 35: five-year outcomes. JAMA Surg 2015; Surg Endosc 2016;30:1725–1732
IDF’s view of bariatric surgery in type 2 diabetes. 150:1117–1124 94. Hutter MM, Schirmer BD, Jones DB, et al.
Lancet 2011;378:108–110 79. Schauer PR, Bhatt DL, Kirwan JP, et al.; First report from the American College of Sur-
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65. Kasama K, Mui W, Lee WJ, et al. IFSO-APC STAMPEDE Investigators. Bariatric surgery ver- geons Bariatric Surgery Center Network: lapa-
consensus statements 2011. Obes Surg 2012;22: sus intensive medical therapy for diabetesd roscopic sleeve gastrectomy has morbidity and
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677–684 3-year outcomes. N Engl J Med 2014;370:2002– effectiveness positioned between the band and
66. Wentworth JM, Burton P, Laurie C, Brown 2013 the bypass. Ann Surg 2011;254:410–420; discus-
WA, O’Brien PE. Five-year outcomes of a ran- 80. Hariri K, Guevara D, Jayaram A, Kini SU, sion 420–422
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domized trial of gastric band surgery in over- Herron DM, Fernandez-Ranvier G. Preoperative 95. Nguyen NT, Slone JA, Nguyen X-MT, Hartman
weight but not obese people with type 2 insulin therapy as a marker for type 2 diabetes JS, Hoyt DB. A prospective randomized trial of
diabetes. Diabetes Care 2017;40:e44–e45 remission in obese patients after bariatric sur- laparoscopic gastric bypass versus laparoscopic
67. Cummings DE, Arterburn DE, Westbrook EO, gery. Surg Obes Relat Dis 2018;14:332–337 adjustable gastric banding for the treatment of
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et al. Gastric bypass surgery vs intensive life- 81. Yu H, Di J, Bao Y, et al. Visceral fat area as a morbid obesity: outcomes, quality of life, and
style and medical intervention for type 2 di- new predictor of short-term diabetes remission costs. Ann Surg 2009;250:631–641
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abetes: the CROSSROADS randomised controlled after Roux-en-Y gastric bypass surgery in Chinese 96. Courcoulas AP, King WC, Belle SH, et al.
trial. Diabetologia 2016;59:945–953 patients with a body mass index less than 35 Seven-year weight trajectories and health out-
68. Liang Z, Wu Q, Chen B, Yu P, Zhao H, Ouyang kg/m2. Surg Obes Relat Dis 2015;11:6–11 comes in the Longitudinal Assessment of Bari-
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X. Effect of laparoscopic Roux-en-Y gastric by- 82. O’Brien R, Johnson E, Haneuse S, et al. atric Surgery (LABS) Study. JAMA Surg 2018;153:
pass surgery on type 2 diabetes mellitus with Microvascular outcomes in patients with diabe- 427–434
hypertension: a randomized controlled trial. Di- tes after bariatric surgery versus usual care: 97. Birkmeyer JD, Finks JF, O’Reilly A, et al.;
abetes Res Clin Pract 2013;101:50–56 a matched cohort study. Ann Intern Med Michigan Bariatric Surgery Collaborative. Surgi-
69. Aminian A, Chang J, Brethauer SA, Kim JJ; 2018;169:300–310 cal skill and complication rates after bariatric
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American Society for Metabolic and Bariatric 83. Halperin F, Ding S-A, Simonson DC, et al. surgery. N Engl J Med 2013;369:1434–1442
Surgery Clinical Issues Committee. ASMBS up- Roux-en-Y gastric bypass surgery or lifestyle with 98. Service GJ, Thompson GB, Service FJ,
dated position statement on bariatric surgery in intensive medical management in patients with Andrews JC, Collazo-Clavell ML, Lloyd RV. Hyper-
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class I obesity (BMI 30–35 kg/m2). Surg Obes type 2 diabetes: feasibility and 1-year results of insulinemic hypoglycemia with nesidioblastosis
Relat Dis 2018;14:1071–1087 a randomized clinical trial. JAMA Surg 2014; after gastric-bypass surgery. N Engl J Med 2005;
70. Isaman DJM, Rothberg AE, Herman WH. 149:716–726 353:249–254
Reconciliation of type 2 diabetes remission rates 84. Kirwan JP, Aminian A, Kashyap SR, Burguera 99. Mechanick JI, Kushner RF, Sugerman HJ,
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in studies of Roux-en-Y gastric bypass. Diabetes B, Brethauer SA, Schauer PR. Bariatric surgery in et al.; American Association of Clinical Endocri-
Care 2016;39:2247–2253 obese patients with type 1 diabetes. Diabetes nologists; Obesity Society; American Society for
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rability of addition of Roux-en-Y gastric bypass to 85. Rubin JK, Hinrichs-Krapels S, Hesketh R, ciation of Clinical Endocrinologists, The Obesity
lifestyle intervention and medical management Martin A, Herman WH, Rubino F. Identifying Society, and American Society for Metabolic &
in achieving primary treatment goals for un- barriers to appropriate use of metabolic/ Bariatric Surgery medical guidelines for clinical
controlled type 2 diabetes in mild to moderate bariatric surgery for type 2 diabetes treatment: practice for the perioperative nutritional, met-
obesity: a randomized control trial. Diabetes Care policy lab results. Diabetes Care 2016;39:954– abolic, and nonsurgical support of the bariatric
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72. Sjöholm K, Pajunen P, Jacobson P, et al. 86. Fouse T, Schauer P. The socioeconomic 17(Suppl. 1):S1–S70
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2 year weight change: the Swedish Obese 2016;96:669–679 gists; Obesity Society; American Society for
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Metabolic & Bariatric Surgery. Clinical prac- 107. Greenberg I, Sogg S, M Perna F. Behavioral Accessed 22 October 2019. Available from
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atric surgery patientd2013 update: cospon- 2009;17:880–884 iramate extended-release) capsules [prescribing
sored by American Association of Clinical 108. Truven Health Analytics. Introduction to RED information]. Accessed 22 October 2019. Avail-
Endocrinologists, The Obesity Society, and Amer- BOOK Online. Accessed 2 October 2019. Avail- able from https://qsymia.com
ican Society for Metabolic & Bariatric Surgery. able from https://www.micromedexsolutions 115. Novo Nordisk. Saxenda (liraglutide) injec-
Obesity (Silver Spring) 2013;21(Suppl. 1):S1–S27 .com/micromedex2/4.34.0/WebHelp/RED_ tion [prescribing information]. Accessed 22 Oc-
101. Lee CJ, Clark JM, Schweitzer M, et al. Prev- BOOK/Introduction_to_REDB_BOOK_Online tober 2019. Available from https://www
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weight loss surgery. JAMA Surg 2013;148:145–150 National-Average-Drug-Acquisition-Cost-/a4y5- (Silver Spring) 2013;21:2163–2171
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2016;151:226–232 .nlm.nih.gov/dailymed/drugInfo.cfm?setid5 obese adults (CONQUER): a randomised, pla-
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Kersting A, Wagner B. Risk of completed suicide 111. Nalpropion Pharmaceuticals. Contrave 1341–1352
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after bariatric surgery: a systematic review. Obes (naltrexone HCl/bupropion HCl) Extended- 118. Bohula EA, Wiviott SD, McGuire DK, et al.;
Rev 2013;14:369–382 Release Tablets [prescribing information]. Ac- CAMELLIA–TIMI 61 Steering Committee and In-
105. Jakobsen GS, Småstuen MC, Sandbu R, et al. cessed 22 October 2019. Available from: https:// vestigators. Cardiovascular safety of lorcaserin
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plications and obesity-related comorbidities. (orlistat) [prescribing information]. Accessed 119. Marso SP, Daniels GH, Brown-Frandsen K,
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American Diabetes Association, 2012 XR (lorcaserin HCl) [prescribing information]. 2016;375:311–322
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Medical Care in Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S98–S110 | https://doi.org/10.2337/dc20-S009
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9. PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT
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provide the components of diabetes care, general treatment goals and guidelines, and
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tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible
be
for updating the Standards of Care annually, or more frequently as warranted. For a
detailed description of ADA standards, statements, and reports, as well as the evidence-
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grading system for ADA’s clinical practice recommendations, please refer to the Standards
of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to com-
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Recommendations
9.1 Most people with type 1 diabetes should be treated with multiple daily injections
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Insulin Therapy
Because the hallmark of type 1 diabetes is absent or near-absent b-cell function,
insulin treatment is essential for individuals with type 1 diabetes. In addition to
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life threatening. Severe metabolic decompensation can be, and was, mostly pre-
vented with once or twice daily injections for the six or seven decades after the
discovery of insulin. However, over the past three decades, evidence has accumulated
supporting more intensive insulin replacement, using multiple daily injections of Suggested citation: American Diabetes Associa-
insulin or continuous subcutaneous administration through an insulin pump, as tion. 2. Pharmacologic approaches to glycemic
providing the best combination of effectiveness and safety for people with type 1 treatment: Standards of Medical Care inDiabetesd
diabetes. The Diabetes Control and Complications Trial (DCCT) demonstrated that 2020. Diabetes Care 2020;43(Suppl. 1):S98–S110
intensive therapy with multiple daily injections or continuous subcutaneous insulin © 2019 by the American Diabetes Association.
infusion (CSII) reduced A1C and was associated with improved long-term outcomes Readers may use this article as long as the work
is properly cited, the use is educational and not
(1–3). The study was carried out with short-acting (regular) and intermediate-acting for profit, and the work is not altered. More infor-
(NPH) human insulins. In this landmark trial, lower A1C with intensive control (7%) mation is available at http://www.diabetesjournals
led to ;50% reductions in microvascular complications over 6 years of treatment. .org/content/license.
care.diabetesjournals.org Pharmacologic Approaches to Glycemic Treatment S99
However, intensive therapy was associ- meta-analysis concluded that pump ther- Typical multidose regimens for pa-
ated with a higher rate of severe hypo- apy has modest advantages for lowering tients with type 1 diabetes combine
glycemia than conventional treatment (62 A1C (–0.30% [95% CI –0.58 to –0.02]) and premeal use of shorter-acting insulins
compared with 19 episodes per 100 pa- for reducing severe hypoglycemia rates with a longer-acting formulation, usually
tient-years of therapy). Follow-up of sub- in children and adults (11). However, there at night. The long-acting basal dose is
jects from the DCCT more than 10 years is no consensus to guide the choice of titrated to regulate overnight, fasting
after the active treatment component of injection or pump therapy in a given glucose. Postprandial glucose excur-
the study demonstrated less macrovas- patient, and research to guide this sions are best controlled by a well-timed
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cular as well as less microvascular com- decision-making is needed (12). The arrival injection of prandial insulin. The opti-
plications in the group that received of continuous glucose monitors to clinical mal time to administer prandial insulin
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intensive treatment. practice has proven beneficial in specific varies, based on the pharmacokinetics
Over the last 25 years, rapid-acting and circumstances. Reduction of nocturnal of the formulation (regular, RAA, in-
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long-acting insulin analogs have been hypoglycemia in people with type 1 di- haled), the premeal blood glucose level,
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developed that have distinct pharmaco- abetes using insulin pumps with glucose and carbohydrate consumption. Recom-
kinetics compared with recombinant hu- sensors is improved by automatic sus- mendations for prandial insulin dose
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man insulins: basal insulin analogs have pension of insulin delivery at a preset administration should therefore be indi-
longer duration of action with flatter, glucose level (12–14). The U.S. Food and vidualized. Physiologic insulin secretion
more constant plasma concentrations Drug Administration (FDA) has also ap- varies with glycemia, meal size, and tissue
As
and activity profiles than NPH insulin; proved the first hybrid closed-loop pump demands for glucose. To approach this
rapid-acting analogs (RAA) have a quicker system. The safety and efficacy of hybrid variability in people using insulin treat-
onset and peak and shorter duration of closed-loop systems has been supported ment, strategies have evolved to adjust
s
action than regular human insulin. In in the literature in adolescents and adults prandial doses based on predicted needs.
people with type 1 diabetes, treatment with type 1 diabetes (15,16), and recent Thus, education of patients on how to
with analog insulins is associated with less
hypoglycemia and weight gain as well as te
evidence suggests that a closed-loop
system is superior to sensor-augmented
adjust prandial insulin to account for
carbohydrate intake, premeal glucose
be
lower A1C compared with human insu- pump therapy for glycemic control levels, and anticipated activity can be
lins (4–6). More recently, two new insulin and reduction of hypoglycemia over 3 effective and should be offered to most
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formulations with enhanced rapid action months of comparison in children and patients (20,21). For individuals in whom
profiles have been introduced. Inhaled adults with type 1 diabetes (17). Intensive carbohydrate counting is effective, esti-
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human insulin has a rapid peak and insulin management using a version of CSII mates of the fat and protein content of
shortened duration of action compared and continuous glucose monitoring should meals can be incorporated into their
with RAA and may cause less hypogly- be considered in most patients. See Sec- prandial dosing for added benefit (22).
an
cemia and weight gain (7), and faster- tion 7 “Diabetes Technology” (https://doi
acting insulin aspart may reduce prandial .org/10.2337/dc20-S007) for a full discus- Insulin Injection Technique
excursions better than RAA (8); further sion of insulin delivery devices. Ensuring that patients and/or caregivers
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investigation is needed to establish a clear In general, patients with type 1 di- understand correct insulin injection tech-
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place for these agents in diabetes man- abetes require 50% of their daily insulin nique is important to optimize glucose
agement. In addition, new longer-acting as basal and 50% as prandial. Total daily control and insulin use safety. Thus, it is
basal analogs (U-300 glargine or degludec) insulin requirements can be estimated important that insulin be delivered into
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may confer a lower hypoglycemia risk based on weight, with typical doses the proper tissue in the right way. Rec-
compared with U-100 glargine in patients ranging from 0.4 to 1.0 units/kg/day. ommendations have been published else-
with type 1 diabetes (9,10). Despite the Higher amounts are required during pu- where outlining best practices for insulin
advantages of insulin analogs in patients berty, pregnancy, and medical illness. injection (23). Proper insulin injection tech-
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with type 1 diabetes, for some patients the The American Diabetes Association/ nique includes injecting into appropriate
expense and/or intensity of treatment JDRF Type 1 Diabetes Sourcebook notes body areas, injection site rotation, ap-
required for their use is prohibitive. There 0.5 units/kg/day as a typical starting dose propriate care of injection sites to avoid
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are multiple approaches to insulin treat- in patients with type 1 diabetes who are infection or other complications, and avoid-
ment, and the central precept in the metabolically stable, with half adminis- ance of intramuscular (IM) insulin delivery.
©
management of type 1 diabetes is tered as prandial insulin given to control Exogenous-delivered insulin should be
that some form of insulin be given in blood glucose after meals and the other injected into subcutaneous tissue, not
a planned regimen tailored to the in- half as basal insulin to control glycemia intramuscularly. Recommended sites for
dividual patient to keep them safe, out of in the periods between meal absorption insulin injection include the abdomen,
diabetic ketoacidosis, and avoid signifi- (18); this guideline provides detailed in- thigh, buttock, and upper arm. Because
cant hypoglycemia, with every effort formation on intensification of therapy insulin absorption from IM sites differs
made to reach the patient’s glycemic to meet individualized needs. In addi- according to the activity of the muscle,
targets. tion, the American Diabetes Association inadvertent IM injection can lead to un-
Most studies comparing multiple daily position statement “Type 1 Diabetes predictable insulin absorption and vari-
injections with CSII have been rela- Management Through the Life Span” able effects on glucose, with IM injection
tively small and of short duration. How- provides a thorough overview of type 1 being associated with frequent and unex-
ever, a recent systematic review and diabetes treatment (19). plained hypoglycemia in several reports.
S100 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 43, Supplement 1, January 2020
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including a study performed in obese A1C and body weight when compared
mmol/mol]) or blood glucose lev-
adults (24). with insulin alone (30,31); however, SGLT2
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els ($300 mg/dL [16.7 mmol/L])
Injection site rotation is additionally inhibitor use in type 1 diabetes is associ-
are very high. E
necessary to avoid lipohypertrophy, an ated with a two- to fourfold increase
9.8 A patient-centered approach
a
accumulation of subcutaneous fat in re- in ketoacidosis. The risks and benefits
should be used to guide the
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sponse to the adipogenic actions of insulin of adjunctive agents continue to be eval-
choice of pharmacologic agents.
at a site of multiple injections. Lipohyper- uated, but only pramlintide is approved
Considerations include cardiovas-
so
trophy appears as soft, smooth raised for treatment of type 1 diabetes.
cular comorbidities, hypoglycemia
areas several centimeters in breadth
risk,impactonweight,cost, riskfor
and can contribute to erratic insulin ab- SURGICAL TREATMENT FOR TYPE 1
As
DIABETES side effects, and patient preferen-
sorption, increased glycemic variability,
ces (Table 9.2 and Figure 9.1). E
and unexplained hypoglycemic episodes. Pancreas and Islet Transplantation
9.9 Among patients with type 2 di-
Patients and/or caregivers should receive Successful pancreas and islet transplan-
abetes who have established
s
education about proper injection site ro- tation can normalize glucose levels and
atherosclerotic cardiovascular
tation and to recognize and avoid areas mitigate microvascular complications of
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disease or indicators of high risk,
of lipohypertrophy. As noted in Table 4.1, type 1 diabetes. However, patients re-
established kidney disease, or heart
examination of insulin injection sites for ceiving these treatments require life-
be
failure, a sodium–glucose cotrans-
the presence of lipohypertrophy, as well long immunosuppression to prevent
porter 2 inhibitor or glucagon-like
as assessment of injection device use graft rejection and/or recurrence of
peptide 1 receptor agonist with
ia
and injection technique, are key compo- autoimmune islet destruction. Given the
demonstrated cardiovascular dis-
nents of a comprehensive diabetes med- potential adverse effects of immunosup-
ease benefit (Table 9.1, Table 10
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medication-taking behavior
type 1 diabetes. Results from random- TYPE 2 DIABETES
should be reevaluated at regular
ized controlled studies show variable
Recommendations intervals (every 3–6 months) and
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*For agent-specific dosing recommendations, please refer to the manufacturers’ prescribing information. †FDA approved for CVD benefit. ‡FDA-approved for heart failure indication; §FDA-approved for CKD
indication. CV, cardiovascular; DPP-4, dipeptidyl peptidase 4; DKA, diabetic ketoacidosis; DKD, diabetic kidney disease; GLP-1 RAs, glucagon-like peptide 1 receptor agonists; HF, heart failure; NASH, nonalcoholic
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steatohepatitis; SGLT2, sodium–glucose cotransporter 2; SQ, subcutaneous; T2DM, type 2 diabetes.
Pharmacologic Approaches to Glycemic Treatment
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S101
S102 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 43, Supplement 1, January 2020
approach to choosing appropriate phar- very high circulating levels (e.g., as a re- positive and negative effects of new drugs
macologic treatment of blood glucose sult of overdose or acute renal failure) and reduces patient risk and expense (42);
(Fig. 9.1). This includes consideration of have been associated with lactic acidosis. based on these factors, sequential addi-
efficacy and key patient factors: 1) im- However, the occurrence of this compli- tion of oral agents to metformin has been
portant comorbidities such as atheroscle- cation is now known to be very rare, and the standard of care. However, there is
rotic cardiovascular disease (ASCVD) and metformin may be safely used in patients data to support initial combination ther-
indicators of high ASCVD risk, chronic with reduced estimated glomerular filtra- apy for more rapid attainment of glycemic
kidney disease (CKD), and heart failure tion rates (eGFR); the FDA has revised the goals (43,44), and a recent clinical trial
n
(HF) (see Section 10 “Cardiovascular Dis- label for metformin to reflect its safety in has demonstrated that this approach is
ease and Risk Management,” https://doi patients with eGFR $30 mL/min/1.73 m2 superior to sequential addition of medica-
tio
.org/10.2337/dc20-S010, and Section 11 (37). A recent randomized trial confirmed tions for extending primary and secondary
“Microvascular Complications and Foot previous observations that metformin use failure (45). In the VERIFY trial, partic-
a
Care,” https://doi.org/10.2337/dc20-S011), is associated with vitamin B12 deficiency ipants receiving the initial combination of
ci
2) hypoglycemia risk, 3) effects on body and worsening of symptoms of neurop- metformin and the dipeptidyl peptidase 4
weight, 4) side effects, 5) cost, and 6) athy (38). This is compatible with a recent (DPP-4) inhibitor vildagliptin had a slower
so
patient preferences. Lifestyle modifica- report from the Diabetes Prevention Pro- decline of glycemic control compared
tions that improve health (see Section gram Outcomes Study (DPPOS) suggesting with metformin alone and to vildagliptin
5 “Facilitating Behavior Change and periodic testing of vitamin B12 (39). added sequentially to metformin. These
As
Well-being to Improve Health Outcomes,” In patients with contraindications or results have not been generalized to oral
https://doi.org/10.2337/dc20-S005) should intolerance to metformin, initial therapy agents other than vildagliptin, but they
be emphasized along with any pharma- should be based on patient factors; suggest that more intensive early treat-
cologic therapy. Section 12 “Older Adults”
s
consider a drug from another class de- ment has some benefits and should be
(https://doi.org/10.2337/dc20-S012)andSec- picted in Fig. 9.1. When A1C is $1.5% considered through a shared decision-
tion 13 “Children and Adolescents”
(https://doi.org/10.2337/dc20-S013) te
(12.5 mmol/mol) above the glycemic
target (see Section 6 “Glycemic Targets,”
making process with patients, as appropriate.
Moreover, since the absolute effectiveness
be
have recommendations specific for older https://doi.org/10.2337/dc20-S006, for of most oral medications rarely exceeds
adults and for children and adolescents selecting appropriate targets), many pa- 1%, initial combination therapy should be
ia
with type 2 diabetes, respectively; Sec- tients will require dual combination ther- considered in patients presenting with
tion 10 “Cardiovascular Disease and Risk apy to achieve their target A1C level (40). A1C levels 1.5–2.0% above target.
D
Management” (https://doi.org/10.2337/ Insulin has the advantage of being effec- The choice of medication added to
dc20-S010) and Section 11 “Microvascular tive where other agents are not and should metformin is based on the clinical char-
Complications and Foot Care” (https://doi be considered as part of any combination acteristics of the patient and their pref-
an
.org/10.2337/dc20-S011) have recommen- regimen when hyperglycemia is severe, erences. Important clinical characteristics
dations for the use of glucose-lowering especially if catabolic features (weight include the presence of established
drugs in the management of cardiovascular loss, hypertriglyceridemia, ketosis) are ASCVD or indicators of high ASCVD risk,
ic
and renal disease, respectively. present. It is common practice to initiate other comorbidities, and risk for specific
er
insulin therapy for patients who present adverse drug effects, as well as safety,
Initial Therapy with blood glucose levels $300 mg/dL tolerability, and cost. Although there are
Metformin should be started at the time (16.7 mmol/L) or A1C .10% (86 mmol/mol) numerous trials comparing dual therapy
Am
type 2 diabetes is diagnosed unless there or if the patient has symptoms of hy- with metformin alone, there is little ev-
are contraindications; for many patients perglycemia (i.e., polyuria or polydipsia) idence to support one combination over
this will be monotherapy in combination or evidence of catabolism (weight loss) another. A comparative effectiveness
with lifestyle modifications. Metformin (Fig. 9.2). As glucose toxicity resolves, meta-analysis suggests that each new
19
is effective and safe, is inexpensive, and simplifying the regimen and/or changing class of noninsulin agents added to initial
may reduce risk of cardiovascular events to oral agents is often possible. However, therapy with metformin generally lowers
and death (35). Metformin is available in there is evidence that patients with un- A1C approximately 0.7–1.0% (46,47). If the
20
an immediate-release form for twice- controlled hyperglycemia associated with A1C target is not achieved after approxi-
daily dosing or as an extended-release type 2 diabetes can also be effectively mately 3 months, metformin can be com-
©
form that can be given once daily. Com- treated with a sulfonylurea (41). bined with any one of the preferred six
pared with sulfonylureas, metformin as treatment options: sulfonylurea, thiazolidine-
first-line therapy has beneficial effects on Combination Therapy dione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1
A1C, weight, and cardiovascular mortal- Because type 2 diabetes is a progressive RA, or basal insulin; the choice of which agent
ity (36); there is little systematic data disease in many patients, maintenance of to add is based on drug-specific effects and
available for other oral agents as initial glycemic targets with monotherapy is patient factors (Fig. 9.1 and Table 9.1).
therapy of type 2 diabetes. The principal often possible for only a few years, after For patients with established ASCVD or
side effects of metformin are gastroin- which combination therapy is necessary. indicators of high ASCVD risk (such as
testinal intolerance due to bloating, ab- Current recommendations have been to patients $55 years of age with coronary,
dominal discomfort, and diarrhea; these use stepwise addition of medications carotid, or lower-extremity artery steno-
can be mitigated by gradual dose titration. to metformin to maintain A1C at target. sis .50% or left ventricular hypertro-
The drug is cleared by renal filtration, and This allows a clearer assessment of the phy), established kidney disease, or heart
©
20
care.diabetesjournals.org
19
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er
ic
an
D
ia
be
te
s
As
so
ci
a
Figure 9.1—Glucose-lowering medication in type 2 diabetes: overall approach. For appropriate context, see Fig. 4.1. ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CV, cardiovascular;
CVD, cardiovascular disease; CVOTs, cardiovascular outcomes trials; DPP-4i, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF,
tio
heart failure; SGLT2i, sodium–glucose cotransporter 2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione. Adapted from Davies and colleagues (33,34).
Pharmacologic Approaches to Glycemic Treatment
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S103
S104 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 43, Supplement 1, January 2020
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a tio
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so
As
s
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er
Am
19
20
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Figure 9.2—Intensifying to injectable therapies. DSMES, diabetes self-management education and support; FPG, fasting plasma glucose; FRC, fixed-ratio
combination; GLP-1 RA, glucagon-like peptide 1 receptor agonist; max, maximum; PPG, postprandial glucose. Adapted from Davies et al. (33).
care.diabetesjournals.org Pharmacologic Approaches to Glycemic Treatment S105
failure, an SGLT-2 inhibitor or GLP-1 RA with preferred option for patients requiring Insulin Therapy
demonstrated CVD benefit (Table 9.1, the potency of an injectable therapy for Many patients with type 2 diabetes even-
Table 10.3B, Table 10.3C) is recommended glucose control (Fig. 9.2). However, high tually require and benefit from insulin
as part of the glucose-lowering regimen costs and tolerability issues are impor- therapy (Fig. 9.2). See the section INSULIN
independent of A1C and in consideration of tant barriers to the use of GLP-1 RAs. INJECTION TECHNIQUE above, for guidance on
patient-specific factors (Figure 9.1). For Cost for diabetes medicine has in- how to administer insulin safely and
patients without established ASCVD, indi- creased dramatically over the past two effectively. The progressive nature of
cators of high ASCVD risk, HF, or CKD, the decades, and an increasing proportion is type 2 diabetes should be regularly
n
choice of a second agent to add to met- now passed on to patients and their families and objectively explained to patients,
formin is not yet guided by empiric evi- (53). Table 9.2 provides cost information for and providers should avoid using insulin
tio
dence. Rather, drug choice is based on currently approved noninsulin therapies. Of as a threat or describing it as a sign of
avoidance of side effects, particularly hy- note, prices listed are average wholesale personal failure or punishment. Rather,
a
poglycemia and weight gain, cost, and prices (AWP) (54) and National Average the utility and importance of insulin to
maintain glycemic control once progres-
ci
patient preferences (48). Similar consider- Drug Acquisition Costs (NADAC) (55), sep-
ations are applied in patients who require a arate measures to allow for a comparison of sion of the disease overcomes the effect of
so
third agent to achieve glycemic goals; there drug pricesbut do notaccountfordiscounts, other agents should be emphasized. Ed-
is very little trial-based evidence to guide rebates, or other price adjustments often ucating and involving patients in insulin
this choice. In all cases, treatment regimens involved in prescription sales that affect the management is beneficial. For example,
As
need to be continuously reviewed for actual cost incurred by the patient. Med- instruction of patients in self-titration of
efficacy, side effects, and patient burden ication costs can be a major source of stress insulin doses based on self-monitoring of
(Table 9.1). In some instances, patients will for patients with diabetes and contribute to blood glucose improves glycemic control
in patients with type 2 diabetes initiating
s
require medication reduction or discontin- worse adherence with medications (56);
uation. Common reasons for this include cost-reducing strategies may improve ad- insulin (58). Comprehensive education re-
ineffectiveness, intolerable side effects, ex-
pense, or a change in glycemic goals (e.g., in
herence in some cases (57).
te garding self-monitoring of blood glucose,
diet, and the avoidance and appropriate
be
response to development of comorbidities Cardiovascular Outcomes Trials treatment of hypoglycemia are critically
or changes in treatment goals). Section There are now multiple large randomized important in any patient using insulin.
12 “Older Adults”(https://doi.org/10.2337/
ia
ment considerations in older adults, a events in patients with type 2 diabetes Basal insulin alone is the most convenient
setting where changes of glycemic goals treated with an SGLT2 inhibitor (em- initial insulin regimen and can be added
and de-escalation of therapy is common. pagliflozin, canagliflozin, dapagliflozin) to metformin and other oral agents.
an
Although most patients prefer oral or GLP-1 RA (liraglutide, semaglutide, Starting doses can be estimated based
medications to drugs that need to be dulaglutide); see Section 10 “Cardiovas- on body weight (0.1–0.2 units/kg/day)
injected, the eventual need for the cular Disease and Risk Management” and the degree of hyperglycemia, with
ic
greater potency of injectable medica- (https://doi.org/10.2337/dc20-S010) for individualized titration over days to weeks
er
tions is common, particularly in people details. The subjects enrolled in the cardio- as needed. The principal action of basal
with a longer duration of diabetes. The vascular outcome trials using empagliflozin, insulin is to restrain hepatic glucose pro-
addition of basal insulin, either human canagliflozin, liraglutide, and semaglutide duction and limit hyperglycemia overnight
Am
NPH or one of the long-acting insulin had A1C $7%, and more than 70% were and between meals (59,60). Control of
analogs, to oral agent regimens is a well- taking metformin at baseline. Thus, a prac- fasting glucose can be achieved with
established approach that is effective for tical extension of these results to clinical human NPH insulin or a long-acting insulin
many patients. In addition, recent evi- practice is to use these drugs preferen- analog. In clinical trials, long-acting basal
19
dence supports the utility of GLP-1 RAs in tially in patients with type 2 diabetes and analogs (U-100 glargine or detemir) have
patients not reaching glycemic targets established ASCVD or indicators of high been demonstrated to reduce the risk of
with use of non-GLP-1 RA oral agent ASCVD risk. For these patients, incorpo- symptomatic and nocturnal hypoglycemia
20
regimens. While most GLP-1 RA products rating one of the SGLT2 inhibitors or compared with NPH insulin (61–66), al-
are injectable, an oral formulation of GLP-1 RAs that have been demonstrated though these advantages are modest and
©
semaglutide is now commercially avail- to have cardiovascular disease benefit is may not persist (67). Longer-acting basal
able (49). In trials comparing the ad- recommended (Table 9.1). In cardiovascular analogs (U-300 glargine or degludec) may
dition of an injectable GLP-1 RAs or outcomes trials, empagliflozin, canagliflozin, convey a lower hypoglycemia risk com-
insulin in patients needing further glu- dapagliflozin, liraglutide, semaglutide, and pared with U-100 glargine when used in
cose lowering, the efficacy of the two dulaglutide all had beneficial effects on combination with oral agents (68–74).
treatments was similar (50–52). How- indices of CKD. See Section 11 “Microvas- Despite evidence for reduced hypoglyce-
ever, GLP-1 RAs in these trials had a cular Complications and Foot Care” (https:// mia with newer, longer-acting basal in-
lower risk of hypoglycemia and beneficial doi.org/10.2337/dc20-S011) for a detailed sulin analogs in clinical trial settings, in
effects on body weight compared with discussion on how CKD may impact treat- practice these effects may be modest
insulin, albeit with greater gastroin- ment choices. Additional large randomized compared with NPH insulin (75).
testinal side effects. Thus, trial results trials of other agents in these classes are The cost of insulin has been rising
support injectable GLP-1 RAs as the ongoing. steadily over the past two decades, at
S106 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 43, Supplement 1, January 2020
Table 9.2—Median monthly (30-day) cost of maximum approved daily dose of noninsulin glucose-lowering agents in the U.S.
Dosage strength/product Median AWP Median NADAC Maximum approved
Class Compound(s) (if applicable) (min, max)† (min, max)† daily dose*
Biguanides c Metformin 500 mg (IR) $84 ($4, $85) $2 2,000 mg
850 mg (IR) $108 ($6, $109) $3 2,550 mg
1,000 mg (IR) $87 ($4, $88) $2 2,000 mg
500 mg (ER) $89 ($87, $7,412) $5 ($5, $988) 2,000 mg
750 mg (ER) $74 ($65, $74) $4 1,500 mg
n
1,000 mg (ER) $242 ($242, $7,214) $224 ($224, $910) 2,000 mg
tio
Sulfonylureas (2nd c Glimepiride 4 mg $74 ($71, $198) $4 8 mg
generation) c Glipizide 10 mg (IR) $75 ($67, $97) $5 40 mg (IR)
10 mg (XL) $48 $15 20 mg (XL)
a
c Glyburide 6 mg (micronized) $50 ($48, $71) $4 12 mg (micronized)
5 mg $93 ($63, $103) $11 20 mg
ci
Thiazolidinediones c Pioglitazone 45 mg $348 ($283, $349) $4 45 mg
c Rosiglitazone 4 mg $407 $330 8 mg
so
a-Glucosidase c Acarbose 100 mg $106 ($104, $106) $23 300 mg
inhibitors c Miglitol 100 mg $241 $311 300 mg
As
Meglitinides (glinides) c Nateglinide 120 mg $155 $39 360 mg
c Repaglinide 2 mg $878 ($162, $897) $39 16 mg
DPP-4 inhibitors c Alogliptin 25 mg $234 $168 25 mg
c Saxagliptin 5 mg $505 $403 5 mg
s
c Linagliptin 5 mg $523 $419 5 mg
c Sitagliptin 100 mg $541 $433 100 mg
SGLT2 inhibitors c
c
Ertugliflozin
Dapagliflozin
15 mg
10 mg
te $338
$591
$271
$473
15 mg
10 mg
be
c Empagliflozin 25 mg $591 $473 25 mg
c Canagliflozin 300 mg $593 $475 300 mg
GLP-1 RAs c Exenatide (extended release) 2 mg powder for $840 $672 2 mg**
ia
suspension or pen
c Exenatide 10 mg pen $876 $730 20 mg
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immediate release; N/A, data not available; NADAC, National Average Drug Acquisition Cost; SGLT2, sodium–glucose cotransporter 2. †Calculated
for 30-day supply (AWP [54] or NADAC [55] unit price 3 number of doses required to provide maximum approved daily dose 3 30 days); median AWP
or NADAC listed alone when only one product and/or price. *Utilized to calculate median AWP and NADAC (min, max); generic prices used, if
available commercially. **Administered once weekly. †††AWP and NADAC calculated based on 120 mg three times daily.
19
a pace several fold that of other medical familiar with its use (75). Human regular patient needs (see Figure 9.2). People
expenditures (76). This expense contrib- insulin, NPH, and 70/30 NPH/regular prod- with type 2 diabetes are generally more
20
utes significant burden to patients as ucts can be purchased for considerably insulin resistant than those with type 1
insulin has become a growing “out-of- less than the AWP and NADAC prices listed diabetes, require higher daily doses (;1
in Table 9.3 at select pharmacies.
©
pocket” cost for people with diabetes, unit/kg), and have lower rates of hypo-
and direct patient costs contribute to glycemia (77). Titration can be based
treatment nonadherence (76). Therefore, Prandial Insulin on home glucose monitoring or A1C.
consideration of cost is an important com- Many individuals with type 2 diabetes With significant additions to the prandial
ponent of effective management. For require doses of insulin before meals, in insulin dose, particularly with the evening
many patients with type 2 diabetes addition to basal insulin, to reach glyce- meal, consideration should be given to
(e.g., individuals with relaxed A1C goals, mic targets. A dose of 4 units or 10% of decreasing basal insulin. Meta-analyses
low rates of hypoglycemia, and prominent the amount of basal insulin at the largest of trials comparing rapid-acting insulin
insulin resistance, as well as those with meal or the meal with the greatest post- analogs with human regular insulin in
cost concerns), human insulin (NPH and prandial excursion is a safe estimate for patients with type 2 diabetes have not
regular) may be the appropriate choice initiating therapy. The prandial insulin reported important differences in A1C
of therapy, and clinicians should be regimen can then be intensified based on or hypoglycemia (78,79).
care.diabetesjournals.org Pharmacologic Approaches to Glycemic Treatment S107
Table 9.3—Median cost of insulin products in the U.S. calculated as AWP (54) and NADAC (55) per 1,000 units of specified dosage
form/product
Insulins Compounds Dosage form/product Median AWP (min, max)* Median NADAC (min, max)*
Rapid-acting c Lispro follow-on U-100 vial $157 $126
product U-100 prefilled pen $202 $162
c Lispro U-100 vial $330 $264
U-100 3 mL cartridges $408 $327
U-100 prefilled pen; U-200 $424 $340
n
prefilled pen
c Glulisine U-100 vial $341 $273
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U-100 prefilled pen $439 $353
c Aspart U-100 vial $347† $278†
U-100 3 mL cartridges $430 $345
a
U-100 prefilled pen $447† $358†
ci
c Inhaled insulin Inhalation cartridges $924 $606
Short-acting c human regular U-100 vial $165 ($165, $178)†† $134 ($134, $146)††
so
Intermediate-acting c human NPH U-100 vial $165 ($165, $178)†† $135 ($135, $146)††
U-100 prefilled pen $377 $304
Concentrated human c U-500 human regular U-500 vial $178 $144
As
regular insulin insulin U-500 prefilled pen $230 $184
Long-acting c Glargine follow-on U-100 prefilled pen $261 $210
product
c Glargine U-100 vial; U-100 prefilled pen $340 $272
s
U-300 prefilled pen $346 $280
te
c Detemir U-100 vial; U-100 prefilled pen $370 $295
c Degludec U-100 vial; U-100 prefilled pen; $407 $326
be
U-200 prefilled pen
Premixed insulin products c NPH/regular 70/30 U-100 vial $165 ($165, $178) $134 ($134, $145)
U-100 prefilled pen $377 $303
ia
AWP, average wholesale price; GLP-1, glucagon-like peptide 1; NADAC, National Average Drug Acquisition Cost. *AWP or NADAC calculated as in
Table 9.2. †Inclusive of both the original and “faster-acting” products. ††AWP and NADAC data presented do not include vials of regular human
er
insulin and NPH available at Walmart for approximately $25/vial; median listed alone when only one product and/or price.
Am
more concentrated than U-100 regular who require large doses of insulin. While lung disease, such as asthma and chronic
insulin. Regular U-500 has distinct phar- U-500 regular insulin is available in both obstructive pulmonary disease, and is not
macokinetics with delayed onset and prefilled pens and vials (a dedicated syringe recommended in patients who smoke or
20
longer duration of action, has character- was approved in July 2016), other concen- who recently stopped smoking. All pa-
istics more like an intermediate-acting trated insulins are available only in prefilled tients require spirometry (FEV1) testing to
(NPH) insulin, and can be used as two or
©
pens to minimize the risk of dosing errors. identify potential lung disease prior to and
three daily injections (80). U-300 glargine after starting inhaled insulin therapy.
and U-200 degludec are three and two Inhaled Insulin
times as concentrated as their U-100 Inhaled insulin is available for prandial Combination Injectable Therapy
formulations, and allow higher doses use with a limited dosing range; studies in If basal insulin has been titrated to an
of basal insulin administration per vol- people with type 1 diabetes suggest rapid acceptable fasting blood glucose level (or
ume used. U-300 glargine has a longer pharmacokinetics (7). A pilot study found if the dose is .0.5 units/kg/day) and A1C
duration of action than U-100 glargine evidence that compared with injectable remains above target, consider advancing
but modestly lower efficacy per unit rapid-acting insulin, supplemental doses to combination injectable therapy (Fig.
administered (81,82). The FDA has also of inhaled insulin taken based on post- 9.2). This approach can use a GLP-1 RA
approved a concentrated formulation of prandial glucose levels may improve blood added to basal insulin or multiple doses of
rapid-acting insulin lispro, U-200 (200 glucose management without additional insulin. The combination of basal insulin
S108 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 43, Supplement 1, January 2020
and GLP-1 RA has potent glucose-lower- in type 1 diabetic participants of the Diabetes 15. Bergenstal RM, Garg S, Weinzimer SA, et al.
ing actions and less weight gain and hypo- Control and Complications Trial/Epidemiology of Safety of a hybrid closed-loop insulin delivery
Diabetes Interventions and Complications (DCCT/ system in patients with type 1 diabetes. JAMA
glycemia compared with intensified insulin EDIC) study. Diabetes 2006;55:3556–3565 2016;316:1407–1408
regimens (84–86). Two different once-daily 2. Nathan DM, Cleary PA, Backlund J-YC, et al.; 16. Garg SK, Weinzimer SA, Tamborlane WV,
fixed-dual combination products contain- Diabetes Control and Complications Trial/ et al. Glucose outcomes with the in-home use of a
ing basal insulin plus a GLP-1 RA are Epidemiology of Diabetes Interventions and hybrid closed-loop insulin delivery system in ado-
available: insulin glargine plus lixisenatide Complications (DCCT/EDIC) Study Research Group. lescents and adults with type 1 diabetes. Diabetes
Intensive diabetes treatment and cardiovascular Technol Ther 2017;19:155–163
and insulin degludec plus liraglutide. disease in patients with type 1 diabetes. N Engl J 17. Tauschmann M, Thabit H, Bally L, et al.;
n
Intensification of insulin treatment can Med 2005;353:2643–2653 APCam11 Consortium. Closed-loop insulin de-
be done by adding doses of prandial to
tio
3. Diabetes Control and Complications Trial livery in suboptimally controlled type 1 diabetes:
basal insulin. Starting with a single pran- (DCCT)/Epidemiology of Diabetes Interventions a multicentre, 12-week randomised trial. Lancet
dial dose with the largest meal of the day and Complications (EDIC) Study Research Group. 2018;392:1321–1329
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Mortality in type 1 diabetes in the DCCT/EDIC 18. Peters A, Laffel L (Eds.). American Diabetes
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advanced to a regimen with multiple 2016;39:1378–1383 Alexandria, VA, American Diabetes Association,
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so
natively, in a patient on basal insulin in effectiveness, and cost effectiveness of long 19. Chiang JL, Kirkman MS, Laffel LMB, Peters AL;
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and network meta-analysis. BMJ 2014;349:g5459 ment of the American Diabetes Association.
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treat-to-target basal-bolus regimen with insulin meta-analysis. Lancet Diabetes Endocrinol 2014;
who eat on irregular schedules. On the
te
aspart at meals: a 2-year, randomized, controlled 2:133–140
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sulin is a simple, convenient means of 6. DeWitt DE, Hirsch IB. Outpatient insulin ther-
be
Nogueira VDS. Effectiveness and safety of car-
spreading insulin across the day. More- apy in type 1 and type 2 diabetes mellitus: bohydrate counting in the management of adult
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ia
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D
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an
Fast-acting insulin aspart improves glycemic con- management in the continuous glucose monitor-
achieve glycemic goals. When initiating trol in basal-bolus treatment for type 1 diabetes: ing era. Diabetes Care 2015;38:1008–1015
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therapy should be maintained while sulfo- treat-to-target, randomized, parallel-group trial
ic
patients with type 1 diabetes: the SWITCH 1 needle in obese patients with diabetes. Mayo
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may help to improve control and reduce the 10. Home PD, Bergenstal RM, Bolli GB, et al. New 25. Ratner RE, Dickey R, Fineman M, et al. Amylin
amountofinsulin needed, though potential insulin glargine 300 units/mL versus glargine replacement with pramlintide as an adjunct to
100 units/mL in people with type 1 diabetes: insulin therapy improves long-term glycaemic
side effects should be considered. Once a a randomized, phase 3a, open-label clinical
19
insulins based on the blood glucose levels Comparative effectiveness and safety of meth- placebo-controlled trial assessing pramlintide treat-
ods of insulin delivery and glucose monitoring for ment in the setting of intensive insulin therapy in
and an understanding of the pharma- diabetes mellitus: a systematic review and meta- type 1 diabetes. Diabetes Care 2006;29:2189–2195
©
codynamic profile of each formulation analysis. Ann Intern Med 2012;157:336–347 27. Meng H, Zhang A, Liang Y, Hao J, Zhang X, Lu J.
(pattern control). As people with type 2 12. Pickup JC. The evidence base for diabetes Effect of metformin on glycaemic control in
diabetes get older, it may become necessary technology: appropriate and inappropriate meta- patients with type 1 diabetes: a meta-analysis
to simplify complex insulin regimens be- analysis. J Diabetes Sci Technol 2013;7:1567–1574 of randomized controlled trials. Diabetes Metab
13. Bergenstal RM, Klonoff DC, Garg SK, et al.; Res Rev 2018;34:e2983
cause of a decline in self-management ASPIRE In-Home Study Group. Threshold-based 28. Petrie JR, Chaturvedi N, Ford I, et al.; RE-
ability (see Section 12 “Older Adults,” insulin-pump interruption for reduction of hy- MOVAL Study Group. Cardiovascular and met-
https://doi.org/10.2337/dc20-S012). poglycemia. N Engl J Med 2013;369:224–232 abolic effects of metformin in patients with
14. Buckingham BA, Raghinaru D, Cameron F, type 1 diabetes (REMOVAL): a double-blind,
et al.; In Home Closed Loop Study Group. Predictive randomised, placebo-controlled trial. Lancet Di-
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2016;101:1754–1761 53. Riddle MC, Herman WH. The cost of diabetes 67. Yki-Järvinen H, Kauppinen-Mäkelin R,
40. Henry RR, Murray AV, Marmolejo MH, care-an elephant in the room. Diabetes Care Tiikkainen M, et al. Insulin glargine or NPH
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metformin XR, or both: initial pharmacotherapy 54. Truven Health Analytics. Micromedex 2.0 the LANMET study. Diabetologia 2006;49:442–
for type 2 diabetes, a randomised controlled Introduction to RED BOOK Online, 2018. Accessed 451
trial. Int J Clin Pract 2012;66:446–456 1 November 2019. Available from http://www 68. Bolli GB, Riddle MC, Bergenstal RM, et al.; on
41. Babu A, Mehta A, Guerrero P, et al. Safe and .micromedexsolutions.com/micromedex2/ behalf of the EDITION 3 study investigators. New
simple emergency department discharge therapy 4.34.0/WebHelp/RED_BOOK/Introduction_to_ insulin glargine 300 U/ml compared with glargine
for patients with type 2 diabetes mellitus and severe REDB_BOOK_Online.htm 100 U/ml in insulin-naı̈ve people with type 2
hyperglycemia. Endocr Pract 2009;15:696–704 55. Centers for Medicare & Medicaid Services. diabetes on oral glucose-lowering drugs: a ran-
42. Cahn A, Cefalu WT. Clinical considerations NADAC (national average drug acquisition cost), domized controlled trial (EDITION 3). Diabetes
for use of initial combination therapy in type 2 drug pricing and payment. Accessed 1 November Obes Metab 2015;17:386–394
diabetes. Diabetes Care 2016;39(Suppl. 2):S137– 2019. Available from https://data.medicaid.gov/ 69. Terauchi Y, Koyama M, Cheng X, et al. New
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Initial combination therapy with metformin, 56. Kang H, Lobo JM, Kim S, Sohn M-W. Cost- using basal insulin and oral antihyperglycaemic
pioglitazone and exenatide is more effective related medication non-adherence among U.S. drugs: glucose control and hypoglycaemia in a
S110 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 43, Supplement 1, January 2020
randomized controlled trial (EDITION JP 2). department visits or hospital admissions and units/mL in people with type 2 diabetes
Diabetes Obes Metab 2016;18:366–374 with glycemic control in patients with type 2 using oral agents and basal insulin: glucose
70. Yki-Järvinen H, Bergenstal RM, Bolli GB, et al. diabetes. JAMA 2018;320:53–62 control and hypoglycemia in a 6-month ran-
Glycaemic control and hypoglycaemia with new 76. Cefalu WT, Dawes DE, Gavlak G, et al.; Insulin domized controlled trial (EDITION 2). Diabetes
insulin glargine 300 U/ml versus insulin glargine Access and Affordability Working Group. Con- Care 2014;37:3235–3243
100 U/ml in people with type 2 diabetes using basal clusions and recommendations. Diabetes Care 83. Akturk HK, Snell-Bergeon JK, Rewers A, et al.
insulin and oral antihyperglycaemic drugs: the 2018;41:1299–1311 Improved postprandial glucose with inhaled
EDITION 2 randomized 12-month trial including 77. McCall AL. Insulin therapy and hypoglycemia. technosphere insulin compared with insulin as-
6-month extension. Diabetes Obes Metab 2015;17: Endocrinol Metab Clin North Am 2012;41:57–87 part in patients with type 1 diabetes on multiple
1142–1149 78. Mannucci E, Monami M, Marchionni N. daily injections: the STAT study. Diabetes Technol
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71. Marso SP, McGuire DK, Zinman B, et al.; Short-acting insulin analogues vs. regular human Ther 2018;20:639–647
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DEVOTE Study Group. Efficacy and safety of insulin in type 2 diabetes: a meta-analysis. Di- 84. Diamant M, Nauck MA, Shaginian R, et al.; 4B
degludec versus glargine in type 2 diabetes. N abetes Obes Metab 2009;11:53–59 Study Group. Glucagon-like peptide 1 receptor
Engl J Med 2017;377:723–732 79. Heller S, Bode B, Kozlovski P, Svendsen AL. agonist or bolus insulin with optimized basal
72. Rodbard HW, Cariou B, Zinman B, et al.; Meta-analysis of insulin aspart versus regular insulin in type 2 diabetes. Diabetes Care 2014;
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insulin-naive subjects with type 2 diabetes: a 2013;5:482–491 Glucagon-like peptide-1 receptor agonist and
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2-year randomized, treat-to-target trial. Diabet 80. Wysham C, Hood RC, Warren ML, Wang T, basal insulin combination treatment for the
Med 2013;30:1298–1304 Morwick TM, Jackson JA. Effect of total daily management of type 2 diabetes: a systematic
73. Wysham C, Bhargava A, Chaykin L, et al. dose on efficacy, dosing, and safety of 2 dose review and meta-analysis. Lancet 2014;384:
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the SWITCH 2 randomized clinical trial. JAMA 2017; type 2 diabetes. Endocr Pract 2016;22:653–665 Capuano A, Esposito K, Giugliano D. Insulin and
318:45–56 81. Riddle MC, Yki-Järvinen H, Bolli GB, et al. glucagon-like peptide 1 receptor agonist combi-
74. Zinman B, Philis-Tsimikas A, Cariou B, et al.; One-year sustained glycaemic control and less nation therapy in type 2 diabetes: a systematic
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NN1250-3579 (BEGIN Once Long) Trial Investi- hypoglycaemia with new insulin glargine 300 review and meta-analysis of randomized con-
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gators. Insulin degludec versus insulin glargine U/ml compared with 100 U/ml in people with trolled trials. Diabetes Care 2017;40:614–624
in insulin-naive patients with type 2 diabetes: type 2 diabetes using basal plus meal-time in- 87. Rodbard HW, Visco VE, Andersen H, Hiort
a 1-year, randomized, treat-to-target trial (BEGIN sulin: the EDITION 1 12-month randomized trial, LC, Shu DHW. Treatment intensification with
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Once Long). Diabetes Care 2012;35:2464–2471 including 6-month extension. Diabetes Obes stepwise addition of prandial insulin aspart
75. Lipska KJ, Parker MM, Moffet HH, Huang ES, Metab 2015;17:835–842 boluses compared with full basal-bolus therapy
Karter AJ. Association of initiation of basal in- 82. Yki-Järvinen H, Bergenstal R, Ziemen M, (FullSTEP Study): a randomised, treat-to-target
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sulin analogs vs neutral protamine Hagedorn et al.; EDITION 2 Study Investigators. New in- clinical trial. Lancet Diabetes Endocrinol 2014;2:
insulin with hypoglycemia-related emergency sulin glargine 300 units/mL versus glargine 100 30–37
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Diabetes Care Volume 43, Supplement 1, January 2020 S111
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Medical Care in Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S111–S134 | https://doi.org/10.2337/dc20-s010
a
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As
s
provide the components of diabetes care, general treatment goals and guidelines,
te
and tools to evaluate quality of care. Members of the ADA Professional Practice
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-
be
SPPC), are responsible for updating the Standards of Care annually, or more
frequently as warranted. For a detailed description of ADA standards, statements,
and reports, as well as the evidence-grading system for ADA’s clinical practice
ia
dc20-S013).
er
ification in patients with diabetes, there is evidence that measures of 10-year coronary
heart disease (CHD) risk among U.S. adults with diabetes have improved significantly over
©
the past decade (2) and that ASCVD morbidity and mortality have decreased (3,4).
This section has received endorsement from the
Heart failure is another major cause of morbidity and mortality from cardiovascu- American College of Cardiology.
lar disease. Recent studies have found that rates of incident heart failure hospitalization
Suggested citation: American Diabetes Asso-
(adjustedforageandsex)weretwofoldhigherinpatientswithdiabetescomparedwiththose ciation. 10. Cardiovascular disease and risk
without (5,6). People with diabetes may have heart failure with preserved ejection fraction management: Standards of Medical Care in
(HFpEF) or with reduced ejection fraction (HFrEF). Hypertension is often a precursor of heart Diabetesd2020. Diabetes Care 2020;43(Suppl.1):
failure of either type, and ASCVD can coexist with either type (7), whereas prior myocardial S111–S134
infarction (MI) is often a major factor in HFrEF. Rates of heart failure hospitalization have © 2019 by the American Diabetes Association.
been improved in recent trials including patients with type 2 diabetes, most of whom also Readers may use this article as long as the work
is properly cited, the use is educational and not
had ASCVD, with sodium–glucose cotransporter 2 (SGLT2) inhibitors (8–10). for profit, and the work is not altered. More infor-
For prevention and management of both ASCVD and heart failure, cardio- mation is available at http://www.diabetesjournals
vascular risk factors should be systematically assessed at least annually in all patients .org/content/license.
S112 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
with diabetes. These risk factors in- epidemiology, diagnosis, and treatment
making process that addresses
clude obesity/overweight, hyperten- of hypertension (17).
cardiovascular risk, potential
sion, dyslipidemia, smoking, a family
Screening and Diagnosis adverse effects of antihyper-
history of premature coronary disease,
tensive medications, and pa-
chronic kidney disease, and the pres- Recommendations tient preferences. C
ence of albuminuria. Modifiable abnor- 10.1 Blood pressure should be mea- 10.4 For individuals with diabetes
mal risk factors should be treated as sured at every routine clinical and hypertension at higher car-
described in these guidelines. visit. Patients found to have el- diovascular risk (existing athero-
n
evated blood pressure ($140/90 sclerotic cardiovascular disease
tio
THE RISK CALCULATOR mmHg) should have blood pres- [ASCVD] or 10-year ASCVD risk
The American College of Cardiology/ sure confirmed using multiple $15%), a blood pressure target
American Heart Association ASCVD risk readings, including measure- of ,130/80 mmHg may be ap-
a
calculator (Risk Estimator Plus) is generally ments on a separate day, to propriate, if it can be safely
diagnose hypertension. B
ci
a useful tool to estimate 10-year ASCVD attained. C
risk (available online at tools.acc.org/ 10.2 All hypertensive patients with 10.5 For individuals with diabetes
so
ASCVD-Risk-Estimator-Plus). The calcu- diabetes should monitor their and hypertension at lower risk
lator includes diabetes as a risk factor, blood pressure at home. B for cardiovascular disease (10-
As
since diabetes itself confers increased risk year atherosclerotic cardio-
for ASCVD, although it should be acknowl- Blood pressure should be measured at vascular disease risk ,15%),
edged that these risk calculators do not every routine clinical visit by a trained treat to a blood pressure target
account for the duration of diabetes or the individual and should follow the of ,140/90 mmHg. A
s
presence of diabetes complications, such guidelines established for the general pop- 10.6 In pregnant patients with dia-
ulation: measurement in the seated posi-
te
as albuminuria. Although some variability betes and preexisting hyperten-
in calibration exists in various subgroups, tion, with feet on the floor and arm sion, a blood pressure target
supported at heart level, after 5 min of
be
including by sex, race, and diabetes, the of #135/85 mmHg is suggested
overall risk prediction does not differ in rest. Cuff size should be appropriate for the in the interest of reducing the
those with or without diabetes (11–14), upper-arm circumference. Elevated values risk for accelerated maternal
ia
validating the use of risk calculators in should be confirmed on a separate day. hypertension A and minimizing
people with diabetes. The 10-year risk of a Postural changes in blood pressure and impaired fetal growth. E
D
first ASCVD event should be assessed to pulse may be evidence of autonomic neu-
better stratify ASCVD risk and help guide ropathy and therefore require adjustment
of blood pressure targets. Orthostatic blood Randomized clinical trials have demon-
an
already high risk because they have monitoring may provide evidence of (21–27). Therefore, patients with type 1
ASCVD) but are not yet in widespread white coat hypertension, masked hyper- or type 2 diabetes who have hyperten-
Am
use (15,16). With newer, more expensive tension, or other discrepancies between sion should, at a minimum, be treated
lipid-lowering therapies now available, office and “true” blood pressure (17). In to blood pressure targets of ,140/90
use of these risk assessments may help addition to confirming or refuting a di- mmHg. The benefits and risks of inten-
target these new therapies to “higher agnosis of hypertension, home blood sifying antihypertensive therapy to tar-
pressure assessment may be useful to get blood pressures lower than ,140/90
19
CONTROL better correlate with ASCVD risk than analyses of clinical trials. Notably, there
Hypertension, defined as a sustained office measurements (18,19). Moreover, is an absence of high-quality data avail-
blood pressure $140/90 mmHg, is com-
©
home blood pressure monitoring may able to guide blood pressure targets in
mon among patients with either type 1 improve patient medication adherence type 1 diabetes.
or type 2 diabetes. Hypertension is a and thus help reduce cardiovascular
major risk factor for both ASCVD and risk (20). Randomized Controlled Trials of Intensive
microvascular complications. Moreover, Versus Standard Blood Pressure Control
numerous studies have shown that anti- Treatment Goals The Action to Control Cardiovascular Risk
hypertensive therapy reduces ASCVD in Diabetes Blood Pressure (ACCORD BP)
Recommendations
events, heart failure, and microvascular trial provides the strongest direct assess-
10.3 For patients with diabetes and
complications. Please refer to the Amer- ment of the benefits and risks of intensive
hypertension, blood pressure
ican Diabetes Association (ADA) position blood pressure control among people
targets should be individual-
statement “Diabetes and Hyperten- with type 2 diabetes (28). In ACCORD
ized through a shared decision-
sion” for a detailed review of the BP, compared with standard blood
care.diabetesjournals.org Cardiovascular Disease and Risk Management S113
pressure control (target systolic blood relevance of their results to people A number of post hoc analyses have
pressure ,140 mmHg), intensive blood with diabetes is less clear. The Action attempted to explain the apparently
pressure control (target systolic blood in Diabetes and Vascular Disease: Pre- divergent results of ACCORD BP and
pressure ,120 mmHg) did not reduce terax and Diamicron MR Controlled SPRINT. Some investigators have argued
total major atherosclerotic cardiovascu- Evaluation–Blood Pressure (ADVANCE that the divergent results are not due to
lar events but did reduce the risk of BP) trial did not explicitly test blood differences between people with and with-
stroke, at the expense of increased ad- pressure targets (29); the achieved out diabetes but rather are due to differ-
verse events (Table 10.1). The ACCORD blood pressure in the intervention ences in study design or to characteristics
n
BP results suggest that blood pressure group was higher than that achieved other than diabetes (31–33). Others have
targets more intensive than ,140/90 in the ACCORD BP intensive arm and opined that the divergent results are most
tio
mmHg are not likely to improve car- would be consistent with a target readily explained by the lack of benefit of
diovascular outcomes among most blood pressure of ,140/ 90 mmHg. intensive blood pressure control on cardio-
a
people with type 2 diabetes but may Notably, ACCORD BP and SPRINT mea- vascular mortality in ACCORD BP, which
ci
be reasonable for patients who may sured blood pressure using automated may be due to differential mechanisms
derive the most benefit and have office blood pressure measurement, underlying cardiovascular disease in type
so
been educated about added treatment which yields values that are generally 2 diabetes, to chance, or both (34).
burden, side effects, and costs, as dis- lower than typical office blood pres-
cussed below. sure readings by approximately 5–10 Meta-analyses of Trials
As
Additional studies, such as the Sys- mmHg (30), suggesting that im- To clarify optimal blood pressure targets
tolic Blood Pressure Intervention Trial plementing the ACCORD BP or SPRINT in patients with diabetes, meta-analyses
(SPRINT) and the Hypertension Optimal protocols in an outpatient clinic might have stratified clinical trials by mean
s
Treatment (HOT) trial, also examined require a systolic blood pressure tar- baseline blood pressure or mean blood
effects of intensive versus standard get higher than ,120 mmHg, such as pressure attained in the intervention (or
control (Table 10.1), though the ,130 mmHg.
te intensive treatment) arm. Based on these
be
Table 10.1—Randomized controlled trials of intensive versus standard hypertension treatment strategies
ia
T2D aged 40–79 years ,120 mmHg 130–140 mmHg of nonfatal MI, nonfatal stroke, and CVD
with prior evidence Achieved (mean) Achieved (mean) death
of CVD or multiple SBP/DBP: SBP/DBP: c Stroke risk reduced 41% with intensive
an
cardiovascular risk 119.3/64.4 mmHg 13.5/70.5 mmHg control, not sustained through follow-up
factors beyond the period of active treatment
c Adverse events more common in intensive
ic
ADVANCE BP (29) 11,140 participants Intervention: a single-pill, Control: placebo c Intervention reduced risk of primary
with T2D aged fixed-dose combination Achieved (mean) composite end point of major
Am
55 years and older of perindopril and SBP/DBP: macrovascular and microvascular events
with prior evidence indapamide 141.6/75.2 mmHg (9%), death from any cause (14%), and
of CVD or multiple Achieved (mean) death from CVD (18%)
cardiovascular risk SBP/DBP: c 6-year observational follow-up found
factors 136/73 mmHg reduction in risk of death in intervention
group attenuated but still significant (174)
19
HOT (185) 18,790 participants, DBP target: DBP target: c In the overall trial, there was no
including 1,501 #80 mmHg #90 mmHg cardiovascular benefit with more intensive
20
events
SPRINT (39) 9,361 participants SBP target: SBP target: c Intensive SBP target lowered risk of the
without diabetes ,120 mmHg ,140 mmHg primary composite outcome 25% (MI, ACS,
Achieved (mean): Achieved (mean): stroke, heart failure, and death due to CVD)
121.4 mmHg 136.2 mmHg c Intensive target reduced risk of death 27%
c Intensive therapy increased risks of
electrolyte abnormalities and AKI
ACCORD BP, Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial; ACS, acute coronary syndrome; ADVANCE BP, Action in Diabetes
and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation–Blood Pressure trial; AKI, acute kidney injury; CVD, cardiovascular
disease; DBP, diastolic blood pressure; HOT, Hypertension Optimal Treatment trial; MI, myocardial infarction; SBP, systolic blood pressure; SPRINT,
Systolic Blood Pressure Intervention Trial; T2D, type 2 diabetes. Data from this table can also be found in the ADA position statement “Diabetes and
Hypertension” (17).
S114 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
analyses, antihypertensive treatment ap- syncope, falls, acute kidney injury, and recommends use of antihypertensive
pears to be beneficial when mean base- electrolyte abnormalities) should also be therapy to maintain systolic blood pres-
line blood pressure is $140/90 mmHg or taken into account (28,39–41). Patients sure between 110 and 140 mmHg and
mean attained intensive blood pressure with older age, chronic kidney disease, diastolic blood pressure between 80 and
is $130/80 mmHg (17,21,22,24–26). and frailty have been shown to be at 85 mmHg (44).
Among trials with lower baseline or higher risk of adverse effects of intensive During pregnancy, treatment with ACE
attained blood pressure, antihyperten- blood pressure control (41). In addition, inhibitors, angiotensin receptor blockers
sive treatment reduced the risk of stroke, patients with orthostatic hypotension, (ARBs), and spironolactone are contra-
n
retinopathy, and albuminuria, but effects substantial comorbidity, functional lim- indicated as they may cause fetal dam-
on other ASCVD outcomes and heart itations, or polypharmacy may be at high age. Antihypertensive drugs known to be
tio
failure were not evident. Taken together, risk of adverse effects, and some patients effective and safe in pregnancy include
these meta-analyses consistently show may prefer higher blood pressure targets methyldopa, labetalol, and long-acting
a
that treating patients with baseline blood to enhance quality of life. Patients with nifedipine, while hydralzine may be con-
pressure $140 mmHg to targets ,140
ci
low absolute cardiovascular risk (10-year sidered in the acute management of
mmHg is beneficial, while more-intensive ASCVD risk ,15%) or with a history of hypertension in pregnancy or severe
so
targets may offer additional (though adverse effects of intensive blood pres- preeclampsia (45). Diuretics are not rec-
probably less robust) benefits. sure control or at high risk of such ommended for blood pressure control in
adverse effects should have a higher pregnancy but may be used during late-
As
Individualization of Treatment Targets blood pressure target. In such patients, stage pregnancy if needed for volume
Patients and clinicians should engage in a blood pressure target of ,140/90 control (45,46). The American College of
a shared decision-making process to de- mmHg is recommended, if it can be safely Obstetricians and Gynecologists also rec-
s
termine individual blood pressure tar- attained. ommends that postpartum patients with
gets (17). This approach acknowledges gestational hypertension, preeclampsia,
that the benefits and risks of intensive
blood pressure targets are uncertain and te
Pregnancy and Antihypertensive
Medications
and superimposed preeclampsia have
their blood pressures observed for
be
may vary across patients and is consis- There are few randomized controlled 72 h in the hospital and for 7–10 days
tent with a patient-focused approach to trials of antihypertensive therapy in preg- postpartum. Long-term follow-up is rec-
ia
care that values patient priorities and nant women with diabetes. A 2014 ommended for these women as they
provider judgment (35). Secondary anal- Cochrane systematic review of antihy- have increased lifetime cardiovascular
risk (47). See Section 14 “Management
D
yses of ACCORD BP and SPRINT suggest pertensive therapy for mild to moder-
that clinical factors can help determine ate chronic hypertension that included of Diabetes in Pregnancy” (https://doi
individuals more likely to benefit and 49 trials and over 4,700 women did not .org/10.2337/dc20-S014) for additional
an
less likely to be harmed by intensive find any conclusive evidence for or information.
blood pressure control (36). against blood pressure treatment to
Absolute benefit from blood pres- reduce the risk of preeclampsia for
ic
Treatment Strategies
sure reduction correlated with absolute the mother or effects on perinatal out- Lifestyle Intervention
er
(11,37). Extrapolation of these studies tension in Pregnancy Study (CHIPS) (43) .120/80 mmHg, lifestyle inter-
suggests that patients with diabetes enrolled mostly women with chronic vention consists of weight loss if
may also be more likely to benefit hypertension. In CHIPS, targeting a di- overweight or obese, a Dietary
from intensive blood pressure control astolic blood pressure of 85 mmHg dur- Approaches to Stop Hyperten-
19
when they have high absolute cardio- ing pregnancy was associated with sion (DASH)-style eating pattern
vascular risk. Therefore, it may be rea- reduced likelihood of developing accel- including reducing sodium and
sonable to target blood pressure erated maternal hypertension and no increasing potassium intake,
20
,130/80 mmHg among patients with demonstrable adverse outcome for in- moderation of alcohol intake,
diabetes and either clinically diag- fants compared with targeting a higher and increased physical activity. A
©
nosed cardiovascular disease (particu- diastolic blood pressure. The mean sys-
larly stroke, which was significantly tolic blood pressure achieved in the Lifestyle management is an important
reduced in ACCORD BP) or 10-year more intensively treated group was component of hypertension treatment
ASCVD risk $15%, if it can be attained 133.1 6 0.5 mmHg, and the mean di- because it lowers blood pressure, enhan-
safely. This approach is consistent with astolic blood pressure achieved in that ces the effectiveness of some antihyper-
guidelines from the American College of group was 85.3 6 0.3 mmHg. Therefore, tensive medications, promotes other
Cardiology/American Heart Association, current evidence supports controlling aspects of metabolic and vascular health,
which advocate a blood pressure target blood pressure to these levels, with a and generally leads to few adverse effects.
,130/80 mmHg for all patients, with or target of #135/85 mmHg. A similar Lifestyle therapy consists of reducing ex-
without diabetes (38). approach is supported by the Interna- cess body weight through caloric restric-
Potential adverse effects of antihyper- tional Society for the Study of Hyperten- tion, restricting sodium intake (,2,300
tensive therapy (e.g., hypotension, sion in Pregnancy, which specifically mg/day), increasing consumption of fruits
care.diabetesjournals.org Cardiovascular Disease and Risk Management S115
and vegetables (8–10 servings per day) the combination of an ACE inhibitor or
patients with diabetes and uri-
and low-fat dairy products (2–3 servings ARB and a direct renin inhibitor, is not
nary albumin-to-creatinine ra-
per day), avoiding excessive alcohol con- recommended given the lack of added
tio $300 mg/g creatinine A or
sumption (no more than 2 servings per ASCVD benefit and increased rate of
30–299 mg/g creatinine. B If
day in men and no more than 1 serving per adverse eventsdnamely, hyperkalemia,
one class is not tolerated, the
day in women) (48), and increasing ac- syncope, and acute kidney injury (AKI)
other should be substituted. B
tivity levels (49). (60–62). Titration of and/or addition of
10.13 For patients treated with an ACE
These lifestyle interventions are rea- further blood pressure medications
inhibitor, angiotensin receptor
n
sonable for individuals with diabetes and should be made in a timely fashion to
blocker, or diuretic, serum cre-
overcome clinical inertia in achieving
tio
mildly elevated blood pressure (systolic
atinine/estimated glomerular fil-
.120 mmHg or diastolic .80 mmHg) blood pressure targets.
tration rate and serum potassium
and should be initiated along with phar- Bedtime Dosing. Growing evidence sug-
levels should be monitored at
a
macologic therapy when hypertension is gests that there is an association be-
least annually. B
diagnosed (Fig. 10.1) (49). A lifestyle tween the absence of nocturnal blood
ci
therapy plan should be developed in Initial Number of Antihypertensive pressure dipping and the incidence of
so
collaboration with the patient and dis- Medications. Initial treatment for people ASCVD. A meta-analysis of randomized
cussed as part of diabetes management. with diabetes depends on the severity clinical trials found a small benefit of
of hypertension (Fig. 10.1). Those with evening versus morning dosing of anti-
As
Pharmacologic Interventions blood pressure between 140/90 mmHg hypertensive medications with regard to
and 159/99 mmHg may begin with a blood pressure control but had no data
Recommendations
single drug. For patients with blood on clinical effects (63). In two subgroup
10.8 Patients with confirmed office-
pressure $160/100 mmHg, initial phar-
s
analyses of a single subsequent random-
based blood pressure $140/
macologic treatment with two antihy- ized controlled trial, moving at least one
te
90 mmHg should, in addition
pertensive medications is recommended antihypertensive medication to bedtime
to lifestyle therapy, have prompt
in order to more effectively achieve significantly reduced cardiovascular events,
be
initiation and timely titration of
adequate blood pressure control (50–52). but results were based on a small num-
pharmacologic therapy to achieve
Single-pill antihypertensive combinations ber of events (64).
blood pressure goals. A
ia
channel blockers (57). For patients cular events and death (67). Therefore,
10.10 Treatment for hypertension serum creatinine and potassium should
with albuminuria (urine albumin-to-
should include drug classes
creatinine ratio [UACR] $30 mg/g), initial be monitored during treatment with an
Am
n
a tio
ci
so
As
s
te
be
ia
D
an
ic
er
Am
19
20
©
Figure 10.1—Recommendations for the treatment of confirmed hypertension in people with diabetes. *An ACE inhibitor (ACEi) or angiotensin receptor
blocker (ARB) is suggested to treat hypertension for patients with urine albumin-to-creatinine ratio 30–299 mg/g creatinine and strongly
recommended for patients with urine albumin-to-creatinine ratio $300 mg/g creatinine. **Thiazide-like diuretic; long-acting agents shown to
reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred. ***Dihydropyridine calcium channel blocker (CCB). BP, blood
pressure. Adapted from de Boer et al. (17).
drugs belonging to different classes at medication nonadherence, white coat should be identified and addressed (Fig.
adequate doses. Prior to diagnosing re- hypertension, and secondary hyperten- 10.1). Mineralocorticoid receptor antag-
sistant hypertension, a number of other sion. In general, barriers to medication onists are effective for management of
conditions should be excluded, including adherence (such as cost and side effects) resistant hypertension in patients with
care.diabetesjournals.org Cardiovascular Disease and Risk Management S117
type 2 diabetes when added to existing increasing plant stanols/sterols, n-3 fatty effects occur. There is evidence for ben-
treatment with an ACE inhibitor or ARB, acids, and viscous fiber (such as in oats, efit from even extremely low, less than
thiazide-like diuretic, and dihydropyri- legumes, and citrus) intake (76). Glyce- daily statin doses (78).
dine calcium channel blocker (69). mic control may also beneficially modify
Mineralocorticoid receptor antagonists plasma lipid levels, particularly in pa- STATIN TREATMENT
also reduce albuminuria and have addi- tients with very high triglycerides and Primary Prevention
tional cardiovascular benefits (70–73). poor glycemic control. See Section 5 Recommendations
However, adding a mineralocorticoid re- “Facilitating Behavior Change and Well- 10.19 For patients with diabetes aged
n
ceptor antagonist to a regimen including being to Improve Health Outcomes” 40–75 years without atheroscle-
an ACE inhibitor or ARB may increase the (https://doi.org/10.2337/dc20-S010) for ad-
tio
rotic cardiovascular disease, use
risk for hyperkalemia, emphasizing the ditional nutrition information. moderate-intensity statin ther-
importance of regular monitoring for apy in addition to lifestyle ther-
Ongoing Therapy and Monitoring
a
serum creatinine and potassium in these apy. A
With Lipid Panel
10.20 For patients with diabetes
ci
patients, and long-term outcome studies
are needed to better evaluate the role of Recommendations aged 20–39 years with addi-
so
mineralocorticoid receptor antagonists 10.17 In adults not taking statins or tional atherosclerotic cardiovas-
in blood pressure management. other lipid-lowering therapy, it cular disease risk factors, it may be
is reasonable to obtain a lipid reasonable to initiate statin ther-
As
LIPID MANAGEMENT profile at the time of diabetes apy in addition to lifestyle
Lifestyle Intervention diagnosis, at an initial medical therapy. C
evaluation, and every 5 years 10.21 In patients with diabetes at
Recommendations
s
thereafter if under the age of higher risk, especially those
10.15 Lifestyle modification focusing
40 years, or more frequently if with multiple atherosclerotic
te
on weight loss (if indicated);
indicated. E cardiovascular disease risk fac-
application of a Mediterranean
10.18 Obtain a lipid profile at initia- tors or aged 50–70 years, it is
be
style or Dietary Approaches
tion of statins or other lipid- reasonable to use high-inten-
to Stop Hypertension (DASH)
lowering therapy, 4–12 weeks sity statin therapy. B
eating pattern; reduction of
10.22 In adults with diabetes and
ia
lesterol (,40 mg/dL [1.0 lipid panel should also be obtained imme-
mmol/L] for men, ,50 mg/dL added to lifestyle therapy. A
diately before initiating statin therapy.
[1.3 mmol/L] for women). C 10.24 For patients with diabetes and
Once a patient is taking a statin, LDL
20
atherosclerotic cardiovascular
cholesterol levels should be assessed 4–
disease considered very high
Lifestyle intervention, including weight 12 weeks after initiation of statin therapy,
risk using specific criteria, if
©
loss (74), increased physical activity, and after any change in dose, and on an in-
LDL cholesterol is $70 mg/dL
medical nutrition therapy, allows some dividual basis (e.g., to monitor for medica-
on maximally tolerated statin
patients to reduce ASCVD risk factors. tion adherence and efficacy). If LDL
dose, consider adding additional
Nutrition intervention should be tailored cholesterol levels are not responding in
LDL-lowering therapy (such as
according to each patient’s age, diabetes spite of medication adherence, clinical
ezetimibe or PCSK9 inhibitor).
type, pharmacologic treatment, lipid judgment is recommended to determine
A Ezetimibe may be preferred
levels, and medical conditions. the need for and timing of lipid panels. In
due to lower cost.
Recommendations should focus on individual patients, the highly variable LDL
10.25 For patients who do not toler-
application of a Mediterranean style cholesterol–lowering response seen with
ate the intended intensity, the
diet (75) or Dietary Approaches to Stop statins is poorly understood (77). Clini-
maximally tolerated statin dose
Hypertension (DASH) eating pattern, re- cians should attempt to find a dose or
should be used. E
ducing saturated and trans fat intake and alternative statin that is tolerable if side
S118 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
the only dose of statin that a patient can it may also be reasonable to add ezeti-
10.26 In adults with diabetes aged
tolerate. For patients who do not tolerate mibe to maximally tolerated statin ther-
.75 years already on statin
the intended intensity of statin, the apy if needed to reduce LDL cholesterol
therapy, it is reasonable to
maximally tolerated statin dose should levels by 50% or more (12). The evidence
continue statin treatment. B
be used. is lower for patients aged .75 years;
10.27 In adults with diabetes aged .75
As in those without diabetes, absolute relatively few older patients with diabe-
years, it may be reasonable to
reductions in ASCVD outcomes (CHD tes have been enrolled in primary pre-
initiate statin therapy after dis-
death and nonfatal MI) are greatest in vention trials. However, heterogeneity
cussion of potential benefits and
n
people with high baseline ASCVD risk by age has not been seen in the relative
risks. C
(known ASCVD and/or very high LDL benefit of lipid-lowering therapy in tri-
tio
10.28 Statin therapy is contraindi-
cholesterol levels), but the overall benefits als that included older participants
cated in pregnancy. B
of statin therapy in people with diabetes (80,87,88), and because older age con-
a
Initiating Statin Therapy Based on Risk at moderate or even low risk for ASCVD fers higher risk, the absolute benefits are
ci
Patients with type 2 diabetes have an are convincing (89,90). The relative ben- actually greater (80,92). Moderate-in-
increased prevalence of lipid abnormalities, efit of lipid-lowering therapy has been tensity statin therapy is recommended
so
contributing to their high risk of ASCVD. uniform across most subgroups tested in patients with diabetes who are 75
Multiple clinical trials have demonstrated (80,88), including subgroups that varied years or older. However, the risk-benefit
with respect to age and other risk factors. profile should be routinely evaluated in
As
the beneficial effects of statin therapy on
this population, with downward titra-
ASCVD outcomes in subjects with and Primary Prevention (Patients Without
ASCVD) tion of dose performed as needed. See
without CHD (79,80). Subgroup analyses
For primary prevention, moderate-dose sta- Section 12 “Older Adults” (https://doi
of patients with diabetes in larger trials
s
tin therapy is recommended for those .org/10.2337/dc20-S012) for more de-
(81–85) and trials in patients with diabetes
tails on clinical considerations for this
te
(86,87) showed significant primary and 40 years and older (82,89,90), though
high-intensity therapy may be consid- population.
secondary prevention of ASCVD events
Age <40 Years and/or Type 1 Diabetes. Very
be
and CHD death in patients with diabetes. ered on an individual basis in the context
little clinical trial evidence exists for
Meta-analyses, including data from over of additional ASCVD risk factors. The
patients with type 2 diabetes under
18,000 patients with diabetes from 14 ran- evidence is strong for patients with di-
ia
for each mmol/L (39 mg/dL) reduction in who also have multiple other coronary Heart Protection Study (lower age limit
LDL cholesterol (88). risk factors have increased risk, equiva- 40 years), the subgroup of ;600 patients
Accordingly, statins are the drugs of lent to that of those with ASCVD. As such, with type 1 diabetes had a proportion-
ic
choice for LDL cholesterol lowering and recent guidelines recommend that in ately similar, although not statistically
cardioprotection. Table 10.2 shows the patients with diabetes who are at higher
er
high-intensity statin therapy will achieve it is reasonable to prescribe high-intensity treatment approaches should be consid-
approximately a $50% reduction in LDL statin therapy (12,91). Furthermore, for ered for patients with type 1 or type 2
cholesterol, and moderate-intensity sta- patients with diabetes whose ASCVD risk diabetes, particularly in the presence
tin regimens achieve 30–49% reductions is $20%, i.e., an ASCVD risk equivalent, of other cardiovascular risk factors. Pa-
19
in LDL cholesterol. Low-dose statin ther- the same high-intensity statin therapy is tients below the age of 40 have lower
apy is generally not recommended in recommended as for those with docu- risk of developing a cardiovascular event
patients with diabetes but is sometimes mented ASCVD (12). In those individuals, over a 10-year horizon; however, their
20
Table 10.2—High-intensity and moderate-intensity statin therapy* or cardiovascular death is high. For
High-intensity statin therapy Moderate-intensity statin therapy patients who are younger than 40 years
(lowers LDL cholesterol by $50%) (lowers LDL cholesterol by 30–49%) of age and/or have type 1 diabetes
Atorvastatin 40–80 mg Atorvastatin 10–20 mg
with other ASCVD risk factors, it is rec-
Rosuvastatin 20–40 mg Rosuvastatin 5–10 mg ommended that the patient and health
Simvastatin 20–40 mg care provider discuss the relative bene-
Pravastatin 40–80 mg fits and risks and consider the use
Lovastatin 40 mg of moderate-intensity statin therapy.
Fluvastatin XL 80 mg Please refer to “Type 1 Diabetes
Pitavastatin 1–4 mg Mellitus and Cardiovascular Dis-
*Once-daily dosing. XL, extended release.
ease: A Scientific Statement From
the American Heart Association and
care.diabetesjournals.org Cardiovascular Disease and Risk Management S119
American Diabetes Association” (93) Guidelines (12) for recommendations for feature who were receiving their maxi-
for additional discussion. primary and secondary prevention and for mally tolerated statin therapy (two-
statin and combination treatmentin adults thirds were on high-intensity statin)
Secondary Prevention (Patients With with diabetes (97). butwhostill had LDLcholesterol $70mg/dL
ASCVD) or non-HDL cholesterol $100 mg/dL (95).
Because risk is high in patients with Combination Therapy for LDL Patients were randomized to receive sub-
ASCVD, intensive therapy is indicated Cholesterol Lowering cutaneous injections of evolocumab (either
and has been shown to be of benefit Statins and Ezetimibe 140 mg every 2 weeks or 420 mg every
n
in multiple large randomized cardiovas- The IMProved Reduction of Outcomes: month based on patient preference)
cular outcomes trials (88,92,94,95). High- Vytorin Efficacy International Trial versus placebo. Evolocumab reduced
tio
intensity statin therapy is recommended (IMPROVE-IT) was a randomized controlled LDL cholesterol by 59% from a me-
for all patients with diabetes and ASCVD. trial in 18,144 patients comparing the dian of 92 to 30 mg/dL in the treatment
a
This recommendation is based on the addition of ezetimibe to simvastatin arm.
therapy versus simvastatin alone. Indi-
ci
Cholesterol Treatment Trialists’ Collab- During the median follow-up of 2.2
oration involving 26 statin trials, of viduals were $50 years of age, had years, the composite outcome of cardio-
so
which 5 compared high-intensity versus experienced a recent acute coronary vascular death, MI, stroke, hospitaliza-
moderate-intensity statins. Together, syndrome (ACS), and were treated for tion for angina, or revascularization
they found reductions in nonfatal car- an average of 6 years. Overall, the ad- occurred in 11.3% vs. 9.8% of the placebo
As
diovascular events with more intensive dition of ezetimibe led to a 6.4% relative and evolocumab groups, respectively,
therapy, in patients with and without benefit and a 2% absolute reduction in representing a 15% relative risk reduc-
diabetes (80,84,94). major adverse cardiovascular events, tion (P , 0.001). The combined end
with the degree of benefit being directly
s
Over the past few years, there have point of cardiovascular death, MI, or
been multiple large randomized trials proportional to the change in LDL cho- stroke was reduced by 20%, from
investigating the benefits of adding
nonstatin agents to statin therapy, in- te
lesterol, which was 70 mg/dL in the statin
group on average and 54 mg/dL in the
7.4% to 5.9% (P , 0.001). Importantly,
similar benefits were seen in a prespe-
be
cluding those that evaluated further combination group (92). In those with cified subgroup of patients with diabe-
lowering of LDL cholesterol with eze- diabetes (27% of participants), the com- tes, comprising 11,031 patients (40% of
bination of moderate-intensity simvas-
ia
inhibitors (95). Each trial found a sig- showed a significant reduction of major
nificant benefit in the reduction of adverse cardiovascular events with an Fractions or Targets
ASCVD events that was directly related absolute risk reduction of 5% (40% vs.
an
Recommendations
to the degree of further LDL cholesterol 45% cumulative incidence at 7 years) and 10.29 For patients with fasting tri-
lowering. These large trials included a a relative risk reduction of 14% (hazard glyceride levels $500 mg/dL,
significant number of participants with ratio [HR] 0.86 [95% CI 0.78–0.94]) over
ic
with ASCVD who are on high-intensity alone (96). sider medical therapy to reduce
(and maximally tolerated) statin the risk of pancreatitis. C
therapy and have an LDL chole- 10.30 In adults with moderate hyper-
Am
efit, safety, and cost. Definition of very participants who were at high risk for (obesity and metabolic syn-
high-risk patients with ASCVD includes ASCVD demonstrated an average reduc- drome), secondary factors
the use of specific criteria (major tion in LDL cholesterol ranging from
20
lege of Cardiology/American Heart patients with ASCVD or familial hyper- and medications that raise tri-
Association multisociety guideline on cholesterolemia who are receiving max- glycerides. C
the management of blood cholesterol imally tolerated statin therapy but
10.31 In patients with atherosclerotic
for further details regarding this def- require additional lowering of LDL cho-
cardiovascular disease or other
inition of risk (12). lesterol (98,99).
cardiovascular risk factors on a
Please see 2018 AHA/ACC/AACVPR/ The effects of PCSK9 inhibition on
statin with controlled LDL cho-
AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/ ASCVD outcomes was investigated in
lesterol but elevated trigly-
NLA/PCNA Guideline on the Manage- the Further Cardiovascular Outcomes
cerides (135–499 mg/dL), the
ment of Blood Cholesterol: Executive Research With PCSK9 Inhibition in Sub-
addition of icosapent ethyl can
Summary: A Report of the American jects With Elevated Risk (FOURIER)
be considered to reduce cardio-
College of Cardiology/American Heart trial, which enrolled 27,564 patients with
vascular risk. A
Association Task Force on Clinical Practice prior ASCVD and an additional high-risk
S120 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
Hypertriglyceridemia should be ad- that for statin therapy (103). In a large [1.3 mmol/L]), and triglyceride levels of
dressed with dietary and lifestyle trial in patients with diabetes, fenofi- 150–400 mg/dL (1.7–4.5 mmol/L) to
changes including weight loss and ab- brate failed to reduce overall cardiovas- statin therapy plus extended-release ni-
stinence from alcohol (101). Severe cular outcomes (104). acin or placebo. The trial was halted early
hypertriglyceridemia (fasting triglycer- due to lack of efficacy on the primary
ides $500 mg/dL and especially .1,000 Other Combination Therapy ASCVD outcome (first event of the com-
mg/dL) may warrant pharmacologic ther- posite of death from CHD, nonfatal MI,
Recommendations
apy (fibric acid derivatives and/or fish ischemic stroke, hospitalization for an
10.32 Statin plus fibrate combination
n
oil) to reduce the risk of acute pancre- ACS, or symptom-driven coronary or
therapy has not been shown to
atitis. Moderate- or high-intensity statin cerebral revascularization) and a possible
tio
improve atherosclerotic car-
therapy should also be used as indicated increase in ischemic stroke in those on
diovascular disease outcomes
to reduce risk of cardiovascular events combination therapy (108).
and is generally not recom-
a
(see STATIN TREATMENT ). In patients with The much larger Heart Protection
mended. A
ci
moderate hypertriglyceridemia, lifestyle Study 2–Treatment of HDL to Reduce
10.33 Statin plus niacin combination
interventions, treatment of secondary the Incidence of Vascular Events (HPS2-
therapy has not been shown to
so
factors, and avoidance of medications THRIVE) trial also failed to show a benefit
provide additional cardiovas-
that might raise triglycerides are recom- of adding niacin to background statin
cular benefit above statin ther-
mended. therapy (109). A total of 25,673 patients
As
apy alone, may increase the
The Reduction of Cardiovascular with prior vascular disease were random-
risk of stroke with additional
Events with Icosapent Ethyl–Intervention ized to receive 2 g of extended-release
side effects, and is generally
Trial (REDUCE-IT) enrolled 8,179 adults niacin and 40 mg of laropiprant (an
not recommended. A
s
receiving statin therapy with mod- antagonist of the prostaglandin D2 re-
erately elevated triglycerides (135– ceptor DP1 that has been shown to
499 mg/dL, median baseline of 216
mg/dL) who had either established car- te
Statin and Fibrate Combination Therapy
Combination therapy (statin and fibrate)
improve adherence to niacin therapy)
versus a matching placebo daily and
be
diovascular disease (secondary preven- is associated with an increased risk for followed for a median follow-up period
tion cohort) or diabetes plus at least one abnormal transaminase levels, myositis, of 3.9 years. There was no significant
and rhabdomyolysis. The risk of rhabdo-
ia
other cardiovascular risk factor (primary difference in the rate of coronary death,
prevention cohort). Patients were ran- myolysis is more common with higher MI, stroke, or coronary revascularization
doses of statins and renal insufficiency
D
demonstrating a 25% relative risk reduc- pared with fenofibrate) (105). was associated with an increased inci-
tion (P , 0.001) for the primary end point In the ACCORD study, in patients dence of new-onset diabetes (absolute
composite of cardiovascular death, non- with type 2 diabetes who were at high excess, 1.3 percentage points; P , 0.001)
ic
fatal myocardial infarction, nonfatal risk for ASCVD, the combination of fe- and disturbances in diabetes control
nofibrate and simvastatin did not reduce
er
infarction, or nonfatal stroke was re- pared with simvastatin alone. Prespeci- tinal system, musculoskeletal system,
duced by 26% (P , 0.001). Additional fied subgroup analyses suggested skin, and, unexpectedly, infection and
ischemic end points were significantly heterogeneity in treatment effects bleeding.
lower in the icosapent ethyl group than in with possible benefit for men with Therefore, combination therapy with
both a triglyceride level $204 mg/dL
19
the placebo group, including cardiovas- a statin and niacin is not recommended
cular death, which was reduced by 20% (2.3 mmol/L) and an HDL cholesterol given the lack of efficacy on major
(P 5 0.03). The proportions of patients level #34 mg/dL (0.9 mmol/L) (106). ASCVD outcomes and increased side
20
experiencing adverse events and serious A prospective trial of a newer fibrate effects.
adverse events were similar between the in this specific population of patients is
ongoing (107).
©
active and placebo treatment groups. It Diabetes Risk With Statin Use
should be noted that data are lacking Statin and Niacin Combination Therapy Several studies have reported a modestly
with other n-3 fatty acids, and results of The Atherothrombosis Intervention in increased risk of incident diabetes with
the REDUCE-IT trial should not be ex- Metabolic Syndrome With Low HDL/ statin use (110,111), which may be lim-
trapolated to other products (102). High Triglycerides: Impact on Global ited to those with diabetes risk factors.
Low levels of HDL cholesterol, often Health Outcomes (AIM-HIGH) trial ran- An analysis of one of the initial studies
associated with elevated triglyceride lev- domized over 3,000 patients (about suggested that although statin use was
els, are the most prevalent pattern of one-third with diabetes) with established associated with diabetes risk, the cardio-
dyslipidemia in individuals with type 2 ASCVD, low LDL cholesterol levels vascular event rate reduction with sta-
diabetes. However, the evidence for the (,180 mg/dL [4.7 mmol/L]), low HDL tins far outweighed the risk of incident
use of drugs that target these lipid frac- cholesterol levels (men ,40 mg/dL diabetes even for patients at highest
tions is substantially less robust than [1.0 mmol/L] and women ,50 mg/dL risk for diabetes (112). The absolute
care.diabetesjournals.org Cardiovascular Disease and Risk Management S121
risk increase was small (over 5 years of outcome was major bleeding (i.e., in-
clopidogrel (75 mg/day) should
follow-up, 1.2% of participants on placebo tracranial hemorrhage, sight-threatening
be used. B
developed diabetes and 1.5% on rosuvas- bleeding in the eye, gastrointestinal bleed-
10.36 Dual antiplatelet therapy (with
tatin developed diabetes) (112). A meta- ing, or other serious bleeding). During a
low-dose aspirin and a P2Y12
analysis of 13 randomized statin trials with mean follow-up of 7.4 years, there was a
inhibitor) is reasonable for a
91,140 participants showed an odds ratio of significant 12% reduction in the primary
year after an acute coronary
1.09 for a new diagnosis of diabetes, so that efficacy end point (8.5% vs. 9.6%; P 5
syndrome A and may have
(on average) treatment of 255 patients with 0.01). In contrast, major bleeding was
benefits beyond this period. B
n
statins for 4 years resulted in one additional significantly increased from 3.2% to
10.37 Aspirin therapy (75–162 mg/day)
case of diabetes while simultaneously pre- 4.1% in the aspirin group (rate ratio
tio
may be considered as a pri-
venting 5.4 vascular events among those 1.29; P 5 0.003), with most of the excess
mary prevention strategy in
255 patients (111). being gastrointestinal bleeding and other
those with diabetes who are
a
extracranial bleeding. There were no sig-
at increased cardiovascular
ci
Lipid-Lowering Agents and Cognitive nificant differences by sex, weight, or
risk, after a comprehensive dis-
Function duration of diabetes or other baseline
cussion with the patient on the
so
Although concerns regarding a potential factors including ASCVD risk score.
benefits versus the comparable
adverse impact of lipid-lowering agents on Two other large randomized trials of
increased risk of bleeding. A
cognitive function have been raised, sev- aspirin for primary prevention, in pa-
As
eral lines of evidence point against this tients without diabetes (ARRIVE [Aspirin
association, as detailed in a 2018 European Risk Reduction to Reduce Risk of Initial Vascular Events])
Atherosclerosis Society Consensus Panel Aspirin has been shown to be effective in (126) and in the elderly (ASPREE [Aspirin
s
statement (113). First, there are three large reducing cardiovascular morbidity and in Reducing Events in the Elderly]) (127),
randomized trials of statin versus placebo mortality in high-risk patients with pre- which included 11% with diabetes, found
where specific cognitive tests were per-
formed, and no differences were seen
te
vious MI or stroke (secondary preven-
tion) and is strongly recommended. In
no benefit of aspirin on the primary efficacy
end point and an increased risk of bleeding.
be
between statin and placebo (114–117). primary prevention, however, among In ARRIVE, with 12,546 patients over a pe-
In addition, no change in cognitive function patients with no previous cardiovascular riod of 60 months follow-up, the primary
has been reported in studies with the
ia
events, its net benefit is more contro- end point occurred in 4.29% vs. 4.48% of
addition of ezetimibe (92) or PCSK9 inhib- versial (120,121). patients in the aspirin versus placebo
groups (HR 0.96; 95% CI 0.81–1.13; P 5
D
recent systematic review of the U.S. Food significant reduction in overall ASCVD of patients in the aspirin group vs. 0.46% in
and Drug Administration’s (FDA’s) post- end points, raising questions about the the placebo group (HR 2.11; 95% CI 1.36–
marketing surveillance databases, ran- efficacy of aspirin for primary preven- 3.28; P 5 0.0007). In ASPREE, including
ic
domized controlled trials, and cohort, tion in people with diabetes, although 19,114 persons, for the rate of cardiovas-
er
case-control, and cross-sectional studies some sex differences were suggested cular disease (fatal CHD, MI, stroke, or
evaluating cognition in patients receiving (122–124). hospitalization for heart failure) after a
statins found that published data do not The Antithrombotic Trialists’ Collabo- median of 4.7 years of follow-up, the rates
Am
reveal an adverse effect of statins on ration published an individual patient– per 1,000 person-years were 10.7 vs. 11.3
cognition (119). Therefore, a concern level meta-analysis (120) of the six large events in aspirin vs. placebo groups (HR
that statins or other lipid-lowering agents trials of aspirin for primary prevention 0.95; 95% CI 0.83–1.08). The rate of major
might cause cognitive dysfunction or in the general population. These trials hemorrhage per 1,000 person-years was
19
dementia is not currently supported collectively enrolled over 95,000 partic- 8.6 events vs. 6.2 events, respectively (HR
by evidence and should not deter their ipants, including almost 4,000 with di- 1.38; 95% CI 1.18–1.62; P , 0.001).
use in individuals with diabetes at high abetes. Overall, they found that aspirin Thus, aspirin appears to have a modest
20
risk for ASCVD (119). reduced the risk of serious vascular effect on ischemic vascular events, with
events by 12% (relative risk 0.88 [95% the absolute decrease in events depend-
©
ANTIPLATELET AGENTS CI 0.82–0.94]). The largest reduction was ing on the underlying ASCVD risk. The
for nonfatal MI, with little effect on CHD main adverse effect is an increased risk
Recommendations
death (relative risk 0.95 [95% CI 0.78–
10.34 Use aspirin therapy (75–162 of gastrointestinal bleeding. The excess
1.15]) or total stroke.
mg/day) as a secondary pre- risk may be as high as 5 per 1,000 per
Most recently, the ASCEND (A Study of
vention strategy in those with year in real-world settings. However, for
Cardiovascular Events iN Diabetes) trial
diabetes and a history of ath- adults with ASCVD risk .1% per year, the
randomized 15,480 patients with diabe-
erosclerotic cardiovascular number of ASCVD events prevented will
tes but no evident cardiovascular disease
disease. A be similar to the number of episodes
to aspirin 100 mg daily or placebo (125).
10.35 For patients with atheroscle- of bleeding induced, although these com-
The primary efficacy end point was vas-
rotic cardiovascular disease and
cular death, MI, or stroke or transient plications do not have equal effects on
documented aspirin allergy,
ischemic attack. The primary safety long-term health (128).
S122 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
n
(e.g., older age, anemia, renal disease) not sensitive to the effects of aspirin
unexplained dyspnea, chest dis-
(129–132).Noninvasiveimagingtechniques (137). “Aspirin resistance” has been de-
tio
comfort); signs or symptoms of
such as coronary calcium scoring may scribed in patients with diabetes when
associated vascular disease in-
potentially help further tailor aspirin ther- measured by a variety of ex vivo and in
cluding carotid bruits, transient
a
apy, particularly in those at low risk (133) vitro methods (platelet aggregometry,
ischemic attack, stroke, claudi-
ci
(134). For patients over the age of 70 years measurement of thromboxane B2)
cation, or peripheral arterial
(with or without diabetes), the balance (138), but other studies suggest no im-
disease; or electrocardiogram
so
appears to have greater risk than benefit pairment in aspirin response among pa-
abnormalities (e.g., Q waves). E
(125,127). Thus, for primary prevention, the tients with diabetes (139). A recent trial
use of aspirin needs to be carefully con- suggested that more frequent dosing
As
sidered and may generally not be recom- regimens of aspirin may reduce platelet Treatment
mended. Aspirin may be considered in the reactivity in individuals with diabetes
Recommendations
context of high cardiovascular risk with low (140); however, these observations
10.40 In patients with known athero-
s
bleeding risk, but generally not in older alone are insufficient to empirically rec-
sclerotic cardiovascular dis-
adults. Aspirin therapy for primary preven- ommend that higher doses of aspirin
te
ease, consider ACE inhibitor
tion may be considered in the context of be used in this group at this time. Another
or angiotensin receptor blocker
shared decision-making, which carefully recent meta-analysis raised the hypoth-
be
therapy to reduce the risk of
weighs the cardiovascular benefits with esis that low-dose aspirin efficacy is
cardiovascular events. B
the fairly comparable increase in risk of reduced in those weighing more than
10.41 In patients with prior myocardial
ia
bleeding. For patients with documented 70 kg (141); however, the ASCEND trial
infarction, b-blockers should
ASCVD, use of aspirin for secondary pre- found benefit of low-dose aspirin in
be continued for at least 2 years
D
vention has far greater benefit than risk; for those in this weight range, which would
after the event. B
this indication, aspirin is still recommended thus not validate this suggested hypoth-
10.42 In patients with type 2 diabe-
(120). esis (125). It appears that 75–162 mg/day
an
low risk of ASCVD (such as men and Antagonist Use mated glomerular filtration
women aged ,50 years with diabetes A P2Y12 receptor antagonist in com- rate remains .30 mL/min
er
with no other major ASCVD risk factors) bination with aspirin is reasonable for but should be avoided in
as the low benefit is likely to be out- at least 1 year in patients following an unstable or hospitalized pa-
Am
weighed by the risks of bleeding. Clinical ACS and may have benefits beyond this tients with heart failure. B
judgment should be used for those at period. Evidence supports use of either 10.43 Among patients with type 2
intermediate risk (younger patients with ticagrelor or clopidogrel if no percu- diabetes who have established
one or more risk factors or older patients taneous coronary intervention was atherosclerotic cardiovascular
disease or established kidney
19
with no risk factors) until further research performed and clopidogrel, ticagrelor,
is available. Patients’ willingness to un- or prasugrel if a percutaneous coro- disease, a sodium–glucose co-
dergo long-term aspirin therapy should nary intervention was performed transporter 2 inhibitor or glu-
20
also be considered (135). Aspirin use in (142). In patients with diabetes and cagon-like peptide 1 receptor
patients aged ,21 years is generally prior MI (1–3 years before), adding agonist with demonstrated
contraindicated due to the associated ticagrelor to aspirin significantly re- cardiovascular disease benefit
©
risk of Reye syndrome. duces the risk of recurrent ischemic (Table 10.3B and Table 10.3C)
events including cardiovascular and is recommended as part of the
Aspirin Dosing
CHD death (143). glucose-lowering regimen. A
Average daily dosages used in most
10.43a In patients with type 2 diabe-
clinical trials involving patients with di-
CARDIOVASCULAR DISEASE tes and established atheroscle-
abetes ranged from 50 mg to 650 mg but
rotic cardiovascular disease,
were mostly in the range of 100–325 mg/ Screening
multiple atherosclerotic cardio-
day. There is little evidence to support
Recommendations vascular disease risk factors,
any specific dose, but using the lowest
10.38 In asymptomatic patients, rou- or diabetic kidney disease, a
possible dose may help to reduce side
tinescreening for coronaryartery sodium–glucose cotransporter
effects (136). In the U.S., the most com-
disease is not recommended as it 2 inhibitor with demonstrated
mon low-dose tablet is 81 mg. Although
care.diabetesjournals.org Cardiovascular Disease and Risk Management S123
n
strated no clinical benefit to routine While clear benefit exists for ACE inhib-
or multiple risk factors for
screening of asymptomatic patients itor or ARB therapy in patients with
tio
atherosclerotic cardiovascular
with type 2 diabetes and normal diabetic kidney disease or hypertension,
disease, a glucagon-like pep-
ECGs (151). Despite abnormal myo- the benefits in patients with ASCVD in the
tide 1 receptor agonist with
a
cardial perfusion imaging in more than absence of these conditions are less
demonstrated cardiovascular
one in five patients, cardiac outcomes
ci
clear, especially when LDL cholesterol
benefit is recommended to
were essentially equal (and very low) in is concomitantly controlled (158,159).
reduce the risk of major ad-
so
screened versus unscreened patients. In patients with prior MI, active angina,
verse cardiovascular events. A
Accordingly, indiscriminate screening is or HFrEF, b-blockers should be used
10.43c In patients with type 2 diabe-
not considered cost-effective. Studies (160).
As
tes and established heart
have found that a risk factor–based
failure, a sodium–glucose co-
approach to the initial diagnostic evalu- GLUCOSE-LOWERING THERAPIES
transporter 2 inhibitor may be
ation and subsequent follow-up for cor- AND CARDIOVASCULAR
considered to reduce risk of
s
onary artery disease fails to identify OUTCOMES
heart failure hospitalization. C
which patients with type 2 diabetes
te
In 2008, the FDA issued a guidance for
will have silent ischemia on screening industry to perform cardiovascular out-
CARDIAC TESTING tests (152,153).
be
comes trials for all new medications for
Candidates for advanced or invasive car- Any benefit of newer noninvasive cor- the treatment for type 2 diabetes amid
diac testing include those with 1) typical onary artery disease screening methods, concerns of increased cardiovascular risk
ia
or atypical cardiac symptoms and 2) an such as computed tomography calcium (161). Previously approved diabetes med-
abnormal resting electrocardiogram scoring and computed tomography an- ications were not subject to the guidance.
D
(ECG). Exercise ECG testing without or giography, to identify patient subgroups Recently published cardiovascular out-
with echocardiography may be used as for different treatment strategies re- comes trials have provided additional
the initial test. In adults with diabetes $ mains unproven in asymptomatic pa- data on cardiovascular outcomes in pa-
an
40 years of age, measurement of coro- tients with diabetes, though research tients with type 2 diabetes with car-
nary artery calcium is also reasonable for is ongoing. Although asymptomatic pa- diovascular disease or at high risk for
cardiovascular risk assessment. Pharma- tients with diabetes with higher coronary cardiovascular disease (see Table 10.3A,
ic
cologic stress echocardiography or nu- disease burden have more future cardiac Table 10.3B, and Table 10.3C). Cardio-
er
clear imaging should be considered in events (148,154,155), the role of these vascular outcomes trials of dipeptidyl
individuals with diabetes in whom resting tests beyond risk stratification is not peptidase 4 (DPP-4) inhibitors have all,
ECG abnormalities preclude exercise clear.
Am
pharmacologic stress echocardiography (156), their routine use leads to radia- SGLT2 Inhibitor Trials
or nuclear imaging. tion exposure and may result in unnec- The BI 10773 (Empagliflozin) Cardiovas-
essary invasive testing such as coronary cular Outcome Event Trial in Type 2 Di-
20
SCREENING ASYMPTOMATIC angiography and revascularization pro- abetes Mellitus Patients (EMPA-REG
PATIENTS cedures. The ultimate balance of ben- OUTCOME) trial was a randomized, dou-
©
The screening of asymptomatic patients efit, cost, and risks of such an approach ble-blind trial that assessed the effect
with high ASCVD risk is not recommen- in asymptomatic patients remains con- of empagliflozin, an SGLT2 inhibitor,
ded (144), in part because these high-risk troversial, particularly in the modern versus placebo on cardiovascular out-
patients should already be receiving in- setting of aggressive ASCVD risk factor comes in 7,020 patients with type 2
tensive medical therapydan approach control. diabetes and existing cardiovascular dis-
that provides similar benefit as invasive ease. Study participants had a mean age
revascularization (145,146). There is also LIFESTYLE AND PHARMACOLOGIC of 63 years, 57% had diabetes for more
some evidence that silent ischemia may INTERVENTIONS than 10 years, and 99% had established
reverse over time, adding to the contro- Intensive lifestyle intervention focusing cardiovascular disease. EMPA-REG OUT-
versy concerning aggressive screening on weight loss through decreased caloric COME showed that over a median fol-
strategies (147). In prospective studies, intake and increased physical activity as low-up of 3.1 years, treatment reduced
coronary artery calcium has been performed in the Action for Health in the composite outcome of MI, stroke,
S124 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
Table 10.3A—Cardiovascular outcomes trials of available antihyperglycemic medications completed after the issuance of the FDA
2008 guidelines: DPP-4 inhibitors
SAVOR-TIMI 53 (181) EXAMINE (186) TECOS (183) CARMELINA (184,187)
(n 5 16,492) (n 5 5,380) (n 5 14,671) (n 5 6,979)
Intervention Saxagliptin/placebo Alogliptin/placebo Sitagliptin/placebo Linagliptin/placebo
Main inclusion criteria Type 2 diabetes and history Type 2 diabetes and ACS Type 2 diabetes Type 2 diabetes and high CV and
of or multiple risk factors within 15–90 days before and preexisting renal risk
for CVD randomization CVD
n
A1C inclusion criteria (%) $6.5 6.5–11.0 6.5–8.0 6.5–10.0
tio
Age (years)†† 65.1 61.0 65.4 65.8
Race (% white) 75.2 72.7 67.9 80.2
Sex (% male) 66.9 67.9 70.7 62.9
a
Diabetes duration (years)†† 10.3 7.1 11.6 14.7
ci
Median follow-up (years) 2.1 1.5 3.0 2.2
Statin use (%) 78 91 80 71.8
so
Metformin use (%) 70 66 82 54.8
Prior CVD/CHF (%) 78/13 100/28 74/18 57/26.8
As
Mean baseline A1C (%) 8.0 8.0 7.2 7.9
Mean difference in A1C 20.3^ 20.3^ 20.3^ 20.36^
between groups at end of
treatment (%)
s
Year started/reported 2010/2013 2009/2013 2008/2015 2013/2018
te
Primary outcome§ 3-point MACE 3-point MACE 4-point MACE 3-point MACE
1.00 (0.89–1.12) 0.96 (95% UL #1.16) 0.98 (0.89–1.08) 1.02 (0.89–1.17)
be
Key secondary outcome§ Expanded MACE 4-point MACE 3-point MACE Kidney composite (ESRD,
1.02 (0.94–1.11) 0.95 (95% UL #1.14) 0.99 (0.89–1.10) sustained $40% decrease in
eGFR, or renal death)
ia
1.04 (0.89–1.22)
Cardiovascular death§ 1.03 (0.87–1.22) 0.85 (0.66–1.10) 1.03 (0.89–1.19) 0.96 (0.81–1.14)
D
Unstable angina 1.19 (0.89–1.60) 0.90 (0.60–1.37) 0.90 (0.70–1.16) 0.87 (0.57–1.31)
hospitalization§
ic
All-cause mortality§ 1.11 (0.96–1.27) 0.88 (0.71–1.09) 1.01 (0.90–1.14) 0.98 (0.84–1.13)
Worsening nephropathy§|| 1.08 (0.88–1.32) d d Kidney composite (see above)
er
d, not assessed/reported; ACS, acute coronary syndrome; CHF, congestive heart failure; CV, cardiovascular; CVD, cardiovascular disease; DPP-4,
dipeptidyl peptidase 4; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GLP-1, glucagon-like peptide 1; HF, heart failure;
MACE, major adverse cardiac event; MI, myocardial infarction; UL, upper limit. Data from this table was adapted from Cefalu et al. (188) in
Am
the January 2018 issue of Diabetes Care. ††Age was reported as means in all trials except EXAMINE, which reported medians; diabetes
duration was reported as means in all trials except SAVOR-TIMI 53 and EXAMINE, which reported medians. §Outcomes reported as
hazard ratio (95% CI). ||Worsening nephropathy is defined as as doubling of creatinine level, initiation of dialysis, renal transplantation, or
creatinine .6.0 mg/dL (530 mmol/L) in SAVOR-TIMI 53. Worsening nephropathy was a prespecified exploratory adjudicated outcome in
SAVOR-TIMI 53. ^Significant difference in A1C between groups (P , 0.05).
19
20
and cardiovascular death by 14% (abso- assessed 1) the cardiovascular effects of drug (163). Thereafter, the postapproval
lute rate 10.5% vs. 12.1% in the placebo treatment in patients at high risk for CANVAS-Renal (CANVAS-R) trial was
©
group, HR in the empagliflozin group major adverse cardiovascular events, started in 2014. Combining both of these
0.86; 95% CI 0.74–0.99; P 5 0.04 for and 2) the impact of canagliflozin therapy trials, 10,142 participants with type 2
superiority) and cardiovascular death by on cardiorenal outcomes in patients with diabetes were randomized to canagliflo-
38% (absolute rate 3.7% vs. 5.9%, HR diabetes-related chronic kidney disease zin or placebo and were followed for an
0.62; 95% CI 0.49–0.77; P , 0.001) (8). have been conducted (162). First, the average 3.6 years. The mean age of
The FDA added an indication for empa- Canagliflozin Cardiovascular Assessment patients was 63 years, and 66% had a
gliflozin to reduce the risk of major Study (CANVAS) Program integrated data history of cardiovascular disease. The
adverse cardiovascular death in adults from two trials. The CANVAS trial that combined analysis of the two trials found
with type 2 diabetes and cardiovascular started in 2009 was partially unblinded that canagliflozin significantly reduced
disease. prior to completion because of the the composite outcome of cardiovascu-
Two large outcomes trials of the SGLT2 need to file interim cardiovascular out- lar death, MI, or stroke versus placebo
inhibitor canagliflozin that separately comes data for regulatory approval of the (occurring in 26.9 vs. 31.5 participants
care.diabetesjournals.org Cardiovascular Disease and Risk Management S125
Table 10.3B—Cardiovascular outcomes trials of available antihyperglycemic medications completed after the issuance
of the FDA 2008 guidelines: GLP-1 receptor agonists
Harmony
ELIXA (170) LEADER (165) SUSTAIN-6 (166)* EXSCEL (171) Outcomes (168) REWIND (169)
(n 5 6,068) (n 5 9,340) (n 5 3,297) (n 5 14,752) (n 5 9,463) (n 5 9,901)
Intervention Lixisenatide/ Liraglutide/ Semaglutide/ Exenatide QW/ Albiglutide/ Dulaglutide/
placebo placebo placebo placebo placebo placebo
Main inclusion Type 2 diabetes Type 2 diabetes Type 2 diabetes and Type 2 diabetes Type 2 diabetes Type 2 diabetes
n
criteria and history of and preexisting preexisting CVD, with or without with preexisting and prior
ACS (,180 days) CVD, CKD, or HF HF, or CKD at preexisting CVD CVD ASCVD event
tio
at $50 years of $50 years of age or risk factors
age or CV risk at or CV risk at $60 for ASCVD
$60 years of years of age
a
age
ci
A1C inclusion 5.5–11.0 $7.0 $7.0 6.5–10.0 $7.0 #9.5
criteria (%)
so
Age (years)†† 60.3 64.3 64.6 62 64.1 66.2
Race (% white) 75.2 77.5 83.0 75.8 84.8 75.7
As
Sex (% male) 69.3 64.3 60.7 62 69.4 53.7
Diabetes duration 9.3 12.8 13.9 12 13.8 10.5
(years)††
Median follow-up 2.1 3.8 2.1 3.2 1.6 5.4
s
(years)
te
Statin use (%) 93 72 73 74 84.0 66
Metformin use (%) 66 76 73 77 73.6 81
be
Prior CVD/CHF (%) 100/22 81/18 60/24 73.1/16.2 100/20.2 32/9
Mean baseline 7.7 8.7 8.7 8.0 8.7 7.4
A1C (%)
ia
groups at end of
treatment (%)
Year started/ 2010/2015 2010/2016 2013/2016 2010/2017 2015/2018 2011/2019
an
reported
Primary outcome§ 4-point MACE 3-point MACE 3-point MACE 3-point MACE 3-point MACE 3-point MACE
1.02 (0.89–1.17) 0.87 (0.78–0.97) 0.74 (0.58–0.95) 0.91 (0.83–1.00) 0.78 (0.68–0.90) 0.88 (0.79–0.99)
ic
Key secondary Expanded MACE Expanded MACE Expanded MACE Individual Expanded MACE Composite
outcome§ (0.90–1.11) 0.88 (0.81–0.96) 0.74 (0.62–0.89) components of (with urgent microvascular
er
angina) outcome)
0.78 (0.69–0.90) 0.87 (0.79–0.95)
CV death or HF
hospitalization
0.85 (0.70–1.04)
19
Individual
components of
MACE (see below)
20
Cardiovascular 0.98 (0.78–1.22) 0.78 (0.66–0.93) 0.98 (0.65–1.48) 0.88 (0.76–1.02) 0.93 (0.73–1.19) 0.91 (0.78–1.06)
death§
MI§ 1.03 (0.87–1.22) 0.86 (0.73–1.00) 0.74 (0.51–1.08) 0.97 (0.85–1.10) 0.75 (0.61–0.90) 0.96 (0.79–1.15)
©
Stroke§ 1.12 (0.79–1.58) 0.86 (0.71–1.06) 0.61 (0.38–0.99) 0.85 (0.70–1.03) 0.86 (0.66–1.14) 0.76 (0.61–0.95)
HF 0.96 (0.75–1.23) 0.87 (0.73–1.05) 1.11 (0.77–1.61) 0.94 (0.78–1.13) d 0.93 (0.77–1.12)
hospitalization§
Unstable angina 1.11 (0.47–2.62) 0.98 (0.76–1.26) 0.82 (0.47–1.44) 1.05 (0.94–1.18) d 1.14 (0.84–1.54)
hospitalization§
Continued on p. S126
S126 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
Table 10.3B—Continued
Harmony
ELIXA (170) LEADER (165) SUSTAIN-6 (166)* EXSCEL (171) Outcomes (168) REWIND (169)
(n 5 6,068) (n 5 9,340) (n 5 3,297) (n 5 14,752) (n 5 9,463) (n 5 9,901)
All-cause 0.94 (0.78–1.13) 0.85 (0.74–0.97) 1.05 (0.74–1.50) 0.86 (0.77–0.97) 0.95 (0.79–1.16) 0.90 (0.80–1.01)
mortality§
Worsening d 0.78 (0.67–0.92) 0.64 (0.46–0.88) d d 0.85 (0.77–0.93)
nephropathy§||
n
d, not assessed/reported; ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CHF, congestive heart failure; CKD, chronic
tio
kidney disease; CV, cardiovascular; CVD, cardiovascular disease; GLP-1, glucagon-like peptide 1; HF, heart failure; MACE, major adverse cardiac event;
MI, myocardial infarction. Data from this table was adapted from Cefalu et al. (188) in the January 2018 issue of Diabetes Care. *Powered to rule out
a hazard ratio of 1.8; superiority hypothesis not prespecified. ††Age was reported as means in all trials; diabetes duration was reported as means in all
trials except EXSCEL, which reported medians. †A1C change of 0.66% with 0.5 mg and 1.05% with 1 mg dose of semaglutide. §Outcomes reported as
a
hazard ratio (95% CI). ||Worsening nephropathy is defined as the new onset of urine albumin-to-creatinine ratio .300 mg/g creatinine or a doubling of
ci
the serum creatinine level and an estimated glomerular filtration rate of ,45 mL/min/1.73 m2, the need for continuous renal replacement therapy, or
death from renal disease in LEADER and SUSTAIN-6 and as new macroalbuminuria, a sustained decline in estimated glomerular filtration rate of 30% or
more from baseline, or chronic renal replacement therapy in REWIND. Worsening nephropathy was a prespecified exploratory adjudicated outcome in
so
LEADER, SUSTAIN-6, and REWIND.^Significant difference in A1C between groups (P , 0.05).
As
per 1,000 patient-years; HR 0.86 [95% CI failure (HR 0.61 [95% CI 0.47–0.80]), and lowerrateofhospitalizationforheartfailure
0.75–0.97]). The specific estimates for of the composite of cardiovascular death
s
(HR 0.73; 95% CI 0.61–0.88). No difference
canagliflozin versus placebo on the or hospitalization for heart failure (HR was seen in cardiovascular death between
primary composite cardiovascular out-
come were HR 0.88 (0.75–1.03) for
te
0.69 [95% CI 0.57–0.83]). In terms of
safety, no significant increase in lower-
groups.
be
the CANVAS trial and 0.82 (0.66–1.01) limb amputations, fractures, acute kidney GLP-1 Receptor Agonist Trials
for CANVAS-R, with no heterogeneity injury, or hyperkalemia was noted for The Liraglutide Effect and Action in Di-
found between trials. Of note, there canagliflozin relative to placebo in CRE-
ia
putation with canagliflozin (6.3 vs. 3.4 ketoacidosis was noted, however, with randomized, double-blind trial that
participants per 1,000 patient-years; HR 2.2 and 0.2 events per 1,000 patient-years assessed the effect of liraglutide, a
1.97 [95% CI 1.41–2.75]) (9). Second, the noted in the canagliflozin and placebo glucagon-like peptide 1 (GLP-1) receptor
an
Canagliflozin and Renal Events in Dia- groups, respectively (HR 10.80 [95% CI agonist, versus placebo on cardiovascular
betes with Established Nephropathy 1.39–83.65]) (162). outcomes in 9,340 patients with type 2
Clinical Evaluation (CREDENCE) trial ran- The Dapagliflozin Effect on Cardiovascu- diabetes at high risk for cardiovascular
ic
domized 4,401 patients with type 2 lar Events–Thrombosis in Myocardial In- disease or with cardiovascular disease.
er
diabetes and chronic diabetes-related farction 58 (DECLARE-TIMI 58) trial was Study participants had a mean age of
kidney disease (UACR .300 mg/g and another randomized, double-blind trial that 64 years and a mean duration of diabetes
estimated glomerular filtration rate 30 assessed the effects of dapagliflozin versus of nearly 13 years. Over 80% of study
Am
to ,90 mL/min/1.73 m2) to canagliflozin placebo on cardiovascular and renal out- participants had established cardiovascu-
100 mg daily or placebo (162). The pri- comes in 17,160 patients with type 2 di- lar disease. After a median follow-up of 3.8
mary outcome was a composite of end- abetes and established ASCVD or multiple years, LEADER showed that the primary
stage kidney disease (ESKD), doubling of risk factors for atherosclerotic cardiovascu- composite outcome (MI, stroke, or car-
19
serum creatinine, or death from renal or lar disease (164). Study participants had a diovascular death) occurred in fewer
cardiovascular causes. The trial was stop- mean age of 64 years, with ;40% of study participants in the treatment group
ped early due to conclusive evidence of participants having established ASCVD at (13.0%) when compared with the pla-
20
efficacy identified during a prespecified baselineda characteristic of this trial that cebo group (14.9%) (HR 0.87; 95% CI
interim analysis with no unexpected differs from other large cardiovascular trials 0.78–0.97; P , 0.001 for noninferiority;
P 5 0.01 for superiority). Deaths from
©
safety signals. The risk of the primary where a majority of participants had estab-
composite outcome was 30% lower with lished cardiovascular disease. DECLARE- cardiovascular causes were significantly
canagliflozin treatment when compared TIMI 58 met the prespecified criteria for reduced in the liraglutide group (4.7%)
with placebo (HR 0.70 [95% CI 0.59– noninferiority to placebo with respect to compared with the placebo group
0.82]). Moreover, it reduced the prespe- MACE but did not show a lower rate of (6.0%) (HR 0.78; 95% CI 0.66–0.93;
cified end point of ESKD alone by 32% (HR MACE when compared with placebo (8.8% P 5 0.007) (165). The FDA approved
0.68 [95% CI 0.54–0.86]). Canagliflozin in the dapagliflozin group and 9.4% in the the use of liraglutide to reduce the risk of
was additionally found to have a lower placebo group; HR 0.93; 95% CI 0.84–1.03; major adverse cardiovascular events,
risk of the composite of cardiovascular P 5 0.17). A lower rate of cardiovascular including heart attack, stroke, and car-
death, myocardial infarction, or stroke death or hospitalization for heart failure diovascular death, in adults with type 2
(HR 0.80 [95% CI 0.67–0.95]), as well as was noted (4.9% vs. 5.8%; HR 0.83; 95% CI diabetes and established cardiovascu-
lower risk of hospitalizations for heart 0.73–0.95; P 5 0.005), which reflected a lar disease.
care.diabetesjournals.org Cardiovascular Disease and Risk Management S127
Table 10.3C—Cardiovascular outcomes trials of available antihyperglycemic medications completed after the issuance
of the FDA 2008 guidelines: SGLT2 inhibitors
EMPA-REG
CANVAS (9)
OUTCOME (8) DECLARE-TIMI 58 (164)
(n 5 7,020) (n 5 4,330) (n 5 5,812) (n 5 17,160)
Intervention Empagliflozin/ Canagliflozin/ Dapagliflozin/placebo
placebo placebo
Main inclusion criteria Type 2 diabetes Type 2 diabetes Type 2 diabetes and
n
and and preexisting established ASCVD or
preexisting CVD at $30 multiple risk factors
tio
CVD years of age for ASCVD
or .2 CV risk
factors at $50
a
years of age
ci
A1C inclusion criteria (%) 7.0–10.0 7.0–10.5 $6.5
Age (years)†† 63.1 63.3 64.0
so
Race (% white) 72.4 78.3 79.6
Sex (% male) 71.5 64.2 62.6
As
Diabetes duration (years)†† 57% .10 13.5 11.0
Median follow-up (years) 3.1 5.7 2.1 4.2
Statin use (%) 77 75 75 (statin or ezetimibe use)
Metformin use (%) 74 77 82
s
Prior CVD/CHF (%) 99/10 65.6/14.4 40/10
Mean baseline A1C (%)
Mean difference in A1C between 20.3^‡
8.1 8.2
20.58^
te 8.3
20.43^
be
groups at end of treatment (%)
Year started/reported 2010/2015 2009/2017 2013/2018
Primary outcome§ 3-point MACE 3-point MACE Progression to 3-point MACE 0.93 (0.84–
ia
0.83 (0.73–0.95)
Key secondary outcome§ 4-point MACE All-cause and CV 40% reduction in Death from any cause
an
0.76 (0.67–0.87)
Cardiovascular death§ 0.62 (0.49–0.77) 0.96 (0.77–1.18)¶ 0.98 (0.82–1.17)
Am
0.87 (0.72–1.06)#
MI§ 0.87 (0.70–1.09) 0.85 (0.65–1.11) 0.85 (0.61–1.19) 0.89 (0.77–1.01)
Stroke§ 1.18 (0.89–1.56) 0.97 (0.70–1.35) 0.82 (0.57–1.18) 1.01 (0.84–1.21)
HF hospitalization§ 0.65 (0.50–0.85) 0.77 (0.55–1.08) 0.56 (0.38–0.83) 0.73 (0.61–0.88)
19
Data from this table was adapted from Cefalu et al. (188) in the January 2018 issue of Diabetes Care. **On the basis of prespecified outcomes, the renal
outcomes are not viewed as statistically significant. ††Age was reported as means in all trials; diabetes duration was reported as means in all trials except
EMPA-REG OUTCOME, which reported as percentage of population with diabetes duration .10 years, and DECLARE-TIMI 58, which reported median.
‡AlC change of 0.30 in EMPA-REG OUTCOME is based on pooled results for both doses (i.e., 0.24% for 10 mg and 0.36% for 25 mg of empagliflozin).
§Outcomes reported as hazard ratio (95% CI). ||Worsening nephropathy is defined as the new onset of urine albumin-to-creatinine ratio .300 mg/g
creatinine or a doubling of the serum creatinine level and an estimated glomerular filtration rate of ,45 mL/min/1.73 m2, the need for continuous
renal replacement therapy, or death from renal disease in EMPA-REG OUTCOME and as $40% decrease in estimated glomerular filtration rate
to ,60 mL/min/1.73 m2, ESRD, or death from renal cause in DECLARE-TIMI 58. Worsening nephropathy was a prespecified exploratory adjudicated
outcome in DECLARE-TIMI 58 but not in EMPA-REG OUTCOME. ¶Truncated data set (prespecified in treating hierarchy as the principal data set
for analysis for superiority of all-cause mortality and cardiovascular death in the CANVAS Program).^Significant difference in A1C between groups
(P , 0.05). #Nontruncated data set. ‡‡Truncated integrated data set (refers to pooled data from CANVAS after 20 November 2012 plus CANVAS-R;
prespecified in treating hierarchy as the principal data set for analysis for superiority of all-cause mortality and cardiovascular death in the
CANVAS Program). ##Nontruncated integrated data (refers to pooled data from CANVAS, including before 20 November 2012 plus CANVAS-R).
S128 Cardiovascular Disease and Risk Management Diabetes Care Volume 43, Supplement 1, January 2020
Results from a moderate-sized trial of blind, placebo-controlled trial that as- disease) were randomized to receive ex-
another GLP-1 receptor agonist, sema- sessed the effect of the once-weekly tended-release exenatide 2 mg or pla-
glutide, were consistent with the LEADER GLP-1 receptor agonist dulaglutide ver- cebo and followed for a median of 3.2
trial (166). Semaglutide is a once-weekly sus placebo on MACE in ;9,990 patients years. The primary end point of cardio-
GLP-1 receptor agonist approved by the with type 2 diabetes at risk for cardio- vascular death, MI, or stroke occurred in
FDA for the treatment of type 2 diabetes. vascular events or with a history of 839 patients (11.4%; 3.7 events per
The Trial to Evaluate Cardiovascular and cardiovascular disease (169). Study par- 100 person-years) in the exenatide
Other Long-term Outcomes With Sem- ticipants had a mean age of 66 years and a group and in 905 patients (12.2%; 4.0
n
aglutide in Subjects With Type 2 Diabe- mean duration of diabetes of ;10 years. events per 100 person-years) in the
tes (SUSTAIN-6) was the initial randomized Approximately 32% of participants had placebo group (HR 0.91; 95% CI 0.83–
tio
trial powered to test noninferiority of prior history of atherosclerotic cardio- 1.00; P , 0.001 for noninferiority) but
semaglutide for the purpose of initial vascular events at baseline. After a me- was not superior to placebo with re-
a
regulatory approval. In this study, 3,297 dian follow-up of 5.4 years, the primary spect to the primary end point (P 5 0.06 for
ci
patients with type 2 diabetes were ran- composite outcome of nonfatal myocar- superiority). However, all-cause mortality
domized to receive once-weekly semaglu- dial infarction, nonfatal stroke, or death was lower in the exenatide group (HR 0.86
so
tide (0.5 mg or 1.0 mg) or placebo for from cardiovascular causes occurred [95% CI 0.77–0.97]). The incidence of acute
2 years. The primary outcome (the first in 12.0% and 13.4% of participants in pancreatitis, pancreatic cancer, medullary
occurrence of cardiovascular death, non- the dulaglutide and placebo treatment thyroid carcinoma, and serious adverse
As
fatal MI, or nonfatal stroke) occurred in groups, respectively (HR 0.88; 95% CI events did not differ significantly between
108 patients (6.6%) in the semaglutide 0.79–0.99; P 5 0.026). These findings the two groups.
group vs. 146 patients (8.9%) in the placebo equated to incidence rates of 2.4 and 2.7 In summary, there are now numerous
group (HR 0.74; 95% CI 0.58–0.95; P ,
s
events per 100 person-years, respec- large randomized controlled trials re-
0.001). More patients discontinued treat- tively. The results were consistent across porting statistically significant reductions
ment in the semaglutide group because of
adverse events, mainly gastrointestinal. te
the subgroups of patients with and with-
out prior history of CV events. All-cause
in cardiovascular events for three of the
FDA-approved SGLT2 inhibitors (empa-
be
The cardiovascular effects of the oral for- mortality did not differ between groups gliflozin, canagliflozin, and dapagliflozin)
mulation of semaglutide compared with (P 5 0.067). and four FDA-approved GLP-1 receptor
ia
placebo have been assessed in Peptide The Evaluation of Lixisenatide in Acute agonists (liraglutide, albiglutide [al-
Innovation for Early Diabetes Treatment Coronary Syndrome (ELIXA) trial studied though that agent was removed from
D
(PIONEER) 6, a preapproval trial designed the once-daily GLP-1 receptor agonist the market for business reasons], sem-
to rule out an unacceptable increase in in lixisenatide on cardiovascular outcomes aglutide [lower risk of cardiovascular
cardiovascular risk. In this trial of 3,183 in patients with type 2 diabetes who had events in a moderate-sized clinical trial
an
patients with type 2 diabetes and high had a recent acute coronary event (170). but one not powered as a cardiovascu-
cardiovascular risk followed for a me- A total of 6,068 patients with type 2 lar outcomes trial], and dulaglutide).
dian of 15.9 months, oral semaglutide diabetes with a recent hospitalization for Meta-analyses of the trials reported
ic
was noninferior to placebo for the pri- MI or unstable angina within the previous to date suggest that GLP-1 receptor
er
mary composite outcome of cardiovas- 180 days were randomized to receive agonists and SGLT2 inhibitors reduce risk
cular death, nonfatal myocardial infarction, lixisenatide or placebo in addition to of atherosclerotic major adverse cardio-
or nonfatal stroke (HR 0.79; 95% CI 0.57– standard care and were followed for a vascular events to a comparable degree
Am
1.11; P , 0.001 for noninferiority) (167). median of ;2.1 years. The primary out- in patients with type 2 diabetes and
The cardiovascular effects of this formu- come of cardiovascular death, MI, stroke, established ASCVD (172). SGLT2 inhib-
lation of semaglutide will be further tested or hospitalization for unstable angina itors also appear to reduce risk of heart
in a large, longer-term outcomes trial. occurred in 406 patients (13.4%) in the failure hospitalization and progression
19
The Harmony Outcomes trial random- lixisenatide group vs. 399 (13.2%) in the of kidney disease in patients with es-
ized 9,463 patients with type 2 diabetes placebo group (HR 1.2 [95% CI 0.89– tablished ASCVD, multiple risk factors
and cardiovascular disease to once- 1.17]), which demonstrated the noninfer- for ASCVD, or diabetic kidney disease
20
weekly subcutaneous albiglutide or match- iority of lixisenatide to placebo (P , 0.001) (173). In patients with type 2 diabetes
ing placebo, in addition to their standard but did not show superiority (P 5 0.81). and established ASCVD, multiple ASCVD
©
care. Over a median duration of 1.6 years, The Exenatide Study of Cardiovascu- risk factors, or diabetic kidney disease,
the GLP-1 receptor agonist reduced the risk lar Event Lowering (EXSCEL) trial also an SGLT2 inhibitor with demonstrated
of cardiovascular death, MI, or stroke to an reported results with the once-weekly cardiovascular benefit is recommended
incidence rate of 4.6 events per 100 per- GLP-1 receptor agonist extended-release to reduce the risk of major adverse
son-years in the albiglutide group vs. 5.9 exenatide and found that major adverse cardiovascular events and heart failure
events in the placebo group (HR ratio 0.78, cardiovascular events were numeri- hospitalization. In patients with type 2
P 5 0.0006 for superiority) (168). This cally lower with use of extended-release diabetes and established ASCVD or mul-
agent is not currently available for clinical exenatide compared with placebo, al- tiple risk factors for ASCVD, a glucagon-
use. though this difference was not statisti- like peptide 1 receptor agonist with
The Researching Cardiovascular Events cally significant (171). A total of 14,752 demonstrated cardiovascular benefit is
With a Weekly Incretin in Diabetes (RE- patients with type 2 diabetes (of whom recommended to reduce the risk of ma-
WIND) trial was a randomized, double- 10,782 [73.1%] had previous cardiovascular jor adverse cardiovascular events. For
care.diabetesjournals.org Cardiovascular Disease and Risk Management S129
many patients, use of either an SGLT2 compared with placebo (Table 10.3B) 5. Cavender MA, Steg PG, Smith SC Jr, et al.;
inhibitor or a GLP-1 receptor agonist to (165,166,169–171). REACH Registry Investigators. Impact of diabetes
mellitus on hospitalization for heart failure,
reduce cardiovascular risk is appropri- Reduced incidence of heart failure has cardiovascular events, and death: outcomes at
ate. It is unknown whether use of both been observed with the use of SGLT2 4 years from the Reduction of Atherothrombosis
classes of drugs will provide an additive inhibitors (162,164). In EMPA-REG OUT- for Continued Health (REACH) registry. Circula-
cardiovascular outcomes benefit. COME, the addition of empagliflozin to tion 2015;132:923–931
standard care led to a significant 35% 6. McAllister DA, Read SH, Kerssens J, et al.
Incidence of hospitalization for heart failure and
Glucose-Lowering Therapies and reduction in hospitalization for heart case-fatality among 3.25 million people with and
n
Heart Failure failure compared with placebo (8). Al- without diabetes mellitus. Circulation 2018;138:
As many as 50% of patients with type 2 though the majority of patients in the
tio
2774–2786
diabetes may develop heart failure (174). study did not have heart failure at base- 7. Lam CSP, Voors AA, de Boer RA, Solomon SD,
Data on the effects of glucose-lowering line, this benefit was consistent in pa- van Veldhuisen DJ. Heart failure with preserved
a
ejection fraction: from mechanisms to therapies.
agents on heart failure outcomes have tients with and without a history of heart Eur Heart J 2018;39:2780–2792
ci
demonstrated that thiazolidinediones failure (10). Similarly, in CANVAS and 8. Zinman B, Wanner C, Lachin JM, et al.; EMPA-
have a strong and consistent relationship DECLARE-TIMI 58, there were 33% and REG OUTCOME Investigators. Empagliflozin, car-
so
with increased risk of heart failure 27% reductions in hospitalization for diovascular outcomes, and mortality in type 2
(175–177). Therefore, thiazolidinedione heart failure, respectively, with SGLT2 diabetes. N Engl J Med 2015;373:2117–2128
9. Neal B, Perkovic V, Mahaffey KW, et al.;
use should be avoided in patients with inhibitor use versus placebo (9,164).
As
CANVAS Program Collaborative Group. Canagli-
symptomatic heart failure. Restrictions to Additional data from the CREDENCE trial flozin and cardiovascular and renal events in
use of metformin in patients with med- with canagliflozin showed a 39% reduc- type 2 diabetes. N Engl J Med 2017;377:644–657
ically treated heart failure were removed tion in hospitalization for heart failure, 10. Fitchett D, Butler J, van de Borne P, et al.;
EMPA-REG OUTCOMEÒ trial investigators. Ef-
s
by the FDA in 2006 (178). In fact, obser- and 31% reduction in the composite of
fects of empagliflozin on risk for cardiovascu-
vational studies of patients with type 2 cardiovascular death or hospitalization
te
lar death and heart failure hospitalization across
diabetes and heart failure suggest that for heart failure, in a diabetic kidney dis- the spectrum of heart failure risk in the EMPA-
metformin users have better outcomes ease population with albuminuria (UACR REG OUTCOMEÒ trial. Eur Heart J 2018;39:363–
be
than patients treated with other antihy- of .300 to 5,000 mg/g) (162). These 370
perglycemic agents (179). Metformin may combined findings from four large out- 11. Blood Pressure Lowering Treatment Trialists’
Collaboration. Blood pressure-lowering treat-
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2067–2076 of the Hypertension Optimal Treatment (HOT) 188. Cefalu WT, Kaul S, Gerstein HC, et al.
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183. Green JB, Bethel MA, Armstrong PW, et al.; randomised trial. Lancet 1998;351:1755– Cardiovascular outcomes trials in type 2 diabe-
TECOS Study Group. Effect of sitagliptin on 1762 tes: where do we go from here? Reflections
cardiovascular outcomes in type 2 diabetes. N 186. White WB, Cannon CP, Heller SR, et al.; from a Diabetes Care Editors’ Expert Forum.
Engl J Med 2015;373:232–242 EXAMINE Investigators. Alogliptin after acute Diabetes Care 2018;41:14–31
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©
Diabetes Care Volume 43, Supplement 1, January 2020 S135
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Medical Care in Diabetes22020
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Diabetes Care 2020;43(Suppl. 1):S135–S151 | https://doi.org/10.2337/dc20-s011
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s
provide the components of diabetes care, general treatment goals and guidelines,
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and tools to evaluate quality of care. Members of the ADA Professional Practice
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-
be
SPPC), are responsible for updating the Standards of Care annually, or more frequently as
warranted. For a detailed description of ADA standards, statements, and reports, as well as
the evidence-grading system for ADA’s clinical practice recommendations, please refer to
ia
Screening
Am
Recommendations
11.1 At least once a year, assess urinary albumin (e.g., spot urinary albumin-to-
creatinine ratio) and estimated glomerular filtration rate (eGFR) in patients
with type 1 diabetes with duration of $5 years and in all patients with type 2
diabetes regardless of treatment. B Patients with urinary albumin .30 mg/g
19
Treatment
Recommendations
©
11.2 Optimize glucose control to reduce the risk or slow the progression of
chronic kidney disease. A
11.3 For patients with type 2 diabetes and diabetic kidney disease, consider use Suggested citation: American Diabetes Associa-
of a sodium–glucose cotransporter 2 inhibitor in patients with an estimated tion. 11. Microvascular complications and
glomerular filtration rate $30 mL/min/1.73 m2 and urinary albumin .30 foot care: Standards of Medical Care in
Diabetesd2020. Diabetes Care 2020;43(Suppl.
mg/g creatinine, particularly in those with urinary albumin .300 mg/g 1):S135–S151
creatinine, to reduce risk of chronic kidney disease (CKD) progression,
© 2019 by the American Diabetes Association.
cardiovascular events, or both. A In patients with CKD who are at increased Readers may use this article as long as the work
risk for cardiovascular events, use of a glucagon-like peptide 1 receptor is properly cited, the use is educational and
agonist may reduce risk of progression of albuminuria, cardiovascular not for profit, and the work is not altered.
events, or both (Table 9.1). C More information is available at http://www
.diabetesjournals.org/content/license.
S136 Microvascular Complications and Foot Care Diabetes Care Volume 43, Supplement 1, January 2020
n
Chronic kidney disease (CKD) is diag- Chronic Kidney Disease Epidemiology
of volume depletion. B
nosed by the persistent presence of Collaboration (CKD-EPI) equation is
tio
11.6 For people with nondialysis-
elevated urinary albumin excretion (al- generally preferred (2). eGFR is routinely
dependent chronic kidney dis-
buminuria), low estimated glomerular reported by laboratories with serum
ease, dietary protein intake should
a
filtration rate (eGFR), or other manifes- creatinine, and eGFR calculators are
be approximately 0.8 g/kg body
ci
tations of kidney damage (1,2). In this available online at nkdep.nih.gov. An
weight per day (the recommen-
section, the focus will be on CKD eGFR persistently ,60 mL/min/1.73 m2
ded daily allowance). A For pa-
so
attributed to diabetes (diabetic kidney is considered abnormal, though optimal
tients on dialysis, higher levels of
disease), which occurs in 20–40% of thresholds for clinical diagnosis are de-
dietary protein intake should be
patients with diabetes (1,3–5). CKD typ- bated in older adults (2,13).
As
considered, since malnutrition
ically develops after diabetes duration
is a major problem in some
of 10 years in type 1 diabetes but may Diagnosis of Diabetic Kidney Disease
dialysis patients. B Diabetic kidney disease is usually a clin-
be present at diagnosis of type 2 di-
11.7 In nonpregnant patients with ical diagnosis made based on the pres-
s
abetes. CKD can progress to end-stage
diabetes and hypertension, ei- ence of albuminuria and/or reduced
renal disease (ESRD) requiring dialysis
te
ther an ACE inhibitor or an eGFR in the absence of signs or symptoms
or kidney transplantation and is the
angiotensin receptor blocker of other primary causes of kidney dam-
leading cause of ESRD in the U.S. (6).
be
is recommended for those age. The typical presentation of diabetic
In addition, among people with type 1 or
with modestly elevated urinary kidney disease is considered to include a
2 diabetes, the presence of CKD mark-
albumin-to-creatinine ratio long-standing duration of diabetes, ret-
ia
(Cr) is less expensive but susceptible eGFR, or the absence of retinopathy (in
recommended for the primary type 1 diabetes) suggests alternative or
to false-negative and false-positive de-
prevention of chronic kidney additional causes of kidney disease. For
terminations as a result of variation in
20
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Figure 11.1—Risk of chronic kidney disease (CKD) progression, frequency of visits, and referral to nephrology according to glomerular filtration rate
(GFR) and albuminuria. The GFR and albuminuria grid depicts the risk of progression, morbidity, and mortality by color, from best to worst (green, yellow,
be
orange, red, dark red). The numbers in the boxes are a guide to the frequency of visits (number of times per year). Green can reflect CKD with normal
eGFR and albumin-to-creatinine ratio only in the presence of other markers of kidney damage, such as imaging showing polycystic kidney disease or
kidney biopsy abnormalities, with follow-up measurements annually; yellow requires caution and measurements at least once per year; orange requires
measurements twice per year; red requires measurements three times per year; and dark red requires measurements four times per year. These are
ia
general parameters only, based on expert opinion, and underlying comorbid conditions and disease state as well as the likelihood of impacting a change
in management for any individual patient must be taken into account. “Refer” indicates that nephrology services are recommended. *Referring
D
clinicians may wish to discuss with their nephrology service, depending on local arrangements regarding treating or referring. Reprinted with permission
from Vassalotti et al. (188).
an
eGFR $60 mL/min/1.73 m2, while stages progression and other adverse health particularly when combined with diu-
3–5 CKD have been defined by progres- outcomes) and cause of kidney damage retics or other medications that reduce
sively lower ranges of eGFR (17) (Fig. (including possible causes other than glomerular filtration; however, this
ic
11.1). At any eGFR, the degree of albu- diabetes) may also affect these decisions has not been found to be true in ran-
er
minuria is associated with risk of cardio- (20). domized clinical outcome trials of ad-
vascular disease (CVD), CKD progression, vanced kidney disease (24) or high
and mortality (7). Therefore, Kidney Acute Kidney Injury cardiovascular disease risk with normal
Am
Disease: Improving Global Outcomes Acute kidney injury (AKI) is diagnosed kidney function (25–27). Timely iden-
(KDIGO) recommends a more compre- by a 50% or greater sustained increase tification and treatment of AKI is im-
hensive CKD staging that incorporates in serum creatinine over a short period portant because AKI is associated with
albuminuria at all stages of eGFR; this of time, which is also reflected as a rapid increased risks of progressive CKD and
19
system is more closely associated with decrease in eGFR (21,22). People with other poor health outcomes (28).
risk but is also more complex and does diabetes are at higher risk of AKI than Small elevations in serum creatinine
not translate directly to treatment deci- those without diabetes (23). Other risk (up to 30% from baseline) with renin-
20
sions (2). Thus, based on the current factors for AKI include preexisting CKD, angiotensin system blockers (such as
classification system, both eGFR and the use of medications that cause ACE inhibitors and ARBs) must not be
©
albuminuria must be quantified to guide kidney injury (e.g., nonsteroidal anti- confused with AKI (29). An analysis
treatment decisions. This is also impor- inflammatory drugs), and the use of of the Action to Control Cardiovascu-
tant since eGFR levels are essential to medications that alter renal blood flow lar Risk in Diabetes Blood Pressure
modify drug dosage or restrictions of use and intrarenal hemodynamics. In partic- (ACCORD BP) trial demonstrates that those
(Fig. 11.1) (18,19). The degree of albu- ular, many antihypertensive medications randomized to intensive blood pressure
minuria may influence choice of antihy- (e.g., diuretics, ACE inhibitors, and an- lowering with up to a 30% increase in
pertensive (see Section 10 “Cardiovascular giotensin receptor blockers [ARBs]) can serum creatinine did not have any in-
Disease and Risk Management,” https:// reduce intravascular volume, renal blood crease in mortality or progressive kidney
doi.org.10.2337/dc20-S010) or glucose- flow, and/or glomerular filtration. There disease (30–32). Moreover, a measure of
lowering medications (see below). Ob- was concern that sodium–glucose co- markers for AKI showed no significant
served history of eGFR loss (which transporter 2 (SGLT2) inhibitors may increase of any markers with increased
is also associated with risk of CKD promote AKI through volume depletion, creatinine (32). Accordingly, ACE inhibitors
S138 Microvascular Complications and Foot Care Diabetes Care Volume 43, Supplement 1, January 2020
Table 11.1—Selected complications of chronic kidney disease recommended because it does not alter
Complication Medical and laboratory evaluation
glycemic measures, cardiovascular risk
measures, or the course of GFR decline (39).
Elevated blood pressure .140/90 mmHg Blood pressure, weight
Restriction of dietary sodium (to ,2,300
Volume overload History, physical examination, weight mg/day) may be useful to control blood
Electrolyte abnormalities Serum electrolytes pressure and reduce cardiovascular risk
Metabolic acidosis Serum electrolytes (40,41), and restriction of dietary potas-
Anemia Hemoglobin; iron testing if indicated sium may be necessary to control se-
n
Metabolic bone disease Serum calcium, phosphate, PTH, vitamin 25(OH)D rum potassium concentration (23,33–35).
These interventions may be most important
tio
Complications of chronic kidney disease (CKD) generally become prevalent when estimated
glomerular filtration rate falls below 60 mL/min/1.73 m2 (stage 3 CKD or greater) and become more for patients with reduced eGFR, for whom
common and severe as CKD progresses. Evaluation of elevated blood pressure and volume urinary excretion of sodium and potassium
overload should occur at every clinical contact possible; laboratory evaluations are generally
a
indicated every 6–12 months for stage 3 CKD, every 3–5 months for stage 4 CKD, and every 1– may be impaired. For patients on dialysis,
ci
3 months for stage 5 CKD, or as indicated to evaluate symptoms or changes in therapy. PTH, higher levels of dietary protein intake should
parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D. be considered, since malnutrition is a major
so
problem in some dialysis patients (42).
Recommendations for dietary sodium and
and ARBs should not be discontinued for 2 diabetes, reducing albuminuria from potassium intake should be individualized
As
minor increases in serum creatinine (,30%), levels $300 mg/g Cr has been associated on the basis of comorbid conditions, med-
in the absense of volume depletion. with improved renal and cardiovascular ication use, blood pressure, and labora-
outcomes, leading some to suggest that tory data.
medications should be titrated to min-
s
Surveillance
Albuminuria and eGFR should be mon- imize UACR. However, this approach has Glycemic Targets
itored regularly to enable timely diagno-
sis of CKD, monitor progression of CKD, te
not been formally evaluated in prospec-
tive trials. In type 1 diabetes, remission
Intensive glycemic control with the goal
of achieving near-normoglycemia has
be
detect superimposed kidney diseases of albuminuria may occur spontane- been shown in large prospective random-
including AKI, assess risk of CKD compli- ously and cohort studies evaluating ized studies to delay the onset and pro-
associations of change in albuminuria
ia
is needed. Among people with existing (43,44) and type 2 diabetes (1,45–51).
kidney disease, albuminuria and eGFR The prevalence of CKD complications Insulin alone was used to lower blood
may change due to progression of CKD, correlates with eGFR (38). When eGFR glucose in the Diabetes Control and
an
development of a separate superim- is ,60 mL/min/1.73 m2, screening for Complications Trial (DCCT)/Epidemiol-
posed cause of kidney disease, AKI, or complications of CKD is indicated (Table ogy of Diabetes Interventions and Com-
other effects of medications, as noted 11.1). Early vaccination against hepatitis plications (EDIC) study of type 1 diabetes,
ic
above. Serum potassium should also B virus is indicated in patients likely to while a variety of agents were used in
progress to ESRD (see Section 4 “Com-
er
be monitored for patients treated with clinical trials of type 2 diabetes, support-
ACE inhibitors, ARBs, and diuretics be- prehensive Medical Evaluation and As- ing the conclusion that glycemic control
cause these medications can cause hy- sessment of Comorbidities,” https://doi itself helps prevent CKD and its progres-
Am
perkalemia or hypokalemia, which are .org/10.2337/dc20-S004, for further in- sion. The effects of glucose-lowering
associated with cardiovascular risk and formation on immunization). therapies on CKD have helped define
mortality (33–35). For patients with A1C targets (see Table 6.2).
eGFR ,60 mL/min/1.73 m2, appropriate Interventions The presence of CKD affects the risks
19
medication dosing should be verified, Nutrition and benefits of intensive glycemic con-
exposure to nephrotoxins (e.g., nonste- For people with nondialysis-dependent trol and a number of specific glucose-
roidal anti-inflammatory drugs and io- CKD, dietary protein intake should be lowering medications. In the Action to
20
dinated contrast) should be minimized, ;0.8 g/kg body weight per day (the Control Cardiovascular Risk in Diabetes
and potential CKD complications should recommended daily allowance) (1). (ACCORD) trial of type 2 diabetes, ad-
be evaluated (Table 11.1).
©
Compared with higher levels of dietary verse effects of intensive glycemic con-
The need for annual quantitative as- protein intake, this level slowed GFR trol (hypoglycemia and mortality) were
sessment of albumin excretion after di- decline with evidence of a greater effect increased among patients with kidney
agnosis of albuminuria, institution of ACE over time. Higher levels of dietary pro- disease at baseline (52,53). Moreover,
inhibitors or ARB therapy, and achiev- tein intake (.20% of daily calories from there is a lag time of at least 2 years in
ing blood pressure control is a subject protein or .1.3 g/kg/day) have been type 2 diabetes to over 10 years in type 1
of debate. Continued surveillance can associated with increased albuminuria, diabetes for the effects of intensive glu-
assess both response to therapy and more rapid kidney function loss, and cose control to manifest as improved
disease progression and may aid in as- CVD mortality and therefore should be eGFR outcomes (49,54,55). Therefore, in
sessing adherence to ACE inhibitor or avoided. Reducing the amount of di- some patients with prevalent CKD and
ARB therapy. In addition, in clinical trials etary protein below the recommended substantial comorbidity, target A1C levels
of ACE inhibitors or ARB therapy in type daily allowance of 0.8 g/kg/day is not may be less intensive (1,56).
care.diabetesjournals.org Microvascular Complications and Foot Care S139
Direct Renal Effects of Glucose-Lowering constraints, metformin should be con- In addition, subgroup analyses of CANVAS
Medications sidered the first-line treatment for all and LEADER suggested that the renal
Some glucose-lowering medications also patients with type 2 diabetes, including benefits of canagliflozin and liraglutide
have effects on the kidney that are direct, those with CKD. were as great or greater for participants
i.e., not mediated through glycemia. For SGLT2 inhibitors and GLP-1 RAs should with CKD at baseline (27,66) and in CANVAS
example, SGLT2 inhibitors reduce renal be considered for patients with type 2 were similar for participants with or with-
tubular glucose reabsorption, weight, diabetes and CKD who require another out atherosclerotic cardiovascular disease
systemic blood pressure, intraglomerular drug added to metformin to attain target (ASCVD) at baseline (72).
n
pressure, and albuminuria and slow GFR A1C or cannot use or tolerate metformin. Several large clinical trials of SGLT2
loss through mechanisms that appear SGLT2 inhibitors reduce risks of CKD inhibitors focused on patients with ad-
tio
independent of glycemia (26,57–60). progression, CVD events, and hypogly- vanced CKD, and assessment of primary
Moreover, recent data support the cemia. GLP-1 RAs are suggested because renal outcomes are completed or ongo-
a
notion that SGLT2 inhibitors reduce ox- they reduce risks of CVD events and ing. Canagliflozin and Renal End points in
idative stress in the kidney by .50% and
ci
hypoglycemia and appear to possibly Diabetes with Established Nephropa-
blunt increases in angiotensinogen as slow CKD progression. thy Clinical Evaluation (CREDENCE), a
so
well as reduce NLRP3 inflammasome A number of large cardiovascular out- placebo-controlled trial of canagliflozin
activity (61–63). Glucagon-like peptide comes trials in patients with type 2 di- among 4,401 adults with type 2 diabetes,
1 receptor agonists (GLP-1 RAs) also have abetes at high risk for CVD or with UACR $300 mg/g Cr, and mean eGFR
As
direct effects on the kidney and have existing CVD examined kidney effects 56 mL/min/1.73 m2 with a mean albu-
been reported to improve renal out- as secondary outcomes. These trials minuria level of over 900 mg/day, has a
comes compared with placebo (64–67). include EMPA-REG OUTCOME [BI primary composite end point of ESRD,
Renal effects should be considered when
s
10773 (Empagliflozin) Cardiovascular doubling of serum creatinine, or renal or
selecting antihyperglycemia agents (see Outcome Event Trial in Type 2 Diabetes cardiovascular death (24,73). It was stop-
Section 9 “Pharmacologic Approaches to
Glycemic Treatment,” https://doi.org/10
te
Mellitus Patients], CANVAS (Canagliflozin
Cardiovascular Assessment Study),
ped early due to positive efficacy and
showed a 32% risk reduction for devel-
be
.2337/dc20-S009). LEADER (Liraglutide Effect and Action opment of ESRD over control (24).
in Diabetes: Evaluation of Cardiovascular Additionally, the development of the
ia
Selection of Glucose-Lowering Medications Outcome Results), and SUSTAIN-6 (Trial primary end point, which included
for Patients With Chronic Kidney Disease to Evaluate Cardiovascular and Other chronic dialysis for $30 days, kidney
transplantation or eGFR ,15 mL/min/
D
For patients with type 2 diabetes and Long-term Outcomes With Semaglutide
established CKD, special considerations in Subjects With Type 2 Diabetes) 1.73 m2 sustained for $30 days by
for the selection of glucose-lowering med- (59,64,67,71). Specifically, compared central laboratory assessment, doubling
an
ications include limitations to available with placebo, empagliflozin reduced from the baseline serum creatinine av-
medications when eGFR is diminished the risk of incident or worsening ne- erage sustained for $30 days by central
and a desire to mitigate high risks of phropathy (a composite of progression laboratory assessment, or renal death or
ic
CKD progression, CVD, and hypoglycemia to UACR .300 mg/g Cr, doubling of cardiovascular death, was reduced by
er
(68,69). Drug dosing may require modifi- serum creatinine, ESRD, or death from 30%. This benefit was on background
cation with eGFR ,60 mL/min/1.73 m2 (1). ESRD) by 39% and the risk of doubling ACE inhibitor or ARB therapy in .99% of
The U.S. Food and Drug Administration of serum creatinine accompanied by the patients (24). Moreover, in this ad-
Am
(FDA) revised its guidance for the use of eGFR #45 mL/min/1.73 m2 by 44%; vanced CKD group, there were clear
metformin in CKD in 2016 (70), recom- canagliflozin reduced the risk of progres- benefits on cardiovascular outcomes
mending use of eGFR instead of serum sion of albuminuria by 27% and the risk demonstrating a 31% reduction in car-
creatinine to guide treatment and ex- of reduction in eGFR, ESRD, or death from diovascular death or heart failure hos-
19
panding the pool of patients with kidney ESRD by 40%; liraglutide reduced the risk pitalization and a 20% reduction in
disease for whom metformin treatment of new or worsening nephropathy (a cardiovascular death, nonfatal myocar-
should be considered. The revised FDA composite of persistent macroalbumin- dial infarction, or nonfatal stroke (24,74).
20
guidance states that metformin is uria, doubling of serum creatinine, ESRD, In addition to renal effects, some
contraindicated in patients with an or death from ESRD) by 22%; and sema- SGLT2 inhibitors and GLP-1 RAs have
eGFR ,30 mL/min/1.73 m2; eGFR should
©
and cardiovascular benefits were still Cardiovascular Disease and Blood Pressure blockers (92). In a trial of people with
seen down to eGFR levels of 30 mL/ Hypertension is a strong risk factor for type 2 diabetes and normal urine albu-
min/1.73 m2 with no significant change the development and progression of CKD min excretion, an ARB reduced or sup-
in glucose (24,26,43,45,52,56,71). Most (78). Antihypertensive therapy reduces pressed the development of albuminuria
participants with CKD in these trials the risk of albuminuria (79–82), and but increased the rate of cardiovascular
also had diagnosed ASCVD at baseline, among patients with type 1 or 2 diabetes events (93). In a trial of people with type 1
though ;28% of CANVAS participants with established CKD (eGFR ,60 mL/ diabetes exhibiting neither albuminuria
with CKD did not have diagnosed min/1.73 m2 and UACR $300 mg/g Cr), nor hypertension, ACE inhibitors or ARBs
n
ASCVD (27). ACE inhibitor or ARB therapy reduces the did not prevent the development of
Based on evidence from the CREDENCE risk of progression to ESRD (83–85). diabetic glomerulopathy assessed by kid-
tio
trial and secondary analyses of cardio- Moreover, antihypertensive therapy re- ney biopsy (90) This was further sup-
vascular outcomes trials with SGLT2 duces risks of cardiovascular events (79). ported by a similar trial in patients with
a
inhibitors, cardiovascular and renal Blood pressure levels ,140/90 mmHg type 2 diabetes (91). Therefore, ACE
are generally recommended to reduce
ci
events are reduced with SGLT2 inhibitor inhibitors or ARBs are not recommended
use in patients down to an eGFR of CVD mortality and slow CKD progres- for patients without hypertension to pre-
so
30 mL/min/1.73 m2 even independent sion among all people with diabetes vent the development of CKD.
of glucose-lowering effects (75). (82). Lower blood pressure targets Two clinical trials studied the combi-
While there is clear cardiovascular risk (e.g., ,130/80 mmHg) should be con- nations of ACE inhibitors and ARBs and
As
reduction associated with GLP-1 RA use sidered for patients based on individual found no benefits on CVD or CKD, and the
in patients with type 2 diabetes and CKD, anticipated benefits and risks. Patients drug combination had higher adverse
the proof of benefit on renal outcome with CKD are at increased risk of CKD event rates (hyperkalemia and/or AKI)
progression (particularly those with al-
s
will come with the results of the ongoing (94,95). Therefore, the combined use of ACE
FLOW (A Research Study to See How buminuria) and CVD and therefore may inhibitors and ARBs should be avoided.
Semaglutide Works Compared to Pla-
cebo in People With Type 2 Diabetes te
be suitable in some cases for lower blood
pressure targets, especially in those
Mineralocorticoid receptor antago-
nists (spironolactone, eplerenone, and
be
and Chronic Kidney Disease) trial with with $300 mg/day albuminuria. finerenone) in combination with ACE
injectable semaglutide (76). As noted ACE inhibitors or ARBs are the pre- inhibitors or ARBs remain an area of
ferred first-line agent for blood pressure
ia
isting ASCVD. Renal events have been agement of resistant hypertension, have
examined, however, as both primary and 1.73 m2, and UACR $300 mg/g Cr be- been shown to reduce albuminuria in
secondary outcomes in published large cause of their proven benefits for pre- short-term studies of CKD, and may
an
trials. Also, adverse event profiles of vention of CKD progression (83–86). In have additional cardiovascular benefits
these agents must be considered. Please general, ACE inhibitors and ARBs are (96–98). There has been, however, an
refer to Table 9.1 for drug-specific considered to have similar benefits
ic
mation, for these agents. Additional levels of albuminuria (30–299 mg/g Cr), trials with clinical outcomes are needed
clinical trials focusing on CKD and car- ACE inhibitor or ARB therapy has been before recommending such therapy.
diovascular outcomes in CKD patients demonstrated to reduce progression to
Am
Referral to a Nephrologist
are ongoing and will be reported in the more advanced albuminuria ($300 mg/g
next few years. Cr) and cardiovascular events but not Consider referral to a physician experi-
For patients with type 2 diabetes and progression to ESRD (86,89). While ACE enced in the care of kidney disease when
CKD, the selection of specific agents may inhibitors or ARBs are often prescribed there is uncertainty about the etiology
19
depend on comorbidity and CKD stage. for high albuminuria without hyperten- of kidney disease, for difficult manage-
SGLT2 inhibitors may be more useful for sion, outcome trials have not been per- ment issues (anemia, secondary hyper-
patients at high risk of CKD progression formed in this setting to determine parathyroidism, metabolic bone disease,
20
(i.e., with albuminuria or a history of whether this improves renal outcomes. resistant hypertension, or electrolyte dis-
documented eGFR loss) (Fig. 9.1) be- Moreover, two long-term, double-blind turbances), or when there is advanced
kidney disease (eGFR ,30 mL/min/
©
also educate their patients about the Diabetic retinopathy is a highly specific
11.18 Women with preexisting type
progressive nature of CKD, the kidney vascular complication of both type 1 and
1 or type 2 diabetes who are
preservation benefits of proactive treat- type 2 diabetes, with prevalence strongly
planning pregnancy or who are
ment of blood pressure and blood glucose, related to both the duration of diabetes
pregnant should be counseled
and the potential need for renal replace- and the level of glycemic control (100).
on the risk of development and/
ment therapy. Diabetic retinopathy is the most frequent
or progression of diabetic reti-
cause of new cases of blindness among
nopathy. B
DIABETIC RETINOPATHY adults aged 20–74 years in developed
11.19 Eye examinations should occur
n
countries. Glaucoma, cataracts, and other
Recommendations before pregnancy or in the first
disorders of the eye occur earlier and
tio
11.12 Optimize glycemic control to trimester in patients with pre-
more frequently in people with diabetes.
reduce the risk or slow the existing type 1 or type 2 di-
In addition to diabetes duration, fac-
abetes, and then patients
a
progression of diabetic reti- tors that increase the risk of, or are
nopathy. A should be monitored every tri-
ci
associated with, retinopathy include
11.13 Optimize blood pressure and mester and for 1 year postpar-
chronic hyperglycemia (101), nephropa-
serum lipid control to reduce tum as indicated by the degree
so
thy (102), hypertension (103), and
the risk or slow the progression of retinopathy. B
dyslipidemia (104). Intensive diabetes
of diabetic retinopathy. A management with the goal of achieving
As
Treatment near-normoglycemia has been shown in
Screening large prospective randomized studies to
Recommendations
prevent and/or delay the onset and pro-
Recommendations 11.20 Promptly refer patients with
s
gression of diabetic retinopathy and po-
11.14 Adults with type 1 diabetes any level of macular edema,
tentially improve patient reported visual
te
should have an initial dilated severe nonproliferative dia-
function (46,105–107).
and comprehensive eye exam- betic retinopathy (a precursor
Several case series and a controlled
be
ination by an ophthalmologist of proliferative diabetic reti-
prospective study suggest that preg-
or optometrist within 5 years nopathy), or any proliferative
nancy in patients with type 1 diabe-
after the onset of diabetes. B diabetic retinopathy to an oph-
ia
inopathy for one or more an- to reduce the risk of vision loss
The preventive effects of therapy and
nual eye exams and glycemia is in patients with high-risk prolif-
er
examination (111). Less frequent intervals comprehensive eye examination at the growth factor (anti-VEGF) agent, specif-
have been found in simulated modeling time of diagnosis. ically ranibizumab, resulted in visual acu-
to be potentially effective in screening for Pregnancy
ity outcomes that were not inferior to
diabetic retinopathy in patients without Pregnancy is associated with a rapid those observed in patients treated with
diabetic retinopathy (112). More frequent progression of diabetic retinopathy panretinal laser at 2 years of followup
examinations by the ophthalmologist will (117,118). Women with preexisting (121). In addition, it was observed that
be required if retinopathy is progressing. type 1 or type 2 diabetes who are plan- patients treated with ranibizumab
Retinal photography with remote ning pregnancy or who have become tended to have less peripheral visual
n
reading by experts has great potential pregnant should be counseled on the field loss, fewer vitrectomy surgeries
to provide screening services in areas for secondary complications from their
tio
risk of development and/or progression
where qualified eye care professionals of diabetic retinopathy. In addition, rapid proliferative disease, and a lower risk of
are not readily available (105,106). High implementation of intensive glycemic developing diabetic macular edema.
a
quality fundus photographs can detect management in the setting of retinopa- However, a potential drawback in using
ci
most clinically significant diabetic reti- thy is associated with early worsening anti-VEGF therapy to manage prolifer-
nopathy. Interpretation of the images of retinopathy (109). Women who de- ative disease is that patients were re-
so
should be performed by a trained eye velop gestational diabetes mellitus do quired to have a greater number of visits
care provider. Retinal photography may not require eye examinations during and received a greater number of
also enhance efficiency and reduce treatments than is typically required
As
pregnancy and do not appear to be
costs when the expertise of ophthalmol- at increased risk of developing diabetic for management with panretinal laser,
ogists can be used for more complex retinopathy during pregnancy (119). which may not be optimal for some pa-
examinations and for therapy (113,114). tients. Other emerging therapies for
s
In-person exams are still necessary Treatment retinopathy that may use sustained intra-
when the retinal photos are of unaccept- Two of the main motivations for screen- vitreal delivery of pharmacologic agents
able quality and for follow-up if abnor-
malities are detected. Retinal photos are te
ing for diabetic retinopathy are to pre-
vent loss of vision and to intervene with
are currently under investigation. The FDA
approved ranibizumab for the treatment
be
not a substitute for comprehensive eye treatment when vision loss can be pre- of diabetic retinopathy in 2017.
exams, which should be performed at vented or reversed. While the ETDRS (122) established the
ia
n
with dyslipidemia, retinopathy progres- 1. Small-fiber function: pinprick and tem-
clinical manifestations. The early recog-
perature sensation
tio
sion may be slowed by the addition of nition and appropriate management of
fenofibrate, particularly with very mild 2. Large-fiber function: vibration percep-
neuropathy in the patient with diabetes
nonproliferative diabetic retinopathy at tion and 10-g monofilament
is important.
a
baseline (104,127). 3. Protective sensation: 10-g monofilament
ci
1. Diabetic neuropathy is a diagnosis of
These tests not only screen for the pres-
NEUROPATHY exclusion. Nondiabetic neuropathies
so
ence of dysfunction but also predict future
Screening
may be present in patients with di-
risk of complications. Electrophysiological
abetes and may be treatable.
Recommendations
testing or referral to a neurologist is rarely
As
2. Numerous treatment options exist for
11.25 All patients should be assessed needed, except in situations where the
symptomatic diabetic neuropathy.
for diabetic peripheral neurop- clinical features are atypical or the di-
3. Up to 50% of diabetic peripheral neu-
athy starting at diagnosis of agnosis is unclear.
ropathy (DPN) may be a symptomatic.
In all patients with diabetes and DPN,
s
type 2 diabetes and 5 years If not recognized and if preventive foot
causes of neuropathy other than diabetes
te
after the diagnosis of type 1 care is not implemented, patients are
diabetes and at least annually should be considered, including toxins
at risk for injuries to their insensate
thereafter. B (e.g., alcohol), neurotoxic medications
be
feet.
11.26 Assessment for distal symmet- (e.g., chemotherapy), vitamin B12 defi-
4. Recognition and treatment of auto-
ric polyneuropathy should ciency, hypothyroidism, renal disease,
nomic neuropathy may improve
malignancies (e.g., multiple myeloma, bron-
ia
at risk for ulceration and am- (128,129) and may modestly slow their The symptoms and signs of autonomic
putation. B progression in type 2 diabetes (48), but it neuropathy should be elicited carefully
11.27 Symptoms and signs of auto-
Am
does not reverse neuronal loss. Thera- during the history and physical exami-
nomic neuropathy should be peutic strategies (pharmacologic and nation. Major clinical manifestations
assessed in patients with mi- nonpharmacologic) for the relief of pain- of diabetic autonomic neuropathy in-
crovascular complications. E ful DPN and symptoms of autonomic clude hypoglycemia unawareness, rest-
neuropathy can potentially reduce pain
19
.10 mmHg, respectively, upon standing a modest slowing of progression without expensive, although it is not FDA ap-
without an appropriate increase in heart reversal of neuronal loss (48,139). Specific proved for this indication (154).
rate). CAN treatment is generally focused glucose-lowering strategies may have dif- Duloxetine is a selective norepineph-
on alleviating symptoms. ferent effects. In a post hoc analysis, par- rine and serotonin reuptake inhibitor.
Gastrointestinal Neuropathies. Gastroin- ticipants, particularly men, in the Bypass Doses of 60 and 120 mg/day showed
testinal neuropathies may involve any Angioplasty Revascularization Investigation efficacy in the treatment of pain associ-
portion of the gastrointestinal tract with in Type 2 Diabetes (BARI 2D) trial treated ated with DPN in multicenter randomized
manifestations including esophageal with insulin sensitizers had a lower inci- trials, although some of these had
n
dysmotility, gastroparesis, constipation, dence of distal symmetric polyneuropathy high drop-out rates (143,145,150,152).
over4yearsthanthosetreatedwith insulin/ Duloxetine also appeared to improve
tio
diarrhea, and fecal incontinence. Gastro-
paresis should be suspected in individ- sulfonylurea (140). neuropathy-related quality of life (155).
uals with erratic glycemic control or with In longer-term studies, a small increase in
a
upper gastrointestinal symptoms with- Neuropathic Pain A1C was reported in people with diabetes
ci
out another identified cause. Exclusion of Neuropathic pain can be severe and can treated with duloxetine compared with
organic causes of gastric outlet obstruc- impact quality of life, limit mobility, and placebo (156). Adverse events may be
so
tion or peptic ulcer disease (with esoph- contribute to depression and social dys- more severe in older people but may be
agogastroduodenoscopy or a barium function (141). No compelling evidence attenuated with lower doses and slower
study of the stomach) is needed before exists in support of glycemic control or titrations of duloxetine.
As
considering a diagnosis of or specialized lifestyle management as therapies for Tapentadol is a centrally acting opioid
testing for gastroparesis. The diagnostic neuropathic pain in diabetes or predia- analgesic that exerts its analgesic effects
gold standard for gastroparesis is the betes, which leaves only pharmaceutical through both m-opioid receptor agonism
s
measurement of gastric emptying with interventions (142). and noradrenaline reuptake inhibition.
Pregabalin and duloxetine have re- Extended-release tapentadol was ap-
te
scintigraphy of digestible solids at
15-min intervals for 4 h after food intake. ceived regulatory approval by the FDA, proved by the FDA for the treatment
The use of 13C octanoic acid breath test Health Canada, and the European Med- of neuropathic pain associated with
be
is emerging as a viable alternative. icines Agency for the treatment of neu- diabetes based on data from two mul-
ropathic pain in diabetes. The opioid ticenter clinical trials in which partici-
Genitourinary Disturbances. Diabetic auto-
ia
of its use is weaker (143). Comparative continue that dose or switch to placebo
dysfunction and bladder dysfunction. In effectiveness studies and trials that in- (157,158). However, both used a design
men, diabetic autonomic neuropathy clude quality-of-life outcomes are rare, enriched for patients who responded to
an
may cause erectile dysfunction and/or so treatment decisions must consider tapentadol and therefore their results are
retrograde ejaculation (130). Female each patient’s presentation and comor- not generalizable. A recent systematic
sexual dysfunction occurs more frequently bidities and often follow a trial-and-error
ic
urinary stream). Evaluation of bladder Pregabalin, a calcium channel a2-d of extended release tapentadol is not
function should be performed for indi- subunit ligand, is the most extensively
generally recommended as a first- or
viduals with diabetes who have recurrent studied drug for DPN. The majority of
20
n
deconditioning, which is known to exac- implantable device has received approval
prior ulcers or amputation). B
from the FDA, although its efficacy is
tio
erbate orthostatic intolerance, and vol- 11.37 Refer patientswhosmokeor who
ume repletion with fluids and salt is variable and use is limited to patients
have histories of prior lower-
critical. There have been clinical studies with severe symptoms that are refractory
extremity complications, loss of
a
that assessed the impact of an approach to other treatments (169).
protective sensation, structural
ci
incorporating the aforementioned non- abnormalities, or peripheral arte-
Erectile Dysfunction
pharmacologic measures. Additionally, rial disease to foot care special-
In addition to treatment of hypogonad-
so
supine blood pressure tends to be ists for ongoing preventive care
much higher in these patients, often re- ism if present, treatments for erectile
dysfunction may include phosphodies- and lifelong surveillance. C
quiring treatment of blood pressure at 11.38
As
terase type 5 inhibitors, intracorporeal Provide general preventive
bedtime with shorter-acting drugs that foot self-care education to
also affect baroreceptor activity such as or intraurethral prostaglandins, vacuum
devices, or penile prostheses. As with all patients with diabetes. B
guanfacine or clonidine, shorter-acting 11.39 The use of specialized therapeu-
DPN treatments, these interventions do
s
calcium blockers (e.g., isradipine), or tic footwear is recommended for
not change the underlying pathology
shorter-acting b-blockers such as atenolol
te
and natural history of the disease pro- high-risk patients with diabetes
or metoprolol tartrate. Alternatives can including those with severe neu-
cess but may improve the patient’s
include enalapril if patients are unable
be
quality of life. ropathy, foot deformities, ulcers,
to tolerate preferred agents (159–161). callousformation,poorperipheral
Midodrine and droxidopa are approved circulation, or history of amputa-
ia
Gastroparesis 11.31 Perform a comprehensive foot Foot ulcers and amputation, which are
Treatment for diabetic gastroparesis evaluation at least annually to consequences of diabetic neuropathy
an
may be very challenging. A low-fiber, identify risk factors for ulcers and/or peripheral arterial disease
low-fat eating plan provided in small and amputations. B (PAD), are common and represent major
frequent meals with a greater propor- 11.32 Patients with evidence of sen- causes of morbidity and mortality in
ic
tion of liquid calories may be useful sory loss or prior ulceration or people with diabetes.
(162–164). In addition, foods with amputation should have their Early recognition and treatment of
er
small particle size may improve key feet inspected at every visit. B patients with diabetes and feet at risk
symptoms (165). Withdrawing drugs 11.33 Obtain a prior history of ulcer- for ulcers and amputations can delay or
Am
with adverse effects on gastrointestinal ation, amputation, Charcot foot, prevent adverse outcomes.
motility including opioids, anticholiner- angioplasty or vascular surgery, The risk of ulcers or amputations is
gics, tricyclic antidepressants, GLP-1 RAs, cigarette smoking, retinopathy, increased in people who have the fol-
pramlintide, and possibly dipeptidyl and renal disease and assess lowing risk factors:
19
foot ulcer recurrence or worsening. How- ulcer and peripheral arterial disease consideration and a thorough workup
ever, there is very little evidence for the should be performed: skin perfusion should be performed when patients with
use of interventions to prevent a first foot pressure ($40 mmHg), toe pressure neuropathy present with the acute onset
ulcer or heal ischemic, infected, non- ($30 mmHG), or transcutaneous oxygen of a red, hot, swollen foot or ankle, and
plantar, or proximal foot ulcers (170). pressure (TcPO2 $25 mmHg). Urgent Charcot neuroarthropathy should be ex-
Studies on specific types of footwear vascular imaging and revascularization cluded. Early diagnosis and treatment of
demonstrated that shape and barefoot should be considered in a patient with Charcot neuroarthropathy is the best
plantar pressure–based orthoses were a diabetic foot ulcer and an ankle pres- way to prevent deformities that increase
n
more effective in reducing submeta- sure (ankle-brachial index) ,50 mmHg, the risk of ulceration and amputation.
tarsal head plantar ulcer recurrence toe pressure ,30 mmHg, or a TcPO2 The routine prescription of therapeutic
tio
than current standard-of-care orthoses ,25 mmHg (130,175). footwear is not generally recommended.
(171). However, patients should be provided
a
Clinicians are encouraged to review Patient Education adequate information to aid in selection
ci
ADA screening recommendations for fur- All patients with diabetes and partic- of appropriate footwear. General foot-
ther details and practical descriptions of ularly those with high-risk foot condi- wear recommendations include a broad
so
how to perform components of the com- tions (history of ulcer or amputation, and square toe box, laces with three or
prehensive foot examination (172). deformity, LOPS, or PAD) and their four eyes per side, padded tongue, qual-
families should be provided general ity lightweight materials, and sufficient
As
Evaluation for Loss of Protective
education about risk factors and ap- size to accommodate a cushioned insole.
Sensation
propriate management (176). Patients Use of custom therapeutic footwear can
All adults with diabetes should undergo a
at risk should understand the implica- help reduce the risk of future foot ulcers
comprehensive foot evaluation at least
s
tions of foot deformities, LOPS, and in high-risk patients (173,176).
annually. Detailed foot assessments may
PAD; the proper care of the foot, in- Most diabetic foot infections are poly-
te
occur more frequently in patients with
cluding nail and skin care; and the microbial, with aerobic gram-positive
histories of ulcers or amputations, foot
importance of foot monitoring on a cocci. Staphylococci and streptococci
be
deformities, insensate feet, and PAD
daily basis. Patients with LOPS should are the most common causative organ-
(173,174). To assess risk, clinicians should
be educated on ways to substitute isms. Wounds without evidence of soft
ask about history of foot ulcers or am-
ia
lance and care should be assessed. Pa- be referred to specialized care centers
part of the foot examination is designed
tients with visual difficulties, physical (177). Foot ulcers and wound care may
to identify LOPS rather than early neu-
constraints preventing movement, or require care by a podiatrist, orthopedic
Am
challenges as randomized controlled type 2 diabetes. J Am Soc Nephrol 2013;24:302– 24. Perkovic V, Jardine MJ, Neal B, et al. Canagli-
studies remain few, with a majority being 308 flozin and renal outcomes in type 2 diabetes and
9. Groop P-H, Thomas MC, Moran JL, et al.; nephropathy. N Engl J Med 2019;380:2295–2306
of poor quality (179). Thus, HBOT does FinnDiane Study Group. The presence and se- 25. Nadkarni GN, Ferrandino R, Chang A, et al.
not have a significant effect on health- verity of chronic kidney disease predicts all-cause Acute kidney injury in patients on SGLT2 inhib-
related quality of life in patients with mortality in type 1 diabetes. Diabetes 2009;58: itors: a propensity-matched analysis. Diabetes
diabetic foot ulcers (183,184). A recent 1651–1658 Care 2017;40:1479–1485
review concluded that the evidence to 10. Gomes MB, Gonçalves MF. Is there a phys- 26. Wanner C, Inzucchi SE, Lachin JM, et al.;
iological variability for albumin excretion rate? EMPA-REG OUTCOME Investigators. Empagli-
date remains inconclusive regarding the Study in patients with diabetes type 1 and non- flozin and progression of kidney disease in
n
clinical and cost-effectiveness of HBOT as diabetic individuals. Clin Chim Acta 2001;304: type 2 diabetes. N Engl J Med 2016;375:323–
an adjunctive treatment to standard
tio
117–123 334
wound care for diabetic foot ulcers 11. Naresh CN, Hayen A, Weening A, Craig JC, 27. Neuen BL, Ohkuma T, Neal B, et al. Cardio-
Chadban SJ. Day-to-day variability in spot urine vascular and renal outcomes with canagliflozin
(185). Results from the Dutch DAMOCLES
albumin-creatinine ratio. Am J Kidney Dis 2013; according to baseline kidney function: data from
a
(Does Applying More Oxygen Cure 62:1095–1101 the CANVAS Program. Circulation 2018;138:
ci
Lower Extremity Sores?) trial demon- 12. Tankeu AT, Kaze FF, Noubiap JJ, Chelo D, 1537–1550
strated that HBOT in patients with di- Dehayem MY, Sobngwi E. Exercise-induced albu- 28. Thakar CV, Christianson A, Himmelfarb J,
so
abetes and ischemic wounds did not minuria and circadian blood pressure abnormalities Leonard AC. Acute kidney injury episodes and
in type 2diabetes. World J Nephrol 2017;6:209–216 chronic kidney disease risk in diabetes mellitus.
significantly improve complete wound
13. Delanaye P, Glassock RJ, Pottel H, Rule AD. Clin J Am Soc Nephrol 2011;6:2567–2572
healing and limb salvage (186). While An age-calibrated definition of chronic kidney 29. Bakris GL, Weir MR. Angiotensin-converting
As
the Centers for Medicare & Medicaid disease: rationale and benefits. Clin Biochem Rev enzyme inhibitor-associated elevations in serum
Services currently covers HBOT for di- 2016;37:17–26 creatinine: is this a cause for concern? Arch
abetic foot ulcers that have failed a 14. Kramer HJ, Nguyen QD, Curhan G, Hsu C-Y. Intern Med 2000;160:685–693
Renal insufficiency in the absence of albuminuria 30. Beddhu S, Greene T, Boucher R, et al. In-
s
standard course of wound therapy and retinopathy among adults with type 2 di- tensive systolic blood pressure control and in-
when there are no measurable signs
te
abetes mellitus. JAMA 2003;289:3273–3277 cident chronic kidney disease in people with and
of healing for at least 30 consecutive 15. Molitch ME, Steffes M, Sun W, et al.; Epide- without diabetes mellitus: secondary analyses of
days (187), given the data not support- miology of Diabetes Interventions and Com- two randomised controlled trials. Lancet Diabe-
be
ing an effect, such an approach is not plications Study Group. Development and progression tes Endocrinol 2018;6:555–563
of renal insufficiency with and without albu- 31. Collard D, Brouwer TF, Peters RJG, Vogt L,
currently warranted. HBOT should be a minuria in adults with type 1 diabetes in the van den Born BH. Creatinine rise during blood
ia
topic of shared decision-making before Diabetes Control and Complications Trial and pressure therapy and the risk of adverse clinical
treatment is considered for selected the Epidemiology of Diabetes Interventions and outcomes in patients with type 2 diabetes mel-
D
patients with diabetic foot ulcers (187). Complications study. Diabetes Care 2010;33: litus. Hypertension 2018;72:1337–1344
1536–1543 32. Malhotra R, Craven T, Ambrosius WT, et al.;
16. He F, Xia X, Wu XF, Yu XQ, Huang FX. Diabetic SPRINT Research Group. Effects of intensive
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Glucose control and diabetic neuropathy: lessons 2D) Cohort. Diabetes Care 2013;36:3208–3215 154. Wiffen PJ, Derry S, Bell RF, et al. Gabapentin
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tion with Enterra therapy improves symptoms Infectious Diseases Society of America. 2012 therapy cost-effective for treating ische-
from diabetic gastroparesis in a prospective study. Infectious Diseases Society of America clinical mic diabetic ulcers? Study protocol for the Dutch
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170. Bus SA, van Deursen RW, Armstrong DG, ment of diabetic foot infections. Clin Infect Dis cal trial. J Diabetes 2015;7:125–132
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tional Working Group on the Diabetic Foot. 178. Elraiyah T, Tsapas A, Prutsky G, et al. A UHMS CPG Oversight Committee. A clinical
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171. Ulbrecht JS, Hurley T, Mauger DT, Cavanaugh Foot. Effectiveness of interventions to enhance RC, Choi M, Sequist TD; National Kidney Foun-
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PR. Prevention of recurrent foot ulcers with healing of chronic ulcers of the foot in diabetes: dation Kidney Disease Outcomes Quality Ini-
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CareFUL Prevention multicenter randomized 2016;32(Suppl. 1):154–168 management of chronic kidney disease for
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1989 Schnabel A, Debus SE, Weibel S. Hyperbaric 129:153–162.e7
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Diabetes Care 2020;43(Suppl. 1):S152–S162 | https://doi.org/10.2337/dc20-S012
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The American Diabetes Association (ADA) “Standards of Medical Care in Diabe-
tes” includes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guidelines,
and tools to evaluate quality of care. Members of the ADA Professional Practice
s
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-
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SPPC), are responsible for updating the Standards of Care annually, or more
12. OLDER ADULTS
Recommendations
12.1 Consider the assessment of medical, psychological, functional (self-
management abilities), and social geriatric domains in older adults to
ic
one-quarter of people over the age of 65 years have diabetes and one-half of
older adults have prediabetes (1), and the number of older adults living
with these conditions is expected to increase rapidly in the coming decades. Dia-
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The comprehensive assessment de- cognitive function or in preventing cog- referral to a behavioral health provider
scribed above may provide a framework nitive decline (17). Pilot studies in pa- for formal cognitive/neuropsychological
to determine targets and therapeutic tients with mild cognitive impairment evaluation (28).
approaches (8–10), including whether evaluating the potential benefits of
referral for diabetes self-management intranasal insulin therapy and metfor-
HYPOGLYCEMIA
education is appropriate (when compli- min therapy provide insights for future
cating factors arise or when transitions in clinical trials and mechanistic studies Recommendation
care occur) or whether the current reg- (18–20). 12.4 Hypoglycemia should be avoided
n
imen is too complex for the patient’s Despite the paucity of therapies to in older adults with diabetes. It
self-management ability or the care- prevent or remedy cognitive decline,
tio
should be assessed and managed
givers providing care. Particular atten- identifying cognitive impairment early by adjusting glycemic targets and
tion should be paid to complications has important implications for diabe- pharmacologic regimens. B
a
that can develop over short periods of tes care. The presence of cognitive im-
ci
time and/or would significantly impair pairment can make it challenging for
functional status, such as visual and clinicians to help their patients reach Older adults are at higher risk of hypo-
so
lower-extremity complications. Please individualized glycemic, blood pressure, glycemia for many reasons, including
refer to the American Diabetes Associ- and lipid targets. Cognitive dysfunction insulin deficiency necessitating insulin
ation (ADA) consensus report “Diabetes makes it difficult for patients to perform therapy and progressive renal insuffi-
As
in Older Adults” for details (2). complex self-care tasks (21), such as ciency (29). As described above, older
monitoring glucose and adjusting insu- adults have higher rates of unidentified
lin doses. It also hinders their ability cognitive impairment and dementia
NEUROCOGNITIVE FUNCTION
s
to appropriately maintain the timing leading to difficulties in adhering to
Recommendation of meals and content of diet. When complex self-care activities (e.g., glu-
12.3 Screening for early detection of
mild cognitive impairment or te
clinicians are managing patients with
cognitive dysfunction, it is critical to
cose monitoring, insulin dose ad-
justment, etc.). Cognitive decline has
be
dementia should be performed simplify drug regimens and to facilitate been associated with increased risk of
for adults 65 years of age or and engage the appropriate support hypoglycemia and, conversely, severe
ia
older at the initial visit and structure to assist the patient in all hypoglycemia has been linked to
annually as appropriate. B aspects of care. increased risk of dementia (30,31).
D
stitutionalization (11,12). The presen- for cognitive screening recommenda- impairment and dementia and discuss
tation of cognitive impairment ranges tions). Several simple assessment tools findings with the patients and their
from subtle executive dysfunction to are available to screen for cognitive caregivers.
ic
memory loss and overt dementia. Peo- impairment (22,23), such as the Mini- Patients should be monitored for hy-
er
ple with diabetes have higher incidences Mental State Examination (24), Mini-Cog poglycemia; glycemic targets and phar-
of all-cause dementia, Alzheimer disease, (25), and the Montreal Cognitive Assess- macologic regimens may need to be
and vascular dementia than people with ment (26), which may help to identify adjusted to minimize the occurrence
Am
normal glucose tolerance (13). The ef- patients requiring neuropsychological of hypoglycemic events (2). Of note, it
fects of hyperglycemia and hyperinsuli- evaluation, particularly those in whom is important to prevent hypoglycemia
nemia on the brain are areas of intense dementia is suspected (i.e., experiencing to reduce the risk of cognitive decline
research. Poor glycemic control is asso- memory loss and decline in their basic (30) and other major adverse outcomes
19
ciated with a decline in cognitive function and instrumental activities of daily liv- (32). Intensive glucose control in the
(14), and longer duration of diabetes is ing). Annual screening is indicated for Action to Control Cardiovascular Risk
associated with worsening cognitive adults 65 years of age or older for early in Diabetes-Memory in Diabetes study
20
function. There are ongoing studies eval- detection of mild cognitive impairment (ACCORD-MIND) was not found to ben-
uating whether preventing or delaying or dementia (4,27). Screening for cogni- efit brain structure or cognitive function
©
diabetes onset may help to maintain tive impairment should additionally be during follow-up (15). In the Diabetes
cognitive function in older adults. How- considered when a patient presents Control and Complications Trial (DCCT),
ever, studies examining the effects of with a significant decline in clinical status no significant long-term declines in cog-
intensive glycemic and blood pressure due to increased problems with self-care nitive function were observed, despite
control to achieve specific targets have activities, such as errors in calculating participants’ relatively high rates of re-
not demonstrated a reduction in brain insulin dose, difficulty counting carbohy- current severe hypoglycemia (33). To
function decline (15,16). drates, skipped meals, skipped insulin achieve the appropriate balance be-
Clinical trials of specific interventionsd doses, and difficulty recognizing, pre- tween glycemic control and risk for hy-
including cholinesterase inhibitors and venting, or treating hypoglycemia. Peo- poglycemia, it is important to carefully
glutamatergic antagonistsdhave not ple who screen positive for cognitive assess and reassess patients’ risk for
shown positive therapeutic benefit in impairment should receive diagnostic worsening of glycemic control and func-
maintaining or significantly improving assessment as appropriate, including tional decline.
S154 Older Adults Diabetes Care Volume 43, Supplement 1, January 2020
TREATMENT GOALS with diabetes have little comorbidity a patient needs a referral for cognitive
and are active. Life expectancies are and physical functional assessment, us-
Recommendations highly variable but are often longer ing age-normalized evaluation tools, as
12.5 Older adults who are otherwise than clinicians realize. Providers caring well as help establishing a support struc-
healthy with few coexisting for older adults with diabetes must take ture for diabetes care (3,28).
chronic illnesses and intact cog- this heterogeneity into consideration
nitive function and functional when setting and prioritizing treatment Patients With Complications and
status should have lower glyce- goals (9,10) (Table 12.1). In addition, Reduced Functionality
mic goals (such as A1C ,7.5%
n
older adults with diabetes should be For patients with advanced diabetes
[58 mmol/mol]), while those assessed for disease treatment and
tio
complications, life-limiting comorbid ill-
with multiple coexisting chronic self-management knowledge, health nesses, or substantial cognitive or func-
illnesses, cognitive impairment, literacy, and mathematical literacy (nu- tional impairments, it is reasonable to set
a
or functional dependence should meracy) at the onset of treatment. See less intensive glycemic goals (Table 12.1).
have less-stringent glycemic Fig. 6.2 for patient- and disease-related
ci
Factors to consider in individualizing
goals (such as A1C ,8.0–8.5% factors to consider when determining glycemic goals are outlined in Fig. 6.2.
[64–69 mmol/mol]). C
so
individualized glycemic targets. These patients are less likely to benefit
12.6 Glycemic goals for some older A1C is used as the standard biomarker from reducing the risk of microvascular
adults might reasonably be re- for glycemic control in all patients with complications and more likely to suffer
As
laxed as part of individualized diabetes but may have limitations in serious adverse effects from hypoglyce-
care, but hyperglycemia lead- patients who have medical conditions mia. However, patients with poorly con-
ing to symptoms or risk of that impact red blood cell turnover (see trolled diabetes may be subject to acute
acute hyperglycemia compli- Section 2 “Classification and Diagnosis of
s
complications of diabetes, including
cations should be avoided in Diabetes” https://doi.org/10.2337/dc20- dehydration, poor wound healing, and
all patients. C
12.7 Screening for diabetes compli-
te
S002, for additional details on the limi-
tations of A1C) (37). Many conditions
hyperglycemic hyperosmolar coma. Gly-
cemic goals should, at a minimum, avoid
be
cations should be individualized associated with increased red blood cell these consequences.
in older adults. Particular atten- turnover, such as hemodialysis, recent
tion should be paid to compli-
ia
adults with functional limitations and end-of-life care, the focus should be to
12.8 Treatment of hypertension to can falsely increase or decrease A1C. In reduce the burdens and avoid the side
individualized target levels is these instances, plasma blood glucose effects of glycemic management. Thus,
an
indicated in most older adults. C and fingerstick readings should be used when organ failure develops, several agents
12.9 Treatment of other cardiovas- for goal setting (Table 12.1). will have to be deintensified or discontin-
cular risk factors should be ued. For the dying patient, most agents
ic
individualized in older adults Healthy Patients With Good for type 2 diabetes may be removed (38).
considering the time frame of
er
those with life expectancies at tensive glycemic, blood pressure, and for additional information.
least equal to the time frame of lipid control. Patients who can be ex-
primary prevention or second- pected to live long enough to reap the Beyond Glycemic Control
ary intervention trials. E benefits of long-term intensive diabetes Although hyperglycemia control may be
19
management, who have good cognitive important in older individuals with dia-
The care of older adults with diabetes is and physical function, and who choose to betes, greater reductions in morbidity and
complicated by their clinical, cognitive, do so via shared decision-making may be mortality are likely to result from control
20
and functional heterogeneity. Some treated using therapeutic interventions of other cardiovascular risk factors rather
older individuals may have developed and goals similar to those for younger than from tight glycemic control alone.
adults with diabetes (Table 12.1).
©
diabetes years earlier and have signifi- There is strong evidence from clinical trials
cant complications, others are newly As with all patients with diabetes, di- of the value of treating hypertension in
diagnosed and may have had years of abetes self-management education and older adults (40,41), with treatment of
undiagnosed diabetes with resultant ongoing diabetes self-management sup- hypertension to individualized target lev-
complications, and still other older adults port are vital components of diabetes care els indicated in most. There is less evi-
may have truly recent-onset disease with for older adults and their caregivers. Self- dence for lipid-lowering therapy and
few or no complications (34). Some older management knowledge and skills should aspirin therapy, although the benefits
adults with diabetes have other under- be reassessed when regimen changes are of these interventions for primary pre-
lying chronic conditions, substantial made or an individual’s functional abili- vention and secondary intervention are
diabetes-related comorbidity, limited ties diminish. In addition, declining or likely to apply to older adults whose life
cognitive or physical functioning, or impaired ability to perform diabetes self- expectancies equal or exceed the time
frailty (35,36). Other older individuals care behaviors may be an indication that frames of the clinical trials.
care.diabetesjournals.org Older Adults S155
Table 12.1—Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with
diabetes
Patient Fasting or
characteristics/ Reasonable preprandial Blood
health status Rationale A1C goal‡ glucose Bedtime glucose pressure Lipids
Healthy (few Longer remaining life ,7.5% 90–130 mg/dL 90–150 mg/dL ,140/90 mmHg Statin unless
coexisting chronic expectancy (58 mmol/mol) (5.0–7.2 mmol/L) (5.0–8.3 contraindicated
illnesses, intact mmol/L) or not tolerated
n
cognitive and
functional status)
tio
Complex/ Intermediate ,8.0% 90–150 mg/dL 100–180 mg/dL ,140/90 mmHg Statin unless
intermediate remaining life (64 mmol/mol) (5.0–8.3 mmol/L) (5.6–10.0 contraindicated
(multiple expectancy, high mmol/L) or not tolerated
a
coexisting chronic treatment burden,
ci
illnesses* or 21 hypoglycemia
instrumental ADL vulnerability,
so
impairments or fall risk
mild-to-moderate
cognitive
As
impairment)
Very complex/poor Limited remaining life ,8.5%† 100–180 mg/dL 110–200 mg/dL ,150/90 mmHg Consider
health (LTC or end- expectancy makes (69 mmol/mol) (5.6–10.0 (6.1–11.1 likelihood of
stage chronic benefit uncertain mmol/L) mmol/L) benefit with
s
illnesses** or statin
moderate-to-
te
(secondary
severe cognitive prevention
impairment or 21 more so than
be
ADL dependencies) primary)
This table represents a consensus framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults
with diabetes. The patient characteristic categories are general concepts. Not every patient will clearly fall into a particular category.
ia
Consideration of patient and caregiver preferences is an important aspect of treatment individualization. Additionally, a patient’s health
status and preferences may change over time. ADL, activities of daily living; LTC, long-term care. ‡A lower A1C goal may be set for an
D
individual if achievable without recurrent or severe hypoglycemia or undue treatment burden. *Coexisting chronic illnesses are conditions
serious enough to require medications or lifestyle management and may include arthritis, cancer, congestive heart failure, depression,
emphysema, falls, hypertension, incontinence, stage 3 or worse chronic kidney disease, myocardial infarction, and stroke. “Multiple”
means at least three, but many patients may have five or more (54). **The presence of a single end-stage chronic illness, such as stage
an
3–4 congestive heart failure or oxygen-dependent lung disease, chronic kidney disease requiring dialysis, or uncontrolled metastatic cancer, may
cause significant symptoms or impairment of functional status and significantly reduce life expectancy. †A1C of 8.5% (69 mmol/mol) equates to
an estimated average glucose of ;200 mg/dL (11.1 mmol/L). Looser A1C targets above 8.5% (69 mmol/mol) are not recommended, as
ic
they may expose patients to more frequent higher glucose values and acute risks from glycosuria, dehydration, hyperglycemic hyperosmolar
syndrome, and poor wound healing. Adapted from Kirkman et al. (2).
er
Am
agents. Cost may be an important con- may impair their ability to follow their the dose of insulin may not be ade-
sideration, especially as older adults regimen safely. Individualized glycemic quate (55). Simplification of the insulin
tend to be on many medications and goals should be established (Fig. 6.3) and regimen to match an individual’s self-
live on fixed incomes (47). Accordingly, periodically adjusted based on coexist- management abilities and their avail-
the costs of care and insurance coverage ing chronic illnesses, cognitive function, able social and medical support in these
rules should be considered when devel- and functional status (2). Tight glycemic situations has been shown to reduce
oping treatment plans to reduce the risk control in older adults with multiple hypoglycemia and disease-related dis-
of cost-related nonadherence (48,49). medical conditions is considered over- tress without worsening glycemic con-
n
See Tables 9.2 and 9.3 for median treatment and is associated with an trol (56–58). Fig. 12.1 depicts an
monthly cost in the U.S. of noninsulin increased risk of hypoglycemia; unfor- algorithm that can be used to simplify
tio
glucose-lowering agents and insulin, re- tunately, overtreatment is common in the insulin regimen (56). There are
spectively. It is important to match com- clinical practice (50–54). Deintensifica- now multiple studies evaluating de-
a
plexity of the treatment regimen to the tion of regimens in patients taking non- intensification protocols; in general,
ci
self-management ability of older pa- insulin glucose-lowering medications the studies demonstrate that de-
tients and their available social and can be achieved by either lowering intensification is safe and possibly
so
medical support. Many older adults the dose or discontinuing some medi- beneficial for older adults (59). Table
with diabetes struggle to maintain the cations, so long as the individualized 12.2 provides examples of and rationale
frequent blood glucose testing and insu- glycemic target is maintained. When pa- for situations where deintensification
As
lin injection regimens they previously fol- tients are found to have an insulin and/or insulin regimen simplifica-
lowed, perhaps for many decades, as regimen with complexity beyond their tion may be appropriate in older
they develop medical conditions that self-management abilities, lowering adults.
s
te
be
ia
D
an
ic
er
Am
19
20
©
Figure 12.1—Algorithm to simplify insulin regimen for older patients with type 2 diabetes. eGFR, estimated glomerular filtration rate. *Basal insulins:
glargine U-100 and U-300, detemir, degludec, and human NPH. **See Table 12.1. UMealtime insulins: short-acting (regular human insulin) or rapid-
acting (lispro, aspart, and glulisine). §Premixed insulins: 70/30, 75/25, and 50/50 products. Adapted with permission from Munshi and colleagues
(56,82,83).
care.diabetesjournals.org Older Adults S157
Table 12.2—Considerations for treatment regimen simplification and deintensification/deprescribing in older adults with
diabetes (56,82)
Patient When may treatment
characteristics/health Reasonable A1C/ When may regimen deintensification/
status treatment goal Rationale/considerations simplification be required? deprescribing be required?
Healthy (few A1C ,7.5% c Patients can generally c If severe or recurrent c If severe or recurrent
coexisting chronic (58 mmol/mol) perform complex tasks to hypoglycemia occurs in hypoglycemia occurs in
illnesses, intact maintain good glycemic patients on insulin therapy patients on noninsulin
n
cognitive and control when health is stable (even if A1C is appropriate) therapies with high risk
functional status) c During acute illness, patients c If wide glucose excursions of hypoglycemia (even if
tio
may be more at risk for are observed A1C is appropriate)
administration or dosing c If cognitive or functional c If wide glucose excursions
errors that can result in decline occurs following are observed
a
hypoglycemia, falls, fractures, acute illness c In the presence of
ci
etc. polypharmacy
Complex/ A1C ,8.0% c Comorbidities may affect self- c If severe or recurrent c If severe or recurrent
so
intermediate (64 mmol/mol) management abilities and hypoglycemia occurs in hypoglycemia occurs in
(multiple coexisting capacity to avoid patients on insulin therapy patients on noninsulin
chronic illnesses or hypoglycemia (even if A1C is appropriate) therapies with high risk
As
21 instrumental c Long-acting medication c If unable to manage of hypoglycemia (even if
ADL impairments or formulations may decrease complexity of an insulin A1C is appropriate)
mild-to-moderate pill burden and complexity of regimen c If wide glucose excursions
cognitive medication regimen c If there is a significant are observed
s
impairment) change in social c In the presence of
circumstances, such as loss polypharmacy
care in a skilled hydration, and avoidance of during hospitalization, it is weight loss, anorexia,
nursing facility for infections reasonable, in many cases, short-term cognitive
D
short-term Glucose target: c Patients recovering from to reinstate the decline, and/or loss of
rehabilitation 100–200 mg/dL illness may not have returned prehospitalization physical functioning
(5.55–11.1 mmol/L) to baseline cognitive function medication regimen during
an
home
Very complex/poor A1C ,8.5% c No benefits of tight glycemic c If on an insulin regimen and c If on noninsulin agents
er
health (long-term (69 mmol/)† control in this population the patient would like to with a high hypoglycemia
care or end-stage c Hypoglycemia should be decrease the number of risk in the context of
chronic illnesses or avoided injections and fingerstick cognitive dysfunction,
Am
moderate-to- c Most important outcomes are blood glucose monitoring depression, anorexia, or
severe cognitive maintenance of cognitive and events each day inconsistent eating
impairment or 21 functional status c If the patient has an pattern
ADL dependencies) inconsistent eating pattern c If taking any medications
without clear benefits
19
Patients at end of life Avoid hypoglycemia c Goal is to provide comfort and c If there is pain or c If taking any medications
and symptomatic avoid tasks or interventions discomfort caused by without clear benefits in
hyperglycemia that cause pain or discomfort treatment (e.g., injections improving symptoms
20
treatment complexity
Treatment regimen simplification refers to changing strategy to decrease the complexity of a medication regimen, e.g., fewer administration times,
fewer fingerstick readings, decreasing the need for calculations (such as sliding scale insulin calculations or insulin-carbohydrate ratio calculations).
Deintensification/deprescribing refers to decreasing the dose or frequency of administration of a treatment or discontinuing a treatment altogether.
ADL, activities of daily living. †Consider adjustment of A1C goal if the patient has a condition that may interfere with erythrocyte life span/turnover.
Metformin glomerular filtration rate $30 mL/min/ hepatic function or congestive heart fail-
Metformin is the first-line agent for older 1.73 m2 (60). However, it is contra- ure because of the increased risk of lactic
adults with type 2 diabetes. Recent indicated in patients with advanced acidosis. Metformin may be temporarily
studies have indicated that it may be renal insufficiency and should be used discontinued before procedures, during
used safely in patients with estimated with caution in patients with impaired hospitalizations, and when acute illness
S158 Older Adults Diabetes Care Volume 43, Supplement 1, January 2020
may compromise renal or liver function. be convenient for older adults with their own medications, whereas those
Additionally, metformin can cause gas- diabetes. In patients with established living in a nursing home (community
trointestinal side effects and a reduc- atherosclerotic cardiovascular disease, living centers) may rely completely on
tion in appetite that can be problematic these agents have shown cardiovascular the care plan and nursing support.
for some older adults. Reduction or benefits (64). This class of agents has also Those receiving palliative care (with or
elimination of metformin may be nec- been found to be beneficial for patients without hospice) may require an ap-
essary for patients experiencing gas- with heart failure and to slow the pro- proach that emphasizes comfort and
trointestinal side effects. gression of chronic kidney disease. See symptom management, while de-
n
Section 9 “Pharmacologic Approaches emphasizing strict metabolic and blood
Thiazolidinediones to Glycemic Treatment” (https://doi.org/ pressure control.
tio
Thiazolidinediones, if used at all, should 10.2337/dc20-S009) for a more extensive
be used very cautiously in those with, or SPECIAL CONSIDERATIONS
discussion regarding the indications for
at risk for, congestive heart failure, os-
a
this class of agents. While understand- FOR OLDER ADULTS WITH
teoporosis, falls or fractures, and/or mac- TYPE 1 DIABETES
ci
ing of the clinical benefits of this class is
ular edema (61,62). evolving, side effects such as volume Due in part to the success of modern
so
Insulin Secretagogues depletion may be more common among diabetes management, patients with
Sulfonylureas and other insulin secreta- older patients. type 1 diabetes are living longer and
gogues are associated with hypoglyce- the population of these patients over
As
Insulin Therapy 65 years of age is growing (65–67). Many
mia and should be used with caution. If
The use of insulin therapy requires that of the recommendations in this section
used, sulfonylureas with a shorter dura-
patients or their caregivers have good regarding a comprehensive geriatric as-
tion of action, such as glipizide or glime-
visual and motor skills and cognitive
s
piride, are preferred. Glyburide is a sessment and personalization of goals
ability. Insulin therapy relies on the and treatments are directly applicable
longer-acting sulfonylurea and should
be avoided in older adults (63).
te
ability of the older patient to admin-
ister insulin on their own or with the
to older adults with type 1 diabetes;
however, this population has unique
be
Incretin-Based Therapies assistance of a caregiver. Insulin doses challenges and requires distinct treat-
Oral dipeptidyl peptidase 4 (DPP-4) inhib- should be titrated to meet individu- ment considerations (68). Insulin is an
itors have few side effects and minimal alized glycemic targets and to avoid
ia
Glucagon-like peptide 1 (GLP-1) re- many older patients. Multiple daily in- form of basal insulin even when they are
ceptor agonists have demonstrated jections of insulin may be too complex unable to ingest meals. Insulin may be
cardiovascular benefits among patients for the older patient with advanced di- delivered through insulin pump or injec-
ic
with established atherosclerotic car- abetes complications, life-limiting co- tions. Continuous glucose monitoring
diovascular disease, and newer trials existing chronic illnesses, or limited
er
(64). See Section 9 “Pharmacologic simplification. reducing risk of hypoglycemia (69) (see
Approaches to Glycemic Treatment” Section 7 “Diabetes Technology,”
(https://doi.org/10.2337/dc20-S009) Other Factors to Consider https://doi.org/10.2337/dc20-S007,
for a more extensive discussion regarding The needs of older adults with diabetes and section 9 “Pharmacologic Approaches
19
the specific indications for this class. While and their caregivers should be evaluated to Glycemic Treatment,” https://doi.org/
the benefits of this class are emerging, to construct a tailored care plan. Im- 10.2337/dc20-S009). In the older patient
these drugs are injectable agents (with the paired social functioning may reduce with type 1 diabetes, administration of
20
exception of oral semaglutide), which these patients’ quality of life and increase insulin may become more difficult as
require visual, motor, and cognitive skills the risk of functional dependency (7). The complications, cognitive impairment,
for appropriate administration. They may
©
patient’s living situation must be consid- and functional impairment arise. This
also be associated with nausea, vomiting, ered as it may affect diabetes manage- increases the importance of caregivers
and diarrhea. Given the gastrointestinal ment and support needs. Social and in the lives of these patients. Many older
side effects of this class, GLP-1 receptor instrumental support networks (e.g., patients with type 1 diabetes require
agonists may not be preferred in older adult children, caretakers) that pro- placement in long-term care (LTC) settings
patients who are experiencing unex- vide instrumental or emotional sup- (i.e., nursing homes and skilled nursing
plained weight loss. port for older adults with diabetes facilities) and, unfortunately, these pa-
should be included in diabetes manage- tients encounter providers that are un-
Sodium–Glucose Cotransporter ment discussions and shared decision- familiar with insulin pumps or CGM. Some
2 Inhibitors making. providers may be unaware of the distinc-
Sodium–glucose cotransporter 2 inhibi- Older adults in assisted living facilities tion between type 1 and type 2 diabetes. In
tors are administered orally, which may may not have support to administer these instances, the patient or the patient’s
care.diabetesjournals.org Older Adults S159
family may be more familiar with di- inadvertently lead to decreased food (16.7 mmol/L) over 2 consecutive
abetes management than the providers. intake and contribute to unintentional days,
Education of relevant support staff and weight loss and undernutrition. Diets d) any reading is too high for the
providers in rehabilitation and LTC set- tailored to a patient’s culture, preferen- glucometer, or
tings regarding insulin dosing and use of ces, and personal goals may increase e) the patient is sick, with vomiting,
pumps and CGM is recommended as quality of life, satisfaction with meals, symptomatic hyperglycemia, or
part of general diabetes education (see and nutrition status (72). It may be help- poor oral intake.
recommendations 12.15 and 12.16). ful to give insulin after meals to ensure
n
that the dose is appropriate for the END-OF-LIFE CARE
TREATMENT IN SKILLED NURSING amount of carbohydrate the patient
tio
Recommendations
FACILITIES AND NURSING HOMES consumed in the meal.
12.17 When palliative care is needed
Recommendations in older adults with diabetes,
a
12.15 Consider diabetes education Hypoglycemia providers should initiate con-
ci
for the staff of long-term care Older adults with diabetes in LTC are versations regarding the goals
and rehabilitation facilities especially vulnerable to hypoglycemia. and intensity of care. Strict
so
to improve the management They have a disproportionately high glucose and blood pressure
of older adults with diabetes. number of clinical complications and control may not be necessary
E comorbidities that can increase hypogly- E, and reduction of therapy
As
12.16 Patients with diabetes residing cemia risk: impaired cognitive and renal may be appropriate. Similarly,
in long-term care facilities function, slowed hormonal regulation the intensity of lipid manage-
need careful assessment to and counterregulation, suboptimal hy- ment can be relaxed, and
s
establish individualized glyce- dration, variable appetite and nutri- withdrawal of lipid-lowering
tional intake, polypharmacy, and slowed
te
mic goals and to make therapy may be appropriate. A
appropriate choices of glucose- intestinal absorption (73). Oral agents 12.18 Overall comfort, prevention
may achieve similar glycemic out-
be
lowering agents based on their of distressing symptoms, and
clinical and functional status. E comes in LTC populations as basal insu- preservation of quality of life
lin (50,74). and dignity are primary goals
ia
Management of diabetes in the LTC Another consideration for the LTC for diabetes management at
setting is unique. Individualization of setting is that, unlike in the hospital the end of life. C
D
health care is important in all patients; setting, medical providers are not re-
however, practical guidance is needed quired to evaluate the patients daily.
for medical providers as well as the LTC According to federal guidelines, assess- The management of the older adult
an
staff and caregivers (70). Training should ments should be done at least every at the end of life receiving palliative
include diabetes detection and institu- 30 days for the first 90 days after ad- medicine or hospice care is a unique
mission and then at least once every situation. Overall, palliative medicine
ic
procedures for prevention and manage- may actually be seen more frequently, and prevention (pain, hypoglycemia,
ment of hypoglycemia. the concern is that patients may have hyperglycemia, and dehydration), and
uncontrolled glucose levels or wide ex- preservation of dignity and quality of life
Am
cursions without the practitioner being in patients with limited life expectancy
Resources notified. Providers may make adjust- (71,75). In the setting of palliative care,
Staff of LTC facilities should receive ap- ments to treatment regimens by tele- providers should initiate conversations
propriate diabetes education to improve phone, fax, or in person directly at the regarding the goals and intensity of
19
the management of older adults with LTC facilities provided they are given diabetes care; strict glucose and blood
diabetes. Treatments for each patient timely notification of blood glucose man- pressure control may not be consistent
should be individualized. Special man- agement issues from a standardized with achieving comfort and quality of
20
agement considerations include the alert system. life. In a multicenter trial, withdrawal of
need to avoid both hypoglycemia and The following alert strategy could be statins among patients in palliative care
the complications of hyperglycemia
©
mindful of quality of life. Careful mon- from https://www.niddk.nih.gov/about-niddk/ MIND randomised trial. Diabetologia 2017;60:
itoring of oral intake is warranted. The strategic-plans-reports/diabetes-in-america-3rd- 69–80
edition 17. Ghezzi L, Scarpini E, Galimberti D. Disease-
decision process may need to involve 2. Kirkman MS, Briscoe VJ, Clark N, et al. Di- modifying drugs in Alzheimer’s disease. Drug Des
the patient, family, and caregivers, abetes in older adults. Diabetes Care 2012;35: Devel Ther 2013;7:1471–1478
leading to a care plan that is both 2650–2664 18. Craft S, Baker LD, Montine TJ, et al. Intranasal
convenient and effective for the goals 3. Young-Hyman D, de Groot M, Hill-Briggs F, insulin therapy for Alzheimer disease and am-
of care (81). The pharmacologic therapy Gonzalez JS, Hood K, Peyrot M. Psychosocial care nestic mild cognitive impairment: a pilot clinical
for people with diabetes: a position statement trial. Arch Neurol 2012;69:29–38
may include oral agents as first line, of the American Diabetes Association. Diabetes 19. Freiherr J, Hallschmid M, Frey WH 2nd, et al.
n
followed by a simplified insulin regi- Care 2016;39:2126–2140 Intranasal insulin as a treatment for Alzheimer’s
men. If needed, basal insulin can be
tio
4. Institute of Medicine of the National Acad- disease: a review of basic research and clinical
implemented, accompanied by oral emies. Cognitive Aging: Progress in Understand- evidence. CNS Drugs 2013;27:505–514
ing and Opportunities for Action, 2015. Accessed 20. Alagiakrishnan K, Sankaralingam S, Ghosh M,
agents and without rapid-acting insulin.
31 October 2019. Available from http:// Mereu L, Senior P. Antidiabetic drugs and their
a
Agents that can cause gastrointestinal nationalacademies.org/hmd/Reports/2015/ potential role in treating mild cognitive impair-
ci
symptoms such as nausea or excess Cognitive-Aging.aspx ment and Alzheimer’s disease. Discov Med 2013;
weight loss may not be good choices 5. Kimbro LB, Mangione CM, Steers WN, et al. 16:277–286
so
in this setting. As symptoms progress, Depression and all-cause mortality in persons 21. Tomlin A, Sinclair A. The influence of cog-
with diabetes mellitus: are older adults at higher nition on self-management of type 2 diabetes in
some agents may be slowly tapered and
risk? Results from the Translating Research Into older people. Psychol Res Behav Manag 2016;9:
discontinued. Action for Diabetes Study. J Am Geriatr Soc 2014;
As
7–20
Different patient categories have been 62:1017–1022 22. National Institute on Aging. Assessing cog-
proposed for diabetes management in 6. Sudore RL, Karter AJ, Huang ES, et al. Symp- nitive impairment in older patients. Accessed
those with advanced disease (39). tom burden of adults with type 2 diabetes across 27 August 2019. Available from https://www.nia
the disease course: diabetes & aging study. J Gen .nih.gov/health/assessing-cognitive-impairment-
s
Intern Med 2012;27:1674–1681 older-patients
1. A stable patient: Continue with the
te
7. Laiteerapong N, Karter AJ, Liu JY, et al. Cor- 23. Alzheimer’s Association. Cognitive assess-
patient’s previous regimen, with a relates of quality of life in older adults with ment Accessed 27 August 2019. Available
focus on the prevention of hypoglyce- diabetes: the Diabetes & Aging Study. Diabetes from https://alz.org/professionals/healthcare-
be
mia and the management of hyper- Care 2011;34:1749–1753 professionals/cognitive-assessment
glycemia using blood glucose 8. McClintock MK, Dale W, Laumann EO, Waite L. 24. Folstein MF, Folstein SE, McHugh PR. “Mini-
Empirical redefinition of comprehensive health mental state”: a practical method for grading the
testing, keeping levels below the
ia
and well-being in the older adults of the United cognitive state of patients for the clinician. J
renal threshold of glucose. There States. Proc Natl Acad Sci U S A 2016;113:E3071– Psychiatr Res 1975;12:189–198
D
is very little role for A1C monitoring 3080 25. Borson S, Scanlan JM, Chen P, Ganguli M. The
and lowering. 9. Laiteerapong N, Iveniuk J, John PM, Laumann Mini-Cog as a screen for dementia: validation
2. A patient with organ failure: Prevent- EO, Huang ES. Classification of older adults who in a population-based sample. J Am Geriatr Soc
an
with type 1 diabetes, insulin admin- diabetes: the Health and Retirement Study. Med impairment. J Am Geriatr Soc 2005;53:695–
Care 2010;48:327–334 699
er
systematic overview of prospective observational Panel on Care of Older Adults with Diabetes
diabetes, agents that may cause hy- studies. Diabetologia 2005;48:2460–2469 Mellitus. Guidelines abstracted from the Amer-
poglycemia should be reduced in 12. Roberts RO, Knopman DS, Przybelski SA, ican Geriatrics Society Guidelines for Improving
dose. The main goal is to avoid hy- et al. Association of type 2 diabetes with brain the Care of Older Adults with Diabetes Mellitus:
atrophy and cognitive impairment. Neurology 2013 update. J Am Geriatr Soc 2013;61:2020–
poglycemia, allowing for glucose val- 2014;82:1132–1141 2026
19
ues in the upper level of the desired 13. Xu WL, von Strauss E, Qiu CX, Winblad B, 28. American Psychological Association. Guide-
target range. Fratiglioni L. Uncontrolled diabetes increases lines for the evaluation of dementia and age-
3. A dying patient: For patients with the risk of Alzheimer’s disease: a population- related cognitive change. Accessed 31 October
20
type 2 diabetes, the discontinuation based cohort study. Diabetologia 2009;52: 2019. Available from http://www.apa.org/
1031–1039 practice/guidelines/dementia.aspx
of all medications may be a reason- 14. Yaffe K, Falvey C, Hamilton N, et al. Diabetes, 29. Lee AK, Lee CJ, Huang ES, Sharrett AR, Coresh
able approach, as patients are unlikely
©
glucose control, and 9-year cognitive decline J, Selvin E. Risk factors for severe hypoglycemia in
to have any oral intake. In patients among older adults without dementia. Arch black and white adults with diabetes: the Ath-
with type 1 diabetes, there is no Neurol 2012;69:1170–1175 erosclerosis Risk in Communities (ARIC) Study.
consensus, but a small amount of 15. Launer LJ, Miller ME, Williamson JD, et al.; Diabetes Care 2017;40:1661–1667
ACCORD MIND investigators. Effects of intensive 30. Feinkohl I, Aung PP, Keller M, et al.; Edin-
basal insulin may maintain glucose glucose lowering on brain structure and func- burgh Type 2 Diabetes Study (ET2DS) Investiga-
levels and prevent acute hyperglyce- tion in people with type 2 diabetes (ACCORD tors. Severe hypoglycemia and cognitive decline
mic complications. MIND): a randomised open-label substudy. in older people with type 2 diabetes: the Edin-
Lancet Neurol 2011;10:969–977 burgh type 2 diabetes study. Diabetes Care 2014;
16. Murray AM, Hsu F-C, Williamson JD, et al.; 37:507–515
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35. Bandeen-Roche K, Seplaki CL, Huang J, et al. control. JAMA Intern Med 2015;175:356–362 66. Miller RG, Secrest AM, Sharma RK, Songer TJ,
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37. NGSP. Factors that interfere with HbA1c with type 2 diabetes mellitus: a retrospective Morb Mortal Wkly Rep 2018;67:359–361
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Guideline For Managing Older People With SN, Kosiborod M. Use of intensive glycemic people with type 1 diabetes. Diabetes 2004;53:
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39. Angelo M, Ruchalski C, Sproge BJ. An ap- 55. Weiner JZ, Gopalan A, Mishra P, et al. use Graham C; DIAMOND Study Group. Continuous
proach to diabetes mellitus in hospice and and discontinuation of insulin treatment among glucose monitoring in older adults with type
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palliative medicine. J Palliat Med 2011;14: adults aged 75 to 79 years with type 2 diabetes. 1 and type 2 diabetes using multiple daily in-
83–87 JAMA Intern Med. 23 September 2019 [Epub jections of insulin: results from the DIAMOND
40. Beckett NS, Peters R, Fletcher AE, et al.; ahead of print]. DOI: 10.1001/jamainternmed. trial. J Diabetes Sci Technol 2017;11:1138–1146
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HYVET Study Group. Treatment of hypertension 2019.3759 70. Munshi MN, Florez H, Huang ES, et al.
in patients 80 years of age or older. N Engl J Med 56. Munshi MN, Slyne C, Segal AR, Saul N, Lyons Management of diabetes in long-term care and
2008;358:1887–1898 C, Weinger K. Simplification of insulin regimen in skilled nursing facilities: a position statement of
41. de Boer IH, Bangalore S, Benetos A, et al. older adults and risk of hypoglycemia. JAMA the American Diabetes Association. Diabetes Care
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Care 2017;40:1273–1284 deintensification of blood pressure and glycemic et al. Diabetes mellitus in older people: position
42. Park SW, Goodpaster BH, Strotmeyer ES, medication treatment based on levels of control statement on behalf of the International Asso-
et al. Decreased muscle strength and quality in and life expectancy in older patients with di- ciation of Gerontology and Geriatrics (IAGG), the
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older adults with type 2 diabetes: the health, abetes mellitus. JAMA Intern Med 2015;175: European Diabetes Working Party for Older
aging, and body composition study. Diabetes 1942–1949 People (EDWPOP), and the International Task
2006;55:1813–1818 58. Abdelhafiz AH, Sinclair AJ. Deintensification Force of Experts in Diabetes. J Am Med Dir Assoc
43. Park SW, Goodpaster BH, Strotmeyer ES, of hypoglycaemic medications-use of a system- 2012;13:497–502
et al.; Health, Aging, and Body Composition atic review approach to highlight safety concerns 72. Dorner B, Friedrich EK, Posthauer ME. Prac-
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Study. Accelerated loss of skeletal muscle in older people with type 2 diabetes. J Diabetes tice paper of the American Dietetic Association:
strength in older adults with type 2 diabetes: Complications 2018;32:444–450 individualized nutrition approaches for older
the Health, Aging, and Body Composition Study. 59. Seidu S, Kunutsor SK, Topsever P, Hambling adults in health care communities. J Am Diet
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Diabetes Care 2007;30:1507–1512 CE, Cos FX, Khunti K. Deintensification in older Assoc 2010;110:1554–1563
44. Villareal DT, Chode S, Parimi N, et al. Weight patients with type 2 diabetes: a systematic re- 73. Migdal A, Yarandi SS, Smiley D, Umpierrez
loss, exercise, or both and physical function in view of approaches, rates and outcomes. Di- GE. Update on diabetes in the elderly and in
abetes Obes Metab 2019;21:1668–1679 nursing home residents. J Am Med Dir Assoc
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a randomized clinical trial. JAMA Intern Med 79. Ford-Dunn S, Smith A, Quin J. Management diabetes: from the Diabetes Care Program of
2015;175:691–700 of diabetes during the last days of life: attitudes Nova Scotia (DCPNS) and the Palliative and
77. Dunning T, Martin P. Palliative and end of life of consultant diabetologists and consultant pal- Therapeutic Harmonization (PATH) program.
care of people with diabetes: issues, challenges liative care physicians in the UK. Palliat Med J Am Med Dir Assoc 2013;14:801–808
and strategies. Diabetes Res Clin Pract 2018;143: 2006;20:197–203 82. Munshi MN, Slyne C, Segal AR, Saul N, Lyons
454–463 80. Petrillo LA, Gan S, Jing B, Lang-Brown S, C, Weinger K. Liberating A1C goals in older
78. Bouça-Machado R, Rosário M, Alarcão J, Boscardin WJ, Lee SJ. Hypoglycemia in hospice adults may not protect against the risk of
Correia-Guedes L, Abreu D, Ferreira JJ. Clinical patients with type 2 diabetes in a national sample of hypoglycemia. J Diabetes Complications 2017;
trials in palliative care: a systematic review of nursing homes.JAMAInternMed2018;178:713–715 31:1197–1199
their methodological characteristics and of the 81. Mallery LH, Ransom T, Steeves B, Cook B, 83. Leung E, Wongrakpanich S, Munshi MN.
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quality of their reporting. BMC Palliat Care 2017; Dunbar P, Moorhouse P. Evidence-informed guide- Diabetes management in the elderly. Diabetes
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16:10 lines for treating frail older adults with type 2 Spectr 2018;31:245–253
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Diabetes Care Volume 43, Supplement 1, January 2020 S163
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Diabetes Care 2020;43(Suppl. 1):S163–S182 | https://doi.org/10.2337/dc20-S013
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The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
s
the components of diabetes care, general treatment goals and guidelines, and tools
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to evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible
be
for updating the Standards of Care annually, or more frequently as warranted. For a
detailed description of ADA standards, statements, and reports, as well as the evidence-
ia
grading system for ADA’s clinical practice recommendations, please refer to the
Standards ofCareIntroduction(https://doi.org/10.2337/dc20-SINT).Readerswhowishto
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The management of diabetes in children and adolescents cannot simply be derived from
care routinely provided to adults with diabetes. The epidemiology, pathophysiology,
developmental considerations, and response to therapy in pediatric-onset diabetes
ic
are different from adult diabetes. There are also differences in recommended care
for children and adolescents with type 1 as opposed to type 2 diabetes. This section
er
first addresses care for children and adolescents with type 1 diabetes and next addresses
care for children and adolescents with type 2 diabetes. Figure 13.1 provides guidance
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with diabetes develops into adulthood. Due to the nature of clinical research in children,
the recommendations for children and adolescents with diabetes are less likely
to be based on clinical trial evidence. However, expert opinion and a review of
20
available and relevant experimental data are summarized in the American Diabetes
Association (ADA) position statements “Type 1 Diabetes in Children and Adoles-
cents” (1) and “Evaluation and Management of Youth-Onset Type 2 Diabetes” (2).
©
The ADA consensus report “Youth-Onset Type 2 Diabetes Consensus Report: Current
Status, Challenges, and Priorities” (3) characterizes type 2 diabetes in children and evalu-
ates treatment options but also discusses knowledge gaps and recruitment
Suggested citation: American Diabetes Associa-
challenges in clinical and translational research in youth-onset type 2 diabetes.
tion. 13. Children and adolescents: Standards of
Monogenic diabetes (neonatal diabetes and maturity-onset diabetes in the young Medical Care in Diabetesd2020. Diabetes Care
[MODY]), which often present in youth, are discussed in section 2 “Classification and 2020;43(Suppl. 1):S163–S182
Diagnosis of Diabetes” (https://doi.org/10.2337/dc20-S002). © 2019 by the American Diabetes Association.
Readers may use this article as long as the work
TYPE 1 DIABETES is properly cited, the use is educational and not
for profit, and the work is not altered. More infor-
Type 1 diabetes is the most common form of diabetes in youth (4), although mation is available at http://www.diabetesjournals
recent data suggest that it may account for a large proportion of cases diagnosed in .org/content/license.
S164 Children and Adolescents Diabetes Care Volume 43, Supplement 1, January 2020
adult life (5). The provider must consider diabetes management throughout child- Physical Activity and Exercise
the unique aspects of care and manage- hood and adolescence. Health care
Recommendations
ment of children and adolescents with providers in the diabetes care team
13.5 Exercise is recommended for all
type 1 diabetes, such as changes in insu- who care for children and adolescents
youth with type 1 diabetes with
lin sensitivity related to physical growth must be capable of evaluating the edu-
the goal of 60 min of moderate-
and sexual maturation, ability to pro- cational, behavioral, emotional, and
to-vigorous intensity aerobic
vide self-care, supervision in the childcare psychosocial factors that impact imple-
activity daily, with vigorous
and school environment, neurological mentation of a treatment plan and must
muscle-strengthening and bone-
n
vulnerability to hypoglycemia and hy- work with the individual and family to
strengthening activities at least
overcome barriers or redefine goals as
tio
perglycemia in young children, and pos- 3 days per week. C
appropriate. Diabetes self-management
sible adverse neurocognitive effects of 13.6 Education about frequent pat-
diabetic ketoacidosis (DKA) (6,7). Atten- education and support requires peri-
terns of glycemia during and
a
tion to family dynamics, developmental odic reassessment, especially as the
after exercise, which may in-
ci
stages, and physiologic differences re- youth grows, develops, and acquires the
clude initial transient hyperglyce-
lated to sexual maturity is essential in need for greater independent self-care
mia followed by hypoglycemia,
so
skills. In addition, it is necessary to as-
developing and implementing an optimal is essential. Families should
sess the educational needs and skills of
diabetes treatment plan (8). also receive education on pre-
day care providers, school nurses, or other
As
A multidisciplinary team of special- vention and management of
school personnel who participate in the
ists trained in pediatric diabetes man- hypoglycemia during and after
care of the child with diabetes (9).
agement and sensitive to the challenges exercise, including ensuring
of children and adolescents with type patients have a preexercise glu-
s
1 diabetes and their families should Nutrition Therapy cose level of 90–250 mg/dL (5.0–
te
provide care for this population. It is 13.9 mmol/L) and accessible
Recommendations
essential that diabetes self-management carbohydrates before engaging
13.2 Individualized medical nutrition
be
education and support, medical nutri- in activity, individualized accord-
therapy is recommended for
tion therapy, and psychosocial support ing to the type/intensity of the
children and adolescents with
be provided at diagnosis and regularly planned physical activity. E
ia
edge by individuals experienced with the mia during exercise, after exercise,
13.3 Monitoring carbohydrate in-
biological, educational, nutritional, be- and overnight following exercise,
take, whether by carbohydrate
an
havioral, and emotional needs of the which may include reducing pran-
counting or experience-based
growing child and family. The appropri- dial insulin dosing for the meal/
estimation, is key to achieving
ate balance between adult supervision snack preceding (and, if needed,
optimal glycemic control. B
ic
schedules, physical activity, and the pa- Exercise positively affects insulin sensitivity,
mentally appropriate individual- tient’s and family’s abilities in numeracy, physical fitness, strength building, weight
ized diabetes self-management literacy, and self-management should be management, social interaction, mood,
education and support according considered. Visits with a registered di- self-esteem building, and creation of
to national standards at diagno- etitian nutritionist should include assess- healthful habits for adulthood, but it
sis and routinely thereafter. B ment for changes in food preferences also has the potential to cause both
over time, access to food, growth and hypoglycemia and hyperglycemia.
No matter how sound the medical reg- development, weight status, cardiovas- See below for strategies to mitigate
imen, it can only be effective if the cular risk, and potential for eating dis- hypoglycemia risk and minimize hyper-
family and/or affected individuals are orders. Dietary adherence is associated glycemia with exercise. For an in-depth
able to implement it. Family involve- with better glycemic control in youth discussion, see recently published re-
ment is a vital component of optimal with type 1 diabetes (10). views and guidelines (11–13).
care.diabetesjournals.org Children and Adolescents S165
n
be medically evaluated for comorbid weight status and encourage a healthy
tally appropriate. E
conditions or diabetes complications diet, exercise, and healthy weight as key
tio
13.15 Starting at puberty, precon-
that may restrict participation in an components of pediatric type 1 diabetes
ception counseling should be
exercise program. As hyperglycemia can care.
incorporated into routine di-
a
occur before, during, and after physi-
School and Child Care abetes care for all girls of child-
ci
cal activity, it is important to ensure
As a large portion of a child’s day is spent bearing potential. A
that the elevated glucose level is not
in school, close communication with and 13.16 Begin screening youth with
so
related to insulin deficiency that would
the cooperation of school or day care type 1 diabetes for eating dis-
lead to worsening hyperglycemia with
personnel are essential for optimal di- orders between 10 and 12
exercise and ketosis risk. Intense activ-
As
abetes management, safety, and maxi- years of age. The Diabetes Eat-
ity should be postponed with marked
mal academic opportunities. Refer to the ing Problems Survey-Revised
hyperglycemia (glucose $350 mg/dL
[19.4 mmol/L]), moderate to large urine ADA position statements “Diabetes Care (DEPS-R) is a reliable, valid,
ketones, and/or b-hydroxybutyrate in the School Setting” (26) and “Care of and brief screening tool for
s
Young Children With Diabetes in the identifying disturbed eating
(B-OHB) .1.5 mmol/L. Caution may
te
Child Care Setting” (27) for additional behavior. B
be needed when B-OHB levels are
$0.6 mmol/L (10,11). details.
be
Rapid and dynamic cognitive, develop-
The prevention and treatment of
mental, and emotional changes occur
hypoglycemia associated with physical Psychosocial Issues
during childhood, adolescence, and
ia
should be 90–250 mg/dL (5.0–13.9 (35). Consider assessing youth for di-
appropriate family involve- abetes distress, generally starting at 7 or
mmol/L). Consider additional carbo-
ment in diabetes management 8 years of age (36). Consider screening
hydrate intake during and/or after
20
tasks for children and adoles- for depression and disordered eating
exercise, depending on the duration
cents, recognizing that prema- behaviors using available screening
and intensity of physical activity, to
ture transfer of diabetes care tools (28,37). Early detection of depres-
©
n
control (38,39). As diabetes-specific fessional on pediatric multidisciplinary
nology, and/or continuous glu-
family conflict is related to poorer teams highlights the importance of at-
tio
cose monitors; cannot check
adherence and glycemic control, it is tending to the psychosocial issues of
blood glucose regularly; or
appropriate to inquire about such diabetes. These psychosocial factors
have nonglycemic factors that
a
conflict during visits and to either are significantly related to self-manage-
increase A1C (e.g., high glyca-
ci
help to negotiate a plan for resolution ment difficulties, suboptimal glycemic
tors). B
or refer to an appropriate mental control, reduced quality of life, and
13.23 Even less-stringent A1C goals
so
health specialist (40). Monitoring of higher rates of acute and chronic di-
(such as ,8% [64 mmol/mol])
social adjustment (peer relationships) abetes complications.
may be appropriate for pa-
and school performance can facili-
As
tients with a history of severe
tate both well-being and academic Glycemic Control
hypoglycemia, limited life ex-
achievement (41). Suboptimal glyce-
Recommendations pectancy, or extensive comor-
mic control is a risk factor for under-
13.17 The majority of children and bid conditions. B
s
performance at school and increased
adolescents with type 1 diabe- 13.24 Providers may reasonably sug-
absenteeism (42).
te
tes should be treated with gest more-stringent A1C goals
Shared decision-making with youth
intensive insulin regimens, (such as ,6.5% [48 mmol/
regarding the adoption of regimen com-
be
either via multiple daily injec- mol]) for selected individ-
ponents and self-management behav-
tions or continuous subcuta- ual patients if they can be
iors can improve diabetes self-efficacy,
neous insulin infusion. A achieved without significant
ia
Preconception counseling resources tai- try data indicate that A1C targets can be
13.20 Automated insulin delivery
lored for adolescents are available at no achieved in children, including those ,6
systems appear to improve
cost through the ADA (46). Refer to the years, without increased risk of severe
glycemic control and reduce
ADA position statement “Psychosocial Care hypoglycemia (51,52). Recent data have
hypoglycemia in children and
for People With Diabetes” for further de- demonstrated that the use of continuous
should be considered in chil-
tails (36). glucose monitors lowered A1C and
dren with type 1 diabetes. B
Youth with type 1 diabetes have an increased time in range in adolescents
13.21 A1C goals must be individual-
increased risk of disordered eating be- and young adults, and, in children ,8
ized and reassessed over time.
havior as well as clinical eating disorders years old, was associated with lower risk
An A1C of ,7% (53 mmol/mol)
with serious short-term and long-term of hypoglycemia (53,54). Please refer to
is appropriate for many chil-
negative effects on diabetes outcomes Section 7 “Diabetes Technology” (https://
dren. B
and health in general. It is important to doi.org/10.2337/dc20-S007) for more
care.diabetesjournals.org Children and Adolescents S167
information on the use of blood glucose continuous glucose monitors are not other autoimmune conditions, such as
meters, continuous glucose monitors, and currently approved for use in children Addison disease (primary adrenal insuf-
insulin pumps. More information on in- and adolescents. A strong relationship ficiency), autoimmune hepatitis, autoim-
sulin injection technique can be found exists between frequency of blood glu- mune gastritis, dermatomyositis, and
in Section 9 “Pharmacologic Approaches cose monitoring and glycemic stability myasthenia gravis, occur more com-
to Glycemic Treatment (https://doi.org/ (77–86). Recent data with newer devi- monly in the population with type 1
10.2337/dc20-S009).” ces and insulins indicate that the risk of diabetes than in the general pediatric
The Diabetes Control and Complica- hypoglycemia with lower A1C is less than population and should be assessed and
n
tions Trial (DCCT), which did not enroll it was before (52,76,87–94). Some data monitored as clinically indicated. In ad-
children ,13 years of age, demonstrated suggest that there could be a threshold dition, relatives of patients should be
tio
that near normalization of blood glucose where lower A1C is associated with more offered testing for islet autoantibodies
levels was more difficult to achieve in hypoglycemia (95,96); however, the con- through research studies (e.g., TrialNet)
a
adolescents than in adults. Nevertheless, fidence intervals were large, suggesting for early diagnosis of preclinical type 1
ci
the increased use of basal-bolus regi- great variability. diabetes (stages 1 and 2).
mens, insulin pumps, frequent blood In selecting glycemic targets, the
so
glucose monitoring, goal setting, and long-term health benefits of achieving a Thyroid Disease
improved patient education in youth lower A1C should be balanced against
from infancy through adolescence has the risks of hypoglycemia and the de- Recommendations
As
been associated with more children velopmental burdens of intensive regi- 13.26 Consider testing children with
reaching the blood glucose targets rec- mens in children and youth. In addition, type 1 diabetes for antithyroid
ommended by ADA (55–58), particularly achieving lower A1C levels is likely fa- peroxidase and antithyroglob-
ulin antibodies soon after
s
in patients of families in which both the cilitated by setting lower A1C targets
parents and the child with diabetes par- (51,97). Lower goals may be possible diagnosis. B
ticipate jointly to perform the required
diabetes-related tasks. Furthermore, diabetes. te
during the “honeymoon” phase of type 1 13.27 Measure thyroid-stimulating
hormone concentrations at di-
be
studies documenting neurocognitive agnosis when clinically stable
Key Concepts in Setting Glycemic or soon after glycemic control
imaging differences related to hy-
Targets has been established. If nor-
ia
targets (6).
on a benefit-risk assessment. patient has positive thyroid
Lower A1C in adolescence and young
c Blood glucose targets should be antibodies or develops symp-
adulthood is associated with lower risk
an
Autoimmune Conditions
velopment and function. Additional fac-
;25% of children with type 1 diabe-
tors (69–72) that contribute to adverse Recommendation
tes have thyroid autoantibodies (105);
effects on brain development and func- 13.25 Assess for additional autoim-
20
weight loss, etc. Therefore, if performed IgA deficiency, screening can include Management of Cardiovascular Risk
at diagnosis and slightly abnormal, thy- measuring IgG tissue transglutaminase Factors
roid function tests should be repeated antibodies or IgG deamidated gliadin Hypertension Screening
soon after a period of metabolic stability peptide antibodies. Because most cases
Recommendations
and achievement of glycemic targets. of celiac disease are diagnosed within
13.31 Blood pressure should be mea-
Subclinical hypothyroidism may be the first 5 years after the diagnosis of
sured at each routine visit. Chil-
associated with increased risk of symp- type 1 diabetes, screening should be
dren found to have elevated
tomatic hypoglycemia (109) and reduced considered at the time of diagnosis and
blood pressure (systolic blood
n
linear growth rate. Hyperthyroidism repeated at 2 and then 5 years (112) or
pressure or diastolic blood
if clinical symptoms indicate, such as
tio
alters glucose metabolism and usu- pressure $90th percentile for
poor growth or increased hypoglycemia
ally causes deterioration of glycemic age, sex, and height or, in
(113,115).
control. adolescents $13 years, systolic
a
Although celiac disease can be di-
blood pressure 120–129 mmHg
ci
agnosed more than 10 years after di-
Celiac Disease with diastolic blood pressure
abetes diagnosis, there are insufficient
,80 mmHg) or hypertension
so
Recommendations data after 5 years to determine the
(systolic blood pressure or di-
13.28 Screen children with type 1 optimal screening frequency. Measure-
astolic blood pressure $95th
diabetes for celiac disease by ment of tissue transglutaminase anti-
As
percentile for age, sex, and
measuring IgA tissue transglu- body should be considered at other
height or, in adolescents $13
taminase (tTG) antibodies, times in patients with symptoms sug-
years, systolic blood pressure
with documentation of normal gestive of celiac disease (112). Moni-
$130 mmHg or diastolic blood
s
total serum IgA levels, soon toring for symptoms should include
pressure $80 mmHg) should
assessment of linear growth and weight
te
after the diagnosis of diabetes, have elevated blood pressure
or IgG to tTG and deamida- gain (113,115). A small bowel biopsy
confirmed on three separate
in antibody-positive children is recom-
be
ted gliadin antibodies if IgA days. B
deficient. B mended to confirm the diagnosis (119).
13.29 Repeat screening within European guidelines on screening for
ia
2 years of diabetes diagno- celiac disease in children (not specific to Hypertension Treatment
sis and then again after children with type 1 diabetes) suggest
Recommendations
D
n
control and other cardiovascular risk
height or ,120/,80 mmHg mmol/L) and one or more car-
factors can change dramatically during
tio
in children $13 years. E diovascular disease risk factors,
adolescence (135).
following reproductive counsel-
Treatment. Pediatric lipid guidelines pro-
Blood pressure measurements should ing because of the potential
a
vide some guidance relevant to children
be performed using the appropriate size teratogenic effects of statins. E
with type 1 diabetes (124,132,136,137);
ci
cuff with the child seated and relaxed. 13.40 The goal of therapy is an LDL
however, there are few studies on
Hypertension should be confirmed on at cholesterol value ,100 mg/dL
so
modifying lipid levels in children with
least three separate days. Evaluation (2.6 mmol/L). E
type 1 diabetes. A 6-month trial of di-
should proceed as clinically indicated
etary counseling produced a signifi-
As
(124). Treatment is generally initiated Population-based studies estimate that
cant improvement in lipid levels (138);
with an ACE inhibitor, but an angiotensin 14–45% of children with type 1 diabe-
likewise, a lifestyle intervention trial
receptor blocker can be used if the ACE tes have two or more atherosclerotic
with 6 months of exercise in adoles-
inhibitor is not tolerated (e.g., due to cardiovascular disease (ASCVD) risk
s
cents demonstrated improvement in
cough) (125). factors (126–128), and the prevalence lipid levels (139). Data from the SEARCH
te
of cardiovascular disease (CVD) risk factors for Diabetes in Youth (SEARCH) study
Dyslipidemia Testing increases with age (128) and among racial/ show that improved glucose over a 2-year
be
ethnic minorities (21), with girls having a period is associated with a more favor-
Recommendations
higher risk burden than boys (127). able lipid profile; however, improved gly-
13.36 Initial lipid testing should be Pathophysiology. The atherosclerotic pro- cemia alone will not normalize lipids in
ia
youth with type 1 diabetes may have rizes children with type 1 diabetes in the
ing should be performed at
subclinical CVD within the first decade of highest tier for cardiovascular risk and
9-11 years of age. B Initial
diagnosis (129–131). Studies of carotid recommends both lifestyle and pharma-
ic
terol level with confirmatory consistent results (124,125). LDL cholesterol levels (137,140). Initial
testing with a fasting lipid Screening. Diabetes predisposes to de- therapy should be with a nutrition plan
velopment of accelerated arteriosclero- that restricts saturated fat to 7% of to-
Am
panel.
13.37 If LDL cholesterol values are sis. Lipid evaluation for these patients tal calories and dietary cholesterol to
within the accepted risk level contributes to risk assessment and iden- 200 mg/day. Data from randomized clin-
(,100 mg/dL [2.6 mmol/L]), a tifies an important proportion of those ical trials in children as young as 7 months
lipid profile repeated every with dyslipidemia. Therefore, initial of age indicate that this diet is safe and
19
3 years is reasonable. E screening should be done soon after does not interfere with normal growth
diagnosis. If the initial screen is normal, and development (141).
subsequent screening may be done at Neither long-term safety nor cardio-
20
Dyslipidemia Treatment 9–11 years of age, which is a stable time vascular outcome efficacy of statin ther-
for lipid assessment in children (132). apy has been established for children;
Recommendations
©
Non-HDL cholesterol level has been however, studies have shown short-term
13.38 If lipids are abnormal, initial
identified as a significant predictor of safety equivalent to that seen in adults
therapy should consist of op-
the presence of atherosclerosisdas pow- and efficacy in lowering LDL cholesterol
timizing glucose control and
erful as any other lipoprotein cholesterol levels in familial hypercholesterolemia or
medical nutrition therapy to
measure in children and adolescents. For severe hyperlipidemia, improving endo-
limit the amount of calories
both children and adults, non-HDL cho- thelial function and causing regression
from fat to 25–30%, saturated
lesterol level seems to be more predictive of carotid intimal thickening (142,143).
fat to ,7%, cholesterol ,200
of persistent dyslipidemia and, therefore, Statins are not approved for patients
mg/day, avoidance of trans
atherosclerosis and future events than aged ,10 years, and statin treatment
fats, and aim for ;10% calo-
total cholesterol, LDL cholesterol, or HDL should generally not be used in chil-
ries from monounsaturated
cholesterol levels alone. A major advan- dren with type 1 diabetes before this
fats. A
tage of non-HDL cholesterol is that it can age. Statins are contraindicated in
S170 Children and Adolescents Diabetes Care Volume 43, Supplement 1, January 2020
n
Intervention Trial (AdDIT) provides safety Nephropathy Treatment of an eye care professional
tio
data on pharmacologic treatment with Recommendations and based on risk factor as-
an ACE inhibitor and statin in adolescents 13.44 An ACE inhibitor or an angio- sessment, including a history
with type 1 diabetes. of glycemic control with A1C
a
tensin receptor blocker, titrated
to normalization of albumin ex- ,8%. B
ci
Smoking
cretion,maybeconsideredwhen
Retinopathy (like albuminuria) most
so
Recommendations elevated urinary albumin-to-
commonly occurs after the onset of
13.41 Elicit a smoking history at initial creatinine ratio (.30 mg/g) is
documented (two of three urine puberty and after 5–10 years of diabetes
and follow-up diabetes visits;
As
samples obtained over a 6- duration (154). It is currently recognized
discourage smoking in youth
who do not smoke and encour- month interval following ef- that there is low risk of development of
age smoking cessation in those forts to improve glycemic vision-threatening retinal lesions prior to
who do smoke. A control and normalize blood 12 years of age (155,156). A 2019 publi-
s
13.42 E-cigarette use should be dis- pressure). E cation based on the follow-up of the
couraged. A
te
Data from 7,549 participants ,20 years
DCCT adolescent cohort supports lower
frequency of eye examinations than pre-
be
The adverse health effects of smoking of age in the T1D Exchange clinic reg- viously recommended, in particular in
are well recognized with respect to fu- istry emphasize the importance of adolescents with A1C closer to the tar-
ture cancer and CVD risk. Despite this, good glycemic and blood pressure con- get range (157,158). Referrals should
ia
smoking rates are significantly higher trol, particularly as diabetes duration be made to eye care professionals
with expertise in diabetic retinopathy
D
among youth with diabetes than among increases, in order to reduce the risk
youth without diabetes (144,145). In of diabetic kidney disease. The data also and experience in counseling pediatric
youth with diabetes, it is important to underscore the importance of routine patients and families on the importance
an
avoid additional CVD risk factors. Smok- of prevention, early detection, and in-
screening to ensure early diagnosis and
ing increases the risk of onset of albu- tervention.
timely treatment of albuminuria (151).
minuria; therefore, smoking avoidance is An estimation of glomerular filtration
ic
Neuropathy
important to prevent both microvascu- rate (GFR), calculated using GFR estimat-
er
lar and macrovascular complications ing equations from the serum creatinine, Recommendation
(132,146). Discouraging cigarette smok- height, age, and sex (152), should be 13.47 Consider an annual compre-
ing, including e-cigarettes (147,148), is hensive foot exam at the start
Am
(149,150), no persons should be advised for early GFR loss, since estimated GFR is
to use e-cigarettes, either as a way to stop inaccurate at GFR .60 mL/min/1.73 m2 Diabetic neuropathy rarely occurs in
smoking tobacco or as a recreational (152,153). The AdDIT study in adoles- prepubertal children or after only 1–2
20
drug. In younger children, it is important cents with type 1 diabetes demonstrated years of diabetes (154), although data
to assess exposure to cigarette smoke in safety of ACE inhibitor treatment, but the suggest a prevalence of distal peripheral
the home because of the adverse effects treatment did not change the albumin-
©
n
and adolescents, please refer to Sec- (see Table 2.4 for evidence patients with features of type 2 diabetes
tio
tion 2 “Classification and Diagnosis grading of other risk factors). (including obesity and acanthosis nigri-
of Diabetes” (https://doi.org/10.2337/ 13.49 If tests are normal, repeat test- cans) (171). The presence of islet auto-
dc20-S002). For additional support for ing at a minimum of 3-year antibodies has been associated with
a
these recommendations, see the ADA intervals E, or more frequently faster progression to insulin deficiency
(171). At onset, DKA occurs in ;6% of
ci
position statement “Evaluation and Man- if BMI is increasing. C
agement of Youth-Onset Type 2 Di- 13.50 Fasting plasma glucose, 2-h youth aged 10–19 years with type 2 di-
so
abetes” (2). plasma glucose during a 75-g abetes (176). Although uncommon, type 2
Type 2 diabetes in youth has increased oral glucose tolerance test, and diabetes has been observed in prepuber-
tal children under the age of 10, and thus it
As
over the past 20 years, and recent esti- A1C can be used to test for
mates suggest an incidence of ;5,000 prediabetes or diabetes in chil- should be part of the differential in chil-
new cases per year in the U.S. (161). The dren and adolescents. B dren with suggestive symptoms (177).
Centers for Disease Control and Preven- 13.51 Children and adolescents with Finally, obesity (178) contributes to the
s
tion published projections for type 2 overweight or obesity in whom development of type 1 diabetes in some
individuals, which further blurs the lines
te
diabetes prevalence using the SEARCH the diagnosis of type 2 diabe-
database; assuming a 2.3% annual in- tes is being considered should between diabetes types. However, accu-
rate diagnosis is critical, as treatment regi-
be
crease, the prevalence in those under have a panel of pancreatic
20 years of age will quadruple in 40 years autoantibodies tested to ex- mens, educational approaches, dietary
(162,163). clude the possibility of auto- advice, and outcomes differ markedly be-
ia
Evidence suggests that type 2 diabetes immune type 1 diabetes. B tween patients with the two diagnoses.
in youth is different not only from type 1 The significant diagnostic difficulties
D
diabetes but also from type 2 diabe- In the last decade, the incidence posed by MODY are discussed in sec-
tes in adults and has unique features, and prevalence of type 2 diabetes in tion 2 “Classification and Diagnosis of
Diabetes” (https://doi.org/10.2337/dc20-
an
cial minorities and can occur in complex more suitable diagnostic tests than A1C Lifestyle Management
psychosocial and cultural environments, in the pediatric population, especially
Am
which may make it difficult to sustain among certain ethnicities (170), al- Recommendations
healthy lifestyle changes and self- though fasting glucose alone may over- 13.52 All youth with type 2 diabetes
management behaviors (22,165–168). diagnose diabetes in children (171,172). and their families should re-
Additional risk factors associated with In addition, many of these studies do not ceive comprehensive diabe-
type 2 diabetes in youth include adiposity, tes self-management education
19
As with type 1 diabetes, youth with rently available in the pediatric popu- tes and is culturally compe-
type 2 diabetes spend much of the day in lation (173). ADA acknowledges the tent. B
school. Therefore, close communication limited data supporting A1C for diag- 13.53 Youth with overweight/obesity
©
with and the cooperation of school per- nosing type 2 diabetes in children and and type 2 diabetes and their
sonnel are essential for optimal diabetes adolescents. Although A1C is not rec- families should be provided
management, safety, and maximal aca- with developmentally and
ommended for diagnosis of diabetes in
demic opportunities. culturally appropriate compre-
children with cystic fibrosis or symptoms
hensive lifestyle programs that
suggestive of acute onset of type 1 di-
are integrated with diabetes
Screening and Diagnosis abetes, and only A1C assays without
management to achieve 7–10%
interference are appropriate for chil-
Recommendations decrease in excess weight. C
13.48 Risk-based screening for pre- dren with hemoglobinopathies, ADA
13.54 Given the necessity of long-
diabetes and/or type 2 diabe- continues to recommend A1C for
term weight management for
tes should be considered in diagnosis of type 2 diabetes in this
children and adolescents with
population (174,175).
S172 Children and Adolescents Diabetes Care Volume 43, Supplement 1, January 2020
type 2 diabetes, lifestyle inter- 13.61 A1C targets for patients on carcinoma or multiple endo-
vention should be based on insulin should be individual- crine neoplasia type 2. A
a chronic care model and of- ized, taking into account the 13.68 Patients treated with basal in-
fered in the context of diabe- relatively low rates of hypogly- sulin up to 1.5 units/kg/day
tes care. E cemia in youth-onset type 2 who do not meet A1C target
13.55 Youth with diabetes, like all diabetes. E should be moved to multiple
children, should be encouraged daily injections with basal and
to participate in at least 30–60 premeal bolus insulins. E
n
Pharmacologic Management
min of moderate-to-vigorous 13.69 In patients initially treated with
tio
Recommendations
physical activity at least 5 days insulin and metformin who are
13.62 Initiate pharmacologic therapy,
per week (and strength train- meeting glucose targets based
in addition to lifestyle therapy,
ing on at least 3 days/week) B on home blood glucose moni-
a
at diagnosis of type 2 diabetes.
and to decrease sedentary be- toring, insulin can be tapered
A
ci
havior. C over 2–6 weeks by decreasing
13.63 In incidentally diagnosed or
13.56 Nutrition for youth with type the insulin dose 10–30% every
so
metabolically stable patients
2 diabetes, like for all chil- few days. B
(A1C ,8.5% [69 mmol/mol] and
dren, should focus on healthy 13.70 Use of medications not ap-
asymptomatic), metforminis the
As
eating patterns that empha- proved by the U.S. Food and
initial pharmacologic treatment
size consumption of nutrient- Drug Administration for youth
of choice if renal function is
dense, high-quality foods and with type 2 diabetes is not
normal. A
decreased consumption of cal- recommended outside of re-
13.64 Youth with marked hypergly-
s
orie-dense, nutrient-poor foods, search trials. B
cemia (blood glucose $250
te
particularly sugar-added bever-
mg/dL [13.9 mmol/L], A1C
ages. B Treatment of youth-onset type 2 diabe-
$8.5% [69 mmol/mol]) with-
be
out acidosis at diagnosis who tes should include lifestyle management,
Glycemic Targets are symptomatic with polyuria, diabetes self-management education,
and pharmacologic treatment. Initial
ia
Recommendations
polydipsia, nocturia, and/or
weight loss should be treated treatment of youth with obesity and
13.57 Home self-monitoring of blood
diabetes must take into account that
D
3 months. E
insulin should be initiated to nificant ketoacidosis (180). Therefore,
13.59 A reasonable A1C target for
er
rapidly correct the hypergly- initial therapy should address the hyper-
most children and adolescents
cemia and the metabolic de- glycemia and associated metabolic de-
with type 2 diabetes treated
rangement. Once acidosis is rangements irrespective of ultimate
Am
significant hypoglycemia or
mmol/L]), consider assessment or obesity.
other adverse effects of treat-
for hyperglycemic hyperosmo- Glycemic targets should be individu-
ment.Appropriatepatientsmight
lar nonketotic syndrome. A
©
n
a tio
ci
so
As
s
te
be
ia
D
an
Figure 13.1—Management of new-onset diabetes in youth with overweight or obesity. A1C 8.5% 5 69 mmol/mol. Adapted from the ADA position
statement “Evaluation and Management of Youth-Onset Type 2 Diabetes” (2). DKA, diabetic ketoacidosis; HHNK, hyperosmolar hyperglycemic
nonketotic syndrome; MDI, multiple daily injections.
ic
er
and maintaining a healthy weight, and (185–187), initial treatment must include recommended. The Treatment Options
exercising regularly. A family-centered management of comorbidities such as for Type 2 Diabetes in Adolescents and
approach to nutrition and lifestyle obesity, dyslipidemia, hypertension, and Youth (TODAY) study found that metfor-
Am
modification is essential in children microvascular complications. min alone provided durable glycemic
with type 2 diabetes, and nutrition rec- Current pharmacologic treatment op- control (A1C #8% [64 mmol/mol] for
ommendations should be culturally ap- tions for youth-onset type 2 diabetes 6 months) in approximately half of the
propriate and sensitive to family are limited to three approved drugsd subjects (189). The RISE Consortium
19
resources (see Section 5 “Facilitating insulin, metformin, and liraglutide (2). study did not demonstrate differences
Behavior Change and Well-being to Im- Presentation with ketoacidosis or marked in measures of glucose or b-cell function
prove Health Outcomes,” https://doi ketosis requires a period of insulin ther- preservation between metformin and
20
.org/10.2337/dc20-S005). Given the com- apy until fasting and postprandial glyce- insulin, but there was more weight gain
plex social and environmental context mia have been restored to normal or with insulin (190).
©
surrounding youth with type 2 diabetes, near-normal levels. Metformin therapy To date, the TODAY study is the only
individual-level lifestyle interventions may may be used as an adjunct after resolu- trial combining lifestyle and metformin
not be sufficient to target the complex tion of ketosis/ketoacidosis. Initial treat- therapy in youth with type 2 diabetes;
interplay of family dynamics, mental health, ment should also be with insulin when the combination did not perform better
community readiness, and the broader the distinction between type 1 diabetes than metformin alone in achieving du-
environmental system (2). and type 2 diabetes is unclear and in rable glycemic control (189).
A multidisciplinary diabetes team, patients who have random blood glu- A recent randomized clinical trial in
including a physician, diabetes nurse cose concentrations $250 mg/dL (13.9 children aged 10–17 years with type 2
educator, registered dietitian, and psy- mmol/L) and/or A1C $8.5% (69 mmol/mol) diabetes demonstrated the addition of
chologist or social worker, is essential. (188). subcutaneous liraglutide (up to 1.8 mg
In addition to achieving glycemic tar- When insulin treatment is not daily) to metformin (with or without
gets and self-management education required, initiation of metformin is basal insulin) as safe and effective to
S174 Children and Adolescents Diabetes Care Volume 43, Supplement 1, January 2020
n
older with type 2 diabetes (192).
Recommendations and is strongly recommended
tio
Metabolic Surgery 13.73 Blood pressure should be mea- for those with urinary albumin-
sured at every visit. A to-creatinine ratio .300 mg/g
Recommendations
13.74 Blood pressure should be op- creatinine and/or estimated
a
13.71 Metabolic surgery may be con- timized to reduce risk and/or glomerular filtration rate ,60
ci
sidered for the treatment of slow the progression of dia- mL/min/1.73 m2. E
adolescents with type 2 diabe- betic kidney disease. A 13.82 For those with nephropathy,
so
tes who are markedly obese 13.75 If blood pressure is $90th per- continued monitoring (yearly
(BMI .35 kg/m2) and who have centile for age, sex, and height urinary albumin-to-creatinine
uncontrolled glycemia and/or or, in adolescents $13 years, ratio, estimated glomerular fil-
As
serious comorbidities despite blood pressure is $120/80 tration rate, and serum potas-
lifestyle and pharmacologic mmHg, increased emphasis sium) may aid in assessing
intervention. A should be placed on lifestyle adherence and detecting pro-
13.72 Metabolic surgery should be
s
managementto promoteweight gression of disease. E
performed only by an experi-
te
loss. If blood pressure remains 13.83 Referral to nephrology is rec-
enced surgeon working as part above the 90th percentile or, ommended in case of uncer-
of a well-organized and en- in adolescents $13 years,
be
tainty of etiology, worsening
gaged multidisciplinary team blood pressure is $120/80 urinary albumin-to-creatinine
including a surgeon, endocri- after 6 months, antihyperten- ratio, or decrease in estimated
ia
nologist, nutritionist, behavioral sive therapy should be initi- glomerular filtration rate. E
health specialist, and nurse. A ated. C
D
n
Recommendations HDL cholesterol .35 mg/dL addressed include polycystic ovary dis-
13.89 Evaluation for nonalcoholic fatty ease and other comorbidities associ-
tio
(0.91 mmol/L), and triglycer-
liver disease (by measuring AST ides ,150 mg/dL (1.7 mmol/L). ated with pediatric obesity, such as
and ALT) should be done at E sleep apnea, hepatic steatosis, ortho-
a
diagnosis and annually there- 13.98 If lipids are abnormal, initial pedic complications, and psychosocial
after. B
ci
therapy should consist of op- concerns. The ADA position statement
13.90 Referral to gastroenterology timizing glucose control and “Evaluation and Management of Youth-
so
should be considered for per- medical nutritional therapy Onset Type 2 Diabetes” (2) provides
sistently elevated or worsen- to limit the amount of calories guidance on the prevention, screening,
ing transaminases. B and treatment of type 2 diabetes and its
As
from fat to 25–30%, satu-
rated fat to ,7%, cholesterol comorbidities in children and adoles-
,200 mg/day, avoid trans cents.
Obstructive Sleep Apnea
fats, and aim for ;10% cal- Youth-onset type 2 diabetes is asso-
s
Recommendation
ories from monounsaturated ciated with significant microvascular
13.91 Screening for symptoms of sleep and macrovascular risk burden and a
te
fats for elevated LDL. For
apnea should be done at each substantial increase in the risk of car-
elevated triglycerides, medi-
visit, and referral to a pediat- diovascular morbidity and mortality at
be
cal nutrition therapy should
ric sleep specialist for evalu- an earlier age than those diagnosed
also focus on decreasing simple
ation and a polysomnogram, later in life (208). The higher complica-
sugar intake and increasing di-
if indicated, is recommen-
ia
etary n-3 fatty acids in addition tion risk in earlier-onset type 2 diabetes
ded. Obstructive sleep apnea is likely related to prolonged lifetime
to the above changes. A
D
13.92 Evaluate for polycystic ovary 13.100 If triglycerides are .400 mg/
dL (4.7 mmol/L) fasting or treated with insulin (209), and there are
syndrome in female adoles-
er
cated for girls with type 2 di- youth-onset type 2 diabetes compared
abetes. C Cardiac Function Testing with type 1 diabetes of similar dura-
13.94 Metformin in addition to life- tion, including ischemic heart disease
20
n
13.107 Pediatric diabetes providers adolescence is necessary to facilitate a
for youth with overweight or
seamless transition from pediatric to
tio
should begin to prepare
obesity and type 2 diabetes,
youth for transition to adult adult health care (222,223,229,230).
consider medication-taking
health care in early adoles- New technologies and other interven-
behavior and their effect on
a
cence and, at the latest, at tions are being tried to support transi-
weight. E
ci
least 1 year before the tran- tion to adult care in young adulthood
13.105 Starting at puberty, precon-
sition. E (231–235) A comprehensive discussion
ception counseling should
so
13.108 Both pediatric and adult di- regarding the challenges faced during
be incorporated into routine
abetes care providers should this period, including specific recommen-
diabetes clinic visits for all
provide support and resour- dations, is found in the ADA position
As
females of childbearing po-
ces for transitioning young statement “Diabetes Care for Emerging
tential because of the ad-
adults. E Adults: Recommendations for Transition
verse pregnancy outcomes
13.109 Youth with type 2 diabetes From Pediatric to Adult Diabetes Care
in this population. A
s
should be transferred to an Systems” (223).
13.106 Patients should be screened
adult-oriented diabetes spe- The Endocrine Society in collaboration
te
for smoking and alcohol use
cialist when deemed appro- with the ADA and other organizations has
at diagnosis and regularly
priate by the patient and developed transition tools for clinicians
be
thereafter. C
provider. E and youth and families (230).
ia
Most youth with type 2 diabetes come Care and close supervision of diabetes
from racial/ethnic minority groups, management are increasingly shifted References
D
have low socioeconomic status, and from parents and other adults to the 1. Chiang JL, Maahs DM, Garvey KC, et al. Type
often experience multiple psychoso- youth with type 1 or type 2 diabetes 1 diabetes in children and adolescents: a posi-
tion statement by the American Diabetes Asso-
cial stressors (22,36,165–168). Consid- throughout childhood and adolescence.
an
minimize barriers to care, enhance ad- developmental stage, referred to as tion statement by the American Diabetes
Association. Diabetes Care 2018;41:2648–
er
8. Markowitz JT, Garvey KC, Laffel LMB. De- and Diabetes Prospective Follow-up Registry. 38. Katz ML, Volkening LK, Butler DA, Anderson
velopmental changes in the roles of patients Obesity in youth with type 1 diabetes in Ger- BJ, Laffel LM. Family-based psychoeducation and
and families in type 1 diabetes management. many, Austria, and the United States. J Pediatr Care Ambassador intervention to improve gly-
Curr Diabetes Rev 2015;11:231–238 2015;167:627–632.e4 cemic control in youth with type 1 diabetes:
9. Driscoll KA, Volkening LK, Haro H, et al. Are 24. Corbin KD, Driscoll KA, Pratley RE, Smith SR, a randomized trial. Pediatr Diabetes 2014;15:
children with type 1 diabetes safe at school? Maahs DM, Mayer-Davis EJ; Advancing Care for 142–150
Examining parent perceptions. Pediatr Diabetes Type 1 Diabetes and Obesity Network (ACT1ON). 39. Laffel LMB, Vangsness L, Connell A, Goebel-
2015;16:613–620 Obesity in type 1 diabetes: pathophysiology, Fabbri A, Butler D, Anderson BJ. Impact of
10. Mehta SN, Volkening LK, Anderson BJ, et al.; clinical impact, and mechanisms. Endocr Rev ambulatory, family-focused teamwork interven-
Family Management of Childhood Diabetes 2018;39:629–663 tion on glycemic control in youth with type 1
n
Study Steering Committee. Dietary behaviors 25. Redondo MJ, Foster NC, Libman IM, et al. diabetes. J Pediatr 2003;142:409–416
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predict glycemic control in youth with type 1 Prevalence of cardiovascular risk factors in youth 40. Anderson BJ, Vangsness L, Connell A, Butler
diabetes. Diabetes Care 2008;31:1318–1320 with type 1 diabetes and elevated body mass D, Goebel-Fabbri A, Laffel LMB. Family conflict,
11. Riddell MC, Gallen IW, Smart CE, et al. index. Acta Diabetol 2016;53:271–277 adherence, and glycaemic control in youth with
a
Exercise management in type 1 diabetes: a con- 26. Jackson CC, Albanese-O’Neill A, Butler KL, short duration type 1 diabetes. Diabet Med 2002;
sensus statement. Lancet Diabetes Endocrinol et al. Diabetes care in the school setting: a po- 19:635–642
ci
2017;5:377–390 sition statement of the American Diabetes As- 41. Helgeson VS, Palladino DK. Implications of
12. Colberg SR, Sigal RJ, Yardley JE, et al. Physical sociation. Diabetes Care 2015;38:1958–1963 psychosocial factors for diabetes outcomes
so
activity/exercise and diabetes: a position state- 27. Siminerio LM, Albanese-O’Neill A, Chiang JL, among children with type 1 diabetes: a review.
ment of the American Diabetes Association. et al.; American Diabetes Association. Care of Soc Personal Psychol Compass 2012;6:228–242
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ia
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D
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an
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©
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childhood: a modifiable risk factor for type 1 weight loss surgery. Obesity (Silver Spring) 2009; and correlates of depressed mood among youth
diabetes development? Diabetes Care 2017;40: 17:901–910 with diabetes: the SEARCH for Diabetes in Youth
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World J Diabetes 2015;6:517–526 Association, the Centers for Disease Control diabetes. Diabetes Care 2017;40:317–324
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Pediatrics, the American Association of Clinical care transition preparation and experiences in a 2015;38:1412–1419
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Diabetes Care Volume 43, Supplement 1, January 2020 S183
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Care in Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S183–S192 | https://doi.org/10.2337/dc20-S014
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the components of diabetes care, general treatment goals and guidelines, and tools to
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evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee (https://doi.org/10.2337/dc20-SPPC), are responsible
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for updating the Standards of Care annually, or more frequently as warranted. For a
detailed description of ADA standards, statements, and reports, as well as the evidence-
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grading system for ADA’s clinical practice recommendations, please refer to the Standards
of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment
D
DIABETES IN PREGNANCY
The prevalence of diabetes in pregnancy has been increasing in the U.S. in parallel with
the worldwide epidemic of obesity. Not only is the prevalence of type 1 diabetes and
ic
type 2 diabetes increasing in women of reproductive age, but there is also a dramatic
increase in the reported rates of gestational diabetes mellitus. Diabetes confers
er
significantly greater maternal and fetal risk largely related to the degree of
hyperglycemia but also related to chronic complications and comorbidities of
Am
PRECONCEPTION COUNSELING
20
Recommendations
14.1 Starting at puberty and continuing in all women with diabetes and re-
©
n
observational studies are confounded Diabetes-specific counseling should
should be augmented with ex-
by the association between elevated include an explanation of the risks to
tio
tra focus on nutrition, diabetes
periconceptional A1C and other poor mother and fetus related to pregnancy
education, and screening for di-
self-care behavior, the quantity and con- and the ways to reduce risk including
abetes comorbidities and com-
a
sistency of data are convincing and sup- glycemic goal setting, lifestyle manage-
plications. E
ci
port the recommendation to optimize ment, and medical nutrition therapy. The
14.6 Women with preexisting type 1
glycemia prior to conception, given most important diabetes-specific com-
or type 2 diabetes who are
so
that organogenesis occurs primarily ponent of preconception care is the
planning pregnancy or who
at 5–8 weeks of gestation, with an attainment of glycemic goals prior to
have become pregnant should
A1C ,6.5% (48 mmol/mol) being as- conception. Diabetes-specific testing
As
be counseled on the risk of de-
sociated with the lowest risk of con- should include A1C, creatinine, and uri-
velopment and/or progression
genital anomalies (3–6). nary albumin-to-creatinine ratio. Special
of diabetic retinopathy. Dilated
There are opportunities to educate all attention should be paid to the review of
eye examinations should occur
s
women and adolescents of reproductive the medication list for potentially harm-
ideally before pregnancy or in
age with diabetes about the risks of ful drugs (i.e., ACE inhibitors [18], angio-
te
the first trimester, and then
unplanned pregnancies and about im- tensin receptor blockers [18], and statins
patients should be monitored
proved maternal and fetal outcomes with [19,20]). A referral for a comprehensive
be
every trimester and for 1 year
pregnancy planning (7). Effective pre- eye exam is recommended. Women with
postpartum as indicated by the
conception counseling could avert sub- preexisting diabetic retinopathy will need
degree of retinopathy and as
ia
stantial health and associated cost close monitoring during pregnancy to as-
recommended by the eye care
burdens in offspring (8). Family planning sess for progression of retinopathy and
provider. B
D
should be discussed, including the ben- provide treatment if indicated (21). The
efits of long-acting, reversable contra- use of aspirin (81–150 mg) can be consid-
The importance of preconception care
ception, and effective contraception ered preconception as it is recommended
an
fective contraception at all times when nancy (15). Prescription of prenatal showed that care of preexisting diabetes
preventing a pregnancy. Preconception vitamins (with at least 400 mg of folic in clinics that included diabetes and
counseling using developmentally ap- acid and 150 mg of potassium iodide [16]) obstetric specialists improved care
20
propriate educational tools enables is recommended prior to conception. (25). However, there is no consensus
adolescent girls to make well-informed Review and counseling on the use of on the structure of multidisciplinary
nicotine products, alcohol, and recrea-
©
decisions (7). Preconception counseling team care for diabetes and pregnancy,
resources tailored for adolescents are tional drugs, including marijuana, is and there is a lack of evidence on the
available at no cost through the American important. Standard care includes impact on outcomes of various methods
Diabetes Association (ADA) (14). screening for sexually transmitted dis- of health care delivery (26).
eases and thyroid disease, recommended
Preconception Care vaccinations, routine genetic screen- GLYCEMIC TARGETS IN
ing, a careful review of all prescription PREGNANCY
Recommendations
and nonprescription medications and
14.4 Women with preexisting diabe- Recommendations
supplements used, and a review of travel
tes who are planning a preg- 14.7 Fasting and postprandial self-
history and plans with special attention
nancy should ideally be managed monitoring of blood glucose
to areas known to have Zika virus, as
beginning in preconception in a are recommended in both
outlined by ACOG. See Table 14.1 for
care.diabetesjournals.org Management of Diabetes in Pregnancy S185
Table 14.1—Checklist for preconception care for women with diabetes (15,17)
Preconception education should include:
☐ Comprehensive nutrition assessment and recommendations for:
c Overweight/obesity or underweight
c Meal planning
c Correction of dietary nutritional deficiencies
c Caffeine intake
c Safe food preparation technique
☐ Lifestyle recommendations for:
n
c Regular moderate exercise
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c Avoidance of hyperthermia (hot tubs)
c Adequate sleep
☐ Comprehensive diabetes self-management education
☐ Counseling on diabetes in pregnancy per current standards, including: natural history of insulin resistance in pregnancy and postpartum;
a
preconception glycemic targets; avoidance of DKA/severe hyperglycemia; avoidance of severe hypoglycemia; progression of retinopathy; PCOS
ci
(if applicable); fertility in patients with diabetes; genetics of diabetes; risks to pregnancy including miscarriage, still birth, congenital
malformations, macrosomia, preterm labor and delivery, hypertensive disorders in pregnancy, etc.
so
☐ Supplementation
c Folic acid supplement (400 mg routine)
c Appropriate use of over-the-counter medications and supplements
As
Medical assessment and plan should include:
☐ General evaluation of overall health
☐ Evaluation of diabetes and its comorbidities and complications, including: DKA/severe hyperglycemia; severe hypoglycemia/
hypoglycemic unawareness; barriers to care; comorbidities such as hyperlipidemia, hypertension, NAFLD, PCOS, and thyroid
s
dysfunction; complications such as macrovascular disease, nephropathy, neuropathy (including autonomic bowel and bladder dysfunction),
te
and retinopathy
☐ Evaluation of obstetric/gynecologic history, including history of: cesarean section, congenital malformations or fetal loss, current methods of
contraception, hypertensive disorders of pregnancy, postpartum hemorrhage, preterm delivery, previous macrosomia, Rh incompatibility, and
be
thrombotic events (DVT/PE)
☐ Review of current medications and appropriateness during pregnancy
Screening should include:
ia
☐ Diabetes complications and comorbidities, including: comprehensive foot exam; comprehensive ophthalmologic exam; ECG in women starting at
age 35 years who have cardiac signs/symptoms or risk factors, and if abnormal, further evaluation; lipid panel; serum creatinine; TSH; and urine
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protein-to-creatinine ratio
☐ Anemia
☐ Genetic carrier status (based on history):
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c Cystic fibrosis
c Sickle cell anemia
c Tay-Sachs disease
ic
c Thalassemia
c Others if indicated
er
☐ Infectious disease
c Neisseria gonorrhea/Chlamydia trachomatis
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c Hepatitis C
c HIV
c Pap smear
c Syphilis
☐ Varicella
☐ Hepatitis B
☐ Influenza
20
☐ Others if indicated
Preconception plan should include:
☐ Nutrition and medication plan to achieve glycemic targets prior to conception, including appropriate implementation of monitoring,
©
n
amounts of carbohydrates to match with they can be achieved safely. In practice,
prandial glucose ,120 mg/dL
insulin dosage and to avoid hyperglycemia it may be challenging for women with
tio
(6.7 mmol/L). Some women
or hypoglycemia. Referral to a registered type 1 diabetes to achieve these
with preexisting diabetes should
dietitian nutritionist is important in order targets without hypoglycemia, particu-
also test blood glucose prepran-
a
to establish a food plan and insulin-to- larly women with a history of recurrent
dially. B
hypoglycemia or hypoglycemia unaware-
ci
carbohydrate ratio and to determine
14.8 Due to increased red blood cell
weight gain goals. ness. If women cannot achieve these
turnover, A1C is slightly lower
so
targets without significant hypoglyce-
in normal pregnancy than in
Insulin Physiology mia, the ADA suggests less-stringent
normal nonpregnant women.
Given that early pregnancy is a time of targets based on clinical experience and
As
Ideally, the A1C target in preg-
enhanced insulin sensitivity and lower glu- individualization of care.
nancy is ,6% (42 mmol/mol) if
cose levels, many women with type 1 di-
this can be achieved without
abetes will have lower insulin requirements A1C in Pregnancy
significant hypoglycemia, but
s
and increased risk for hypoglycemia (27). The In studies of women without preexisting
the target may be relaxed to
situation rapidly reverses by approximately diabetes, increasing A1C levels within the
te
,7%(53mmol/mol)ifnecessary
16 weeks as insulin resistance increases normal range are associated with ad-
to prevent hypoglycemia. B
exponentially during the second and early verse outcomes (33). In the Hyperglyce-
be
14.9 When used in addition to pre-
third trimesters to 2–3 times the preprandial mia and Adverse Pregnancy Outcome
and postprandial self-monitoring
requirement. The insulin requirement levels (HAPO) study, increasing levels of glyce-
of blood glucose, continuous
ia
off toward the end of the third trimester mia were also associated with worsen-
glucose monitoring can help
with placental aging. A rapid reduction ing outcomes (34). Observational studies
to achieve A1C targets in dia-
D
women with diabetes, hyperglycemia goals should account for the risk of
natal hypoglycemia in preg-
occurs if treatment is not adjusted ap- maternal hypoglycemia in setting an
nancy complicated by type 1
propriately. individualized target of ,6% (42
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diabetes. B
mmol/mol) to ,7% (53 mmol/mol). Due
14.11 Continuous glucose monitor-
Glucose Monitoring to physiological increases in red blood
ing metrics should not be
Reflecting this physiology, fasting and cell turnover, A1C levels fall during nor-
used as a substitute for self-
postprandial monitoring of blood glucose mal pregnancy (36,37). Additionally, as
monitoring of blood glucose to
19
sulin dosage can be adjusted. Postprandial ary measure of glycemic control in preg-
used in pregnancy as estimates
monitoring is associated with better gly- nancy, after self-monitoring of blood
of A1C. C
cemic control and lower risk of preeclamp- glucose.
sia (29–31). There are no adequately In the second and third trimesters,
Pregnancy in women with normal glu- powered randomized trials comparing A1C ,6% (42 mmol/mol) has the lowest
cose metabolism is characterized by fast- different fasting and postmeal glycemic risk of large-for-gestational-age in-
ing levels of blood glucose that are targets in diabetes in pregnancy. fants (35,38,39), preterm delivery (40),
lower than in the nonpregnant state Similar to the targets recommended and preeclampsia (1,41). Taking all of
due to insulin-independent glucose up- by ACOG (the same as for GDM; de- this into account, a target of ,6%
take by the fetus and placenta and by scribed below) (32), the ADA-recommended (42 mmol/mol) is optimal during preg-
mild postprandial hyperglycemia and targets for women with type 1 or type 2 nancy if it can be achieved without
carbohydrate intolerance as a result of diabetes are as follows: significant hypoglycemia. The A1C target
care.diabetesjournals.org Management of Diabetes in Pregnancy S187
in a given patient should be achieved between the woman and an RD/RDN fa-
medications lack long-term
without hypoglycemia, which, in addition miliar with the management of GDM
safety data.
to the usual adverse sequelae, may in- (50,51). The food plan should provide
14.15 Metformin, when used to treat
crease the risk of low birth weight (42). adequate calorie intake to promote
polycystic ovary syndrome and
Given the alteration in red blood cell fetal/neonatal and maternal health,
induce ovulation, should be
kinetics during pregnancy and physiolog- achieve glycemic goals, and promote
discontinued by the end of
ical changes in glycemic parameters, A1C weight gain according to 2009 Institute
the first trimester. A
levels may need to be monitored more of Medicine recommendations (52).
n
frequently than usual (e.g., monthly). There is no definitive research that
GDM is characterized by increased risk identifies a specific optimal calorie intake
tio
Continuous Glucose Monitoring in of macrosomia and birth complications for women with GDM or suggests that
Pregnancy and an increased risk of maternal type 2 their calorie needs are different from
a
CONCEPTT (Continuous Glucose Moni- diabetes after pregnancy. The associa- those of pregnant women without
toring in Pregnant Women With Type 1 tion of macrosomia and birth complica-
ci
GDM. The food plan should be based
Diabetes Trial) was a randomized con- tions with oral glucose tolerance test on a nutrition assessment with guidance
(OGTT) results is continuous with no
so
trolled trial of continuous glucose mon- from the Dietary Reference Intakes
itoring (CGM) in addition to standard clear inflection points (34). In other (DRI). The DRI for all pregnant women
care, including optimization of pre- words, risks increase with progressive recommends a minimum of 175 g of
As
and postprandial glucose targets versus hyperglycemia. Therefore, all women carbohydrate, a minimum of 71 g of
standard care for pregnant women with should be tested as outlined in Sec- protein, and 28 g of fiber. The diet should
type 1 diabetes. It demonstrated the tion 2 “Classification and Diagnosis of not be high in saturated fat. As is true
Diabetes” (https://doi.org/10.2337/dc20-
s
value of CGM in pregnancy complicated for all nutrition therapy in patients with
by type 1 diabetes by showing a mild S002). Although there is some heteroge- diabetes, the amount and type of car-
improvement in A1C without an increase
in hypoglycemia and reductions in large-
te
neity, many randomized controlled trials
(RCTs) suggest that the risk of GDM may be
bohydrate will impact glucose levels.
Simple carbohydrates will result in higher
be
for-gestational-age births, length of stay, reduced by diet, exercise, and lifestyle postmeal excursions.
and neonatal hypoglycemia (43). An ob- counseling, particularly when interven-
servational cohort study that evaluated tions are started during the first or early Pharmacologic Therapy
ia
medical nutrition therapy, physical ac- U.S. Preventive Services Task Force re-
than time in range, time below range, or
tivity, and weight management depend- view (53). Insulin is the first-line agent
time above range (44). Using the CGM-
ing on pregestational weight, as outlined recommended for treatment of GDM in
reported mean glucose is superior to the
ic
in the section below on preexisting type 2 the U.S. While individual RCTs support
use of estimated A1C, glucose manage-
diabetes, and glucose monitoring aiming limited efficacy of metformin (54,55) and
er
Recommendations
14.13 Lifestyle behavior change is an mg/dL (7.8 mmol/L) or formin failed to provide adequate glyce-
essential component of man- c Two-hour postprandial glucose ,120 mic control in separate randomized
20
agement of gestational diabe- mg/dL (6.7 mmol/L) controlled trials, failing in 23% and
tes mellitus and may suffice for 25–28% of women with GDM, respec-
the treatment of many women. Depending on the population, studies tively (57,58).
©
More recently, glyburide failed to be cost, language barriers, comprehension, While many providers prefer insulin
found noninferior to insulin based on a or cultural influences, may not be able to pumps in pregnancy, it is not clear that
composite outcome of neonatal hypogly- use insulin safely or effectively in preg- they are superior to multiple daily
cemia, macrosomia, and hyperbilirubine- nancy. Oral agents may be an alternative injections (88–90). Closed-loop technol-
mia (60). Long-term safety data for in these women after a discussion of ogy that is U.S. Food and Drug Admin-
offspring exposed to glyburide are not the known risks and the need for more istration approved outside of pregnancy
available (60). long-term safety data in offspring. How- can only target a glucose of 120 mg/dL at
Metformin ever, due to the potential for growth this time, which is likely to be too high for
n
Metformin was associated with a lower restriction or acidosis in the setting optimal nocturnal control in pregnancy.
of placental insufficiency, metformin However, given potential benefits, on-
tio
risk of neonatal hypoglycemia and less
maternal weight gain than insulin in should not be used in women with hy- going work is being done in this area.
systematic reviews (59,61,62,65). How- pertension, preeclampsia, or at risk for
Type 1 Diabetes
a
ever, metformin readily crosses the pla- intrauterine growth restriction (78,79).
Women with type 1 diabetes have an
ci
centa, resulting in umbilical cord blood Insulin increased risk of hypoglycemia in the first
levels of metformin as high or higher than Insulin use should follow the guidelines trimester and, like all women, have al-
so
simultaneous maternal levels (66,67). In below. Both multiple daily insulin injec- tered counterregulatory response in
the Metformin in Gestational Diabetes: tions and continuous subcutaneous in- pregnancy that may decrease hypogly-
As
The Offspring Follow-Up (MiG TOFU) sulin infusion are reasonable delivery cemia awareness. Education for patients
study’s analyses of 7- to 9-year-old off- strategies, and neither has been shown and family members about the preven-
spring, the 9-year-old offspring exposed to be superior to the other during preg- tion, recognition, and treatment of hy-
to metformin in the Auckland cohort for nancy (80). poglycemia is important before, during,
s
the treatment of GDM were heavier and and after pregnancy to help to prevent
te
had a higher waist-to-height ratio and MANAGEMENT OF PREEXISTING and manage the risks of hypoglycemia.
waist circumference than those exposed TYPE 1 DIABETES AND TYPE Insulin resistance drops rapidly with de-
be
to insulin (68). This was not found in the 2 DIABETES IN PREGNANCY livery of the placenta.
Adelaide cohort. In two RCTs of metfor- Insulin Use Pregnancy is a ketogenic state, and
min use in pregnancy for polycystic ovary women with type 1 diabetes, and to a
ia
Recommendations
syndrome, follow-up of 4-year-old off- lesser extent those with type 2 diabetes,
14.16 Insulin is the preferred agent
spring demonstrated higher BMI and are at risk for diabetic ketoacidosis (DKA)
D
study at 5–10 years showed that the diabetes should be prescribed ketone
14.17 Either multiple daily injections
offspring had higher BMI, weight-to- strips and receive education on diabetic
or insulin pump technology
height ratios, waist circumferences, ketoacidosis prevention and detection.
can be used in pregnancy com-
ic
and a borderline increase in fat mass DKA carries a high risk of stillbirth.
plicated by type 1 diabetes. C
(70,71). Metformin is being studied in Women in DKA who are unable to eat
er
two ongoing trials in type 2 diabetes often require 10% dextrose with an in-
The physiology of pregnancy necessi-
(Metformin in Women with Type 2 Di- sulin drip to adequately meet the higher
tates frequent titration of insulin to
Am
abetes in Pregnancy Trial [MiTY] [72] and carbohydrate demands of the placenta
match changing requirements and
Medical Optimization of Management of and fetus in the third trimester in order to
underscores the importance of daily
Type 2 Diabetes Complicating Pregnancy resolve their ketosis.
and frequent self-monitoring of blood
[MOMPOD] [73]), but long-term off- Retinopathy is a special concern in
glucose. Due to the complexity of insulin
19
spring data will not be available for pregnancy. Rapid implementation of eu-
management in pregnancy, referral to a
some time. A recent meta-analysis con- glycemia in the setting of retinopathy is
specialized center offering team-based
cluded that metformin exposure resulted associated with worsening of retinopa-
care (with team members including
20
n
ration, with pregnancy loss appearing to
chronic hypertension, a target goal blood mellitus at 4–12 weeks post-
be more prevalent in the third trimester
tio
in women with type 2 diabetes compared pressure of ,135/85 mmHg is reason- partum, using the 75-g oral
able (98,99). Blood pressure targets glucose tolerance test and clin-
with the first trimester in women with
lower than 120/80 mmHg may be as- ically appropriate nonpreg-
a
type 1 diabetes (91,92).
sociated with impaired fetal growth, nancy diagnostic criteria. B
ci
especially in the setting of placental in- 14.24 Women with a history of ges-
PREECLAMPSIA AND ASPIRIN tational diabetes mellitus found
sufficiency. In a 2015 study targeting
so
Recommendation diastolic blood pressure of 100 mmHg to have prediabetes should re-
14.18 Women with type 1 or type 2 versus 85 mmHg in pregnant women, ceive intensive lifestyle inter-
As
diabetes should be prescribed only 6% of whom had GDM at enroll- ventions and/or metformin to
low-dose aspirin 60–150 mg/ ment, there was no difference in preg- prevent diabetes. A
day (usual dose 81 mg/day) by nancy loss, neonatal care, or other 14.25 Women with a history of gesta-
the end of the first trimester neonatal outcomes, although women tional diabetes mellitus should
s
in order to lower the risk of in the less intensive treatment group have lifelong screening for the
preeclampsia. A
te
had a higher rate of uncontrolled hyper- development of type 2 diabetes
tension (100). or prediabetes at least every
be
Diabetes in pregnancy is associated with During pregnancy, treatment with 3 years. B
an increased risk of preeclampsia (93). ACE inhibitors and angiotensin receptor 14.26 Women with a history of ges-
Based upon the results of clinical trials blockers is contraindicated because tational diabetes mellitus should
ia
and meta-analyses (94), the U.S. Preven- they may cause fetal renal dysplasia, seek preconception screen-
tive Services Task Force recommends the oligohydramnios, pulmonary hypoplasia, ing for diabetes and precon-
D
use of low-dose aspirin (81 mg/day) as a and intrauterine growth restriction (18). ception care to identify and treat
preventive medication at 12 weeks of Antihypertensive drugs known to be hyperglycemia and prevent con-
genital malformations. E
an
gestation in women who are at high risk effective and safe in pregnancy include
for preeclampsia (95). A cost-benefit methyldopa, nifedipine, labetalol, diltia- 14.27 Postpartum care should in-
analysis has concluded that this approach zem, clonidine, and prazosin. Atenolol is clude psychosocial assessment
ic
would reduce morbidity, save lives, and not recommended, but other b-blockers and support for self-care. E
lower health care costs (96). However, may be used, if necessary. Chronic di-
er
more study is needed to assess the long- uretic use during pregnancy is not rec-
Gestational Diabetes Mellitus
term effects of prenatal aspirin exposure ommended as it has been associated
Am
Initial Testing
on offspring (97). with restricted maternal plasma volume,
Because GDM often represents previ-
which may reduce uteroplacental perfu-
ously undiagnosed prediabetes, type 2
sion (101). On the basis of available
PREGNANCY AND DRUG diabetes, maturity-onset diabetes of the
CONSIDERATIONS evidence, statins should also be avoided
young, or even developing type 1 di-
19
in pregnancy (102).
Recommendations abetes, women with GDM should be
See PREGNANCY AND ANTIHYPERTENSIVE MEDI-
14.19 In pregnant patients with di- tested for persistent diabetes or predi-
CATIONS in Section 10 “Cardiovascular Dis-
abetes at 4–12 weeks postpartum with a
20
including both prediabetes and diabetes. following 1–2 weeks. In women taking pregnancy outcome in 933 women with type 1
Women of reproductive age with pre- insulin, particular attention should be diabetes. Diabetes Care 2009;32:1046–1048
5. Nielsen GL, Møller M, Sørensen HT. HbA1c in
diabetes may develop type 2 diabetes by directed to hypoglycemia prevention in
early diabetic pregnancy and pregnancy out-
the time of their next pregnancy and will the setting of breastfeeding and erratic comes: a Danish population-based cohort study
need preconception evaluation. Because sleep and eating schedules (111). of 573 pregnancies in women with type 1 di-
GDM is associated with an increased abetes. Diabetes Care 2006;29:2612–2616
lifetime maternal risk for diabetes esti- Lactation 6. Suhonen L, Hiilesmaa V, Teramo K. Glycaemic
control during early pregnancy and fetal
mated at 50–70% after 15–25 years In light of the immediate nutritional and malformations in women with type I diabetes
n
(103,104), women should also be tested immunological benefits of breastfeeding mellitus. Diabetologia 2000;43:79–82
every 1–3 years thereafter if the 4–
tio
for the baby, all women including those 7. Charron-Prochownik D, Sereika SM, Becker D,
12 weeks postpartum 75-g OGTT is with diabetes should be supported in et al. Long-term effects of the booster-enhanced
normal. Ongoing evaluation may be attempts to breastfeed. Breastfeeding READY-Girls preconception counseling program
a
on intentions and behaviors for family planning
performed with any recommended gly- may also confer longer-term metabolic in teens with diabetes. Diabetes Care 2013;36:
ci
cemic test (e.g., annual A1C, annual benefits to both mother (112) and off- 3870–3874
fasting plasma glucose, or triennial spring (113) However, lactation can 8. Peterson C, Grosse SD, Li R, et al. Preventable
so
75-g OGTT using nonpregnant thresh- increase the risk of overnight hypogly- health and cost burden of adverse birth outcomes
olds). cemia, and insulin dosing may need to associated with pregestational diabetes in the
United States. Am J Obstet Gynecol 2015;212:
be adjusted.
As
74.e1–74.e9
Gestational Diabetes Mellitus and
9. Britton LE, Hussey JM, Berry DC, Crandell JL,
Type 2 Diabetes Contraception Brooks JL, Bryant AG. Contraceptive use among
Women with a history of GDM have a A major barrier to effective preconcep- women with prediabetes and diabetes in a US
greatly increased risk of conversion to national sample. J Midwifery Womens Health
s
tion care is the fact that the majority of
type 2 diabetes over time (103). In the 2019;64:36–45
pregnancies are unplanned. Planning
te
10. Morris JR, Tepper NK. Description and com-
prospective Nurses’ Health Study II (NHS pregnancy is critical in women with pre- parison of postpartum use of effective contra-
II), subsequent diabetes risk after a his- existing diabetes due to the need for ception among women with and without diabetes.
be
tory of GDM was significantly lower in preconception glycemic control to pre- Contraception. 1 September 2019 [Epub ahead
women who followed healthy eating vent congenital malformations and re- of print]. DOI: 10.1016/j.contraception.2019
patterns (105). Adjusting for BMI mod- .08.008
ia
duce the risk of other complications. 11. Goldstuck ND, Steyn PS. The intrauterine
erately, but not completely, attenuated Therefore, all women with diabetes of device in women with diabetes mellitus type I
this association. Interpregnancy or post-
D
childbearing potential should have family and II: a systematic review. ISRN Obstet Gynecol
partum weight gain is associated with planning options reviewed at regular 2013. Accessed 3 October 2019. Available
increased risk of adverse pregnancy out- from https://www.ncbi.nlm.nih.gov/pmc/articles/
intervals to make sure that effective
an
versable contraception may be ideal for and Reproductive Health for Girls. Alexandria, VA,
with a history of GDM and prediabetes, many women. The risk of an unplanned American Diabetes Association, 2016
only 5–6 women need to be treated with pregnancy outweighs the risk of any 15. ACOG Committee Opinion No. 762: Prepreg-
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2211 the paradigm on well-woman health. Obstet
tion of a healthier diet, building on these
©
2. Holmes VA, Young IS, Patterson CC, et al.; Gynecol Clin North Am 2019;46:399–408
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©
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69. Hanem LGE, Stridsklev S, Júlı́usson PB, et al. Transfer of insulin lispro across the human Hypertension in Pregnancy. Obstet Gynecol
Metformin use in PCOS pregnancies increases placenta. Eur J Obstet Gynecol Reprod Biol 2019;133:e26–e50
the risk of offspring overweight at 4 years of age: 2004;115:117–118 100. Magee LA, von Dadelszen P, Rey E, et al.
a
follow-up of two RCTs. J Clin Endocrinol Metab 84. Boskovic R, Feig DS, Derewlany L, Knie B, Less-tight versus tight control of hypertension in
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2018;103:1612–1621 Portnoi G, Koren G. Transfer of insulin lispro pregnancy. N Engl J Med 2015;372:407–417
70. Tarry-Adkins JL, Aiken CE, Ozanne SE. Neo- across the human placenta: in vitro perfusion 101. Sibai BM. Treatment of hypertension in preg-
so
natal, infant, and childhood growth following studies. Diabetes Care 2003;26:1390–1394 nant women. N Engl J Med 1996;335:257–265
metformin versus insulin treatment for gesta- 85. McCance DR, Damm P, Mathiesen ER, et al. 102. Kazmin A, Garcia-Bournissen F, Koren G.
tional diabetes: a systematic review and meta- Evaluation of insulin antibodies and placental Risks of statin use during pregnancy: a systematic
analysis. PLoS Med 2019;16:e1002848 transfer of insulin aspart in pregnant women review. J Obstet Gynaecol Can 2007;29:906–908
As
71. Hanem LGE, Salvesen Ø, Juliusson PB, et al. with type 1 diabetes mellitus. Diabetologia 103. Kim C, Newton KM, Knopp RH. Gestational
Intrauterine metformin exposure and offspring 2008;51:2141–2143 diabetes and the incidence of type 2 diabetes:
cardiometabolic risk factors (PedMet study): 86. Suffecool K, Rosenn B, Niederkofler EE, et al. a systematic review. Diabetes Care 2002;25:
a 5-10 year follow-up of the PregMet randomised Insulin detemir does not cross the human pla- 1862–1868
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controlled trial. Lancet Child Adolesc Health centa. Diabetes Care 2015;38:e20–e21 104. Drury MI. Carbohydrate metabolism in
te
2019;3:166–174 87. O’Neill SM, Kenny LC, Khashan AS, West HM, pregnancy and the newborn. Sutherland HW,
72. Mount Sinai Hospital, Canada. Metformin in Smyth RM, Kearney PM. Different insulin types Stowers JM, Eds. Edinburgh, Churchill Living-
Women With Type 2 Diabetes in Pregnancy Trial and regimens for pregnant women with pre- stone, 1984
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(MiTy). In: ClinicalTrials.gov. Bethesda, MD, Na- existing diabetes. Cochrane Database Syst Rev 105. Tobias DK, Hu FB, Chavarro J, Rosner B,
tional Library of Medicine, 2019. Accessed 3 Oc- 2017;2:CD011880 Mozaffarian D, Zhang C. Healthful dietary patterns
tober 2019. Available from https://clinicaltrials 88. Carta Q, Meriggi E, Trossarelli GF, et al. and type 2 diabetes mellitus risk among women
ia
.gov/ct2/show/NCT01353391 Continuous subcutaneous insulin infusion versus with a history of gestational diabetes mellitus.
73. University of North Carolina, Chapel Hill. intensive conventional insulin therapy in type I Arch Intern Med 2012;172:1566–1572
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Medical Optimization of Management of and type II diabetic pregnancy. Diabete Metab 106. Villamor E, Cnattingius S. Interpregnancy
Type 2Diabetes Complicating Pregnancy (MOMPOD). 1986;12:121–129 weight change and risk of adverse pregnancy
In: ClinicalTrials.gov. Bethesda, MD, National 89. Kernaghan D, Farrell T, Hammond P, Owen P. outcomes: a population-based study. Lancet
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Library of Medicine, 2019. Accessed 3 October Fetal growth in women managed with insulin 2006;368:1164–1170
2019. Available from https://clinicaltrials.gov/ pump therapy compared to conventional insulin. 107. Ratner RE, Christophi CA, Metzger BE, et al.;
ct2/show/NCT02932475 Eur J Obstet Gynecol Reprod Biol 2008;137:47–49 Diabetes Prevention Program Research Group.
74. Vanky E, Stridsklev S, Heimstad R, et al. 90. Feig DS, Corcoy R, Donovan LE, et al.; CON- Prevention of diabetes in women with a history
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Metformin versus placebo from first trimester CEPTT Collaborative Group. Pumps or multiple daily of gestational diabetes: effects of metformin
to delivery in polycystic ovary syndrome: a ran- injections in pregnancy involving type 1 diabetes: and lifestyle interventions. J Clin Endocrinol
er
domized, controlled multicenter study. J Clin a prespecified analysis of the CONCEPTT random- Metab 2008;93:4774–4779
Endocrinol Metab 2010;95:E448–E455 ized trial. Diabetes Care 2018;41:2471–2479 108. Aroda VR, Christophi CA, Edelstein SL, et al.;
75. Legro RS, Barnhart HX, Schlaff WD, et al.; 91. Clausen TD, Mathiesen E, Ekbom P, Hellmuth Diabetes Prevention Program Research Group.
Am
Cooperative Multicenter Reproductive Medi- E, Mandrup-Poulsen T, Damm P. Poor pregnancy The effect of lifestyle intervention and metfor-
cine Network. Clomiphene, metformin, or both outcome in women with type 2 diabetes. Di- min on preventing or delaying diabetes among
for infertility in the polycystic ovary syndrome. abetes Care 2005;28:323–328 women with and without gestational diabetes:
N Engl J Med 2007;356:551–566 92. Cundy T, Gamble G, Neale L, et al. Differing the Diabetes Prevention Program outcomes
76. Palomba S, Orio F Jr, Falbo A, et al. Prospec- causes of pregnancy loss in type 1 and type 2 study 10-year follow-up. J Clin Endocrinol Metab
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tive parallel randomized, double-blind, double- diabetes. Diabetes Care 2007;30:2603–2607 2015;100:1646–1653
dummy controlled clinical trial comparing 93. Duckitt K, Harrington D. Risk factors for pre- 109. Achong N, Duncan EL, McIntyre HD,
clomiphene citrate and metformin as the eclampsia at antenatal booking: systematic re- Callaway L. Peripartum management of glycemia
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first-line treatment for ovulation induction view of controlled studies. BMJ 2005;330:565 in women with type 1 diabetes. Diabetes Care
in nonobese anovulatory women with poly- 94. Roberge S, Bujold E, Nicolaides KH. Aspirin 2014;37:364–371
cystic ovary syndrome. J Clin Endocrinol for the prevention of preterm and term pre- 110. Roeder HA, Moore TR, Ramos GA. Changes
Metab 2005;90:4068–4074 eclampsia: systematic review and metaanalysis. in postpartum insulin requirements for patients
©
77. Palomba S, Orio F Jr, Nardo LG, et al. Met- Am J Obstet Gynecol 2018;218:287–293.e1 with well-controlled type 1 diabetes. Am J Peri-
formin administration versus laparoscopic ovar- 95. Henderson JT, Whitlock EP, O’Conner E, natol 2016;33:683–687
ian diathermy in clomiphene citrate-resistant Senger CA, Thompson JH, Rowland MG. Low- 111. Riviello C, Mello G, Jovanovic LG. Breastfeed-
women with polycystic ovary syndrome: a pro- dose aspirin for the prevention of morbidity and ing and the basal insulin requirement in type 1
spective parallel randomized double-blind mortality from preeclampsia: a systematic evi- diabetic women. Endocr Pract 2009;15:187–193
placebo-controlled trial. J Clin Endocrinol dence review for the U.S. Preventive Services 112. Stuebe AM, Rich-Edwards JW, Willett WC,
Metab 2004;89:4801–4809 Task Force, 2014. Rockville, MD, Agency for Manson JE, Michels KB. Duration of lactation and
78. Barbour LA, Scifres C, Valent AM, et al. A Healthcare Research and Quality (Report No. incidence of type 2 diabetes. JAMA 2005;294:
cautionary response to SMFM statement: phar- 14-05207-EF-1) 2601–2610
macological treatment of gestational diabetes. 96. Werner EF, Hauspurg AK, Rouse DJ. A cost- 113. Pereira PF, Alfenas RdeCG, Araújo RMA. Does
Am J Obstet Gynecol 2018;219:367.e1–367.e7 benefit analysis of low-dose aspirin prophylaxis breastfeeding influence the risk of developing di-
79. Barbour LA, Feig DS. Metformin for gesta- for the prevention of preeclampsia in the United abetes mellitus in children? A review of current
tional diabetes mellitus: progeny, perspective, States. Obstet Gynecol 2015;126:1242–1250 evidence. J Pediatr (Rio J) 2014;90:7–15
Diabetes Care Volume 43, Supplement 1, January 2020 S193
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Diabetesd2020
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Diabetes Care 2020;43(Suppl. 1):S193–S202 | https://doi.org/10.2337/dc20-S015
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so
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The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
includes the ADA’s current clinical practice recommendations and is intended to
s
and tools to evaluate quality of care. Members of the ADA Professional Practice
te
Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc20-
SPPC), are responsible for updating the Standards of Care annually, or more
be
frequently as warranted. For a detailed description of ADA standards, statements,
and reports, as well as the evidence-grading system for ADA’s clinical practice
ia
and reduce the need for readmission, as well as improve patient outcomes. Some
in-depth reviews of hospital care for patients with diabetes have been published
(5,6).
HOSPITAL CARE DELIVERY STANDARDS
19
Recommendations
15.1 Perform an A1C test on all patients with diabetes or hyperglycemia (blood
20
glucose .140 mg/dL [7.8 mmol/L]) admitted to the hospital if not performed
in the prior 3 months. B
15.2 Insulin should be administered using validated written or computerized
©
protocols that allow for predefined adjustments in the insulin dosage based
on glycemic fluctuations. C
Initial orders should state the type of following hospitalization that has been and Diagnosis of Diabetes,” https://doi
diabetes (i.e., type 1, type 2, gestational attributed to diabetes can be reduced, .org/10.2337/dc20-S002) (2,25). Hypo-
diabetes mellitus, pancreatic diabetes) and costs saved, when inpatient care glycemia in hospitalized patients is cate-
when it is known. Because inpatient is provided by a specialized diabetes gorized by blood glucose concentration
treatment and discharge planning are management team (20,21). In a cross- and clinical correlates (Table 6.4) (26):
more effective if based on preadmission sectional comparison of usual care to Level 1 hypoglycemia is a glucose concen-
glycemia, an A1C should be measured on management by specialists who re- tration 54–70 mg/dL (3.0–3.9 mmol/L).
all patients with diabetes or hyperglyce- viewed cases and made recommenda- Level 2 hypoglycemia is a blood glucose
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mia admitted to the hospital if the test tions solely through the electronic concentration ,54 mg/dL (3.0 mmol/L),
has not been performed in the previous medical record, rates of both hyper- which is typically the threshold for neuro-
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3 months (7–10). In addition, diabetes and hypoglycemia were reduced 30– glycopenic symptoms. Level 3 hypoglyce-
self-management knowledge and behav- 40% by electronic “virtual care” (22). mia is a clinical event characterized by
a
iors should be assessed on admission Details of team formation are available altered mental and/or physical function-
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and diabetes self-management educa- in The Joint Commission Standards for ing that requires assistance from another
tion provided, if appropriate. Diabetes programs and from the Society of Hos- person for recovery. Levels 2 and 3
so
self-management education should in- pital Medicine (23,24). require immediate correction of low
clude appropriate skills needed after Even the best orders may not be blood glucose.
discharge, such as medication dosing and carried out in a way that improves qual-
As
administration, glucose monitoring, and ity, nor are they automatically updated Glycemic Targets
recognition and treatment of hypogly- when new evidence arises. To this end, In a landmark clinical trial, Van den
cemia (2). There is evidence to support the Joint Commission has an accredita- Berghe et al. (27) demonstrated that
s
preadmission treatment of hyperglyce- tion program for the hospital care of an intensive intravenous insulin regimen
mia in patients scheduled for elective diabetes (23), and the Society of Hospital to reach a target glycemic range of 80–
surgery as an effective means of reducing
adverse outcomes (11–13). development (24). te
Medicine has a workbook for program 110 mg/dL (4.4–6.1 mmol/L) reduced
mortality by 40% compared with a stan-
be
The National Academy of Medicine dard approach targeting blood glucose of
recommends CPOE to prevent medication- GLYCEMIC TARGETS IN 180–215 mg/dL (10–12 mmol/L) in crit-
ia
related errors and to increase efficiency HOSPITALIZED PATIENTS ically ill patients with recent surgery (4).
in medication administration (14). A This study provided robust evidence that
Recommendations
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found significant improvement in the hyperglycemia starting at a thresh- follow-up study, the Normoglycemia in
percentage of time patients spent in old $180 mg/dL (10.0 mmol/L). Intensive Care Evaluation and Survival
the target glucose range, lower mean Once insulin therapy is started, a Using Glucose Algorithm Regulation
ic
blood glucose levels, and no increase in target glucose range of 140–180 (NICE-SUGAR) trial (28), led to a recon-
mg/dL (7.8–10.0 mmol/L) is rec-
er
hypoglycemia (15). Thus, where feasible, sideration of the optimal target range for
there should be structured order sets ommended for the majority of glucose lowering in critical illness. In this
that provide computerized advice for critically ill patients and non- trial critically ill patients randomized
Am
glucose control. Electronic insulin critically ill patients. A to intensive glycemic control (80–110
order templates also improve mean 15.5 More stringent goals, such as 110– mg/dL) derived no significant treatment
glucose levels without increasing hy- 140 mg/dL (6.1–7.8 mmol/L), advantage compared with a group with
poglycemia in patients with type 2 may be appropriate for selected more moderate glycemic targets (140–
19
diabetes, so structured insulin order patients if they can be achieved 180 mg/dL [7.8–10.0 mmol/L]) and in fact
sets should be incorporated into the without significant hypoglyce- had slightly but significantly higher mor-
CPOE (16,17). mia. C tality (27.5% vs. 25%). The intensively
20
140–180 mg/dL (7.8–10.0 mmol/L) for Administration (FDA) has established GLUCOSE-LOWERING TREATMENT
the majority of critically ill patients (2). standards for capillary (fingerstick) blood IN HOSPITALIZED PATIENTS
Although not as well supported by data glucose meters used in the ambulatory Recommendations
from randomized controlled trials, these setting, as well as standards to be 15.6 Basal insulin or a basal plus bolus
recommendations have been extended applied for POC measures in the correction insulin regimen is the
to hospitalized patients without critical hospital (34). The balance between preferred treatment for noncriti-
illness. More stringent goals, such as analytic requirements (e.g., accuracy, cally ill hospitalized patients with
110–140 mg/dL (6.1–7.8 mmol/L), may precision, interference) and clinical re- poor oral intake or those who are
n
be appropriate for selected patients (e.g., quirements (rapidity, simplicity, point of taking nothing by mouth. A An
critically ill postsurgical patients or pa- care) has not been uniformly resolved
tio
insulin regimen with basal, pran-
tients with cardiac surgery), as long as (33,35), and most hospitals/medical dial, and correction components is
they can be achieved without significant centers have arrived at their own policies the preferred treatment for non-
a
hypoglycemia. On the other hand, glu- to balance these parameters. It is criti- critically ill hospitalized patients
cose concentrations .180 mg/dL (10
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cally important that devices selected for with good nutritional intake. A
mmol/L) may be acceptable in terminally in-hospital use, and the work flow 15.7 Use of only a sliding scale insulin
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ill patients, in patients with severe co- through which they are applied, have regimen in the inpatient hospi-
morbidities, and in inpatient care set- careful analysis of performance and re- tal setting is strongly discour-
tings where frequent glucose monitoring liability and ongoing quality assess- aged. A
As
or close nursing supervision is not fea- ments. Recent studies indicate that
sible. In these patients less aggressive POC measures provide adequate infor- In most instances, insulin is the preferred
insulin regimens to minimize glucosuria, mation for usual practice, with only rare treatment for hyperglycemia in hospital-
s
dehydration, and electrolyte disturban- instances where care has been com- ized patients (2). However, in certain
ces are often more appropriate. Clinical promised (36,37). Good practice dic-
te
circumstances, it may be appropriate
judgment combined with ongoing as- tates that any glucose result that does to continue home regimens including
sessment of clinical status, including not correlate with the patient’s clinical
be
oral glucose-lowering medications (42).
changes in the trajectory of glucose status should be confirmed through If oral medications are held in the hos-
measures, illness severity, nutritional measurement of a serum sample in the pital, there should be a protocol for
ia
status, or concomitant medications clinical laboratory. resuming them 1–2 days before dis-
that might affect glucose levels (e.g., charge. For patients using insulin, recent
D
glucocorticoids), should be incorporated Continuous Glucose Monitoring reports indicate that inpatient use of
into the day-to-day decisions regarding Real-time continuous glucose monitor- insulin pens is safe and may be associated
insulin dosing (2). ing (CGM) provides frequent measure- with improved nurse satisfaction com-
an
ments of interstitial glucose levels, as pared with the use of insulin vials and
BEDSIDE BLOOD GLUCOSE well as direction and magnitude of glu- syringes (43–45). Insulin pens have been
MONITORING cose trends. It has theoretical advantages
ic
who are eating, glucose monitoring reducing the incidence of hypoglycemia warning “For single patient use only”
should be performed before meals; in in the hospital setting that have been should be rigorously followed (46).
those not eating, glucose monitoring borne out in some but not all studies
Am
is advised every 4–6 h (2). More frequent (38,39). Several inpatient studies have
Insulin Therapy
blood glucose testing ranging from every shown that CGM use did not improve
Critical Care Setting
30 min to every 2 h is the required glucose control but detected a greater
In the critical care setting, continuous
standard for safe use of intravenous number of hypoglycemic events than
19
n
insulin regimen with basal, prandial, and cutaneous regimen should receive a dose
of subcutaneous basal insulin 2–4 h be- essary to prevent further hypo-
correction components is the preferred
tio
fore the intravenous infusion is discon- glycemia when a blood glucose
treatment for noncritically ill hospitalized
tinued. Converting to basal insulin at value of ,70 mg/dL (3.9 mmol/L)
patients with good nutritional intake.
is documented. C
a
For patients who are eating, insulin 60–80% of the daily infusion dose is an
effective approach (2,53,54). For patients
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injections should align with meals. In
transitioning to regimens with concen- Patients with or without diabetes may
such instances, POC glucose testing
experience hypoglycemia in the hospital
so
should be performed immediately before trated insulin (U-200, U-300, or U-500) in
the inpatient setting, it is important to setting. While hypoglycemia is associated
meals. If oral intake is poor, a safer
ensure correct dosing by utilizing an with increased mortality (65), in many
procedure is to administer prandial in-
As
individual pen and cartridge for each cases it is a marker of underlying disease
sulin immediately after the patient eats,
patient and by meticulous supervision rather than the cause of fatality. However,
with the dose adjusted to be appropriate
of the dose administered (55,56). New hypoglycemia is a severe consequence of
for the amount ingested (47).
studies support the use of closed-loop dysregulated metabolism and/or diabetes
s
A randomized controlled trial has
insulin delivery with linked pump/sensor treatment, and it is imperative that it be
shown that basal-bolus treatment im-
te
devices to control blood glucose in se- minimized in hospitalized patients. Many
proved glycemic control and reduced
lected groups of hospitalized patients episodes of hypoglycemia among inpa-
hospital complications compared with
be
with type 2 diabetes (57,58). The effect tients are preventable. Therefore, a hy-
reactive, or sliding scale, insulin regimens
of closed-loop treatment on clinical out- poglycemia prevention and management
(i.e., dosing given in response to elevated
comes, the best application of these protocol should be adopted and imple-
ia
insulin based solely on premeal glucose severe illness, in patients with ketonemia
levels does not account for basal insulin or ketonuria, and during prolonged fast- Triggering Events and Prevention of
ing and surgical procedures (5). Until
©
to an unexpected interruption of nutri- reduce rates of hypoglycemia in hospi- management is appropriate. If CSII or
tion. A recent study describes acute kid- talized patients. CGM is to be used, hospital policy and
ney injury as an important risk factor for procedures delineating guidelines for
hypoglycemia in the hospital (68), possibly MEDICAL NUTRITION THERAPY IN CSII therapy, including the changing of
as a result of decreased insulin clearance. THE HOSPITAL infusion sites, are advised (39,81).
Studies of “bundled” preventive thera- The goals of medical nutrition therapy in
pies, including proactive surveillance of the hospital are to provide adequate STANDARDS FOR SPECIAL
glycemic outliers and an interdisciplinary calories to meet metabolic demands, SITUATIONS
n
data-driven approach to glycemic man- optimize glycemic control, address per- Enteral/Parenteral Feedings
agement, showed that hypoglycemic sonal food preferences, and facilitate For patients receiving enteral or paren-
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episodes in the hospital could be pre- creation of a discharge plan. The ADA teral feedings who require insulin, the
vented. Compared with baseline, two does not endorse any single meal plan or regimen should include coverage of
a
such studies found that hypoglycemic specified percentages of macronutrients. basal, prandial, and correctional needs.
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events fell by 56–80% (69,70). The Joint Current nutrition recommendations ad- It is particularly important that patients
Commission recommends that all hypo- vise individualization based on treatment with type 1 diabetes continue to receive
so
glycemic episodes be evaluated for a goals, physiological parameters, and basal insulin even if feedings are discon-
root cause and the episodes be aggre- medication use. Consistent carbohydrate tinued. A reasonable estimate of basal
gated and reviewed to address systemic meal plans are preferred by many hos- needs can be made from the preadmis-
As
issues (23). pitals as they facilitate matching the sion dose of long-acting or intermediate
In addition to errors with insulin treat- prandial insulin dose to the amount of insulin or a percentage of the total daily
ment, iatrogenic hypoglycemia may be carbohydrate consumed (77). For enteral requirements established in the hospital
s
induced by a sudden reduction of corti- nutritional therapy, diabetes-specific for- (usually 30–50% of the total daily dose of
costeroid dose, reduced oral intake, eme- mulas appear to be superior to standard insulin). In the absence of previous in-
sis, inappropriate timing of short- or rapid-
acting insulin in relation to meals, re- te
formulas in controlling postprandial glu-
cose, A1C, and the insulin response (78).
sulin dosing, a reasonable starting point
is to use 5 units of NPH/detemir insulin
be
duced infusion rate of intravenous When the nutritional issues in the subcutaneously every 12 h or 10 units of
dextrose, unexpected interruption of hospital are complex, involvement of a insulin glargine every 24 h (82).
ia
enteral or parenteral feedings, and al- registered dietitian nutritionist can con- For patients receiving continuous tube
tered ability of the patient to report tribute to patient care by integrating feedings, the total daily nutritional com-
D
symptoms (5). information about the patient’s clinical ponent may be calculated as 1 unit of
condition, meal planning, and lifestyle insulin for every 10–15 g carbohydrate
Predictors of Hypoglycemia habits and by establishing realistic treat- per day or as a percentage of the total
an
In ambulatory patients with diabetes, it ment goals after discharge. Orders should daily dose of insulin when the patient is
is well established that an episode of also indicate that the meal delivery and being fed (usually 50–70% of the total
severe hypoglycemia increases the risk nutritional insulin coverage should be daily dose of insulin). Correctional insulin
ic
for a subsequent event, in part be- coordinated, as their variability often should also be administered subcutane-
er
cause of impaired counterregulation creates the possibility of hyperglycemic ously every 6 h using human regular
(71,72). This relationship also holds for and hypoglycemic events. insulin or every 4 h using a rapid-acting
inpatients. For example, in a study of insulin such as lispro, aspart, or glulisine.
Am
hospitalized patients treated for hyper- SELF-MANAGEMENT IN THE For patients receiving enteral bolus
glycemia, 84% who had an episode of HOSPITAL feedings, approximately 1 unit of regular
“severe hypoglycemia” (defined as ,40 Diabetes self-management in the hospi- human insulin or rapid-acting insulin per
mg/dL [2.2 mmol/L]) had a preceding tal may be appropriate for specific pa- 10–15 g carbohydrate should be given
19
episode of hypoglycemia (,70 mg/dL tients (79,80). Candidates include both subcutaneously before each feeding.
[3.9 mmol/L]) during the same admission adolescent and adult patients who suc- Correctional insulin coverage should
(73). In another study of hypoglyce- cessfully conduct self-management of be added as needed before each feeding.
20
mic episodes (defined as ,50 mg/dL diabetes at home, and whose cognitive For patients receiving continuous pe-
[2.8 mmol/L]), 78% of patients were and physical skills needed to successfully ripheral or central parenteral nutrition,
©
using basal insulin, with the incidence self-administer insulin and perform self- human regular insulin may be added to
of hypoglycemia peaking between mid- monitoring of blood glucose are not the solution, particularly if .20 units of
night and 6:00 A.M. Despite recognition of compromised. In addition, they should correctional insulin have been required
hypoglycemia, 75% of patients did not have adequate oral intake, be proficient in the past 24 h. A starting dose of 1 unit
have their dose of basal insulin changed in carbohydrate estimation, use multiple of human regular insulin for every 10 g
before the next insulin administration (74). daily insulin injections or continuous sub- dextrose has been recommended (83),
Recently, several groups have devel- cutaneous insulin infusion (CSII), have stable and should be adjusted daily in the
oped algorithms to predict episodes of insulin requirements, and understand sick- solution. Correctional insulin should be
hypoglycemia among inpatients (75,76). day management. If self-management is to administered subcutaneously. For full
Models such as these are potentially be used, a protocol should include a re- enteral/parenteral feeding guidance,
important and, once validated for gen- quirement that the patient, nursing staff, the reader is encouraged to consult re-
eral use, could provide a valuable tool to and physician agree that patient self- view articles detailing this topic (2,84).
S198 Diabetes Care in the Hospital Diabetes Care Volume 43, Supplement 1, January 2020
Glucocorticoid Therapy A recent review concluded that peri- down units (97), an approach that
The prevalence of glucocorticoid therapy operative glycemic control tighter than may be safer and more cost-effective
in hospitalized patients can approach 80–180 mg/dL (4.4–10.0 mmol/L) did not than treatment with intravenous insulin
10%, and these medications can induce improve outcomes and was associated (98). If subcutaneous insulin adminis-
hyperglycemia in patients with and with- with more hypoglycemia (89); therefore, tration is used, it is important to pro-
out antecedent diabetes (85). Glucocor- in general, tighter glycemic targets are vide adequate fluid replacement,
ticoid type and duration of action must not advised. Evidence from a recent frequent bedside testing, appropriate
be considered in determining insulin study indicates that compared with usual treatment of any concurrent infections,
n
treatment regimens. Daily ingestion of dosing, a reduction of insulin given the and appropriate follow-up to avoid re-
short-acting glucocorticoids such as evening before surgery by ;25% was current DKA. Several studies have shown
tio
prednisone reach peak plasma levels more likely to achieve perioperative that the use of bicarbonate in patients
in 4–6 h (86) but have pharmacologic blood glucose levels in the target range with DKA made no difference in resolu-
a
actions that last through the day. Pa- with lower risk for hypoglycemia (90). tion of acidosis or time to discharge, and
tients on morning steroid regimens have
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In noncardiac general surgery pa- its use is generally not recommended
disproportionate hyperglycemia during tients, basal insulin plus premeal short- (99). For further information regarding
so
the day, but they frequently reach nor- or rapid-acting insulin (basal-bolus) treatment, refer to recent in-depth re-
mal blood glucose levels overnight re- coverage has been associated with im- views (5).
gardless of treatment (85). In subjects proved glycemic control and lower rates
As
on once-daily steroids, prandial insulin TRANSITION FROM THE HOSPITAL
of perioperative complications compared
dosing, often with intermediate-acting TO THE AMBULATORY SETTING
with the reactive, sliding scale regimens
(NPH) insulin, is a standard approach. For (short- or rapid-acting insulin coverage Recommendation
long-acting glucocorticoids such as dexa- 15.10 There should be a structured dis-
s
only with no basal insulin dosing) (48,91).
methasone and multidose or continuous charge plan tailored to the in-
glucocorticoid use, long-acting insulin
may be required to control fasting blood
te
Diabetic Ketoacidosis and
Hyperosmolar Hyperglycemic State
dividual patient with diabetes. B
be
glucose (42,84). For higher doses of There is considerable variability in the A structured discharge plan tailored to
glucocorticoids, increasing doses of pran- presentation of diabetic ketoacidosis the individual patient may reduce length
dial and correctional insulin, sometimes
ia
in glucocorticoid dosing and POC glucose based on a careful clinical and laboratory Transition from the acute care setting
test results are critical. assessment is needed (92–95). presents risks for all patients. Inpatients
Management goals include restora- may be discharged to varied settings,
ic
Perioperative Care tion of circulatory volume and tissue including home (with or without visiting
er
Many standards for perioperative care perfusion, resolution of hyperglycemia, nurse services), assisted living, rehabili-
lack a robust evidence base. However, and correction of electrolyte imbalance tation, or skilled nursing facilities. For the
the following approach (88) may be and acidosis. It is also important to treat patient who is discharged to home or to
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considered: any correctable underlying cause of assisted living, the optimal program will
DKA such as sepsis, myocardial infarction, need to consider diabetes type and se-
1. The target range for blood glucose in or stroke. In critically ill and mentally verity, effects of the patient’s illness on
the perioperative period should be obtunded patients with DKA or hyper- blood glucose levels, and the patient’s
19
80–180 mg/dL (4.4–10.0 mmol/L). osmolar hyperglycemia, continuous in- capacities and preferences. See Section
2. A preoperative risk assessment should travenous insulin is the standard of care. 12 “Older Adults” (https://doi.org/10
be performed for patients with diabe- Successful transition of patients from .2337/dc20-S012) for more information.
20
tes who are at high risk for ischemic intravenous to subcutaneous insulin re- An outpatient follow-up visit with the
heart disease and those with auto- quires administration of basal insulin primary care provider, endocrinologist,
nomic neuropathy or renal failure.
©
guide treatment decisions and signif- c Information on making healthy food patients 80 years of age or older are
icantly improved A1C after discharge choices at home and referral to an more than twice as likely as those 45–64
(8). Therefore, if an A1C from the prior outpatient registered dietitian nutri- years of age to visit the emergency
3 months is unavailable, measuring the tionist to guide individualization of department and nearly five times as
A1C in all patients with diabetes or hy- meal plan, if needed. If relevant, likely to be admitted for insulin-related
perglycemia admitted to the hospital is when and how to take blood glucose– hypoglycemia (110). One approach to
recommended. lowering medications, including insulin reducing insulin-related morbidity in
Clear communication with outpatient administration. older adults with type 2 diabetes is to
n
providers either directly or via hospital c Sick-day management. substitute oral agents for insulin in
discharge summaries facilitates safe c Proper use and disposal of needles and patients in whom these drugs are
tio
transitions to outpatient care. Providing syringes. effective. Among elderly patients in
information regarding the cause of hy- long-term care facilities, there was no
a
perglycemia (or the plan for determining It is important that patients be pro- significant difference in glycemic control
vided with appropriate durable med-
ci
the cause), related complications and between those taking basal insulin and
comorbidities, and recommended treat- ical equipment, medications, supplies those on oral glucose-lowering medica-
so
ments can assist outpatient providers as (e.g., blood glucose test strips), and tions (111). In addition, many older
they assume ongoing care. prescriptions along with appropriate adults with diabetes are overtreated
The Agency for Healthcare Research education at the time of discharge in (112), with half of those maintaining an
As
and Quality (AHRQ) recommends that, order to avoid a potentially dangerous A1C ,7% (53 mmol/mol) being treated
at a minimum, discharge plans include hiatus in care. with insulin or a sulfonylurea, which
the following (101): are associated with hypoglycemia. To
PREVENTING ADMISSIONS AND
s
further lower the risk of hypoglycemia-
READMISSIONS related admissions in older adults,
te
Medication Reconciliation
c The patient’s medications must be In patients with diabetes, the hospital providers should consider relaxing
readmission rate is between 14% and A1C targets to 8% (64 mmol/mol) or
be
cross-checked to ensure that no
chronic medications were stopped and 20%, nearly twice that in patients without 8.5% (69 mmol/mol) in patients with
to ensure the safety of new prescriptions. diabetes (102,103). This reflects increased shortened life expectancies and signif-
ia
c Prescriptions for new or changed med- disease burden for patients and has im- icant comorbidities (refer to Section
ication should be filled and reviewed portant financial implications. Of patients 12 “Older Adults,” https://doi.org/10
D
with the patient and family at or with diabetes who are hospitalized, 30% .2337/dc20-S012, for detailed criteria).
before discharge. have two or more hospital stays, and these
admissions account for over 50% of in- References
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It is recommended that the following sulin treatment of patients withadmission emergenciesdketoacidosis, hyperglycaemic hy-
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©
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blood glucose, home blood glucose erate predictive power but identifies a e202–e203
goals, and when to call the provider. promising future strategy (109). 8. Umpierrez GE, Reyes D, Smiley D, et al.
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patients with diabetic ketoacidosis. Am J Med importance of an interdisciplinary approach. Consensus Conference. Diabetes Care 2014;37:
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ity. Readmissions and adverse events after dis- with post-discharge insulin continuity in US patients oral agents and basal insulin in elderly patients with
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mission in high-risk patients with diabetes: the abetic kidney disease: a report from an ADA 362
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The American Diabetes Association position statements. The ADA publishes Diabetes Care in the School Setting
a
(ADA) “Standards of Medical Care in evidence-based, peer-reviewed state- A sizable portion of a child’s day is spent in
ci
Diabetes” includes the ADA’s current ments on topics such as diabetes and school, so close communication with and
clinical practice recommendations and employment, diabetes and driving, in- cooperation of school personnel are es-
so
is intended to provide the components sulin access and affordability, and dia- sential to optimize diabetes management,
of diabetes care, general treatment betes management in certain settings safety, and academic opportunities. See
As
goals and guidelines, and tools to eval- such as schools, childcare programs, and the following ADA position statement for
uate quality of care. Members of the correctional institutions. In addition to the diabetes management information for
ADA Professional Practice Committee, ADA’s clinical documents, these advocacy students with diabetes in the elementary
statements are important tools in educating and secondary school settings.
a multidisciplinary expert committee
s
schools, employers, licensing agencies,
(https://doi.org/10.2337/dc20-SPPC),
te
policy makers, and others about the
are responsible for updating the Stand- et al.; American Diabetes Association.
intersection of diabetes medicine and
ards of Care annually, or more fre- Diabetes care in the school setting:
be
the law and for providing scientifically
quently as warranted. For a detailed supported policy recommendations. a position statement of the American
description of ADA standards, state- Diabetes Association. Diabetes Care
ments, and reports, as well as the evi-
ia
professional.diabetes.org/SOC. The ADA’s Insulin Access and Affordabil- legal protections and can be safely
ity Working Group compiled public in- cared for by childcare providers with
er
the insulin supply chain to learn how each parents and the child’s diabetes pro-
with diabetes should not have to face
entity affects the cost of insulin for the vider. See the following ADA position state-
discrimination due to diabetes. By advo-
consumer. Their conclusions and recom- ment for information on young children
cating for the rights of those with di-
mendations are published in the follow- aged ,6 years in settings such as day
abetes at all levels, ADA can help to
ing ADA statement. care centers, preschools, camps, and
19
abetes to live free from the burden of Group. Insulin Access and Affordability JL, et al.; American Diabetes Association.
discrimination. The ADA is also focused Working Group: conclusions and recom- Care of young children with diabetes in
on making sure cost is not a barrier to mendations. Diabetes Care 2018;41:1299– the childcare setting: a position statement
©
successful diabetes management. 1311 [published correction appears in of the American Diabetes Association.
One tactic for achieving these goals Diabetes Care 2018;41:1831]; https://doi Diabetes Care 2014;37:2834–2842; https://
has been to implement the ADA Stan- .org/10.2337/dci18-0019 (first publication doi.org/10.2337/dc14-1676 (first publication
dards of Care through advocacy-oriented 2018) 2014)
Suggested citation: American Diabetes Association. 16. Diabetes advocacy: Standards of Medical Care in Diabetesd2020. Diabetes Care 2020;
43(Suppl. 1):S203–S204
© 2019 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
S204 Diabetes Advocacy Diabetes Care Volume 43, Supplement 1, January 2020
Diabetes and Driving Diabetes and Employment (first publication 1984; latest revision
People with diabetes who wish to oper- Any person with diabetes, whether 2009)
ate motor vehicles are subject to a great insulin treated or noninsulin treated,
variety of licensing requirements applied should be eligible for any employment
Diabetes Care in Correctional
by both state and federal jurisdictions. for which he or she is otherwise qualified.
Institutions
For an overview of existing licensing rules Employment decisions should never be
for people with diabetes, factors that People with diabetes in correctional
based on generalizations or stereotypes
impact driving for this population, and facilities should receive care that meets
regarding the effects of diabetes. For a
n
general guidelines for assessing driver national standards. Correctional insti-
general set of guidelines for evaluating tutions should have written policies and
fitness and determining appropriate li-
tio
censing restrictions, see the following individuals with diabetes for employ- procedures for the management of di-
ADA position statement. ment, including how an assessment abetes and for the training of medical
a
Editor’s note: Federal commercial driving should be performed and what changes and correctional staff in diabetes care
practices. For a general set of guidelines
ci
rules for individuals with insulin-related di- (accommodations) in the workplace
abetes changed on 19 November 2018. may be needed for an individual with for diabetes care in correction institu-
so
These changes will be reflected in tions, see the following ADA position
diabetes, see the following ADA position
a future updated ADA statement. statement.
statement.
As
Lorber D, Anderson J, Arent S, et al.; American Diabetes Association. Diabetes
American Diabetes Association. Diabetes Anderson JE, Greene MA, Griffin JW management in correctional institutions.
and driving. Diabetes Care 2014;37- Jr, et al.; American Diabetes Associa- Diabetes Care 2014;37(Suppl. 1):S104–
(Suppl. 1):S97–S103; https://doi.org/ tion. Diabetes and employment. Dia- S111; https://doi.org/10.2337/dc14-S104
s
10.2337/dc14-S097 (first publication betes Care 2014;37(Suppl. 1):S112–S117; (first publication 1989; latest revision
2012)
te
https://doi.org/10.2337/dc14-S112 2008)
be
ia
D
an
ic
er
Am
19
20
©
Diabetes Care Volume 43, Supplement 1, January 2020 S205
n
Diabetes Care 2020;43(Suppl. 1):S205–S206 | https://doi.org/10.2337/dc20-SDIS
a tio
Committee members disclosed the following covering the period 12 months before December 2019
Other Speakers’
ci
research bureau/ Ownership Consultant/advisory
Member Employment Research grant support honoraria interest board Other
so
Professional Practice Committee
Joshua J. Neumiller, Washington State None None Diabetes Spectrum, None None None
PharmD, CDE, University Associate
As
FASCP, Chair Editorship
George Bakris, MD University of Chicago Bayer, Janssen, Vascular None None None Novo Nordisk, Merck, None
Medicine Dynamics# KBP Biosciences
William T. Cefalu, MD National Institute of None None None None None None
Diabetes and Digestive
s
and Kidney Diseases
Jill Crandall, MD Albert Einstein College None None None
te
None None None
of Medicine
DISCLOSURES
David D’Alessio, MD Duke University, Division Merck, Eli Lilly None Novo Nordisk None Lilly, Intarcia Endocrine Society
be
of Endocrinology Meeting Committee
Jennifer Green, MD Duke University, Division Boehringer Ingelheim None None None Boehringer None
of Endocrinology Ingelheim*,
Novo Nordisk, Astra
ia
Zeneca
Elbert Huang, MD, University of Chicago None None None GlaxoSmithKline* None Medical Research
D
Economic Review,
Midwest Comparative
Effectiveness Public
Advisory Council
ic
Kathryn Evans Duke University Medical None None None None Amgen None
Kreider, DNP, Center, Division of
er
Maria Jose Redondo, Texas Children’s Caladrius# None ADA Scientific None None TrialNet Steering
MD, PhD, MPH Hospital-Baylor Sessions 2019 Committee member
College of Medicine
Jane Reusch, MD University of Colorado None None Sanofi keynote None Medtronic None
address#
Emily Weatherup, University of Michigan None None ADA Scientific None None None
MS, RDN, CDE Sessions 2019
Jennifer Wyckoff, University of Michigan None None ADA speaker None EPIC Endocrine None
MD honoraria Steering Committee
member
S206 Disclosures Diabetes Care Volume 43, Supplement 1, January 2020
Other Speakers’
research bureau/ Ownership Consultant/advisory
Member Employment Research grant support honoraria interest board Other
Deborah Young- National Institutes of None None None None None None
Hyman, PhD, Health, Office of
CDE Behavioral Health
and Social Science
Research
n
American College of CardiologydDesignated Representatives (Section 10)
tio
Sandeep Das, MD, University of Texas None None Circulation None None None
MPH, FACC Southwestern Medical (Associate
Center Editor)
a
Mikhail Saint Luke’s Mid AstraZeneca*, AstraZeneca*# None None AstraZeneca*, None
Kosiborod, America Heart Boehringer Sanofi*,
ci
MD, FACC Institute Ingelheim* GlaxoSmithKline,
Amgen*,
Boehringer
so
Ingelheim*, Novo
Nordisk*, Merck
(Diabetes)*,
As
Eisai*, Glytec,
Janssen*, Intarcia
Therapeutics,
Novartis, Bayer,
AppliedTherapeutics
s
American Diabetes Association Staff
te
Kenneth P. American Diabetes None None None First Samurai None None
Moritsugu, MD, Association, First Consulting, LLC
MPH Samurai Consulting,
be
LLC
Mindy Saraco, MHA American Diabetes None None None None None None
Association
Malaika I. Hill, MA American Diabetes None None None None None None
ia
Association
Matthew P. Petersen American Diabetes None None None None None None
D
Association
Shamera Robinson, American Diabetes None None None None None None
MPH, RDN Association
an
*$$10,000 per year from company to individual. #Grant or contract is to university or other employer. William T. Cefalu, MD, joined the Professional Practice Committee in August 2019 subsequent to his
resignation as Chief Scientific, Medical, and Mission Officer of ADA. Kenneth P. Moritsugu, MD, MPH, FACPM, is currently the Interim Chief Scientific and Medical Officer of ADA and continues his work with
First Samurai Consulting, LLC. Prior to joining ADA in September 2019, Malaika I. Hill, MA, was the principal of MD Writing & Editing Solutions, LLC. Jane Reusch, MD, joined the Professional Practice
Committee in April 2019. Christine Lee, MD, joined the Professional Practice Committee in June 2019.
ic
er
Am
19
20
©
Diabetes Care Volume 43, Supplement 1, January 2020 S207
Index
A1C, S15–S17, S66–S71. see also Glycemic targets alpha-glucosidase inhibitors, S106 physical therapy, S54–S56
age and, S16 Alzheimer disease, S153 psychosocial issues, S57–S60
at hospital admission, S193–S194 ambulatory glucose report (AGP), S5, S69 revisions summary, S5
at hospital discharge, S199 amputations, foot, S145 smoking cessation, S56–S57
n
cardiovascular disease outcomes and, amylin mimetic, S106 in type 2 diabetes prevention/delay,
S68–S71 angiotensin receptor blockers (ARBs) S32–S34
tio
differences in children, S67, S167 in CKD patients, S141 b blockers, S115, S145, S189
differences in ethnic populations, S67–S68 in diabetic retinopathy, S143 b cell demise/dysfunction, S15
glucose assessment, S68 for hypertension, S114–S117 bevacizumab, S142
a
goals, S68–S71, S166 in pregnancy, S114, S184, S189 biguanides. see also metformin, S106
ci
hemoglobinopathies, S16 anti-vascular endothelial growth factor bile acid sequestrant, S106
HIV and, S44 (anti-VEGF) treatment, S142 blood glucose monitoring, bedside, S195
in hospitalized patients, S193 antibiotic therapy blood glucose self-monitoring (SMBG), S5
so
limitations of, S67 for diabetic foot infections, S144 blood pressure targets, S5. see also hypertension
mean glucose and, S67 antihyperglycemics in children/adolescents with type 1,
microvascular complications and, S68 in obesity management, S91 S168–S169
As
other conditions affecting, S16 selection of, S101 body mass index (BMI), S5, S20, S89–S90
periodontal disease and, S45 for type 2 diabetes, S101 bolus calculators, S82
physical activity benefits, S55 antihypertensives, S115–S117 bone mineral density, S44
in prediabetes, S18 bedtime dosing, S115 bromocriptine, S106
s
in pregnancy, S184, S186–S187 classes of, S115 bupropion/naltrexone, S93
race/ethnicity, S16 hyperkalemia and AKI, S115
recommendations, S66
setting individualized goals, S70–S71
initial number of, S115
te
multiple-drug therapy, S115 calcium channel blockers, S115–S117
be
target in CKD, S138 in pregnancy, S189 canagliflozin, S105, S106, S124, S126, S127, S128,
testing frequency, S66 resistant hypertension, S115–117 S129, S139
validity in children/adolescents, S22 antiplatelet agents, S121–S122 cancer, S42
CANVAS trial, S124, S126, S127, S129, S139
ia
ACE inhibitors BMI cut point, S20, S90, S92 A1C and outcomes of, S69–S71
in CKD patients, S141 metabolic surgery in, S92, S94 ACCORD study, S69
in diabetic retinopathy, S143 risk-based screening, S20, S21 ADVANCE study, S69
ic
ADA statements, S1, S203–S204 in people less than 50 years of age, S122 S123–S129
ADAG study, S71, S73 preeclampsia and, S189 history of, S18
adolescents. see children and adolescents. resistance, S122 hypertension, S112
ADVANCE BP trial, S69, S70, S113 assisted living facilities, S158 hypoglycemia as risk factor for, S70
advocacy statements, S6, S203–S204 atenolol, S145, S189 lifestyle and pharmacologic interventions,
19
Aging. see Older adults cardiovascular disease and, S123 care teams, S8–S9
AIM-HIGH trial, S120 DSMES, S48–S50 chronic care model, S8
Albiglutide, S125–S126, S128 in gestational diabetes mellitus, S187 cost considerations, S9
Albuminuria, S136, S137 in hypertension management, S114–S115 telemedicine, S9
alcohol intake, S51, S54 medical nutrition therapy, S50–S54 CARMELINA trial, S124, S129
alogliptin, S106, S124, S196 in obesity management, S90–S91 Caucasians, S94. see also ethnicity
S208 Index Diabetes Care Volume 43, Supplement 1, January 2020
celiac disease, S4, S168 clopidogrel, S122 diabetes self-management education and
cerebrovascular disease. see cardiovascular closed-loop pump system, S84, S196 support (DSMES), S9
disease cognitive impairment, S42–S43 in children/adolescents with type 1, S164
Charcot neuroarthropathy of foot, S56, S146 evaluation, S42–S43 facilitation of, S48–S50
child care settings in older adults, S153 in prediabetes, S35
ADA statement of diabetes care in, S203 statins and, S121 recommendations, S48–S49
children with type 1 diabetes, S165 colesevelam, S106 reimbursement, S50
children and adolescents, S6, S163–S182 community health workers, S11 diabetic ketoacidosis (DKA)
A1C validity in, S22 community screening, S20, S22 in children with type 1, S167
autoimmune conditions, S167–S168 community support, S11 due to intercurrent illness, S74
n
cardiac function testing, S175 comorbidities, S4, S42–S45 in hospitalized patients, S198
tio
cardiovascular disease, S175 computerized physician order entry (CPOE), in type 1 diabetes, S17–S18
cardiovascular risk factor management, S193–S194 diabetic kidney disease
S168–S170 CONCEPTT study, S187 exercise in presence of, S56
celiac disease, S168 congenital diabetes. see neonatal diabetes protein intake, S53
a
complications, S174–S175 consensus reports, S1–S2 Diabetic Retinopathy Study (DRS), S142
ci
diabetes care in child care setting, S203 continuous glucose monitoring (CGM), S5, S68, diabetic retinopathy. see retinopathy
diabetes care in school setting, S203 S79–S82 diagnosis, S4, S15–S31
so
DSMES in, S164 blinded (professional) devices, S82 A1C, S15–S16
dyslipidemia, S169–S170, S175 in children/adolescents, S81, S167 chronic kidney disease, S136
exercise and, S55 devices, S80 confirming, S17
glycemic control, S166–S167 glucose assessment using, S68 cystic fibrosis-related diabetes, S22
As
glycemic targets, S172 in hospitals, S195 fasting and 2-hour plasma glucose,
hypertension, S168–S169 in hypoglycemia prevention, S73–S74 S15–S16
intermittent CGM use in, S81 impact of frequency on, S81 gestational diabetes mellitus, S25–S27
lifestyle management, S171–S172 intermittent, S81 monogenic diabetes syndromes, S23,
s
metabolic surgery, S174 in pregnancy, S81, S187 S24–S25
te
microvascular complications, S170–S171 real-time, S80–S82 posttransplantation diabetes mellitus,
nephropathy, S170, S174 recommendations, S79 S22–S24
neuropathy, S170–S171, S174 side effects, S82 type 1 diabetes, S17–S18
be
nonalcoholic fatty liver disease, S175 standardized metrics for clinical care, type 2 diabetes and prediabetes, S18–S22
nutrition therapy in, S164 S68 diet. see also medical nutrition therapy
obstructive sleep apnea, S175 continuous subcutaneous insulin infusion (CSII), for weight loss, S90–S91
ia
pharmacologic management, S172–S174 S98, S99. see also pumps, insulin digital health technology, S84
physical activity and exercise, S164–S165 contraception, S183–S184, S190 dihydropyridine calcium channel blockers,
D
polycystic ovary syndrome, S175 Coronary heart disease. see cardiovascular S115–S117
psychosocial issues, S165–S166, S175–S176 disease diltiazem, S189
real-time CGM use in, S81 correctional institutions, ADA statement on discharge planning, S198–S199
an
smoking, S170 CREDENCE trial, S6, S129 DPP-4 inhibitors, S101, S106
thyroid disease, S167–S168 cystic fibrosis-related diabetes (CFRD), S4, S14, cardiovascular outcome trials, S124
er
transition from pediatric to adult care, S176 S22 heart failure and, S129
type 1 diabetes in, S63–S171 dapagliflozin, S105, S106, S126, S127, S128 in hospital care, S196
type 2 diabetes in, S171–S176 DASH diet, S114 in older adults, S158
Am
CHIPS study, S114 DECLARE-TMI trial, S126, S127, S129 driving, ADA statement on diabetes and,
chronic care model, S8, S37 degludec, S99, S107 S203–S204
chronic kidney disease, S6, S135–S141 degludec/liraglutide, S107 droxidopa, S145
acute kidney injury, S137–S138 deintensification of regimens, S155–S157 dulaglutide, S105, S106, S125–S126, S128
albuminuria assessment, S136 delay, type 2 diabetes, S4, S32–S36 duloxetine, S144
19
complications, S138 cardiovascular disease prevention, S35 Dying patients, end-of-life/palliative care,
diagnosis, S136 lifestyle interventions, S32–S34 S159–S160
epidemiology, S136 pharmacologic interventions, S34–S35 dyslipidemia, S35, S169–S170
20
referral to nephrologist, S140–S141 dental practices, screening in, S22 eating patterns, S50–S52
renal effects of glucose-lowering agents, DEPS-R study, S166 EDIC study, S138
S139 Detemir, S107 electrocardiogram, S123
risk assessment, S137 Diabetes Control and Complications Trial (DCCT), ELIXA trial, S125, S128
screening recommendations, S135 S15, S16, S44, S71, S98–S99, S138, S153 EMPA-REG OUTCOME trial, S123–S124, S127,
selection of glucose-lowering agents, diabetes distress, S57–S58 S129, S139
S139–S140 diabetes plate method, S52 empagliflozin, S105, S106, S123–S124, S127,
staging, S136–S137 Diabetes Prevention Program (DPP), S33, S34, S128, S129, S139
surveillance, S138 S84 employment, ADA statement on diabetes and,
treatment recommendations, S135–S136 Diabetes Prevention Program Outcomes Study S204
cigarettes, S34, S56, S170 (DPPOS), S34 enalapril, S145
classification, S4, S14–S15 Diabetes Prevention Recognition Program (DPRP), end-of-life care, S159–S160
clonidine, S145, S189 S534 end-stage renal disease, S136, S139, S140
care.diabetesjournals.org Index S209
enteral/parenteral feedings, S197 use in older adults, S158 Human NPH, S107
epidemiology, of diabetes and CKD, S136 glucocorticoid therapy, S198 Human Regular insulin, S107
eplerenone, S140 glucose assessment Hydralazine, S114
erectile dysfunction, S146 recommendations, S68 hyperbaric oxygen therapy, S146–S147
ertugliflozin, S106 using CGM, S68 hyperglycemia
erythromycin, S145 Glucose Management Indicator, S68 definition in hospitalized patients, S194
ETDRS study, S142 glucose meters. see self-monitoring of blood effects on cognition, S43
ethnicity, S16, S18, S20. see also specific glucose in HIV, S44
ethnicities glucose monitoring. see also self- monitoring with intercurrent illness, S74
evidence-grading system, S2 in pregnancy, S186 posttransplant, S23
n
EXAMINE trial, S124, S129 glulisine, S107 hyperkalemia, S115
tio
exenatide, S100, S106, S125–S126, S128 glyburide, S106, S158, S187–S188 hyperosmolar hyperglycemic states, S198
exercise. see physical activity glycemic control hypertension, S18, S35, S112–S117
exocrine pancreas disease, S14–S15, S25 in diabetic neuropathy, S144 in children/adolescents, S168–S169
EXSCEL trial, S125, S128 physical activity and, S55 intensive versus standard treatment,
a
ezetimibe, S119 real-time CGM impact on, S81 S112–113
ci
glycemic targets, S5, S66–S76 lifestyle interventions, S114–S115
A1C goals, S68–S71 pharmacologic interventions, S115–S117
family planning, S183–S184
so
A1C testing, S66–S68 pregnancy and antihypertensives, S114
fasting plasma glucose (FPG) test, S15, S19 assessment of, S66–S68 recommendations, S116
fats, dietary, S51, S53 in children/adolescents with type 1 resistant, S115–S117
fenofibrate, S120, S143 diabetes, S166–S167 screening and diagnosis, S117
As
fibrates, S120 in chronic kidney disease, S138 treatment goals, S112–114
finerenone, S140 in hospitalized patients, S194–S195 treatment strategies, S114–117
first-degree relatives, with diabetes, S18 hypoglycemia, S71–S74 hypertriglyceridemia, S119–S120
fluvastatin, S118 individualization of, S70–S71 hypoglycemia, S71–S74
s
food insecurity, S10 intercurrent illness, S74 CGM in prevention, S73–S74
foot care, S6, S145–S147
te
in pregnancy, S184, S186–S187 classification, S72
loss of protective sensation, S144 preprandial, S73 definition in hospitalized patients, S194
patient education, S144 revisions summary, S5 effects on cognition, S43
be
peripheral arterial disease, S144 summary of recommendations, S72 glucagon, S73
recommendations, S145 guanfacine, S145 glucose for, S71, S72
revisions summary, S6 hospital management, S96–S197
ia
recommendations, S71
galactose, S79 hemoglobinopathies, S16 risk assessment, S41
gastroparesis, S145 hepatitis B vaccination, S42 symptoms, S72
gemfibrozil, S120 hepatitis C virus infection, S4, S43 treatment, S73
ic
genetic causes, MODY, S23, S24 hip fractures, S44 triggering events, S196–S197
genetic testing, S25 HIV, S44 unawareness, S72
er
gestational diabetes mellitus (GDM), S4, S14–S15, homelessness, S10 in young children with type 1 diabetes, S73
S25–S27, S187–S188 hospital care, S6, S74, S193–S202
definition, S25–S26 admission considerations, S193–S194
Am
diagnosis, S25–S27 bedside blood glucose monitoring, S105 idiopathic diabetes, S17
lifestyle management, S187 CGM, S195 illness, intercurrent, S74
medical nutrition therapy, S187 delivery standards, S193–S194 immune-mediated diabetes, S17
one-step strategy, S26–S27 diabetes care providers, S194 immunizations, S39, S41–S42, S185
pharmacologic therapy, S187–S188 discharge planning, S198–S199 impaired fasting glucose (IFG), S15
19
postpartum care, S189–S190 DKA, S198 impaired glucose tolerance (IPG), S15
postpartum conversion to type 2, S190 enteral/parenteral feedings, S197 IMPROVE-IT trial, S119
screening, S26 glucocorticoid therapy, S198 incretin-based therapies, S158. see also DPP4
glucose-lowering treatment in, S195–S196
20
n
recommendations, S82, S83 referrals, S41–S42 monogenic diabetes syndromes, S14–S15, S23,
medical nutrition therapy, S4, S5, S50–S54. see S24–S25
tio
syringes and pens, S82
transitioning from IV to subcutaneous, also nutrition
S196 alcohol, S54
insulin secretagogues, S158 naltrexone/bupropion, S93
a
carbohydrates, S52–S53
insulin sensitizers, S144 in children/adolescentswithtype 1 diabetes, nateglinide, S106
ci
insulin therapy S164 National Diabetes Education Program, S8, S9
basal, SMBG in patents using, S78–S79 in chronic kidney disease, S138 National Health and Nutrition Examination
so
carbohydrates intake and, S53 eating patterns, S50–S52 Survey (NHANES), S44
in critical care setting, S195 in gestational diabetes mellitus, S187 National Institute of Diabetes and Digestive and
intensifying to injectable, S104, S105 goals for adults, S48 Kidney Diseases, S9
in noncritical care setting, S195–S196 national policy
As
in the hospital, S197
in pregnancy, S188–S189 macronutrient distribution, S50–S52 in diabetes prevention/delay, S34
simplification of, for older adults, S156, S158 meal planning, S50–S52 neonatal diabetes, S14–S15, S23, S24
for type 1 diabetes, S98–S100 micronutrients and supplements, S53–S54 nephropathy. see also chronic kidney disease,
for type 2 diabetes, S104–S108 nonnutritive sweeteners, S54 S170
s
intensification, S108 protein, S53 neurocognitive function
te
intravenous insulin therapy, S196 revisions summary, S5 in older adults, S153
intravitreal therapy, S142 sodium, S53 neuropathy, diabetic, S143–S145
islet autotransplantation, S43–S44 in type 2 diabetes prevention/delay, S33 autonomic, S143
be
islet transplantation, S100 weight management, S52 cardiac autonomic, S143–S144
isradipine, S145 medications. see also pharmacologic interven- in children/adolescents, S170–S171
tions diagnosis, S143
ia
liraglutide, S93, S100, S105, S106, S107, for type 1 diabetes, S100
S125–S126, S127, S128, S139 for type 2 diabetes, S101, S105 in children/adolescents, S174
lixisenatide, S106, S107, S125–S126, S128 methyldopa, S114, S190 concomitant medications, S91–S92
long-term care facilities, S158, S159 metoclopramide, S145 diet, S90–S91
longer-acting insulin analogs, S99 metoprolol, S145 glucose-lowering therapy, S91
Look AHEAD trial, S45, S90–S91 micronutrients, S51, S53–S54 lifestyle interventions, S91
lorcaserin, S93 microvascular complications, S6, S135–S151 medical devices for, S92
lorcaserin XR, S93 A1C and, S69 metabolic surgery, S92–S94, S174
loss of protective sensation (LOPS), S146 in children/adolescents with type diabetes, pharmacotherapy, S91–S92
lovastatin, S118 S170–S171 physical activity, S90–S91
chronic kidney disease, S135–S141 revisions summary, S5
diabetic retinopathy, S141–S143 weight management, S52, S174
macronutrient distribution, S50–S52 exercise in presence of, S56 obstructive sleep apnea, S45
macular edema, S142 foot care, S145–S147 olanzapene, S60
care.diabetesjournals.org Index S211
older adults, S6, S152–S162 in type 2 diabetes prevention/delay, subcutaneous insulin infusion, S98, S99
deintensification/deprescribing, S155–S157 S33–S34 in type 2 diabetes, S83
end-of-life care, S159–S160 physical inactivity, S18
hypoglycemia in, S73, S153 pioglitazone, S106
lifestyle management, S155 quality improvement, 59
PIONEER trial, S128
neurocognitive function, S153 pitavastatin, S118
pharmacologic therapy, S155–S158 plant-based diet, S50 race, S16, S18
recommendations, S152 pneumococcal pneumonia vaccination, S42 ranibizumab, S142
revisions summary, S6 polycystic ovary syndrome, S18 rapid-acting insulin analogs, S99, S107
simplification of insulin therapy, S156, S157 population health, S4, S7–S13 real-time CGM
n
in skilled nursing facilities/nursing homes, care delivery systems, S8–S9 in adults, S80–S81
tio
S159 recommendations, S7 in children/adolescents, S81
treatment goals, S154–S155 revisions summary, S4, S9–S11 in pregnancy, S81
with type 1 diabetes, S158–S160 social context, S9–S11 in type 1 diabetes, S80–S81
one-step strategy, GDM, S26–S27
a
postpartum care, S189–190 in type 2 diabetes, S81
oral agents. see also specific medications postsurgical diabetes, S44 REDUCE-IT, S5, S120
ci
SMBG in patients using, S78–79 posttransplantation diabetes mellitus, S22–S24 referrals
oral glucose tolerance test (OGTT), S15, S16, S23, pramlintide, S100, S106 for initial care management, S42
so
S26 prandial insulin, S106 to nephrologist for CKD, S140–S141
organ failure, end-of-life/palliative care, S160 prasugrel, S122 reimbursement, for DSMES, S50
orlistat, S93 pravastatin, S118 repaglinide, S106
orthostatic hypotension, S144–S145
As
prazosin, S189 resistance exercise, S55
P2Y12 receptor antagonist, S122 preconception counseling, S166, S183–S184 retinopathy, S141–S143
pain, neuropathic, S144 prediabetes adjunctive therapy, S143
palliative care, S159–S160 children and adolescents, S22 in children/adolescents with type 1
pancreas transplantation, S100 diabetes, S170
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criteria, S19
pancreatectomy, S43–S44 diagnosis, S18–S19 exercise in presence of, S56
pancreatic-related diabetes, S4, S14–S15, S25
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nutrition and, S4 focal laser photocoagulation surgery, S142
pancreatitis, S43–S44 macular edema in, S141S6
screening/testing, S19, S21
parenteral feedings, S197 in pregnancy, S141, S142
preeclampsia, S189
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patch, insulin, S82 retinal photography, S142
pregabalin, S144
pathophysiology, S15 revisions summary, S6
pregnancy, S6, S183–S192
patient education, on foot care, S146 screening, S141–S142
antihypertensive medications in,
ia
medication classes real-time CGM in, S81 children/adolescents with type 1 diabetes,
approved medications, S92, S93 revisions summary, S6 S165
assessing safety and efficacy, S92 prevention, type 2 diabetes, S4, S32–S36 scientific evidence-grading system, S2
for cardiovascular disease, S123 cardiovascular disease, S35 scientific review, S2
concomitant medications, S91–S92 lifestyle interventions, S32–S34 screening
19
costs of noninsulin medications, S106 pharmacologic interventions, S34–S35 asymptomatic adults, S20–S22
glucose-lowering therapy, S91 revisions summary, S4 for cardiovascular disease, S123
revisions summary, S5 self-management education/support, children and adolescents, S22
S36
20
semaglutide, S5, S105, S106, S125–S126, S128, subcutaneous insulin infusion, continuous (CSII), real-time CGM in children/adolescents, S81
S139, S158 S98, S99 screening for risk, S17–S18, S21
sensory impairment, S4, S44 sulfonylureas, 2nd generation, S100, S106, S158, staging, S15
SGLT2 inhibitors S187–S188 surgical treatment, S100
AKI and, S137 supplements, S51, S53–S54 type 2 diabetes
cardiovascular outcomes trials, S105, S111, surgical treatment, for type 1 diabetes, S100 A1C and cardiovascular disease in, S69–S71
S123–S129 SUSTAIN trial, S126, S128, S139 cardiovascular outcomes trials, S105
costs of, S106 sweeteners, nonnutritive, S51, S54 children and adolescents, S22
direct renal effects, S139 syringes, insulin, S82 in children and adolescents, S171–S176
hospital care, S196 classification, S14–S15
n
revisions, S5–S6 combination therapy, S102
tai chi, S55
tio
use in CKD patients, S139–S140 diagnosis, S19–S22, S171
use in older adults, S158 tapentadol, S144 DPP-4 inhibitors and cardiovascular out-
short-acting insulins, S107 technology, S5, S77–S88 come trials, S124
simvastatin, S118 for CGM, S79–S82
a
GLP1 receptor agonists and cardiovascular
sitagliptin, S106, S124 in diabetes prevention/delay, S34 outcome trials, S125–S126
ci
skilled nursing facilities, S158, S159 for insulin delivery, S82–S85 initial therapy, S102
hypoglycemia, S159 overall recommendations, S77 intensifying to injectable therapies, S104
so
nutritional considerations, S159 revisions summary, S5 intermittent CGM in adults, S81
resources, S159 for SMBG, S77–S79
lifestyle management, S171–S172
sleep, obstructive sleep apnea, S45 TECOS trial, S124, S129
metabolic surgery, S174
smoking cessation, S56–S57 TEDDY study, S18
As
metabolic surgery in, S92, S94
e-cigarettes, S57 telemedicine, S9
overall approach, S103
tobacco, S56 temperature, effect on SMBG, S79
pharmacologic therapy, S100–S108
in type 2 diabetes prevention/delay, S34 testosterone, low, S44–S45
postpartum conversion of GDM to, S190
in youth, S170 thiazide-like diuretics, S115–S117
preexisting, in pregnancy, S188–S189
s
social context, S9–S11 thiazolidinediones, S44, S100, S106, S129, S158
prevention/delay, S32–S36
te
sodium, S51, S53 thought disorders, S60
thyroid disease, S167–S168 real-time CGM in adults, S81
spironolactone, S114, S140
ticagrelor, S122 screening/testing, S20–S22, S171
SPRINT trial, S113
be
staging, of CKD, S136–S137 tobacco use
statins smoking cessation, S56–S57
U-300 glargine, S99
in children, S169 in type 2 diabetes prevention/delay, S34
UK Prospective Diabetes Study (UKPDS), S69,
ia
VERIFY trial, S5
primary prevention with, S117, S118–S119 A1C and cardiovascular disease in, S69 Veterans Affairs Diabetes Trial (VADT), S69, S70
randomized trials, S119 in children and adolescents, S163–S171
er
risk reduction, S113, S114, S118, S119, intermittent CGM in children/adolescents, xylose, S79
S120, S121, S122 S81
SGLT2 inhibitors and, S123–S124, S126, pharmacologic therapy, S98–S100
20
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