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TH E J O U R N A L O F C L I N I CA L A N D A P P L I E D R E S EA RC H A N D E D U CATI O N VOLUME 39 | SUPPLEMENT 1

WWW.DIABETES.ORG/DIABETESCARE JANUARY 2016

AMERICAN DIABETES ASSOCIATION


1
STANDARDS
OF
MEDICAL CARE
IN DIABETES2016
ISSN 0149-5992

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EME
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American Diabetes Association
Standards of
Medical Care in
Diabetesd2016
January 2016 Volume 39, Supplement 1

[T]he simple word Care may sufce to express [the journals] 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
Diabetes Care as a reafrmation of Francis Weld Peabodys contention that
the secret of the care of the patient is in caring for the patient.
Norbert Freinkel, Diabetes Care, January-February 1978

EDITOR IN CHIEF

William T. Cefalu, MD

ASSOCIATE EDITORS EDITORIAL BOARD

George Bakris, MD Nicola Abate, MD Rita Rastogi Kalyani, MD, MHS, FACP
Lawrence Blonde, MD, FACP Silva Arslanian, MD Rory J. McCrimmon, MBChB, MD, FRCP
Andrew J.M. Boulton, MD Angelo Avogaro, MD, PhD Harold David McIntyre, MD, FRACP
David DAlessio, MD Ananda Basu, MD, FRCP Gianluca Perseghin, MD
Sherita Hill Golden, MD, MHS, FAHA John B. Buse, MD, PhD Anne L. Peters, MD
Mary de Groot, PhD Sonia Caprio, MD Jonathan Q. Purnell, MD
Eddie L. Greene, MD Robert Chilton, DO Peter Reaven, MD
Frank B. Hu, MD, MPH, PhD Kenneth Cusi, MD, FACP, FACE Helena Wachslicht Rodbard, MD
Derek LeRoith, MD, PhD Paresh Dandona, MD, PhD David J. Schneider, MD
Robert G. Moses, MD Stefano Del Prato, MD Elizabeth R. Seaquist, MD
Stephen Rich, PhD Dariush Elahi, PhD Norbert Stefan, MD
Matthew C. Riddle, MD Franco Folli, MD, PhD Jeff Unger, MD
Julio Rosenstock, MD Robert G. Frykberg, DPM, MPH Ram Weiss, MD, PhD
William V. Tamborlane, MD W. Timothy Garvey, MD Deborah J. Wexler, MD, MSc
Katie Weinger, EdD, RN Ronald B. Goldberg, MD Joseph Wolfsdorf, MD, BCh
Judith Wylie-Rosett, EdD, RD Margaret Grey, DrPH, RN, FAAN Tien Yin Wong, MBBS, FRCSE, FRANZCO,
Richard Hellman, MD MPH, PhD

AMERICAN DIABETES ASSOCIATION OFFICERS

CHAIR OF THE BOARD PRESIDENT-ELECT, MEDICINE & SCIENCE


Robin J. Richardson Alvin C. Powers, MD
PRESIDENT, MEDICINE & SCIENCE PRESIDENT-ELECT, HEALTH CARE &
Desmond Schatz, MD EDUCATION
Brenda Montgomery, RN, MSHS, CDE
PRESIDENT, HEALTH CARE & EDUCATION
Margaret A. Powers, PhD, RD, CDE SECRETARY/TREASURER-ELECT
Umesh Verma
SECRETARY/TREASURER
Lorrie Welker Liang CHIEF EXECUTIVE OFFICER
Kevin L. Hagan
CHAIR OF THE BOARD-ELECT
David A. DeMarco, PhD CHIEF SCIENTIFIC & MEDICAL OFFICER
Robert E. Ratner, MD, FACP, FACE

The mission of the American Diabetes Association


is to prevent and cure diabetes and to improve
the lives of all people affected by diabetes.
Diabetes Care is a journal for the health care practitioner that is intended to
increase knowledge, stimulate research, and promote better management of people
with diabetes. To achieve these goals, the journal publishes original research on
human studies in the following categories: Clinical Care/Education/Nutrition/
Psychosocial Research, Epidemiology/Health Services Research, Emerging
Technologies and Therapeutics, Pathophysiology/Complications, and Cardiovascular
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
of view. Topics covered are of interest to clinically oriented physicians, researchers,
epidemiologists, psychologists, diabetes educators, and other health professionals.
More information about the journal can be found online at care.diabetesjournals.org.

Copyright 2016 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)
750-8400; fax: (978) 646-8600. Requests for permission to translate should be sent to
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.
Commercial reprint orders should be directed to Sheridan Content Services,
(800) 635-7181, ext. 8065.
Single issues of Diabetes Care can be ordered by calling toll-free (800) 232-3472, 8:30 A.M.
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
numbers listed above, e-mail membership@diabetes.org, or visit the online journal for
PRINT ISSN 0149-5992 more information about submitting manuscripts, publication charges, ordering reprints,
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AMERICAN DIABETES ASSOCIATION PERSONNEL AND CONTACTS


EDITORIAL OFFICE DIRECTOR PRODUCTION MANAGER DIRECTOR, MEMBERSHIP/SUBSCRIPTION
Lyn Reynolds Amy S. Gavin SERVICES
Donald Crowl
PEER REVIEW MANAGER TECHNICAL EDITOR PHARMACEUTICAL DIGITAL ADVERTISING
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EDITORIAL OFFICE SECRETARIES
MANAGING DIRECTOR, MEDIA SALES Chief Revenue Ofcer
Raquel Castillo
Clare Liberis sales@ehsmail.com
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JOURNAL PUBLISHING
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jdevoss@diabetes.org Paul Nalbandian
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EDITORIAL MANAGERS Tina Auletta
Valentina Such ASSOCIATE DIRECTOR, BILLING & COLLECTIONS tinaauletta@jacksongaeta.com
Nancy C. Baldino Laurie Ann Hall (973) 403-7677
January 2016 Volume 39, Supplement 1

Standards of Medical Care in Diabetes2016


S1 Introduction S60 8. Cardiovascular Disease and Risk
S3 Professional Practice Committee Management
S4 Standards of Medical Care in Diabetes2016: Hypertension/Blood Pressure Control
Lipid Management
Summary of Revisions Antiplatelet Agents
S6 1. Strategies for Improving Care Coronary Heart Disease
Diabetes Care Concepts
Care Delivery Systems S72 9. Microvascular Complications and Foot Care
When Treatment Goals Are Not Met
Diabetic Kidney Disease
Tailoring Treatment to Vulnerable Populations
Diabetic Retinopathy
S13 2. Classication and Diagnosis of Diabetes Neuropathy
Classication Foot Care
Diagnostic Tests for Diabetes S81 10. Older Adults
Categories of Increased Risk for Diabetes (Prediabetes)
Type 1 Diabetes Overview
Type 2 Diabetes Neurocognitive Function
Gestational Diabetes Mellitus Hypoglycemia
Monogenic Diabetes Syndromes Treatment Goals
Cystic FibrosisRelated Diabetes Pharmacological Therapy
Treatment in Skilled Nursing Facilities
S23 3. Foundations of Care and Comprehensive Medical and Nursing Homes
Evaluation End-of-Life Care
Foundations of Care S86 11. Children and Adolescents
Basis for Initial Care
Ongoing Care Management Type 1 Diabetes
Diabetes Self-management Education and Support Type 2 Diabetes
Medical Nutrition Therapy Transition From Pediatric to Adult Care
Physical Activity S94 12. Management of Diabetes in Pregnancy
Smoking Cessation: Tobacco and e-Cigarettes
Immunization Diabetes in Pregnancy
Psychosocial Issues Preconception Counseling
Comprehensive Medical Evaluation Glycemic Targets in Pregnancy
Comorbidities Management of Gestational Diabetes Mellitus
Management of Pregestational Type 1 Diabetes
S36 4. Prevention or Delay of Type 2 Diabetes and Type 2 Diabetes in Pregnancy
Lifestyle Modication Postpartum Care
Pharmacological Interventions Pregnancy and Antihypertensive Drugs
Diabetes Self-management Education and Support S99 13. Diabetes Care in the Hospital
S39 5. Glycemic Targets Hospital Care Delivery Standards
Assessment of Glycemic Control Considerations on Admission
A1C Testing Glycemic Targets in Hospitalized Patients
A1C Goals Antihyperglycemic Agents in Hospitalized
Hypoglycemia Patients
Intercurrent Illness Standards for Special Situations
Treating and Preventing Hypoglycemia
S47 6. Obesity Management for the Treatment of Type 2 Self-management in the Hospital
Diabetes Medical Nutrition Therapy in the Hospital
Look AHEAD Transition From the Acute Care Setting
Assessment Diabetes Care Providers in the Hospital
Diet, Physical Activity, and Behavioral Therapy Bedside Blood Glucose Monitoring
Pharmacotherapy
Bariatric Surgery
S105 14. Diabetes Advocacy
Advocacy Position Statements
S52 7. Approaches to Glycemic Treatment
Pharmacological Therapy for Type 1 Diabetes S107 Professional Practice Committee for the Standards
Pharmacological Therapy for Type 2 Diabetes of Medical Care in Diabetes2016
Bariatric Surgery S109 Index

This issue is freely accessible online at care.diabetesjournals.org.

Keep up with the latest information for Diabetes Care and other ADA titles via Facebook (/ADAJournals) and Twitter (@ADA_Journals).
Diabetes Care Volume 39, Supplement 1, January 2016 S1

INTROD ION
UCT
Introduction
Diabetes Care 2016;39(Suppl. 1):S1S2 | DOI: 10.2337/dc16-S001

Diabetes is a complex, chronic illness re- diabetes care standards, guidelines, and to diabetes. Workgroup reports fall into
quiring continuous medical care with related documents for over 25 years. this category. Scientic statements are
multifactorial risk-reduction strategies ADAs clinical practice recommenda- published in the ADA journals and other
beyond glycemic control. Ongoing patient tions are viewed as important resources scientic/medical publications, as ap-
self-management education and support for health care professionals who care propriate. Scientic statements also
are critical to preventing acute complica- for people with diabetes. ADAs Stan- undergo a formal review process.
tions and reducing the risk of long-term dards of Medical Care in Diabetes,
complications. Signicant evidence exists Consensus Report
position statements, and scientic
that supports a range of interventions to statements undergo a formal review A consensus report contains a compre-
improve diabetes outcomes. process by ADAs Professional Practice hensive examination by an expert panel
The American Diabetes Associations Committee (PPC) and the Executive (i.e., consensus panel) of a scientic or
(ADAs) Standards of Medical Care in Committee of the Board of Directors. medical issue related to diabetes. A con-
Diabetes is intended to provide clini- The Standards and all ADA position sensus report is not an ADA position and
cians, patients, researchers, payers, statements, scientic statements, and represents expert opinion only. The cat-
and other interested individuals with consensus reports are available on the As- egory may also include task force and
the components of diabetes care, gen- sociations Web site at http://professional expert committee reports. The need
eral treatment goals, and tools to eval- .diabetes.org/adastatements. for a consensus report arises when clini-
uate the quality of care. The Standards cians or scientists desire guidance on a
of Care recommendations are not in- Standards of Medical Care in subject for which the evidence is contra-
tended to preclude clinical judgment Diabetes dictory or incomplete. A consensus re-
and must be applied in the context of Standards of Care: ADA position state- port is developed following a consensus
excellent clinical care, with adjustments ment that provides key clinical practice conference where the controversial issue
for individual preferences, comorbid- recommendations. The PPC performs an is extensively discussed. The report
ities, and other patient factors. For extensive literature search and updates represents the panels collective anal-
more detailed information about man- the Standards annually based on the ysis, evaluation, and opinion at that
agement of diabetes, please refer to quality of new evidence. point in time based in part on the con-
Medical Management of Type 1 Diabe- ference proceedings. A consensus re-
ADA Position Statement
tes (1) and Medical Management of
port does not undergo a formal ADA
A position statement is an ofcial ADA review process.
Type 2 Diabetes (2). point of view or belief that contains clin-
The r ec omme nd at io ns inclu de
ical or research recommendations. Posi- GRADING OF SCIENTIFIC EVIDENCE
screening, diagnostic, and therapeutic
tion statements are issued on scientic Since the ADA rst began publishing
actions that are known or believed to or medical issues related to diabetes.
favorably affect health outcomes of pa- They are published in the ADA journals practice guidelines, there has been con-
tients with diabetes. Many of these in- siderable evolution in the evaluation of
and other scientic/medical publica-
terventions have also been shown to be tions. ADA position statements are typ- scientic evidence and in the develop-
cost-effective (3). ically based on a systematic review or ment of evidence-based guidelines. In
The ADA strives to improve and up- other review of published literature. 2002, the ADA developed a classication
date the Standards of Care to ensure Position statements undergo a formal system to grade the quality of scientic
that clinicians, health plans, and policy- review process. They are updated every evidence supporting ADA recommenda-
makers can continue to rely on them as 5 years or as needed. tions for all new and revised ADA posi-
the most authoritative and current tion statements. A recent analysis of the
guidelines for diabetes care. ADA Scientic Statement evidence cited in the Standards of Care
A scientic statement is an ofcial ADA found steady improvement in quality
ADA STANDARDS, STATEMENTS, point of view or belief that may or may over the past 10 years, with the 2014
AND REPORTS Standards for the rst time having the
not contain clinical or research recom-
The ADA has been actively involved in majority of bulleted recommendations
mendations. Scientic statements con-
the development and dissemination of tain scholarly synopsis of a topic related supported by A- or B-level evidence

Standards of Medical Care in Diabetes was originally approved in 1988. Most recent review/revision: November 2015.
2016 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 pro t,
and the work is not altered.
S2 Introduction Diabetes Care Volume 39, Supplement 1, January 2016

Table 1ADA evidence-grading system for Standards of Medical Care in Diabetes


dence may be equally important but
Level of are not as well supported. Of course,
evidence Description evidence is only one component of clin-
ical decision making. Clinicians care for
A Clear evidence from well-conducted, generalizable randomized controlled trials
that are adequately powered, including
patients, not populations; guidelines
c Evidence from a well-conducted multicenter trial must always be interpreted with the in-
c Evidence from a meta-analysis that incorporated quality ratings in the dividual patient in mind. Individual cir-
analysis cumstances, such as comorbid and
Compelling nonexperimental evidence, i.e., all or none rule developed by the coexisting diseases, age, education, dis-
Centre for Evidence-Based Medicine at the University of Oxford
ability, and, above all, patients values
Supportive evidence from well-conducted randomized controlled trials that are
and preferences, must be considered
adequately powered, including
and may lead to different treatment tar-
c Evidence from a well-conducted trial at one or more institutions
c Evidence from a meta-analysis that incorporated quality ratings in the gets and strategies. Furthermore, con-
analysis ventional evidence hierarchies, such as
B Supportive evidence from well-conducted cohort studies the one adapted by the ADA, may miss
c Evidence from a well-conducted prospective cohort study or registry nuances important in diabetes care. For
c Evidence from a well-conducted meta-analysis of cohort studies example, although there is excellent ev-
Supportive evidence from a well-conducted case-control study idence from clinical trials supporting
C Supportive evidence from poorly controlled or uncontrolled studies the importance of achieving multiple
c Evidence from randomized clinical trials with one or more major or three or
risk factor control, the optimal way to
more minor methodological aws that could invalidate the results
achieve this result is less clear. It is dif-
c Evidence from observational studies with high potential for bias (such as
case series with comparison with historical controls) cult to assess each component of
c Evidence from case series or case reports such a complex intervention.
Conicting evidence with the weight of evidence supporting the
recommendation References
E Expert consensus or clinical experience 1. American Diabetes Association. Medical
Management of Type 1 Diabetes. 6th ed.
Kaufman FR, Ed. Alexandria, VA, American Di-
abetes Association, 2012
2. American Diabetes Association. Medical
(4). A grading system (Table 1) devel- in which clinical trials may be impracti- Management of Type 2 Diabetes. 7th ed.
Burant CF, Young LA, Eds. Alexandria, VA, Amer-
oped by the ADA and modeled after ex- cal, or in which there is conicting evi-
ican Diabetes Association, 2012
isting methods was used to clarify and dence. Recommendations with an A 3. Li R, Zhang P, Barker LE, Chowdhury FM,
codify the evidence that forms the basis rating are based on large well-designed Zhang X. Cost-effectiveness of interventions to
for the recommendations. ADA recom- clinical trials or well-done meta-analyses. prevent and control diabetes mellitus: a sys-
mendations are assigned ratings of A, B, Generally, these recommendations tematic review. Diabetes Care 2010;33:1872
have the best chance of improving out- 1894
or C, depending on the quality of evi- 4. Grant RW, Kirkman MS. Trends in the evi-
dence. Expert opinion E is a separate comes when applied to the population dence level for the American Diabetes Associa-
category for recommendations in which to which they are appropriate. Recom- tions Standards of Medical Care in Diabetes
there is no evidence from clinical trials, mendations with lower levels of evi- from 2005 to 2014. Diabetes Care 2015;38:68
PROFESSIONALPRACTICE COMMITTEE
Diabetes Care Volume 39, Supplement 1, January 2016 S3

Professional Practice Committee


Diabetes Care 2016;39(Suppl. 1):S3 | DOI: 10.2337/dc16-S002

The Professional Practice Committee for human studies related to each sec- Emma Morton-Eggleston, MD, MPH;
(PPC) of the American Diabetes Associ- tion and published since 1 January Margaret A. Powers, PhD, RD, CDE;
ation (ADA) is responsible for the Stan- 2015. Recommendations were revised Robert E. Ratner, MD; Erinn Rhodes,
dards of Medical Care in Diabetes based on new evidence or, in some MD, MPH; Amy Rothberg, MD; Sharon
position statement, referred to as the cases, to clarify the prior recommenda- D. Solomon, MD; Guillermo E. Umpierrez,
Standards of Care. The PPC is a multi- tion or match the strength of the word-
MD; Willy Valencia, MD; and Kristina F.
disciplinary expert committee com- ing to the strength of the evidence. A
Zdanys, MD.
prised of physicians, diabetes educators, table linking the changes in recommen-
registered dietitians, and others who dations to new evidence can be re-
have expertise in a range of areas, in- viewed at http://professional.diabetes Members of the PPC
cluding adult and pediatric endocrinol- .org/SOC. As for all position statements,
William H. Herman, MD, MPH (Chair)*
ogy, epidemiology, public health, lipid the Standards of Care position state-
research, hypertension, preconception ment was reviewed and approved by Thomas W. Donner, MD
planning, and pregnancy care. Appoint- the Executive Committee of ADAs R. James Dudl, MD
ment to the PPC is based on excellence Board of Directors, which includes Hermes J. Florez, MD, PhD, MPH*
in clinical practice and research. Al- health care professionals, scientists,
though the primary role of the PPC is and lay people. Judith E. Fradkin, MD
to review and update the Standards of Feedback from the larger clinical Charlotte A. Hayes, MMSc, MS, RD, CDE,
Care, it is also responsible for oversee- community was valuable for the 2016 ACSM CCEP
ing the review and revisions of ADAs revision of the Standards of Care. Readers Rita Rastogi Kalyani, MD, MHS, FACP
position statements and scientic who wish to comment on the Standards
Suneil Koliwad, MD, PhD
statements. of Medical Care in Diabetesd2016 are
The ADA adheres to the Institute of invited to do so at http://professional Joseph A. Stankaitis, MD, MPH*
Medicine Standards for Developing .diabetes.org/SOC. Tracey H. Taveira, PharmD, CDOE,
Trustworthy Clinical Practice Guidelines. The ADA funds development of the CVDOE*
All members of the PPC are required to Standards of Care and all ADA position
Deborah J. Wexler, MD, MSc*
disclose potential conicts of interest statements out of its general revenues
with industry and/or other relevant or- and does not use industry support for Joseph Wolfsdorf, MB, BCh*
ganizations. These disclosures are dis- these purposes. The PPC would like to *Subgroup leaders
cussed at the onset of each Standards thank the following individuals who
of Care revision meeting. Members of the provided their expertise in reviewing
committee, their employer, and their dis- and/or consulting with the committee:
ADA Staff
closed conicts of interest are listed in Lloyd Paul Aiello, MD, PhD; Sheri Jane L. Chiang, MD
the Professional Practice Committee Colberg-Ochs, PhD; Jo Ellen Condon, RD, (Corresponding author:
for the Standards of Medical Care in CDE; Donald R. Coustan, MD; Silvio E. jchiang@diabetes.org)
Diabetesd2016 table (see p. S107). Inzucchi, MD; George L. King, MD; Erika Gebel Berg, PhD
For the current revision, PPC mem- Shihchen Kuo, RPh, PhD; Ira B. Lamster, DDS,
bers systematically searched MEDLINE Allison T. McElvaine, PhD
MMSc; Greg Maynard, MD, MSc, SFHM;

2016 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 pro t,
and the work is not altered.
S4 Diabetes Care Volume 39, Supplement 1, January 2016
SUMMARYOF REVISIONS

Standards of Medical Care in Diabetesd2016:


Summary of Revisions
Diabetes Care 2016;39(Suppl. 1):S4S5 | DOI: 10.2337/dc16-S003

GENERAL CHANGES screening recommendations. The rec- the ADA added the recommendation
In alignment with the American Diabe- ommendation is now to test all adults that people who use continuous glucose
tes Associations (ADAs) position that beginning at age 45 years, regardless monitoring and insulin pumps should
diabetes does not dene people, the of weight. have continued access after they turn
Testing is also recommended for 65 years of age.
word diabetic will no longer be used
when referring to individuals with dia- asymptomatic adults of any age who
are overweight or obese and who have Section 6. Obesity Management for
betes in the Standards of Medical Care
one or more additional risk factors for the Treatment of Type 2 Diabetes
in Diabetes. The ADA will continue to This new section, which incorporates
diabetes. Please refer to Section 2 for
use the term diabetic as an adjective prior recommendations related to bari-
for complications related to diabetes testing recommendations for gesta-
tional diabetes mellitus. atric surgery, has new recommenda-
(e.g., diabetic retinopathy).
For monogenic diabetes syndromes, tions related to the comprehensive
Although levels of evidence for several
assessment of weight in diabetes and
recommendations have been updated, there is specic guidance and text on
testing, diagnosing, and evaluating indi- to the treatment of overweight/obesity
these changes are not included below as
viduals and their family members. with behavior modication and pharma-
the clinical recommendations have re- cotherapy.
mained the same. Changes in evidence Section 3. Foundations of Care and This section also includes a new table
level from, for example, C to E are not Comprehensive Medical Evaluation of currently approved medications for
noted below. The Standards of Medical Section 3 Initial Evaluation and Diabe- the long-term treatment of obesity.
Care in Diabetesd2016 contains, in addi- tes Management Planning and Section
tion to many minor changes that clarify Section 7. Approaches to Glycemic
4 Foundations of Care: Education, Nu-
trition, Physical Activity, Smoking Cessa- Treatment
recommendations or reect new evidence,
Bariatric surgery was removed from this
the following more substantive revisions. tion, Psychosocial Care, and Immunization
from the 2015 Standards were com- section and placed in a new section en-
SECTION CHANGES titled Obesity Management for the
bined into one section for 2016 to re-
Section 1. Strategies for Improving Care
ect the importance of integrating Treatment of Type 2 Diabetes.
This section was revised to include rec-
medical evaluation, patient engage- Section 8. Cardiovascular Disease and
ommendations on tailoring treatment
ment, and ongoing care that highlight
to vulnerable populations with diabetes, Risk Management
the importance of lifestyle and behav-
including recommendations for those Atherosclerotic cardiovascular disease
ioral modication. The nutrition and
with food insecurity, cognitive dysfunc- (ASCVD) has replaced the former term
vaccination recommendations were
tion and/or mental illness, and HIV, cardiovascular disease (CVD), as
streamlined to focus on those aspects
and a discussion on disparities related ASCVD is a more specic term.
of care most important and most rele-
to ethnicity, culture, sex, socioeconomic A new recommendation for pharma-
vant to people with diabetes. cological treatment of older adults was
differences, and disparities.
added.
Section 4. Prevention or Delay of
Section 2. Classication and Diagnosis Type 2 Diabetes To reect new evidence on ASCVD
of Diabetes risk among women, the recommenda-
To reect the changing role of technology
The order and discussion of diagnostic in the prevention of type 2 diabetes, a re- tion to consider aspirin therapy in
tests (fasting plasma glucose, 2-h plasma commendation was added encouraging w o m e n a g e d .6 0 y e a r s h a s b e e n
glucose after a 75-g oral glucose tolerance the use of new technology such as apps changed to include women aged $50
test, and A1C criteria) were revised to and text messaging to affect lifestyle years. A recommendation was also
make it clear that no one test is preferred
modication to prevent diabetes. added to address antiplatelet use in pa-
over another for diagnosis. tients aged ,50 years with multiple risk
To clarify the relationship between Section 5. Glycemic Targets factors.
age, BMI, and risk for type 2 diabetes Because of the growing number of older A recommendation was made to re-
and prediabetes, the ADA revised the adults with insulin-dependent diabetes, ect new evidence that adding ezetimibe

2016 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 pro t,
and the work is not altered.
care.diabetesjournals.org Summary of Revisions S5

to moderate-intensity statin provides ad- includes neurocognitive function, hypo- from a recommendation of ,6% (42
ditional cardiovascular benets for select glycemia, treatment goals, care in skilled mmol/mol) to a target of 66.5% (42
individuals with diabetes and should be nursing facilities/nursing homes, and 48 mmol/mol), although depending on
considered. end-of-life considerations. hypoglycemia risk the target may be
A new table provides efcacy and tightened or relaxed.
Section 11. Children and Adolescents
dose details on high- and moderate- Glyburide in gestational diabetes
The scope of this section is more com-
intensity statin therapy. mellitus was deemphasized based on
prehensive, capturing the nuances of di-
new data suggesting that it may be in-
abetes care in the pediatric population.
Section 9. Microvascular ferior to insulin and metformin.
This includes new recommendations
Complications and Foot Care
addressing diabetes self-management
Nephropathy was changed to dia- Section 13. Diabetes Care in the
education and support, psychosocial
betic kidney disease to emphasize Hospital
issues, and treatment guidelines for
that, while nephropathy may stem This section was revised to focus solely
type 2 diabetes in youth.
from a variety of causes, attention is on diabetes care in the hospital setting.
The recommendation to obtain a fast-
placed on kidney disease that is directly This comprehensive section addresses
related to diabetes. There are several ing lipid prole in children starting at
age 2 years has been changed to age hospital care delivery standards, more
minor edits to this section. The signi- detailed information on glycemic tar-
cant ones, based on new evidence, are
10 years, based on a scientic statement
on type 1 diabetes and cardiovascular gets and antihyperglycemic agents,
as follows: standards for special situations, and
disease from the American Heart Asso-
Diabetic kidney disease: guidance was transitions from the acute care setting.
ciation and the ADA.
added on when to refer for renal re- This section also includes a new table
placement treatment and when to refer on basal and bolus dosing recommenda-
to physicians experienced in the care of Section 12. Management of Diabetes
tions for continuous enteral, bolus en-
diabetic kidney disease. in Pregnancy
The scope of this section is more com- teral, and parenteral feedings.
Diabetic retinopathy: guidance was
prehensive, providing new recommen-
added on the use of intravitreal anti-
dations on pregestational diabetes, Section 14. Diabetes Advocacy
VEGF age nts for the treatment of
gestational diabetes mellitus, and gen- Diabetes Care in the School Setting: A
center-involved diabetic macular edema,
eral principles for diabetes management Position Statement of the American Di-
as they were more effective than mono-
in pregnancy. abetes Association was revised in 2015.
therapy or combination therapy with
A new recommendation was added to This position statement was previously
laser.
highlight the importance of discussing fam- called Diabetes Care in the School and
Section 10. Older Adults ily planning and effective contraception Day Care Setting. The ADA intentionally
The scope of this section is more compre- with women with preexisting diabetes. separated these two populations be-
hensive, capturing the nuances of diabe- A1C recommendations for pregnant cause of the signicant differences in di-
tes care in the older adult population. This women with diabetes were changed, abetes care between the two cohorts.
S6 Diabetes Care Volume 39, Supplement 1, January 2016

1. Strategies for Improving Care


American Diabetes Association

Diabetes Care 2016;39(Suppl. 1):S6S12 | DOI: 10.2337/dc16-S004

Recommendations
c A patient-centered communication style that incorporates patient prefer-
ences, assesses literacy and numeracy, and addresses cultural barriers to
care should be used. B
c Treatment decisions should be timely and based on evidence-based guide-
lines that are tailored to individual patient preferences, prognoses, and co-
morbidities. B
c Care should be aligned with components of the Chronic Care Model to ensure
ES FOR IMPROVINGCARE

productive interactions between a prepared proactive practice team and an


informed activated patient. A
c When feasible, care systems should support team-based care, community
involvement, patient registries, and decision support tools to meet patient
needs. B

DIABETES CARE CONCEPTS


1. STRATEGI

In the following sections, different components of the clinical management of


patients with (or at risk for) diabetes are reviewed. Clinical practice guidelines are
key to improving population health; however, for optimal outcomes, diabetes care
must be individualized for each patient. The American Diabetes Association high-
lights the following three themes that clinicians, policymakers, and advocates
should keep in mind:

1. Patient-Centeredness: Practice recommendations, whether based on evi-


dence or expert opinion, are intended to guide an overall approach to
care. The science and art of medicine come together when the clinician is
faced with making treatment recommendations for a patient who would not
have met eligibility criteria for the studies on which guidelines were based.
Recognizing that one size does not t all, these Standards provide guid-
ance for when and how to adapt recommendations. Because patients with
diabetes have greatly increased risk for cardiovascular disease, a patient-
centered approach should include a comprehensive plan to reduce cardio-
vascular risk by addressing blood pressure and lipid control, smoking prevention
and cessation, weight management, physical activity, and healthy lifestyle
choices.
2. Diabetes Across the Life Span: An increasing proportion of patients with type 1
diabetes are adults. For less salutary reasons, the incidence of type 2 diabetes is
increasing in children and young adults. Patients with type 1 diabetes and those
with type 2 diabetes are living well into older age, a stage of life for which there is
little evidence from clinical trials to guide therapy. All these demographic
changes highlight another challenge to high-quality diabetes care, which is the
need to improve coordination between clinical teams as patients transition
through different stages of the life span.
3. Advocacy for Patients With Diabetes: Advocacy can be dened as active support
and engagement to advance a cause or policy. Advocacy is needed to improve
the lives of patients with (or at risk for) diabetes. Given the tremendous toll that Suggested citation: American Diabetes Associa-
obesity, physical inactivity, and smoking have on the health of patients with tion. Strategies for improving care. Sec. 1. In
diabetes, efforts are needed to address and change the societal determinants Standards of Medical Care in Diabetesd2016.
at the root of these problems. Within the narrower domain of clinical practice Diabetes Care 2016;39(Suppl. 1):S6S12
guidelines, the application of evidence level grading to practice recommenda- 2016 by the American Diabetes Association.
tions can help to identify areas that require more research (1). Refer to Section Readers may use this article as long as the work
is properly cited, the use is educational and not
14 Diabetes Advocacy.
for prot, and the work is not altered.
care.diabetesjournals.org Strategies for Improving Care S7

CARE DELIVERY SYSTEMS 2. Self-management support 1. Healthy lifestyle choices (physical


There has been steady improvement in 3. Decision support (basing care on activity, healthy eating, tobacco ces-
the proportion of patients with diabetes evidence-based, effective care guide- sation, weight management, and ef-
treated with statins and achieving recom- lines) fective coping)
mended levels of A1C, blood pressure, 4. Clinical information systems (using 2. Disease self-management (taking
and LDL cholesterol in the last 10 years registries that can provide patient- and managing medications and, when
(2). The mean A1C nationally has declined specic and population-based sup- clinically appropriate, self-monitoring
from 7.6% (60 mmol/mol) in 19992002 port to the care team) of glucose and blood pressure)
to 7.2% (55 mmol/mol) in 20072010 5. Community resources and policies 3. Prevention of diabetes complica-
based on the National Health and Nutri- (identifying or developing resources tions (self-monitoring of foot health;
tion Examination Survey (NHANES), with to support healthy lifestyles) active participation in screening for
younger adults less likely to meet treat- 6. Health systems (to create a quality- eye, foot, and renal complications;
ment targets compared with older adults oriented culture) and immunizations)
(2). This has been accompanied by im-
provements in cardiovascular outcomes Redening the roles of the health care High-quality diabetes self-management
and has led to substantial reductions in delivery team and promoting self- education (DSME) has been shown to
end-stage microvascular complications. management on the part of the patient improve patient self-management,
Nevertheless, 3349% of patients still are fundamental to the successful imple- satisfaction, and glucose control. Na-
do not meet targets for glycemic, blood mentation of the CCM (8). Collaborative, tional DSME standards call for an inte-
pressure, or cholesterol control, and multidisciplinary teams are best suited to grated approach that includes clinical
only 14% meet targets for all three mea- provide care for people with chronic con- content and skills, behavioral strategies
sures and nonsmoking status (2). Evi- ditions such as diabetes and to facilitate (goal setting, problem solving), and en-
dence also suggests that progress in patients self-management (911). gagement with psychosocial concerns
cardiovascular risk factor control (par- (23).
Key Objectives
ticularly tobacco use) may be slowing The National Diabetes Education Pro- Objective 3: Change the Care System
(2,3). Certain patient groups, such as gram (NDEP) maintains an online re- An institutional priority in most success-
young adults and patients with complex source (www.betterdiabetescare.nih ful care systems is providing high quality
comorbidities, nancial or other social .gov) to help health care professionals of care (24). Changes that have been
hardships, and/or limited English pro- to design and implement more effective shown to increase quality of diabetes
ciency, may present particular chal- health care delivery systems for those care include basing care on evidence-
lenges to goal-based care (46). Even with diabetes. Three specic objectives, based guidelines (18); expanding the
after adjusting for patient factors, with references to literature outlining role of teams to implement more inten-
the persistent variation in quality of di- practical strategies to achieve each, are sive disease management strategies
abetes care across providers and prac- as follows: (6,21,25); redesigning the care process
tice settings indicates that there is
Objective 1 : Optimize Provider and Team (26); implementing electronic health
potential for substantial system-level
Behavior record tools (27,28); activating and
improvements.
The care team should prioritize timely educating patients (29,30); removing -
Chronic Care Model and appropriate intensication of life- nancial barriers and reducing patient
Numerous interventions to improve ad- style and/or pharmacological therapy out-of-pocket costs for diabetes educa-
herence to the recommended standards for patients who have not achieved ben- tion, eye exams, self-monitoring of
have been implemented. However, a ma- ecial levels of glucose, blood pressure, blood glucose, and necessary medica-
jor barrier to optimal care is a delivery or lipid control (12). Strategies such as tions (6); and identifying/developing/
system that is often fragmented, lacks explicit goal setting with patients (13); engaging community resources and
clinical information capabilities, dupli- identifying and addressing language, nu- public policy that support healthy life-
cates services, and is poorly designed for meracy, or cultural barriers to care (14 styles (31).
the coordinated delivery of chronic care. 17); integrating evidence-based guide- Initiatives such as the Patient-Centered
The Chronic Care Model (CCM) has been lines and clinical information tools into Medical Home show promise for improv-
shown to be an effective framework for the process of care (1820); and incor- ing outcomes through coordinated pri-
improving the quality of diabetes care (7). porating care management teams in- mary care and offer new opportunities
Six Core Elements cluding nurses, pharmacists, and other for team-based chronic disease care
The CCM includes six core elements for providers (21,22) have each been shown (32). Additional strategies to improve di-
the provision of optimal care of patients to optimize provider and team behavior abetes care include reimbursement
with chronic disease: and thereby catalyze reductions in A1C, structures that, in contrast to visit-based
blood pressure, and LDL cholesterol. billing, reward the provision of appropriate
1. Delivery system design (moving Objective 2: Support Patient Behavior and high-quality care (33), and incen-
from a reactive to a proactive care Change tives that accommodate personalized
delivery system where planned visits Successful diabetes care requires a sys- care goals (6,34).
are coordinated through a team- tematic approach to supporting patients Optimal diabetes management re-
based approach) behavior change efforts, including quires an organized, systematic approach
S8 Strategies for Improving Care Diabetes Care Volume 39, Supplement 1, January 2016

and the involvement of a coordinated pressure, or lipids (40). Although there TAILORING TREATMENT TO
team of dedicated health care profes- are many ways to measure adherence VULNERABLE POPULATIONS
sionals working in an environment where (40), Medicare uses percent of days cov- Health Disparities
patient-centered high-quality care is a ered (PDC), which is a measure of the The causes of health disparities are com-
priority (6). number of pills prescribed divided by plex and include societal issues such as
the days between rst and last prescrip- institutional racism, discrimination, socio-
WHEN TREATMENT GOALS ARE tions. Adequate adherence is dened economic status, poor access to health
NOT MET as 80% (40). This metric can be used to care, and lack of health insurance. Disparities
In general, providers should seek evidence- nd and track poor adherence and help are particularly well documented for car-
based approaches that improve the to guide system improvement efforts to diovascular disease.
clinical outcomes and quality of life of pa- overcome the barriers to adherence.
tients with diabetes. Recent reviews of Barriers to adherence may include pa- Ethnic/Cultural/Sex/Socioeconomic
quality improvement strategies in diabe- tient factors (remembering to obtain Differences
tes care (24,35,36) have not identied a or take medications, fears, depression, Ethnic, cultural, religious, and sex differ-
particular approach that is more effective or health beliefs), medication factors ences and socioeconomic status may
than others. However, the Translating Re- (complexity, multiple daily dosing, affect diabetes prevalence and out-
search Into Action for Diabetes (TRIAD) cost, or side effects), and system factors comes. Type 2 diabetes develops more
study provided objective data from large (inadequate follow-up or support). frequently in women with prior gesta-
managed care systems demonstrating ef- tional diabetes mellitus (42), in individu-
fective tools for specic targets (6). TRIAD Improving Adherence als with hypertension or dyslipidemia,
found it useful to divide interventions into Simplifying a complex treatment regi- and in certain racial/ethnic groups
those that affected processes of care and men may improve adherence. Nurse- (African American, Native American,
intermediate outcomes. directed interventions, home aides, Hispanic/Latino, and Asian American) (43).
diabetes education, and pharmacy-
Processes of Care Access to Health Care
derived interventions improved ad-
Processes of care included periodic test- Ethnic, cultural, religious, sex, and socio-
herence but had a very small effect on
ing of A1C, lipids, and urinary albumin; economic differences affect health care
outcomes, including metabolic control
examining the retina and feet; advising access and complication risk in people
(41). Success in overcoming barriers
on aspirin use; and smoking cessation. with diabetes. Recent studies have rec-
may be achieved if the patient and pro-
TRIAD results suggest that providers ommended lowering the BMI cut point
vider agree on a targeted treatment
control these activities. Performance for testing for Asian Americans to $23
for a specic barrier. For example, one kg/m (44). Women with diabetes, com-
2
feedback, reminders, and structured
study found that when depression was pared with men with diabetes, have a
care (e.g., guidelines, formal case man-
identied as a barrier, agreement on 40% greater risk of incident coronary
agement, and patient education re-
antidepressant treatment subsequently heart disease (45). Socioeconomic and
sources) may inuence providers to allowed for improvements in A1C,
improve processes of care (6). ethnic inequalities exist in the provision
blood pressure, and lipid control (10). of health care to individuals with diabe-
Thus, to improve adherence, systems tes (46). As a result, children with type 1
Intermediate Outcomes and
should continually monitor and prevent
Treatment Intensication diabetes from racial/ethnic populations
or treat poor adherence by identifying
For intermediate outcomes, such as with lower socioeconomic status are at
A1C, blood pressure, and lipid goals, barriers and implementing treatments risk for poor metabolic control and poor
tools that improved processes of care that are barrier specic and effective. emotional functioning (47). Signicant
did not perform as well in addressing A systematic approach to achieving in- racial differences and barriers exist in
termediate outcomes involves three steps:
barriers to treatment intensication self-monitoring and outcomes (48).
and adherence (6). In 35% of cases, un-
controlled A1C, blood pressure, or lipids 1. Assess adherence. Adherence should Addressing Disparities
were associated with a lack of treatment be addressed as the rst priority. If Therefore, diabetes management re-
adherence is 80% or above, then treat- quires individualized, patient-centered,
intensication, dened as a failure to
either increase a drug dose or change a ment intensication should be consid- and culturally appropriate strategies. To
ered (e.g., up-titration). If medication overcome disparities, community health
drug class (37). Treatment intensica-
tion was associated with improvement
up-titration is not a viable option, then workers (49), peers (50,51), and lay lead-
in A1C, hypertension, and hyperlipid- consider initiating or changing to a dif- ers (52) may assist in the delivery of
emia control (38). A large multicenter ferent medication class. DSME and diabetes self-management
2. Explore barriers to adherence with support services (53). Strong social sup-
study conrmed the strong association
the patient/caregiver and nd a mutu- port leads to improved clinical outcomes,
between treatment intensication and
ally agreeable approach to overcom- reduced psychosocial symptomatology,
improved A1C (39).
ing the barriers. and adoption of healthier lifestyles (54).
Intermediate Outcomes and 3. Establish a follow-up plan that con- Structured interventions, tailored to eth-
Adherence rms the planned treatment change nic populations that integrate culture,
In 23% of cases, poor adherence was and assess progress in reaching the language, religion, and literacy skills, pos-
associated with uncontrolled A1C, blood target. itively inuence patient outcomes (55).
care.diabetesjournals.org Strategies for Improving Care S9

To decrease disparities, all providers and Providers should recognize that FI com- Additionally, homeless patients with dia-
groups are encouraged to use the National plicates diabetes management and seek betes need secure places to keep their
Quality Forums National Voluntary Con- local resources that can help patients and diabetes supplies and refrigerator access
sensus Standards for Ambulatory Cared the parents of patients with diabetes to to properly store their insulin.
Measuring Healthcare Disparities (56). more regularly obtain nutritious food (59). Literacy and Numeracy Deciencies. FI
and
Lack of Health Insurance
Food Insecurity and Hyperglycemia. Hy- diabetes are more common among non-
Not having health insurance affects the perglycemia is more common in those English speaking individuals and those
processes and outcomes of diabetes with diabetes and FI. Reasons for this with poor literacy and numeracy skills.
care. Individuals without insurance include the steady consumption of Therefore, it is important to consider
coverage for blood glucose monitoring carbohydrate-rich processed foods, screening for FI, proper housing, and di-
supplies have a 0.5% higher A1C than binge eating, not lling antidiabetes med- abetes in this population. Programs that
those with coverage (57). The afford- ication prescriptions owing to nancial see such patients should work to develop
able care act has improved access to constraint, and anxiety/depression that services in multiple languages with the
health care; however, many remain lead to poor diabetes self-care behaviors. specic goal of preventing diabetes and
without coverage. In a recent study of Providers should be well versed in these building diabetes awareness in people
predominantly African American or risk factors for hyperglycemia and take who cannot easily read or write in English.
Hispanic uninsured patients with dia- practical steps to alleviate them in order
to improve glucose control. Cognitive Dysfunction
betes, 5060% were hypertensive, but
only 2237% had systolic blood pres- Recommendations
Food Insecurity and Hypoglycemia
sure controlled by treatments to under c Intensive glucose control is not ad-
130 mmHg (58). Type 1 Diabetes. Individuals with type 1 vised for the improvement of poor
diabetes and FI may develop hypoglycemia cognitive function in hyperglycemic
Food Insecurity as a result of inadequate or erratic carbo- individuals with type 2 diabetes. B
Recommendations hydrate consumption following insulin c In individuals with poor cognitive
c Providers should evaluate hyper- administration. Long-acting insulin, as op- function or severe hypoglycemia,
glycemia and hypoglycemia in the posed to shorter-acting insulin that may glycemic therapy should be tailored
context of food insecurity and pro- peak when food is not available, may to avoid signicant hypoglycemia. C
pose solutions accordingly. A lower the risk for hypoglycemia in those c In individuals with diabetes at high
c Providers should recognize that with FI. Short-acting insulin analogs, cardiovascular risk, the cardiovascular
homelessness, poor literacy, and preferably delivered by a pen, may be benets of statin therapy outweigh
poor numeracy often occur with used immediately after consumption the risk of cognitive dysfunction. A
food insecurity, and appropriate of a meal, whenever food becomes c If a second-generation antipsychotic
resources should be made avail- available. Unfortunately, the greater medication is prescribed, changes in
able for patients with diabetes. A cost of insulin analogs should be weighed weight, glycemic control, and cho-
against their potential advantages. Caring lesterol levels should be carefully
Food insecurity (FI) is the unreliable for those with type 1 diabetes in the set- monitored and the treatment regi-
availability of nutritious food and the ting of FI may mirror sick day manage- men should be reassessed. C
inability to consistently obtain food ment protocols.
without resorting to socially unaccept- Dementia
Type 2 Diabetes. Thosewith type 2 diabe-
able practices. Over 14% (or one out of The most severe form of cognitive
tes and FI can develop hypoglycemia for dysfunction is dementia. A recent meta-
every seven people in the U.S.) are food
similar reasons after taking certain oral analysis of prospective observational stud-
insecure. The rate is higher in some
hypoglycemic agents. If using a sulfonyl- ies in people with diabetes showed a 73%
racial/ethnic minority groups including
urea, glipizide is the preferred choice increased risk of all types of dementia, a
African American and Latino popula-
due to the shorter half-life. Glipizide 56% increased risk of Alzheimer dementia,
tions, in low-income households, and
can be taken immediately before meal and 127% increased risk of vascular de-
in homes headed by a single mother. FI
may involve a tradeoff between purchas-
consumption, thus limiting its tendency mentia compared with individuals without
ing nutritious food for inexpensive and to produce hypoglycemia as compared diabetes (60). The reverse is also true: peo-
more energy- and carbohydrate-dense
with longer-acting sulfonylureas (e.g., ple with Alzheimer dementia are more
processed foods. glyburide). likely to develop diabetes than people
In people with FI, interventions should Homelessness. Homelessness often ac- without Alzheimer dementia.
focus on preventing diabetes and, in companies the most severe form of FI. Hyperglycemia. In those with type 2
those with diabetes, limiting hyperglyce- Therefore, providers who care for those diabetes, the degree and duration of
mia and preventing hypoglycemia. The with FI who are uninsured and homeless hyperglycemia are related to dementia.
risk for type 2 diabetes is increased two- and individuals with poor literacy and nu- More rapid cognitive decline is associated
fold in those with FI. The risks of uncontrolled meracy should be well versed or have with both increased A1C and longer du-
hyperglycemia and severe hypoglycemia access to social workers to facilitate tem- ration of diabetes (61). The Action to
are increased in those with diabetes who porary housing for their patients as a Control Cardiovascular Risk in Diabetes
are also food insecure. means to prevent and control diabetes. (ACCORD) study found that each 1%
S10 Strategies for Improving Care Diabetes Care Volume 39, Supplement 1, January 2016

higher A1C level was associated with analysis showed a signicantly increased progression toward diabetes. Among
lower cognitive function in individuals risk of incident depression (relative risk HIV patients with diabetes, preventive
with type 2 diabetes (62). However, the [RR] 5 1.15), and, in turn, depression was health care using an approach similar
ACCORD study found no difference in associated with a signicantly increased to that used in patients without HIV is
cognitive outcomes between intensive risk of diabetes (RR 5 1.6) (71). Depression critical to reduce the risks of microvas-
and standard glycemic control, support- and psychosocial issues are discussed cular and macrovascular complications.
ing the recommendation that intensive more extensively in Section 3 Founda- For patients with HIV and ARV-
glucose control should not be advised for tions of Care and Comprehensive Medical associated hyperglycemia, it may be
the improvement of cognitive function in Evaluation. appropriate to consider discontinuing
individuals with type 2 diabetes (63). the problematic ARV agents if safe and
Hypoglycemia. In type 2 diabetes, severe
Medications effective alternatives are available (76).
Diabetes medications are effective, re- Before making ARV substitutions, carefully
hypoglycemia is associated with reduced
gardless of mental health status. Treat- consider the possible effect on HIV viro-
cognitive function, and those with poor
ments for depression are effective in logical control and the potential adverse
cognitive function have more severe hy- patients with diabetes, and treating de- effects of new ARV agents. In some cases,
poglycemia. In a long-term study of older pression may improve short-term glyce- antidiabetes agents may still be necessary.
patients with type 2 diabetes, individuals
mic control (72). If a second-generation
with one or more recorded episode of
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19. Garg AX, Adhikari NKJ, McDonald H, et al. 50. Heisler M, Vijan S, Makki F, Piette JD. Di-
quality improvement: the state of the science.
Effects of computerized clinical decision sup- abetes control with reciprocal peer support ver-
port systems on practitioner performance and Health Aff (Millwood) 2005;24:138150 sus nurse care management: a randomized trial.
36. Shojania KG, Ranji SR, Shaw LK, et al. Closing
patient outcomes: a systematic review. JAMA Ann Intern Med 2010;153:507515
the quality gap: a critical analysis of quality im-
2005;293:12231238 51. Long JA, Jahnle EC, Richardson DM,
provement strategies (vol. 2: diabetes care).
20. Smith SA, Shah ND, Bryant SC, et al.; Evi- Loewenstein G, Volpp KG. Peer mentoring and
Rockville, MD, Agency for Healthcare Research
dens Research Group. Chronic Care Model and nancial incentives to improve glucose control
and Quality, 2004 (Report no. 04-0051-2. AHRQ
shared care in diabetes: randomized trial of an in African American veterans: a randomized tri-
Technical Reviews)
electronic decision support system. Mayo Clin al. Ann Intern Med 2012;156:416424
37. Schmittdiel JA, Uratsu CS, Karter AJ, et al.
Proc 2008;83:747757 52. Foster G, Taylor SJC, Eldridge SE, Ramsay J,
Why dont diabetes patients achieve recom-
21. Jaffe MG, Lee GA, Young JD, Sidney S, Go Grifths CJ. Self-management education pro-
mended risk factor targets? Poor adherence
AS. Improved blood pressure control associated grammes by lay leaders for people with chronic
versus lack of treatment intensication. J Gen
with a large-scale hypertension program. JAMA conditions. Cochrane Database Syst Rev 2007;4:
Intern Med 2008;23:588594 CD005108
2013;310:699705 38. Selby JV, Uratsu CS, Fireman B, et al. Treat-
22. Stone RA, Rao RH, Sevick MA, et al. Active 53. Siminerio L, Ruppert KM, Gabbay RA. Who
ment intensication and risk factor control: to-
care management supported by home telemo- can provide diabetes self-management sup-
ward more clinically relevant quality measures.
nitoring in veterans with type 2 diabetes: the port in primary care? Findings from a random-
Med Care 2009;47:395402
DiaTel randomized controlled trial. Diabetes 39. Raebel MA, Ellis JL, Schroeder EB, et al. In- ized controlled trial. Diabetes Educ 2013;39:
Care 2010;33:478484 tensication of antihyperglycemic therapy among 705713
23. Powers MA, Bardsley J, Cypress M, et al. patients with incident diabetes: a Surveillance 54. Strom JL, Egede LE. The impact of social
Diabetes self-management education and sup- Prevention and Management of Diabetes Mellitus support on outcomes in adult patients with
port in type 2 diabetes: a joint position state- (SUPREME-DM) study. Pharmacoepidemiol Drug type 2 diabetes: a systematic review. Curr
ment of the American Diabetes Association, the Saf 2014;23:699710 Diab Rep 2012;12:769781
American Association of Diabetes Educators, 40. Raebel MA, Schmittdiel J, Karter AJ, 55. Zeh P, Sandhu HK, Cannaby AM, Sturt JA.
and the Academy of Nutrition and Dietetics. Di- Konieczny JL, Steiner JF. Standardizing terminol- The impact of culturally competent diabetes
abetes Care 2015;38:13721382 ogy and denitions of medication adherence and care interventions for improving diabetes-
24. Tricco AC, Ivers NM, Grimshaw JM, et al. persistence in research employing electronic da- related outcomes in ethnic minority groups: a
Effectiveness of quality improvement strategies tabases. Med Care 2013;51(Suppl. 3):S11 S21 systematic review. Diabet Med 2012;29:1237
on the management of diabetes: a systematic 41. Vermeire E, Wens J, Van Royen P, Biot Y, 1252
review and meta-analysis. Lancet 2012;379: Hearnshaw H, Lindenmeyer A. Interventions 56. National Quality Forum. National Voluntary
22522261 for improving adherence to treatment recom- Consensus Standards for Ambulatory Cared
25. Peikes D, Chen A, Schore J, Brown R. Effects mendations in people with type 2 diabetes mel- Measuring Healthcare Disparities [Internet],
of care coordination on hospitalization, quality litus. Cochrane Database Syst Rev 2005;2: 2008. Available from https://www.qualityforum
of care, and health care expenditures among CD003638 .org/Publications/2008/03/National_Voluntary_
Medicare beneciaries: 15 randomized trials. 42. Kim C, Newton KM, Knopp RH. Gestational Consensus_Standards_for_Ambulatory_Care%
JAMA 2009;301:603 618 diabetes and the incidence of type 2 diabetes: a E2%80%94Measuring_Healthcare_Disparities
26. Feifer C, Nemeth L, Nietert PJ, et al. Differ- systematic review. Diabetes Care 2002;25: .aspx. Accessed 2 September 2015
ent paths to high-quality care: three archetypes 18621868 57. Bowker SL, Mitchell CG, Majumdar SR, Toth
of top-performing practice sites. Ann Fam Med 43. Hutchinson RN, Shin S. Systematic review of EL, Johnson JA. Lack of insurance coverage for
2007;5:233241 health disparities for cardiovascular diseases testing supplies is associated with poorer
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glycemic control in patients with type 2 diabe- 64. Whitmer RA, Karter AJ, Yaffe K, Quesenberry depression and bipolar disorder. World Psychi-
tes. CMAJ 2004;171:39 43 CP Jr, Selby JV. Hypoglycemic episodes and risk of atry 2015;14:119136
58. Baumann LC, Chang M-W, Hoebeke R. Clinical dementia in older patients with type 2 diabetes 71. Mezuk B, Eaton WW, Albrecht S, Golden SH.
outcomes for low-income adults with hyperten- mellitus. JAMA 2009;301:1565 1572 Depression and type 2 diabetes over the lifespan: a
sion and diabetes. Nurs Res 2002;51:191 198 65. Punthakee Z, Miller ME, Launer LJ, et al.; meta-analysis. Diabetes Care 2008;31:23832390
59. Seligman HK, Schillinger D. Hunger and so- ACCORD Group of Investigators; ACCORD- 72. Baumeister H, Hutter N, Bengel J. Psycho-
cioeconomic disparities in chronic disease. N MIND Investigators. Poor cognitive function logical and pharmacological interventions for
Engl J Med 2010;363:69 and risk of severe hypoglycemia in type 2 dia- depression in patients with diabetes mellitus
60. Gudala K, Bansal D, Schifano F, Bhansali A. betes: post hoc epidemiologic analysis of the and depression. Cochrane Database Syst Rev
Diabetes mellitus and risk of dementia: a meta- ACCORD trial. Diabetes Care 2012;35:787793 2012;12:CD008381
analysis of prospective observational studies. J 66. Scarmeas N, Stern Y, Mayeux R, Manly JJ, 73. American Diabetes Association; American
Schupf N, Luchsinger JA. Mediterranean diet Psychiatric Association; American Association
Diabetes Investig 2013;4:640650
61. Rawlings AM, Sharrett AR, Schneider AL, and mild cognitive impairment. Arch Neurol of Clinical Endocrinologists; North American As-
et al. Diabetes in midlife and cognitive change 2009;66:216225 sociation for the Study of Obesity. Consensus
67. Ooi CP, Loke SC, Yassin Z, Hamid T-A. Car- development conference on antipsychotic
over 20 years: a cohort study. Ann Intern Med
bohydrates for improving the cognitive per- drugs and obesity and diabetes. Diabetes Care
2014;161:785793
formance of independent-living older adults 2004;27:596601
62. Cukierman-Yaffe T, Gerstein HC, Williamson
with normal cognition or mild cognitive impair- 74. Dub e MP. Disorders of glucose metabo-
JD, et al.; Action to Control Cardiovascular Risk
ment. Cochrane Database Syst Rev 2011;4: lism in patients infected with human immuno-
in Diabetes-Memory in Diabetes (ACCORD-
CD007220 deciency virus. Clin Infect Dis 2000;31:
MIND) Investigators. Relationship between
68. Richardson K, Schoen M, French B, et al. 14671475
baseline glycemic control and cognitive func- Statins and cognitive function: a systematic re- 75. Schambelan M, Benson CA, Carr A, et al.;
tion in individuals with type 2 diabetes and International AIDS Society-USA. Management
view. Ann Intern Med 2013;159:688697
other cardiovascular risk factors: the action to 69. Osborn DPJ, Wright CA, Levy G, King MB, of metabolic complications associated with
control cardiovascular risk in diabetes-memory Deo R, Nazareth I. Relative risk of diabetes, dys- antiretroviral therapy for HIV-1 infection: rec-
in diabetes (ACCORD-MIND) trial. Diabetes lipidaemia, hypertension and the metabolic syn- ommendations of an International AIDS Society-
Care 2009;32:221226 drome in people with severe mental illnesses: USA panel. J Acquir Immune Dec Syndr 2002;31:
63. Launer LJ, Miller ME, Williamson JD, et al.; systematic review and metaanalysis. BMC Psy- 257275
ACCORD MIND investigators. Effects of intensive chiatry 2008;8:84 76. Wohl DA, McComsey G, Tebas P, et al.
glucose lowering on brain structure and function 70. Correll CU, Detraux J, De Lepeleire J, De Current concepts in the diagnosis and man-
in people with type 2 diabetes (ACCORD MIND): a Hert M. Effects of antipsychotics, antidepres- agement of metabolic complications of HIV
randomised open-label substudy. Lancet Neurol sants and mood stabilizers on risk for physi- infection and its therapy. Clin Infect Dis
2011;10:969977 cal diseases in people with schizophrenia, 2006;43:645653
Diabetes Care Volume 39, Supplement 1, January 2016 S13

2. Classication and Diagnosis of American Diabetes Association

Diabetes
Diabetes Care 2016;39(Suppl. 1):S13S22 | DOI: 10.2337/dc16-S005

CLASSIFICATION
Diabetes can be classied into the following general categories:

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin

2. CLASSIFICATION AND DIAGNOSIS OF DIABETES


deciency)
2. Type 2 diabetes (due to a progressive loss of insulin secretion on the background
of insulin resistance)
3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third
trimester of pregnancy that is not clearly overt diabetes)
4. Specic types of diabetes due to other causes, e.g., monogenic diabetes syn-
dromes (such as neonatal diabetes and maturity-onset diabetes of the young
[MODY]), diseases of the exocrine pancreas (such as cystic brosis), and drug- or
chemical-induced diabetes (such as with glucocorticoid use, in the treatment of
HIV/AIDS or after organ transplantation)

This section reviews most common forms of diabetes but is not comprehensive. For
additional information, see the American Diabetes Association (ADA) position state-
ment Diagnosis and Classication of Diabetes Mellitus (1).
Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinical
presentation and disease progression may vary considerably. Classication is im-
portant for determining therapy, but some individuals cannot be clearly classied as
having type 1 or type 2 diabetes at the time of diagnosis. The traditional paradigms
of type 2 diabetes occurring only in adults and type 1 diabetes only in children are no
longer accurate, as both diseases occur in both cohorts. Occasionally, patients with
type 2 diabetes may present with diabetic ketoacidosis (DKA). Children with type 1
diabetes typically present with the hallmark symptoms of polyuria/polydipsia and
approximately one-third with DKA (2). The onset of type 1 diabetes may be more
variable in adults, and they may not present with the classic symptoms seen in
children. Although difculties in distinguishing diabetes type may occur in all age-
groups at onset, the true diagnosis becomes more obvious over time.

DIAGNOSTIC TESTS FOR DIABETES


Diabetes may be diagnosed based on the plasma glucose criteria, either the fasting
plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oral
glucose tolerance test (OGTT) or the A1C criteria (1,3) (Table 2.1).
The same tests are used to screen for and diagnose diabetes and to detect individ-
uals with prediabetes. Diabetes may be identied anywhere along the spectrum of
clinical scenarios: in seemingly low-risk individuals who happen to have glucose testing,
in individuals tested based on diabetes risk assessment, and in symptomatic patients.

Fasting and 2-Hour Plasma Glucose


Suggested citation: American Diabetes Associa-
The FPG and 2-h PG may be used to diagnose diabetes (Table 2.1). The concordance
between the FPG and 2-h PG tests is imperfect, as is the concordance between A1C tion. Classication and diagnosis of diabetes.
Sec. 2. In Standards of Medical Care in
and either glucose-based test. Numerous studies have conrmed that, compared
Diabetesd2016. Diabetes Care 2016;39(Suppl. 1):
with FPG cut points and A1C, the 2-h PG value diagnoses more people with diabetes.
S13S22
A1C 2016 by the American Diabetes Association.
The A1C test should be performed using a method that is certied by the NGSP Readers may use this article as long as the work
(www.ngsp.org) and standardized or traceable to the Diabetes Control and is properly cited, the use is educational and not
for prot, and the work is not altered.
S14 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

the test result that is above the diagnos-


Table 2.1Criteria for the diagnosis of diabetes
tic cut point should be repeated. The di-
FPG $126 mg/dL (7.0 mmol/L). Fasting is dened as no caloric intake for at least 8 h.*
agnosis is made on the basis of the
OR
2-h PG $200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described by conrmed test. For example, if a patient
the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in meets the diabetes criterion of the A1C
water.* (two results $6.5% [48 mmol/mol]) but not
OR FPG (,126 mg/dL [7.0 mmol/L]), that
A1C $6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is
person should nevertheless be consid-
NGSP certied and standardized to the DCCT assay.*
ered to have diabetes.
OR Since all the tests have preanalytic and
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma analytic variability, it is possible that an
glucose $200 mg/dL (11.1 mmol/L). abnormal result (i.e., above the diagnostic
threshold), when repeated, will produce a
*In the absence of unequivocal hyperglycemia, results should be conrmed by repeat testing.
value below the diagnostic cut point. This
scenario is least likely for A1C, more likely
Complications Trial (DCCT) reference as- of fructosamine and glycated albumin and for FPG, and most likely for the 2-h PG,
say. Although point-of-care A1C assays lower levels of 1,5-anhydroglucitol, sug- especially if the glucose samples remain
may be NGSP certied, prociency testing gesting that their glycemic burden (partic- at room temperature and are not centri-
is not mandated for performing the test, ularly postprandially) may be higher (8). fuged promptly. Barring laboratory error,
so use of point-of-care assays for diagnos- Moreover, the association of A1C with such patients will likely have test results
tic purposes is not recommended. risk for complications is similar in African near the margins of the diagnostic thresh-
The A1C has several advantages com- Americans and non-Hispanic whites (9). old. The health care professional should
pared with the FPG and OGTT, including follow the patient closely and repeat the
Hemoglobinopathies/Anemias
greater convenience (fasting not re- test in 36 months.
Interpreting A1C levels in the presence of
quired), greater preanalytical stability, certain hemoglobinopathies and anemia
and less day-to-day perturbations during CATEGORIES OF INCREASED RISK
may be problematic. For patients with an
stress and illness. However, these advan- FOR DIABETES (PREDIABETES)
abnormal hemoglobin but normal red blood
tages may be offset by the lower sensitiv- Recommendations
cell turnover, such as those with the sickle
ity of A1C at the designated cut point, cell trait, an A1C assay without interference c Testing to assess risk for future di-
greater cost, limited availability of A1C from abnormal hemoglobins should be abetes in asymptomatic people
testing in certain regions of the develop- should be considered in adults of
used. An updated list of interferences is
ing world, and the imperfect correlation any age who are overweight or
available at www.ngsp.org/interf.asp.
between A1C and average glucose in cer- obese (BMI $25 kg/m or $23 2

Red Blood Cell Turnover


tain individuals. National Health and kg/m in Asian Americans) and
2

In conditions associated with increased who have one or more additional


Nutrition Examination Survey (NHANES)
red blood cell turnover, such as pregnancy
data indicate that an A1C cut point of risk factors for diabetes. B
(second and third trimesters), recent blood c For all patients, testing should begin
$6.5% (48 mmol/mol) identies one-
loss or transfusion, erythropoietin therapy,
third fewer cases of undiagnosed diabe- at age 45 years. B
tes than a fasting glucose cut point of or hemolysis, only blood glucose criteria c If tests are normal, repeat testing
should be used to diagnose diabetes. carried out at a minimum of 3-year
$126 mg/dL (7.0 mmol/L) (4).
It is important to take age, race/ intervals is reasonable. C
ethnicity, and anemia/hemoglobinop- Conrming the Diagnosis c To test for prediabetes, fasting
athies into consideration when using Unless there is a clear clinical diagnosis plasma glucose, 2-h plasma glucose
the A1C to diagnose diabetes. (e.g., patient in a hyperglycemic crisis or after 75-g oral glucose tolerance test,
with classic symptoms of hyperglycemia and A1C are equally appropriate. B
Age
and a random plasma glucose $200 c In patients with prediabetes, iden-
The epidemiological studies that formed
mg/dL [11.1 mmol/L]), a second test is re- tify and, if appropriate, treat other
the basis for recommending A1C to di-
quired for conrmation. It is recom- cardiovascular disease risk factors. B
agnose diabetes included only adult
mended that the same test be repeated c Testing to detect prediabetes should
populations. Therefore, it remains un-
without delay using a new blood sample be considered in children and ado-
clear if A1C and the same A1C cut point
for conrmation because there will be a lescents who are overweight or
should be used to diagnose diabetes in
greater likelihood of concurrence. For ex- obese and who have two or more
children and adolescents (4,5).
ample, if the A1C is 7.0% (53 mmol/mol) additional risk factors for diabetes. E
Race/Ethnicity and a repeat result is 6.8% (51 mmol/mol),
A1C levels may vary with patients race/ the diagnosis of diabetes is conrmed. If
ethnicity (6,7). For example, African Amer- two different tests (such as A1C and FPG) Description
icans may have higher A1C levels than are both above the diagnostic threshold, In 1997 and 2003, the Expert Committee
non-Hispanic whites despite similar fast- this also conrms the diagnosis. On the on the Diagnosis and Classication of Di-
ing and postglucose load glucose levels. other hand, if a patient has discordant abetes Mellitus (10,11) recognized a
African Americans also have higher levels results from two different tests, then group of individuals whose glucose
care.diabetesjournals.org Classication and Diagnosis of Diabetes S15

levels did not meet the criteria for di- Hence, it is reasonable to consider an islet cell autoantibodies and autoanti-
abetes but were too high to be consid- A1C range of 5.76.4% (3946 mmol/mol) bodies to insulin, GAD (GAD65), the ty-
ered normal. Prediabetes is the term as identifying individuals with prediabe- rosine phosphatases IA-2 and IA-2b, and
used for individuals with impaired fast- tes. As with those with IFG and/or IGT, ZnT8. Type 1 diabetes is dened by one
ing glucose (IFG) and/or impaired glu- individuals with an A1C of 5.76.4% or more of these autoimmune markers.
cose tolerance (IGT) and indicates an (3946 mmol/mol) should be informed The disease has strong HLA associations,
increased risk for the future develop- of their increased risk for diabetes and with linkage to the DQA and DQB genes.
ment of diabetes. IFG and IGT should CVD and counseled about effective strate- These HLA-DR/DQ alleles can be either
not be viewed as clinical entities in their gies to lower their risks (see Section 4 Pre- predisposing or protective.
own right but rather risk factors for di- vention or Delay of Type 2 Diabetes). The rate of b-cell destruction is quite
abetes (Table 2.2) and cardiovascular Similar to glucose measurements, the con- variable, being rapid in some individu-
disease (CVD). IFG and IGT are associ- tinuum of risk is curvilinear, so as A1C rises, als (mainly infants and children) and
ated with obesity (especially abdominal the diabetes risk rises disproportionately slow in others (mainly adults). Children
or visceral obesity), dyslipidemia with (12). Aggressive interventions and vigilant and adolescents may present with ke-
high triglycerides and/or low HDL cho- follow-up should be pursued for those toacidosis as the rst manifestation of
lesterol, and hypertension. considered at very high risk (e.g., those the disease. Others have modest fast-
with A1C .6.0% [42 mmol/mol]). ing hyperglycemia that can rapidly
Diagnosis Table 2.3 summarizes the categories change to severe hyperglycemia and/or
In 1997 and 2003, the Expert Committee of prediabetes and Table 2.2 the criteria ketoacidosis with infection or other
on the Diagnosis and Classication of Di- for prediabetes testing. For recommen- stress. Adults may retain sufcient b-cell
abetes Mellitus (10,11) dened IFG as dations regarding risk factors and function to prevent ketoacidosis for
FPG levels 100125 mg/dL (5.66.9 screening for prediabetes, see pp. S17 many years; such individuals eventually
mmol/L) and IGT as 2-h PG after 75-g S18 (Testing for Type 2 Diabetes and Pre- become dependent on insulin for survival
OGTT levels 140199 mg/dL (7.811.0 diabetes in Asymptomatic Adults and and are at risk for ketoacidosis. At this
mmol/L). It should be noted that the Testing for Type 2 Diabetes and Pre- latter stage of the disease, there is little
World Health Organization (WHO) and diabetes in Children and Adolescents). or no insulin secretion, as manifested by
numerous diabetes organizations dene low or undetectable levels of plasma C-
the IFG cutoff at 110 mg/dL (6.1 mmol/L). TYPE 1 DIABETES peptide. Immune-mediated diabetes
As with the glucose measures, several Recommendations commonly occurs in childhood and ado-
prospective studies that used A1C to c Blood glucose rather than A1C should lescence, but it can occur at any age, even
predict the progression to diabetes be used to diagnose acute onset of in the 8th and 9th decades of life.
demonstrated a strong, continuous as- type 1 diabetes in individuals with Autoimmune destruction of b-cells
sociation between A1C and subsequent symptoms of hyperglycemia. E has multiple genetic predispositions
diabetes. In a systematic review of c Inform the relatives of patients with and is also related to environmental fac-
44,203 individuals from 16 cohort stud- type 1 diabetes of the opportunity tors that are still poorly dened. Al-
ies with a follow-up interval averaging to be tested for type 1 diabetes risk, though patients are not typically obese
5.6 years (range 2.812 years), those but only in the setting of a clinical when they present with type 1 diabetes,
with an A1C between 5.56.0% (3742 research study. E obesity should not preclude the diagno-
mmol/mol) had a substantially in- sis. These patients are also prone to
creased risk of diabetes (5-year inci- other autoimmune disorders such as
Diagnosis
dence from 9% to 25%). An A1C range Hashimoto thyroiditis, celiac disease,
In a patient with acute symptoms, mea-
of 6.06.5% (4248 mmol/mol) had a Graves disease, Addison disease, viti-
surement of blood glucose is part of the
5-year risk of developing diabetes be- ligo, autoimmune hepatitis, myasthenia
tween 25% and 50% and a relative
denition of diabetes (classic symptoms of gravis, and pernicious anemia.
hyperglycemia or hyperglycemic crisis plus
risk 20 times higher compared with an
a random plasma glucose $200 mg/dL
A1C of 5.0% (31 mmol/mol) (12). In a Idiopathic Type 1 Diabetes
[11.1 mmol/L]). In these cases, knowing
community-based study of African Some forms of type 1 diabetes have no
the blood glucose level is critical because,
American and non-Hispanic white adults known etiologies. These patients have
in addition to conrming that symptoms
without diabetes, baseline A1C was a permanent insulinopenia and are prone
are due to diabetes, this will inform man-
stronger predictor of subsequent diabe- to ketoacidosis, but have no evidence of
agement decisions. Some providers may
tes and cardiovascular events than fast- b-cell autoimmunity. Although only a
also want to know the A1C to determine
ing glucose (13). Other analyses suggest minority of patients with type 1 diabetes
how long a patient has had hyperglycemia.
that an A1C of 5.7% (39 mmol/mol) is fall into this category, of those who do,
associated with a diabetes risk similar Immune-Mediated Diabetes most are of African or Asian ancestry.
to that of the high-risk participants in This form, previously called insulin- Individuals with this form of diabetes
the Diabetes Prevention Program (DPP) dependent diabetes or juvenile-onset suffer from episodic ketoacidosis and
(14), and A1C at baseline was a strong diabetes, accounts for 510% of diabe- exhibit varying degrees of insulin de-
predictor of the development of glucose- tes and is due to cellular-mediated auto- ciency between episodes. This form of
dened diabetes during the DPP and its immune destruction of the pancreatic diabetes is strongly inherited and is not
follow-up (15). b-cells. Autoimmune markers include HLA associated. An absolute requirement
S16 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

Table 2.2Criteria for testing for diabetes or prediabetes in asymptomatic adults


being conducted to test various meth-
ods of preventing type 1 diabetes in
1. Testing should be considered in all adults who are overweight (BMI $25 kg/m2or $23 kg/m2in
Asian Americans) and have additional risk factors: those with evidence of autoimmunity
c physical inactivity (www.clinicaltrials.gov).
c rst-degree relative with diabetes
c high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, TYPE 2 DIABETES
Pacic Islander)
Recommendations
c women who delivered a baby weighing .9 lb or were diagnosed with GDM
c hypertension ($140/90 mmHg or on therapy for hypertension) c Testing to detect type 2 diabetes in
c HDL cholesterol level ,35 mg/dL (0.90 mmol/L) and/or a triglyceride level .250 mg/dL asymptomatic people should be con-
(2.82 mmol/L) sidered in adults of any age who are
c women with polycystic ovary syndrome
overweight or obese (BMI $25
c A1C $5.7% (39 mmol/mol), IGT, or IFG on previous testing
c other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis kg/m or $23 kg/m in Asian Amer-
2 2

nigricans) icans) and who have one or more


c history of CVD additional risk factors for diabetes. B
2. For all patients, testing should begin at age 45 years. c For all patients, testing should be-
3. If results are normal, testing should be repeated at a minimum of 3-year intervals, with gin at age 45 years. B
consideration of more frequent testing depending on initial results (e.g., those with c If tests are normal, repeat testing
prediabetes should be tested yearly) and risk status. carried out at a minimum of 3-year
intervals is reasonable. C
c To test for type 2 diabetes, fasting
for insulin replacement therapy in af- type 1 diabetes within 10 years and 84% plasma glucose, 2-h plasma glucose
fected patients may be intermittent. within 15 years (19,20). Thesendings are after 75-g oral glucose tolerance test,
highly signicant because, while the and A1C are equally appropriate. B
Testing for Type 1 Diabetes Risk German group was recruited from off- c In patients with diabetes, identify
The incidence and prevalence of type 1 spring of parents with type 1 diabetes, and, if appropriate, treat other car-
diabetes is increasing (16). Patients with the Finnish and American groups were diovascular disease risk factors. B
type 1 diabetes often present with acute recruited from the general population. c Testing to detect type 2 diabetes
symptoms of diabetes and markedly el- Remarkably, the ndings in all three should be considered in children
evated blood glucose levels, and ap- groups were the same, suggesting that and adolescents who are overweight
proximately one-third are diagnosed the same sequence of events led to clin- or obese and who have two or more
with life-threatening ketoacidosis (2). ical disease in both sporadic and famil- additional risk factors for diabetes. E
Several studies indicate that measuring ial cases of type 1 diabetes.
islet autoantibodies in relatives of those Although there is currently a lack of
Description
with type 1 diabetes may identify individ- accepted screening programs, one
Type 2 diabetes, previously referred to
uals who are at risk for developing type 1 should consider referring relatives of
as noninsulin-dependent diabetes or
diabetes (17). Such testing, coupled with those with type 1 diabetes for antibody
adult-onset diabetes, accounts for
education about diabetes symptoms and testing for risk assessment in the setting
9095% of all diabetes. This form en-
close follow-up in an observational clini- of a clinical research study (http://www2
compasses individuals who have insulin
cal study, may enable earlier identica- .diabetestrialnet.org). Widespread clini-
resistance and usually relative (rather
tion of type 1 diabetes onset (18). There cal testing of asymptomatic low-risk in-
than absolute) insulin deciency. At
is evidence to suggest that early diagnosis dividuals is not currently recommended
least initially, and often throughout
may limit acute complications (19). due to lack of approved therapeutic in-
their lifetime, these individuals may
A recent study reported the risk of pro- terventions. Higher-risk individuals may not need insulin treatment to survive.
gression to type 1 diabetes from the be tested, but only in the context of a There are various causes of type 2 di-
time of seroconversion to autoantibody clinical research setting. Individuals
abetes. Although the specic etiologies
positivity in three pediatric cohorts from who test positive will be counseled
are not known, autoimmune destruction
Finland, Germany, and the U.S. Of the 585 about the risk of developing diabetes,
of b-cells does not occur, and patients do
children who developed more than two diabetes symptoms, and DKA preven-
not have any of the other known causes
autoantibodies, nearly 70% developed tion. Numerous clinical studies are of diabetes. Most, but not all, patients
with type 2 diabetes are overweight or
Table 2.3Categories of increased risk for diabetes (prediabetes)* obese. Excess weight itself causes some
FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG) degree of insulin resistance. Patients who
OR are not obese or overweight by traditional
2-h PG in the 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT)
weight criteria may have an increased
OR
percentage of body fat distributed pre-
dominantly in the abdominal region.
A1C 5.76.4% (3946 mmol/mol)
Ketoacidosis seldom occurs sponta-
*For all three tests, risk is continuous, extending below the lower limit of the range and
neously in type 2 diabetes; when seen,
becoming disproportionately greater at the higher end of the range.
it usually arises in association with the
care.diabetesjournals.org Classication and Diagnosis of Diabetes S17

stress of another illness such as infec- individuals to identify those with predi- (sensitivity of 80%) for nearly all Asian
tion. Type 2 diabetes frequently goes abetes or diabetes might seem reason- American subgroups (with levels slightly
undiagnosed for many years because hy- able, rigorous clinical trials to prove the lower for Japanese Americans). This
perglycemia develops gradually and, at effectiveness of such screening have not makes a rounded cut point of 23 kg/m 2

earlier stages, is often not severe enough been conducted and are unlikely to occur. practical. In determining a single BMI cut
for the patient to notice the classic diabe- A large European randomized con- point, it is important to balance sensitivity
tes symptoms. Nevertheless, even undi- trolled trial compared the impact of and specicity so as to provide a valuable
agnosed patients are at increased risk of screening for diabetes and intensive screening tool without numerous false
developing macrovascular and microvas- multifactorial intervention with that of positives. An argument can be made to
cular complications. screening and routine care (22). General push the BMI cut point to lower than
Whereas patients with type 2 diabetes practice patients between the ages of 23 kg/m in favor of increased sensitivity;
2

may have insulin levels that appear nor- 4069 years were screened for diabetes however, this would lead to an unaccept-
mal or elevated, the higher blood glucose and randomly assigned by practice to ably low specicity (13.1%). Data from the
levels in these patients would be expected intensive treatment of multiple risk fac- WHO also suggest that a BMI $23 kg/m 2

to result in even higher insulin values had tors or routine diabetes care. After 5.3 should be used to dene increased risk
their b-cell function been normal. Thus, years of follow-up, CVD risk factors were in Asian Americans (27). The nding
insulin secretion is defective in these pa- modestly but signicantly improved that half of diabetes in Asian Americans
tients and insufcient to compensate for with intensive treatment compared is undiagnosed suggests that testing is not
insulin resistance. Insulin resistance may with routine care, but the incidence of occurring at lower BMI thresholds (21).
improve with weight reduction and/or rst CVD events or mortality was not Evidence also suggests that other
pharmacological treatment of hypergly- signicantly different between the populations may benet from lower
cemia but is seldom restored to normal. groups (22). The excellent care provided BMI cut points. For example, in a large
The risk of developing type 2 diabetes to patients in the routine care group and multiethnic cohort study, for an equiva-
increases with age, obesity, and lack of the lack of an unscreened control arm lent incidence rate of diabetes, a BMI of
physical activity. It occurs more fre- limited the authors ability to prove that 30 kg/m in non-Hispanic whites was
2

quently in women with prior GDM, in screening and early intensive treatment equivalent to a BMI of 26 kg/m in Afri-
2

those with hypertension or dyslipidemia, impact outcomes. Mathematical model- can Americans (28).
and in certain racial/ethnic subgroups ing studies suggest that major benets Medications
(African American, American Indian, are likely to accrue from the early diag-
Certain medications, such as glucocorti-
Hispanic/Latino, and Asian American). It nosis and treatment of glycemia and car-
coids, thiazide diuretics, and atypical an-
is often associated with a strong genetic diovascular risk factors in type 2 diabetes
tipsychotics (29), are known to increase
predisposition, more so than type 1 dia- (23); moreover, screening, beginning at
the risk of diabetes and should be con-
betes. However, the genetics of type 2 age 30 or 45 years and independent
sidered when ascertaining a diagnosis.
diabetes is poorly understood. of risk factors, may be cost-effective
(,$11,000 per quality-adjusted life- Diagnostic Tests
Testing for Type 2 Diabetes and year gained) (24). FPG, 2-h PG after 75-g OGTT, and A1C
Prediabetes in Asymptomatic Adults Additional considerations regarding are equally appropriate for testing. It
Prediabetes and type 2 diabetes meet cri- testing for type 2 diabetes and predia- should be noted that the tests do not
teria for conditions in which early detec- betes in asymptomatic patients include necessarily detect diabetes in the same
tion is appropriate. Both conditions are the following: individuals. The efcacy of interventions
common and impose signicant clinical Age for primary prevention of type 2 diabe-
and public health burdens. There is often Testing recommendations for diabetes tes (30,31) has primarily been demon-
a long presymptomatic phase before the in asymptomatic adults are listed in strated among individuals with IGT, not
diagnosis of type 2 diabetes. Simple tests
Table 2.2. Age is a major risk factor for for individuals with isolated IFG or for
to detect preclinical disease are readily diabetes. Testing should begin at age 45 those with prediabetes dened by A1C
available. The duration of glycemic burden years for all patients. criteria.
is a strong predictor of adverse outcomes.
Testing Interval
There are effective interventions that pre- BMI and Ethnicity
The appropriate interval between tests is
vent progression from prediabetes to dia- Testing should be considered in adults
not known (32). The rationale for the
betes (see Section 4 Prevention or Delay of any age with BMI $25 kg/m and one
2
3-year interval is that with this interval,
of Type 2 Diabetes) and reduce the risk of or more additional risk factors for dia-
the number of false-positive tests that re-
diabetes complications (see Section 8 betes. However, recent data (25) and
evidence from the ADA position state- quire conrmatory testing will be reduced
Cardiovascular Disease and Risk Man-
and individuals with false-negative tests
agement and Section 9 Microvascular ment BMI Cut Points to Identify At-Risk
will be retested before substantial time
Complications and Foot Care). Asian Americans for Type 2 Diabetes
elapses and complications develop (32).
Approximately one-quarter of people Screening (26) suggest that the BMI
with diabetes in the U.S. and nearly half cut point should be lower for the Asian Community Screening
of Asian and Hispanic Americans with American population. For diabetes Ideally, testing should be carried out
diabetes are undiagnosed (21). Al- screening purposes, the BMI cut points within a health care setting because of
though screening of asymptomatic fall consistently between 23 and 24 kg/m 2
the need for follow-up and treatment.
S18 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

Community testing outside a health care 1. One-step 75-g OGTT or


using the oral glucose tolerance
setting is not recommended because test and clinically appropriate non- 2. Two-step approach with a 50-g (non-
people with positive tests may not fasting) screen followed by a 100-g
pregnancy diagnostic criteria. E
seek, or have access to, appropriate OGTT for those who screen positive
c Women with a history of gesta-
follow-up testing and care. Community
tional diabetes mellitus should
testing may also be poorly targeted; i.e., Different diagnostic criteria will identify
have lifelong screening for the de-
it may fail to reach the groups most at different degrees of maternal hyperglyce-
velopment of diabetes or predia-
risk and inappropriately test those at mia and maternal/fetal risk, leading some
betes at least every 3 years. B experts to debate, and disagree on, opti-
very low risk or even those who have
c Women with a history of gesta-
already been diagnosed. mal strategies for the diagnosis of GDM.
tional diabetes mellitus found to
have prediabetes should receive
Testing for Type 2 Diabetes and One-Step Strategy
lifestyle interventions or metfor-
Prediabetes in Children and In the 2011 Standards of Care (39), the
Adolescents
min to prevent diabetes. A
ADA for the rst time recommended
In the last decade, the incidence and that all pregnant women not known to
prevalence of type 2 diabetes in ado- have prior diabetes undergo a 75-g
Denition
lescents has increased dramatically, es- OGTT at 2428 weeks of gestation, based
For many years, GDM was dened as any
pecially in ethnic populations (16). on a recommendation of the Interna-
Recent studies question the validity of degree of glucose intolerance that was rst
recognized during pregnancy (10), regard- tional Association of the Diabetes and
A1C in the pediatric population, espe-
less of whether the condition may have pre- Pregnancy Study Groups (IADPSG) (40).
cially among certain ethnicities, and The IADPSG dened diagnostic cut points
dated the pregnancy or persisted after the
suggest OGTT or FPG as more suitable
pregnancy. This denition facilitated a uni- for GDM as the average glucose values
diagnostic tests (33). However, many of (fasting, 1-h, and 2-h PG) in the HAPO
form strategy for detection and classication
these studies do not recognize that di-
of GDM, but it was limited by imprecision. study at which odds for adverse out-
abetes diagnostic criteria are based on comes reached 1.75 times the estimated
The ongoing epidemic of obesity and
long-term health outcomes, and valida- odds of these outcomes at the mean glu-
diabetes has led to more type 2 diabetes
tions are not currently available in the cose levels of the study population. This
in women of childbearing age, with an in-
pediatric population (34). The ADA ac- one-step strategy was anticipated to sig-
crease in the number of pregnant women
knowledges the limited data support- with undiagnosed type 2 diabetes (37). Be- nicantly increase the incidence of GDM
ing A1C for diagnosing type 2 diabetes (from 56% to 1520%), primarily be-
cause of the number of pregnant women
in children and adolescents. Although
with undiagnosed type 2 diabetes, it is rea- cause only one abnormal value, not two,
A1C is not recommended for diagnosis
sonable to test women with risk factors for became sufcient to make the diagnosis.
of diabetes in children with cystic bro- The ADA recognized that the anticipated
type 2 diabetes (Table 2.2) at their initial
sis or symptoms suggestive of acute on- increase in the incidence of GDM would
prenatal visit, using standard diagnostic
set of type 1 diabetes and only A1C have signicant impact on the costs, med-
criteria (Table 2.1). Women with diabetes
assays without interference are appro- ical infrastructure capacity, and potential
in the rst trimester would be classied as
priate for children with hemoglobinopa- for increased medicalization of preg-
having type 2 diabetes. GDM is diabetes
thies, the ADA continues to recommend nancies previously categorized as normal,
diagnosed in the second or third trimester
A1C for diagnosis of type 2 diabetes in but recommended these diagnostic crite-
of pregnancy that is not clearly either
this cohort (35,36). The modied recom- type 1 or type 2 diabetes (see Section 12 ria changes in the context of worrisome
mendations of the ADA consensus
Management of Diabetes in Pregnancy). worldwide increases in obesity and diabe-
report Type 2 Diabetes in Children tes rates with the intent of optimizing
and Adolescents are summarized in Diagnosis gestational outcomes for women and
Table 2.4. GDM carries risks for the mother and ne- their offspring.
onate. Not all adverse outcomes are of The expected benets to these preg-
GESTATIONAL DIABETES equal clinical importance. The Hypergly- nancies and offspring are inferred from
MELLITUS cemia and Adverse Pregnancy Outcome intervention trials that focused on
(HAPO) study (38), a large-scale (25,000 women with lower levels of hyperglyce-
Recommendations
pregnant women) multinational cohort mia than identied using older GDM di-
c Test for undiagnosed type 2 diabe-
study, demonstrated that risk of adverse agnostic criteria and that found modest
tes at the rst prenatal visit in
maternal, fetal, and neonatal outcomes benets including reduced rates of
those with risk factors, using stan-
continuously increased as a function of large-for-gestational-age births and pre-
dard diagnostic criteria. B
maternal glycemia at 2428 weeks, even eclampsia (41,42). It is important to
c Test for gestational diabetes mel-
within ranges previously considered nor- note that 8090% of women being
litus at 2428 weeks of gestation mal for pregnancy. For most complica- treated for mild GDM in two random-
in pregnant women not previously
tions, there was no threshold for risk. ized controlled trials (whose glucose val-
known to have diabetes. A
These results have led to careful reconsid- ues overlapped with the thresholds
c Screen women with gestational di-
eration of the diagnostic criteria for GDM. recommended by the IADPSG) could
abetes mellitus for persistent diabe-
GDM diagnosis (Table 2.5) can be accom- be managed with lifestyle therapy
tes at 612 weeks postpartum,
plished with either of two strategies: alone. Data are lacking on how the
care.diabetesjournals.org Classication and Diagnosis of Diabetes S19

Table 2.4Testing for type 2 diabetes or prediabetes in asymptomatic children* c Because a diagnosis of maturity-
Criteria onset diabetes of the young may
c Overweight (BMI .85th percentile for age and sex, weight for height .85th percentile, or impact therapy and lead to identi-
weight .120% of ideal for height) cation of other affected family
Plus any two of the following risk factors: members, consider referring indi-
c Family history of type 2 diabetes in rst- or second-degree relative
viduals with diabetes not typical of
c Race/ethnicity (Native American, African American, Latino, Asian American, Paci c Islander)
c Signsof insulin resistance or conditions associated with insulin resistance (acanthosis
type 1 or type 2 diabetes and oc-
nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small-for-gestational- curing in successive generations
age birth weight) (suggestive of an autosomal dom-
c Maternal history of diabetes or GDM during the childs gestation inant pattern of inheritance) to a
Age of initiation: age 10 years or at onset of puberty, if puberty occurs at a younger age specialist for further evaluation. E
Frequency: every 3 years
*Persons aged #18 years. Monogenic defects that cause b-cell
dysfunction, such as neonatal diabetes
treatment of lower levels of hyperglyce- its guidelines in 2013 and supported the and MODY, represent a small fraction of
mia affects a mothers risk for the devel- two-step approach (45). patients with diabetes (,5%). These
opment of type 2 diabetes in the future forms of diabetes are frequently charac-
Future Considerations
and her offsprings risk for obesity, di-
terized by onset of hyperglycemia at an
The conicting recommendations from early age (generally before age 25 years).
abetes, and other metabolic dysfunc- expert groups underscore the fact that
tion. Additional well-designed clinical there are data to support each strategy. Neonatal Diabetes
studies are needed to determine the op- The decision of which strategy to imple- Neonatal diabetes is a monogenic form of
timal intensity of monitoring and treat- ment must therefore be made based on diabetes with onset in the rst 6 months of
ment of women with GDM diagnosed by the relative values placed on factors that life. It can be mistaken for the more com-
the one-step strategy. mon type 1 diabetes, but type 1 diabetes
have yet to be measured (e.g., costbenet
estimation, willingness to change prac- rarely occurs before 6 months of age. Neo-
Two-Step Strategy
tice based on correlation studies rather natal diabetes can either be transient or
In 2013, the National Institutes of Health
than clinical intervention trial results, rel- permanent. The most common genetic
(NIH) convened a consensus develop-
ative role of cost considerations, and avail- defect causing transient disease is a defect
ment conference on diagnosing GDM.
able infrastructure locally, nationally, and on ZAC/HYAMI imprinting, whereas per-
The 15-member panel had representatives
internationally). manent neonatal diabetes is most com-
from obstetrics/gynecology, maternal-
As the IADPSG criteria have been adop- monly an autosomal dominant defect in
fetal medicine, pediatrics, diabetes re-
ted internationally, further evidence has the gene encoding the Kir6.2 subunit of
search, biostatistics, and other related
emerged to support improved pregnancy the b-cell K channel. Correct diagnosis
ATP
elds to consider diagnostic criteria (43).
outcomes with cost savings (46) and may has important implications, because chil-
The panel recommended the two-step
be the preferred approach. In addition, dren with neonatal diabetes due to muta-
approach of screening with a 1-h 50-g
pregnancies complicated by GDM per tions affecting Kir6.2 should be treated
glucose load test (GLT) followed by a 3-h
IADPSG criteria, but not recognized as with sulfonylureas rather than insulin.
100-g OGTT for those who screen posi-
such, have comparable outcomes to preg-
tive, a strategy commonly used in the U.S. Maturity-Onset Diabetes of the Young
nancies diagnosed as GDM by the more
Key factors reported in the NIH pan- MODY is characterized by impaired insulin
stringent two-step criteria (47). There
els decision-making process were the secretion with minimal or no defects in
remains strong consensus that estab-
lack of clinical trial interventions dem- insulin action. It is inherited in an autoso-
lishing a uniform approach to diagnosing
onstrating the benets of the one-step mal dominant pattern. Abnormalities at
GDM will benet patients, caregivers, six genetic loci on different chromosomes
strategy and the potential negative con-
and policymakers. Longer-term outcome
sequences of identifying a large new have been identied to date. The most
studies are currently under way.
group of women with GDM, including common form (MODY 3) is associated
medicalization of pregnancy with in- MONOGENIC DIABETES with mutations on chromosome 12 in a
creased interventions and costs. More- SYNDROMES hepatic transcription factor referred to as
over, screening with a 50-g GLT does not hepatocyte nuclear factor (HNF)-1a and
Recommendations
require fasting and is therefore easier to also referred to as transcription factor-1
c All children diagnosed with diabe-
accomplish for many women. Treat- (TCF-1). The second most common form
tes in the rst 6 months of life
ment of higher threshold maternal (MODY 2) is associated with mutations in
should have genetic testing. B the glucokinase gene on chromosome 7p
hyperglycemia, as identied by the two-
c Maturity-onset diabetes of the
step approach, reduces rates of neonatal and results in a defective glucokinase mol-
young should be considered in indi-
macrosomia, large-for-gestational-age ecule. Glucokinase converts glucose to
viduals who have mild stable fasting
births (44), and shoulder dystocia, with- glucose-6-phosphate, the metabolism of
hyperglycemia and multiple family
out increasing small-for-gestational-age which, in turn, stimulates insulin secretion
members with diabetes not charac-
births. The American College of Obstetri- by the b-cell. The less common forms of
teristic of type 1 or type 2 diabetes. E
cians and Gynecologists (ACOG) updated MODY result from mutations in other
S20 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

occurring in about 20% of adolescents


Table 2.5Screening for and diagnosis of GDM
and 4050% of adults. Diabetes in this
One-step strategy
population, compared with individuals
Perform a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and
with type 1 or type 2 diabetes, is asso-
2 h, at 2428 weeks of gestation in women not previously diagnosed with overt diabetes.
The OGTT should be performed in the morning after an overnight fast of at least 8 h. ciated with worse nutritional status,
The diagnosis of GDM is made when any of the following plasma glucose values are met or more severe inammatory lung dis-
exceeded: ease, and greater mortality. Insulin in-
c Fasting: 92 mg/dL (5.1 mmol/L) sufciency is the primary defect in
c 1 h: 180 mg/dL (10.0 mmol/L) CFRD. Genetically determined b-cell
c 2 h: 153 mg/dL (8.5 mmol/L) function and insulin resistance associ-
Two-step strategy ated with infection and inammation
Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 2428 may also contribute to the develop-
weeks of gestation in women not previously diagnosed with overt diabetes. ment of CFRD. Milder abnormalities
If the plasma glucose level measured 1 h after the load is $140 mg/dL* (7.8 mmol/L), proceed of glucose tolerance are even more
to a 100-g OGTT.
common and occur at earlier ages
Step 2: The 100-g OGTT should be performed when the patient is fasting. than CFRD. Although screening for di-
The diagnosis of GDM is made if at least two of the following four plasma glucose levels abetes before the age of 10 years can
(measured fasting and 1 h, 2 h, 3 h after the OGTT) are met or exceeded:
identify risk for progression to CFRD
Carpenter/Coustan (55) or NDDG (56) in those with abnormal glucose toler-
c Fasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L) ance, no benet has been established
c1 h 180 mg/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L) with respect to weight, height, BMI,
c2 h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L) or lung function. Continuous glucose
c3 h 140 mg/dL (7.8 mmol/L) 145 mg/dL (8.0 mmol/L) monitoring may be more sensitive
NDDG, National Diabetes Data Group. *The ACOG recommends a lower threshold of 135 mg/dL than OGTT to detect risk for progres-
(7.5 mmol/L) in high-risk ethnic populations with higher prevalence of GDM; some experts also sion to CFRD, but evidence linking
recommend 130 mg/dL (7.2 mmol/L). continuous glucose monitoring results
to long-term outcomes is lacking
transcription factors, including HNF-4a, without typical clinical features of and its use is not recommended for
HNF-1b, insulin promoter factor-1 (IPF-1), type 2 diabetes screening (50).
and NeuroD1. CRFD mortality has signicantly de-
Diagnosis CYSTIC FIBROSISRELATED creased over time, and the gap in mor-
A diagnosis of MODY should be consid- DIABETES tality between cystic brosis patients
ered in individuals who have atypical di- Recommendations with and without diabetes has consider-
abetes and multiple family members c Annual screening for cystic brosis ably narrowed (51). There are limited
with diabetes not characteristic of related diabetes with oral glucose clinical trial data on therapy for CFRD.
type 1 or type 2 diabetes. These individ- tolerance test should begin by age The largest study compared three regi-
uals should be referred to a specialist for 10 years in all patients with cystic mens: premeal insulin aspart, repagli-
further evaluation. Readily available brosis who do not have cystic nide, or oral placebo in cystic brosis
commercial genetic testing now enables brosisrelated diabetes. B patients with diabetes or abnormal
a genetic diagnosis. It is important to cor- c A1C as a screening test for cystic glucose tolerance. Participants all had
rectly diagnose one of the monogenic brosisrelated diabetes is not weight loss in the year preceding treat-
forms of diabetes because these patients recommended. B ment; however, in the insulin-treated
may be incorrectly diagnosed with type 1 c Patients with cystic brosisrelated group, this pattern was reversed, and
or type 2 diabetes, leading to suboptimal diabetes should be treated with patients gained 0.39 (6 0.21) BMI units
treatment regimens and delays in diag- insulin to attain individualized gly- (P 5 0.02). The repaglinide-treated
nosing other family members (48,49). cemic goals. A group had initial weight gain, but this
The diagnosis of monogenic diabetes c In patients with cystic brosis and was not sustained by 6 months. The pla-
should be considered in children with impaired glucose tolerance with- cebo group continued to lose weight
the following ndings: out conrmed diabetes, prandial (52). Insulin remains the most widely
insulin therapy should be consid- used therapy for CFRD (53).
Diabetes diagnosed within the rst ered to maintain weight. B Recommendations for the clinical
6 months of life c Beginning 5 years after the diagnosis management of CFRD can be found in
Strong family history of diabetes but with- of cystic brosisrelated diabetes, the ADA position statement Clinical
out typical features of type 2 diabetes annual monitoring for complications Care Guidelines for Cystic Fibrosis
(nonobese, low-risk ethnic group) of diabetes is recommended. E Related Diabetes: A Position Statement
Mild fasting hyperglycemia (100150 of the American Diabetes Association
mg/dL [5.58.5 mmol/L]), especially if and a Clinical Practice Guideline of
young and nonobese Cy s t ic b r o s i sr e la ted d ia betes the Cystic Fibrosis Foundation, En-
Diabetes with negative diabetes- (CFRD) is the most common comor- dorsed by the Pediatric Endocrine
a s s o c i a t e d a u t o a n t i b o d ie s a n d bidity in people with cystic brosis, Society (54).
care.diabetesjournals.org Classication and Diagnosis of Diabetes S21

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Classication of Diabetes Mellitus. Diabetes 24. Kahn R, Alperin P, Eddy D, et al. Age at ini- Care 2011;34(Suppl. 1):S11S61
Care 1997;20:11831197 tiation and frequency of screening to detect 40. Metzger BE, Gabbe SG, Persson B, et al.;
11. Genuth S, Alberti KG, Bennett P, et al.; Expert type 2 diabetes: a cost-effectiveness analysis. International Association of Diabetes and
Committee on the Diagnosis and Classi cation of Lancet 2010;375:13651374 Pregnancy Study Groups Consensus Panel.
Diabetes Mellitus. Follow-up report on the diag- 25. Araneta MR, Kanaya AM, Hsu WC, et al. Opti- International Association of Diabetes and
nosis of diabetes mellitus. Diabetes Care 2003;26: mum BMI cut points to screen Asian Americans for Pregnancy Study Groups recommendations
31603167 type 2 diabetes. Diabetes Care 2015;38:814820 on the diagnosis and classication of hyper-
12. Zhang X, Gregg EW, Williamson DF, et al. 26. Hsu WC, Araneta MR, Kanaya AM, Chiang glycemia in pregnancy. Diabetes Care 2010;
A1C level and future risk of diabetes: a system- JL, Fujimoto W. BMI cut points to identify at-risk 33:676682
atic review. Diabetes Care 2010;33:16651673 Asian Americans for type 2 diabetes screening. 41. Landon MB, Spong CY, Thom E, et al.; Eunice
13. Selvin E, Steffes MW, Zhu H, et al. Glycated Diabetes Care 2015;38:150158 Kennedy Shriver National Institute of Child
hemoglobin, diabetes, and cardiovascular risk 27. WHO Expert Consultation. Appropriate Health and Human Development Maternal-Fetal
in nondiabetic adults. N Engl J Med 2010;362: body-mass index for Asian populations and its Medicine Units Network. A multicenter, ran-
800811 implications for policy and intervention strate- domized trial of treatment for mild gestational
14. Ackermann RT, Cheng YJ, Williamson DF, gies. Lancet 2004;363:157163 diabetes. N Engl J Med 2009;361:13391348
Gregg EW. Identifying adults at high risk for di- 28. Chiu M, Austin PC, Manuel DG, Shah BR, Tu 42. Crowther CA, Hiller JE, Moss JR, McPhee AJ,
abetes and cardiovascular disease using hemo- JV. Deriving ethnic-specic BMI cutoff points for Jeffries WS, Robinson JS; Australian Carbohy-
globin A1c National Health and Nutrition assessing diabetes risk. Diabetes Care 2011;34: drate Intolerance Study in Pregnant Women
Examination Survey 2005-2006. Am J Prev 17411748 (ACHOIS) Trial Group. Effect of treatment of
Med 2011;40:1117 29. Erickson SC, Le L, Zakharyan A, et al. New- gestational diabetes mellitus on pregnancy out-
15. Diabetes Prevention Program Research onset treatment-dependent diabetes mellitus comes. N Engl J Med 2005;352:24772486
Group. HbA1c as a predictor of diabetes and and hyperlipidemia associated with atypical an- 43. Vandorsten JP, Dodson WC, Espeland MA,
as an outcome in the Diabetes Prevention Pro- tipsychotic use in older adults without schizo- et al. NIH consensus development confer-
gram: a randomized clinical trial. Diabetes Care phrenia or bipolar disorder. J Am Geriatr Soc ence: diagnosing gestational diabetes melli-
2015;38:5158 2012;60:474479 tus. NIH Consens State Sci Statements 2013;
16. Dabelea D, Mayer-Davis EJ, Saydah S, et al.; 30. Knowler WC, Barrett-Connor E, Fowler SE, 29:131
SEARCH for Diabetes in Youth Study. Prevalence et al.; Diabetes Prevention Program Research 44. Horvath K, Koch K, Jeitler K, et al. Effects of
of type 1 and type 2 diabetes among children Group. Reduction in the incidence of type 2 di- treatment in women with gestational diabetes
and adolescents from 2001 to 2009. JAMA 2014; abetes with lifestyle intervention or metformin. mellitus: systematic review and meta-analysis.
311:17781786 N Engl J Med 2002;346:393403 BMJ 2010;340:c1395
S22 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

45. Committee on Practice BulletinsObstetrics. 49. Rubio-Cabezas O, Hattersley AT, Njlstad Therapy trial. Diabetes Care 2009;32:1783
Practice Bulletin No. 137: gestational diabetes PR, et al.; International Society for Pediatric 1788
mellitus. Obstet Gynecol 2013;122:406 416 and Adolescent Diabetes. ISPAD Clinical Practice 53. Onady GM, Stol A. Insulin and oral agents
46. Duran A, S aenz S, Torrej on MJ, et al. Intro- Consensus Guidelines 2014. The diagnosis and for managing cystic brosis-related diabetes.
duction of IADPSG criteria for the screening and management of monogenic diabetes in children Cochrane Database Syst Rev 2013;7:CD004730
diagnosis of gestational diabetes mellitus re- and adolescents. Pediatr Diabetes 2014;15 54. Moran A, Brunzell C, Cohen RC, et al.; CFRD
sults in improved pregnancy outcomes at a (Suppl. 20):4764 Guidelines Committee. Clinical care guidelines
lower cost in a large cohort of pregnant women: 50. Ode KL, Moran A. New insights into cystic for cystic brosis-related diabetes: a position
the St. Carlos Gestational Diabetes Study. brosis-related diabetes in children. Lancet Di- statement of the American Diabetes Associa-
Diabetes Care 2014;37:24422450 tion and a clinical practice guideline of the Cystic
abetes Endocrinol 2013;1:5258
47. Ethridge JK Jr, Catalano PM, Waters TP. Peri- 51. Moran A, Dunitz J, Nathan B, Saeed A, Fibrosis Foundation, endorsed by the Pediatric
natal outcomes associated with the diagnosis of Holme B, Thomas W. Cystic brosis-related di- Endocrine Society. Diabetes Care 2010;33:
gestational diabetes made by the International abetes: current trends in prevalence, incidence, 26972708
Association of the Diabetes and Pregnancy Study and mortality. Diabetes Care 2009;32:1626 55. Carpenter MW, Coustan DR. Criteria for
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578 52. Moran A, Pekow P, Grover P, et al.; Cystic Obstet Gynecol 1982;144:768773
48. Hattersley A, Bruining J, Shield J, Njolstad P, Fibrosis Related Diabetes Therapy Study Group. 56. National Diabetes Data Group. Classica-
Donaghue KC. The diagnosis and management of Insulin therapy to improve BMI in cystic brosis- tion and diagnosis of diabetes mellitus and
monogenic diabetes in children and adolescents. related diabetes without fasting hyperglycemia: other categories of glucose intolerance. Diabe-
Pediatr Diabetes 2009;10(Suppl. 12):33 42 results of the Cystic Fibrosis Related Diabetes tes 1979;28:10391057
Diabetes Care Volume 39, Supplement 1, January 2016 S23

3. Foundations of Care and American Diabetes Association

Comprehensive Medical
Evaluation
Diabetes Care 2016;39(Suppl. 1):S23S35 | DOI: 10.2337/dc16-S006

The foundations of care include self-management education, nutrition, counseling,


physical activity, smoking cessation, immunizations, psychosocial care, and med-
ications (covered in other sections). The comprehensive medical evaluation in-
cludes the initial and ongoing evaluations, assessment of complications,
management of comorbid conditions, and engagement of the patient throughout
the process.

3. FOUNDATIONS OF CARE
FOUNDATIONS OF CARE
Optimal diabetes management starts with laying down the foundations of care. The
health care provider must take a holistic approach in providing care, accounting for
all aspects of the patients life circumstances. A team approach to diabetes man-
agement facilitates a comprehensive assessment and development of a plan that
addresses the patients values and circumstances. The investment of time and
collaboration can facilitate, and potentially expedite, care delivery and achieve
and maintain outcomes.
The initial clinical evaluation should be as comprehensive as possible as the pa-
tient will now have to address behavioral, dietary, lifestyle, and pharmaceutical
interventions to effectively manage this newly identied chronic condition. The
components for the comprehensive medical evaluation (Table 3.1) will provide
the health care team with information necessary to optimally support a patient
with diabetes. In addition to the medical history and physical examination, labora-
tory tests, nutrition, and psychosocial assessments should be obtained.
Patient Engagement
As discussed in Section 1 Strategies for Improving Care, the Chronic Care Model
(CCM) has been shown to be an effective framework for improving the quality of
diabetes care (13). This is a patient-centered approach to care that requires a close
working relationship between the patient and clinicians involved in care planning
and delivery. The foundation of successful diabetes management includes ongoing
individual lifestyle and behavioral changes, engagement of the patient, and assess-
ment of the patients level of understanding about the disease and level of pre-
paredness for self-management.

BASIS FOR INITIAL CARE


Diabetes self-management education (DSME), diabetes self-management sup-
port (DSMS), medical nutrition therapy (MNT), counseling on smoking cessa-
tion, education on physical activity, guidance on routine immunizations, and
psychosocial care are the cornerstone of diabetes management. Patients
should be referred for such services if not readily available in the clinical
care setting, i.e., referral for DSME, DSMS, MNT, and emotional health con-
cerns. Additionally, specialty and lifestyle change services and programs may Suggested citation: American Diabetes Associa-
be benecial (Table 3.2). Patients should also receive recommended preven- tion. Foundations of care and comprehensive
tive care services (e.g., cancer screening and immunizations); referral for smok- medical evaluation. Sec. 3. In Standards of Med-
ing cessation, if needed; and podiatric, ophthalmological, and dental referrals. ical Care in Diabetesd2016. Diabetes Care
Clinicians should ensure that individuals with diabetes are screened for com- 2016;39(Suppl. 1):S23S35
plications and comorbidities. Identifying and implementing the initial approach 2016 by the American Diabetes Association.
to glycemic control with the patient is one part, not the sole aspect, of the Readers may use this article as long as the work
comprehensive care strategy. is properly cited, the use is educational and not
for prot, and the work is not altered.
S24 Foundations of Care and Comprehensive Medical Evaluation Diabetes Care Volume 39, Supplement 1, January 2016

Table 3.1Components of the comprehensive diabetes medical evaluation psychosocial care). Various strategies
Medical history and techniques should be used to enable
c Age and characteristics of onset of diabetes (e.g., diabetic ketoacidosis, asymptomatic patients to self-manage diabetes, includ-
laboratory nding) ing providing education on problem-
c Eating patterns, nutritional status, weight history, and physical activity habits; nutrition solving skills for all aspects of diabetes
education and behavioral support history and needs management. Treatment goals and plans
c Presence of common comorbidities, psychosocial problems, and dental disease
should be individualized and take patient
c Screen for depression using PHQ-2 (PHQ-9 if PHQ-2 is positive) or Edinburgh Postnatal
Depression Scale (EPDS) preferences into account. In developing
c Screen for diabetes distress using DDS or PAID-1 the plan, health care providers should
c History of smoking, alcohol consumption, and substance use consider the patients age, school/work
c Diabetes education, self-management, and support history and needs schedule and conditions, physical activ-
c Review of previous treatment regimens and response to therapy (A1C records) ity, eating patterns, social situation, cul-
c Results of glucose monitoring and patients use of data tural factors, diabetes complications,
c Diabetic ketoacidosis frequency, severity, and cause
health priorities, other medical condi-
c Hypoglycemia episodes, awareness, and frequency and causes
c History of increased blood pressure, increased lipids, and tobacco use
tions, preferences for care and self-
c Microvascular complications: retinopathy, nephropathy, and neuropathy (sensory, management, and life expectancy.
including history of foot lesions; autonomic, including sexual dysfunction and
gastroparesis)
c Macrovascular complications: coronary heart disease, cerebrovascular disease, and
DIABETES SELF-MANAGEMENT
peripheral arterial disease EDUCATION AND SUPPORT
Physical examination
Recommendations
c Height, weight, and BMI; growth and pubertal development in children and adolescents
c Blood pressure determination, including orthostatic measurements when indicated
c In accordance with the national
c Fundoscopic examination standards for diabetes self-man-
c Thyroid palpation agement education (DSME) and
c Skin examination (e.g., for acanthosis nigricans, insulin injection or infusion set insertion support (DSMS), all people with di-
sites) abetes should participate in DSME
c Comprehensive foot examination to facilitate the knowledge, skills,
c Inspection
and ability necessary for diabetes
c Palpation of dorsalis pedis and posterior tibial pulses
self-care and in DSMS to assist with
c Presence/absence of patellar and Achilles reexes
c Determination of proprioception, vibration, and monolament sensation
implementing and sustaining skills
Laboratory evaluation and behaviors needed for ongoing
c A1C, if the results are not available within the past 3 months self-management, both at diagnosis
c If not performed/available within the past year and as needed thereafter. B
c Fasting lipid prole, including total, LDL, and HDL cholesterol and triglycerides, as needed c Effective self-management, im-
c Liver function tests proved clinical outcomes, health
c Spot urinary albumintocreatinine ratio
status, and quality of life are key
c Serum creatinine and estimated glomerular ltration rate
c Thyroid-stimulating hormone in patients with type 1 diabetes or dyslipidemia or women
outcomes of DSME and DSMS and
aged .50 years should be measured and moni-
tored as part of care. C
c DSME and DSMS should be patient
centered, respectful, and respon-
ONGOING CARE MANAGEMENT with diabetes must assume an active
sive to individual patient prefer-
People with diabetes should receive role in their care. ences, needs, and values, which
medical care from a collaborative, inte- The patient, family, physician, and should guide clinical decisions. A
grated team with diabetes expertise. other members of the health care team c DSME and DSMS programs should
This team may include physicians, nurse should formulate the management plan. have the necessary elements in
practitioners, physician assistants, Integral components of the management their curricula that are needed to
nurses, dietitians, exercise specialists, plan include the foundations of care prevent the onset of diabetes.
pharmacists, dentists, podiatrists, and (DSME, DSMS, MNT, smoking cessation, DSME and DSMS programs should
mental health professionals. Individuals physical activity, immunizations, and therefore tailor their content spe-
cically when prevention of diabe-
tes is the desired goal. B
Table 3.2Referrals for initial care management c Because DSME and DSMS can re-
c Eye care professional for annual dilated eye exam sult in cost savings and improved
c Family planning for women of reproductive age outcomes B, DSME and DSMS
c Registered dietitian for MNT should be adequately reimbursed
c DSME/DSMS by third-party payers. E
c Dentistfor comprehensive dental and periodontal examination
c Mental health professional, if indicated DSME and DSMS are the ongoing
processes of facilitating the knowledge,
care.diabetesjournals.org Foundations of Care and Comprehensive Medical Evaluation S25

skills, and ability necessary for diabetes (10,13), healthy coping (14,15), and types of diabetes and be supportive of
self-care. These processes incorporate lower costs (16,17). Better outcomes their implementation. See Table 3.3 for
the needs, goals, and life experiences were reported for DSME interventions specic nutrition recommendations.
of the person with diabetes. The overall that were longer (.10 h) and included
Goals of Medical Nutrition Therapy
objectives of DSME and DSMS are to follow-up support (DSMS) (18,19), were
support informed decision making, culturally (20,21) and age appropriate for Adults With Diabetes
1. To promote and support healthful eat-
self-care behaviors, problem solving, (22,23), were tailored to individual
ing patterns, emphasizing a variety of
and active collaboration with the health needs and preferences, and addressed
nutrient-dense foods in appropriate
care team to improve clinical outcomes, psychosocial issues and incorporated
portion sizes, in order to improve
health status, and quality of life in a behavioral strategies (5,14,24,25). Both
cost-effective manner (4). individual and group approaches have overall health and specically to
Achieve and maintain body weight
DSME and DSMS are essential ele- been found effective (12,26). There is
goals
ments of diabetes care (5,6), and the growing evidence for the role of com-
Attain individualized glycemic,
current national standards for DSME munity health workers (27), as well as
blood pressure, and lipid goals
and DSMS (4) are based on the evidence peer (2729) and lay (30) leaders, in pro-
Delay or prevent complications of
of their benets. Education helps people viding ongoing support.
diabetes
with diabetes to initiate effective self- DSME is associated with increased pri-
2. To address individual nutrition needs
management and cope with diabetes mary and preventive service use
based on personal and cultural prefer-
when they are rst diagnosed. Ongoing (16,31,32) and lower acute, inpatient hos-
ences, health literacy and numeracy,
DSMS helps people with diabetes to pital service use (11). Patients who partic-
access to healthful foods, willingness
maintain effective self-management ipate in DSME are more likely to follow
and ability to make behavioral changes,
throughout a lifetime of diabetes as best practice treatment recommenda-
and barriers to change
they face new challenges and as treat- tions, particularly among the Medicare
3. To maintain the pleasure of eating by
ment advances become available. population, and have lower Medicare
providing nonjudgmental messages
The DSME and DSMS algorithm de- and insurance claim costs (17,31).
about food choices
nes four critical time points for DSME
4. To provide an individual with diabe-
and DSMS delivery (7): Reimbursement
DSME and DSMS, when provided by a tes with practical tools for develop-
1. At diagnosis ing healthful eating patterns rather
program that meets the national stan-
2. Annually for assessment of educa- dards (4) and is recognized by the Amer- than focusing on individual macronu-
tion, nutrition, and emotional needs ican Diabetes Association (ADA) or other trients, micronutrients, or single
3. When new complicating factors arise approval bodies, are reimbursed as part foods
that inuence self-management of the Medicare program as overseen by
4. When transitions in care occur the Centers for Medicare & Medicaid Ser- MNT is an integral component of diabe-
vices. DSME is also covered by most tes prevention, management, and self-
Current best practice of DSME is a skill- health insurance plans. Although DSMS management education. All individuals
based approach that focuses on helping has been shown to be instrumental for with diabetes should receive individual-
those with diabetes to make informed improving outcomes and can be provided ized MNT, preferably provided by a reg-
self-management choices (4,5). DSME has via phone calls and telehealth, it currently istered dietitian who is knowledgeable
changed from a didactic approach that and skilled in providing diabetes-specic
has limited reimbursement as compared
focused on providing information to em- with in-person follow-up to DSME. MNT. MNT delivered by a registered di-
powerment models that focus on helping etitian shows A1C decreases of 0.31%
those with diabetes to make informed self- for people with type 1 diabetes (3537)
MEDICAL NUTRITION THERAPY
management decisions (5). Diabetes care and 0.52% for people with type 2 di-
For many individuals with diabetes, the
has shifted to an approach that is more abetes (3841).
patient centered and places the person
most challenging part of the treatment
plan is determining what to eat. It is the Weight Management
with diabetes and his or her family at the
position of the ADA that there is not a Intensive lifestyle programs with fre-
center of the care model, working in col-
one-size-ts-all eating pattern for individ- quent follow-up are required to achieve
laboration with health care professionals.
Patient-centered care is respectful of and
uals with diabetes. The ADA recognizes signicant reductions in excess body
the integral role of MNT in overall diabe- weight and improve clinical indicators.
responsive to individual patient prefer-
tes management and recommends that There is strong and consistent evidence
ences, needs, and values. It ensures that
each person with diabetes be actively en- that obesity management can delay pro-
patient values guide all decision making (8).
gaged in self-management, education, gression from prediabetes to type 2 di-
and treatment planning with his or her abetes (42,43) and benets type 2
Evidence for the Benets health care team, including the collabora- diabetes treatment.
Studies have found that DSME is associ- tive development of an individualized In overweight and obese patients
ated with improved diabetes knowl- eating plan (33,34). Therefore, it is impor- with type 2 diabetes, modest weight
edge, improved self-care behaviors (4), tant that each member of the health care loss, dened as sustained reduction of
lower A1C (6,9,10), lower self-reported team be knowledgeable about nutrition 5% of initial body weight, has been
weight (11,12), improved quality of life therapy principles for people with all shown to improve glycemic control
S26 Foundations of Care and Comprehensive Medical Evaluation Diabetes Care Volume 39, Supplement 1, January 2016

Table 3.3Nutrition therapy recommendations


Topic Recommendations Evidence rating
Effectiveness of nutrition therapy c An individualized MNT program, preferably provided by a registered dietitian, is A
recommended for all people with type 1 or type 2 diabetes.
c For people with type 1 diabetes or those with type 2 diabetes who are prescribed A
a exible insulin therapy program, education on how to use carbohydrate
counting or estimation to determine mealtime insulin dosing can improve
glycemic control.
c For individuals whose daily insulin dosing is xed, having a consistent pattern of B
carbohydrate intake with respect to time and amount can result in improved
glycemic control and a reduced risk of hypoglycemia.
c A simple and effective approach to glycemia and weight management C
emphasizing healthy food choices and portion control may be more helpful for
those with type 2 diabetes who are not taking insulin, who have limited health
literacy or numeracy, and who are elderly and prone to hypoglycemia.
c Because diabetes nutrition therapy can result in cost savings B and improved B, A, E
outcomes (e.g., A1C reduction) A, MNT should be adequately reimbursed by
insurance and other payers. E
Energy balance c Modest weight loss achievable by the combination of lifestyle modication and A
the reduction of energy intake benets overweight or obese adults with type 2
diabetes and also those at risk for diabetes. Interventional programs to facilitate
this process are recommended.
Eating patterns and macronutrient c As there is no single ideal dietary distribution of calories among carbohydrates, E
distribution fats, and proteins for people with diabetes, macronutrient distribution should be
individualized while keeping total calorie and metabolic goals in mind.
c Carbohydrate intake from whole grains, vegetables, fruits, legumes, and dairy B
products, with an emphasis on foods higher in ber and lower in glycemic load,
should be advised over other sources, especially those containing sugars.
c People with diabetes and those at risk should avoid sugar-sweetened beverages B, A
in order to control weight and reduce their risk for CVD and fatty liver B and
should minimize the consumption of sucrose-containing foods that have the
capacity to displace healthier, more nutrient-dense food choices. A
Protein c In individuals with type 2 diabetes, ingested protein appears to increase insulin B
response without increasing plasma glucose concentrations. Therefore,
carbohydrate sources high in protein should not be used to treat or prevent
hypoglycemia.
Dietary fat c Whereas data on the ideal total dietary fat content for people with diabetes are B
inconclusive, an eating plan emphasizing elements of a Mediterranean-style diet
rich in monounsaturated fats may improve glucose metabolism and lower CVD
risk and can be an effective alternative to a diet low in total fat but relatively high
in carbohydrates.
c Eating foods rich in long-chain omega-3 fatty acids, such as fatty sh (EPA and B, A
DHA) and nuts and seeds (ALA), is recommended to prevent or treat CVD B;
however, evidence does not support a benecial role for omega-3 dietary
supplements. A
Micronutrients and herbal supplements c There is no clear evidence that dietary supplementation with vitamins, minerals, C
herbs, or spices can improve diabetes, and there may be safety concerns
regarding the long-term use of antioxidant supplements such as vitamins E and C
and carotene.
Alcohol c Adults with diabetes who drink alcohol should do so in moderation (no more C
than one drink per day for adult women and no more than two drinks per day for
adult men).
c Alcohol consumption may place people with diabetes at increased risk for B
delayed hypoglycemia, especially if taking insulin or insulin secretagogues.
Education and awareness regarding the recognition and management of delayed
hypoglycemia are warranted.
Sodium c As for the general population, people with diabetes should limit sodium B
consumption to ,2,300 mg/day, although further restriction may be indicated
for those with both diabetes and hypertension.
care.diabetesjournals.org Foundations of Care and Comprehensive Medical Evaluation S27

and to reduce the need for glucose- from meal to meal and improving glycemic omega-3 fatty acids did not improve glyce-
lowering medications (4446). Weight control (36,51,57,58). For individuals on a mic control in individuals with type 2 di-
loss can be attained with lifestyle programs xed daily insulin schedule, meal planning abetes (53). Randomized controlled trials
that achieve a 500750 kcal/day energy should emphasize a relatively xed carbo- also do not support recommending
decit or provide ;1,2001,500 kcal/day hydrate consumption pattern with respect omega-3 supplements for primary or sec-
for women and 1,5001,800 kcal/day for to both time and amount (34). By ondary prevention of CVD (6973). People
men, adjusted for the individuals baseline contrast, a simpler diabetes meal planning with diabetes should be advised to follow
body weight. Although benets may be approach emphasizing portion control and the guidelines for the general population
seen with as little as 5% weight loss, sus- healthful food choices may be better for the recommended intakes of saturated
tained weight loss of $7% is optimal. suited for some elderly individuals, those fat, dietary cholesterol, and trans fat (64).
These diets may differ in the types of with cognitive dysfunction, and those for In general, trans fats should be avoided.
foods they restrict (such as high-fat or whom there are concerns over health lit-
high-carbohydrate foods) but are effec- eracy and numeracy (3436,38,51,57). Sodium
tive if they create the necessary energy As for the general population, people with
decit (4750). The diet choice should diabetes should limit their sodium con-
Protein
be based on the patients health status For individuals without evidence of dia- sumption to ,2,300 mg/day. Lowering
and preferences. sodium intake (i.e., 1,500 mg/day) may
betic kidney disease, the evidence is incon-
clusive about recommending an ideal benet blood pressure in certain circum-
Carbohydrates stances (74). The American Heart Associa-
amount of protein for optimizing glycemic
Studies examining the ideal amount of tion recommends 1,500 mg/day for
control or for improving one or more CVD
carbohydrate intake for people with dia- African Americans; people diagnosed
risk measures (53). Therefore, these goals
betes are inconclusive, although monitor- with hypertension, diabetes, or chronic
should be individualized. For those with di-
ing carbohydrate intake and considering kidney disease; and people over 51 years
abetic kidney disease (with albuminuria,
the blood glucose response to dietary car- of age (75). However, other studies (76,77)
reduced estimated glomerular ltration
bohydrate are key for improving post- have recommended caution for universal
rate), dietary protein should be maintained
prandial glucose control (51,52). The sodium restriction to 1,500 mg in this pop-
at the recommended daily allowance of
literature concerning glycemic index and ulation. Sodium intake recommendations
0.8 g/kg body weight per day. Reducing
glycemic load in individuals with diabetes should take into account palatability, avail-
the amount of dietary protein below
is complex. Although in some studies low- the recommended daily allowance is ability, affordability, and the difculty of
ering the glycemic load of consumed achieving low-sodium recommendations
not recommended because it does not
carbohydrates has demonstrated A1C in a nutritionally adequate diet (78).
alter glycemic measures, cardiovascular
reductions of 20.2% to 20.5% (53,54), a For complete discussion and refer-
risk measures, or the rate at which glo-
systematic review (53) found that whole- ences of all recommendations, see the
merular ltration rate declines (59,60).
grain consumption was not associated ADA position statement Nutrition Ther-
In individuals with type 2 diabetes, in-
with improvements in glycemic control apy Recommendations for the Manage-
gested protein may enhance the insulin
in type 2 diabetes. One study did nd a response to dietary carbohydrates (61). ment of Adults With Diabetes (34).
potential benet of whole-grain intake in Therefore, carbohydrate sources high in
reducing mortality and cardiovascular dis- protein should not be used to treat or pre- PHYSICAL ACTIVITY
ease (CVD) among individuals with type 2 vent hypoglycemia. The effects of protein Recommendations
diabetes (55). As for all Americans, indi- intake on blood glucose levels in type 1 c Children with diabetes or predia-
viduals with diabetes should be encour- diabetes are less clear. betes should be encouraged to en-
aged to replace rened carbohydrates
gage in at least 60 min of physical
and added sugars with whole grains, Fats
activity each day. B
legumes, vegetables, and fruits. The con- Limited research exists concerning the
c Adults with diabetes should be ad-
sumption of sugar-sweetened beverages ideal amount of fat for individuals with di-
vised to perform at least 150 min/
and low-fat or nonfat products with abetes. The Institute of Medicine has
week of moderate-intensity aerobic
high amounts of rened grains and added dened an acceptable macronutrient dis-
physical activity (5070% of maxi-
sugars should be discouraged (56). tribution range for all adults for total fat of
mum heart rate), spread over at least
Individuals with type 1 or type 2 diabe- 2035% of energy with no tolerable upper 3 days/week with no more than 2
tes taking insulin at mealtimes should be intake level dened (62). The type of fatty
consecutive days without exercise. A
offered intensive education on coupling acids consumed is more important than
c All individuals, including those with
insulin administration with carbohydrate total amount of fat when looking at meta-
diabetes, should be encouraged to
intake. For people whose meal schedules bolic goals and CVD risk (6365). Multiple reduce sedentary time, particularly
or carbohydrate consumption is variable, randomized controlled trials including pa-
by breaking up extended amounts
regular counseling to help them to under- tients with type 2 diabetes have reported
of time (.90 min) spent sitting. B
stand the complex relationship between that a Mediterranean-style eating pattern
c In the absence of contraindications,
carbohydrate intake and insulin needs, as (63,6668), rich in monounsaturated fats,
adults with type 2 diabetes should be
well as the carbohydrate-counting ap- can improve both glycemic control and
encouraged to perform resistance
proach to meal planning, can assist them blood lipids. However, a systematic review
training at least twice per week. A
with effectively modifying insulin dosing concluded that dietary supplements with
S28 Foundations of Care and Comprehensive Medical Evaluation Diabetes Care Volume 39, Supplement 1, January 2016

Physical activity is a general term that over age 18 years do 150 min/week of careful history being aware of the atyp-
includes all movement that increases en- moderate-intensity or 75 min/week of ical presentation of coronary artery dis-
ergy use and is an important part of the vigorous-intensity aerobic physical activ- ease in patients with diabetes and assess
diabetes management plan. Exercise is a ity, or an equivalent combination of the other cardiovascular risk factors. Cer-
more specic form of physical activity two. In addition, the guidelines suggest tainly, high-risk patients should be en-
that is structured and designed to im- that adults do muscle-strengthening activ- couraged to start with short periods of
prove physical tness. Although both ities that involve all major muscle groups 2 low-intensity exercise and slowly in-
are important, exercise has been shown or more days/week. The guidelines sug- crease the intensity and duration. Pro-
to improve blood glucose control, reduce gest that adults over age 65 years or those viders should assess patients for
cardiovascular risk factors, contribute to with disabilities follow the adult guide- conditions that might contraindicate
weight loss, and improve well-being. lines if possible or, if this is not possible, certain types of exercise or predis-
Physical activity is as important for those be as physically active as they are able. pose to injury, such as uncontrolled
with type 1 diabetes as it is for the general Recent evidence supports that all indi- hypertension, autonomic neuropathy,
population, but its specic role in pre- viduals, including those with diabetes, peripheral neuropathy, a history of
venting diabetes complications and con- should be encouraged to reduce the foot lesions, and untreated proliferative
trolling blood glucose is not as clear as it is amount of time spent being sedentary retinopathy. The patients age and pre-
for those with type 2 diabetes. (e.g., working at a computer, watching vious physical activity level should be
Furthermore, regular exercise may TV), particularly, by breaking up extended considered. The provider should cus-
prevent type 2 diabetes in high-risk in- amounts of time (.90 min) spent sitting tomize the exercise regimen to the
dividuals (43,79,80) (see Section 4 Pre- by briey standing or walking (87). individuals needs. Those with compli-
vention or Delay of Type 2 Diabetes). cations may require a more thorough
Structured exercise interventions of at Physical Activity and Glycemic evaluation (81).
least 8 weeks duration have been Control
shown to lower A1C by an average of On the basis of physical activity studies Hypoglycemia
0.66% in people with type 2 diabetes, that include people with diabetes, it is In individuals taking insulin and/or insu-
even with no signicant change in BMI lin secretagogues, physical activity may
reasonable to recommend that people
(80). There are also considerable data cause hypoglycemia if the medication
with diabetes will specically benet
for the health benets (e.g., increased dose or carbohydrate consumption is
from following the U.S. Department of
not altered. Individuals on these thera-
cardiovascular tness, muscle strength, Health and Human Services physical ac-
improved insulin sensitivity, etc.) of reg- pies may need to ingest some added
tivity guidelines. For example, studies in-
ular exercise for those with type 1 dia- carbohydrate if pre-exercise glucose lev-
cluded in the meta-analysis of the effects
betes (81). Higher levels of exercise of exercise interventions on glycemic con- els are ,100 mg/dL (5.6 mmol/L), de-
intensity are associated with greater im- trol (80) reported a mean of 3.4 sessions/ pending on whether they can lower
provements in A1C and in tness (82). insulin levels during the workout (such
week, with a mean of 49 min/session.
as with an insulin pump or reduced pre-
Other benets include slowing the de- Clinical trials have provided strong evi-
cline in mobility among overweight pa- exercise insulin dosage), the time of day
dence for the A1C-lowering value of resis-
tients with diabetes (83). Exercise and exercise is done, and the intensity and
tance training in older adults with type 2
Type 2 Diabetes: The American College duration of the activity. Hypoglycemia is
diabetes (84) and for an additive benet of
of Sports Medicine and the American less common in patients with diabetes
combined aerobic and resistance exercise
Diabetes Association: Joint Position who are not treated with insulin or in-
in adults with type 2 diabetes (88,89). If
Statement (84) reviews the evidence sulin secretagogues, and no preventive
not contraindicated, patients with type 2
measures for hypoglycemia are usually
for the benets of exercise in people diabetes should be encouraged to do at
with type 2 diabetes. advised in these cases. Intense activities
least two weekly sessions of resistance ex-
may actually raise blood glucose levels
ercise (exercise with free weights or
Exercise and Children instead of lowering them (91).
weight machines), with each session con-
As is recommended for all children, chil-
sisting of at least one set of ve or more
dren with diabetes or prediabetes should Exercise in the Presence of Specic
different resistance exercises involving the
be encouraged to engage in at least 60 Long-term Complications of Diabetes
large muscle groups (84).
min of physical activity each day. Included Retinopathy
in the 60 min each day, children should If proliferative diabetic retinopathy or se-
Pre-exercise Evaluation
engage in vigorous-intensity aerobic ac- vere nonproliferative diabetic retinopa-
As discussed more fully in Section 8 Car-
tivity, muscle-strengthening activities, diovascular Disease and Risk Manage- thy is present, then vigorous-intensity
and bone-strengthening activities at least ment, the best protocol for screening aerobic or resistance exercise may be
3 of those days (85). asymptomatic patients with diabetes contraindicated because of the risk of
for coronary artery disease remains triggering vitreous hemorrhage or retinal
unclear. The ADA consensus report detachment (92).
Frequency and Type of Physical
Activity Screening for Coronary Artery Disease Peripheral Neuropathy
The U.S. Department of Health and Hu- in Patients With Diabetes (90) con- Decreased pain sensation and a higher
man Services physical activity guidelines cluded that routine testing is not recom- pain threshold in the extremities result
for Americans (86) suggest that adults mended. Providers should perform a in an increased risk of skin breakdown,
care.diabetesjournals.org Foundations of Care and Comprehensive Medical Evaluation S29

infection, and Charcot joint destruction Results from epidemiological, case-control,


with some forms of exercise. There- c Administer hepatitis B vaccine to
and cohort studies provide convincing ev-
fore, a thorough assessment should unvaccinated adults with diabetes
idence to support the causal link between
be done to ensure that neuropathy cigarette smoking and health risks (97). who are aged 1959 years. C
does not alter kinesthetic or propriocep- Other studies of individuals with diabetes c Consider administering hepatitis B
vaccine to unvaccinated adults
tive sensation during physical activity. consistently demonstrate that smokers
with diabetes who are aged $60
Studies have shown that moderate- (and people exposed to secondhand
intensity walking may not lead to an smoke) have a heightened risk of CVD, years. C
increased risk of foot ulcers or reulcera- premature death, and microvascular
As for the general population, all chil-
tion in those with peripheral neuropa- complications. Smoking may have a role
dren and adults with diabetes should re-
thy who use proper footwear (93). In in the development of type 2 diabetes
ceive routine vaccinations (105,106)
addition, 150 min/week of moderate (98). One study in smokers with newly
according to age-specic recommenda-
exercise was reported to improve out- diagnosed type 2 diabetes found that
tions (see the adult vaccination sched-
comes in patients with milder forms smoking cessation was associated with
of neuropathy (94). All individuals with amelioration of metabolic parameters ule available from http://www.cdc.gov/
vaccines/schedules/hcp/imz/adult.html
peripheral neuropathy should wear and reduced blood pressure and albumin-
and the child and adolescent vaccina-
proper footwear and examine their uria at 1 year (99).
feet daily to detect lesions early. Any- The routine and thorough assessment
tion schedule available from http://
www.cdc.gov/vaccines/schedules/hcp/
one with a foot injury or open sore of tobacco use is essential to prevent
imz/child-adolescent.html).
should be restricted to nonweight- smoking or encourage cessation. Nu-
The Centers for Disease Control and
bearing activities. merous large randomized clinical trials
Prevention (CDC) Advisory Committee
Autonomic Neuropathy have demonstrated the efcacy and cost- on Immunization Practices recommends
Autonomic neuropathy can increase the effectiveness of brief counseling in smoking
inuenza and pneumococcal vaccines
risk of exercise-induced injury or ad- cessation, including the use of telephone
for all individuals with diabetes (http://
verse events through decreased cardiac quit lines, in reducing tobacco use. For the
www.cdc.gov/vaccines/schedules).
responsiveness to exercise, postural hy- patient motivated to quit, the addition of
potension, impaired thermoregulation, pharmacological therapy to counseling
Inuenza
impaired night vision due to impaired is more effective than either treatment
Inuenza is a common, preventable in-
papillary reaction, and greater suscepti- alone. Special considerations should in- fectious disease associated with high
bility to hypoglycemia (95). Cardiovas- clude assessment of level of nicotine mortality and morbidity in vulnerable
cular autonomic neuropathy is also an dependence, which is associated with populations, such as the young and
independent risk factor for cardiovascu- difculty in quitting and relapse (100). the elderly and people with chronic
lar death and silent myocardial ischemia Although some patients may gain weight diseases. Regardless of sex, race, and
(96). Therefore, individuals with dia- in the period shortly after smoking ces- socioeconomic status, adults with dia-
betic autonomic neuropathy should un- sation, recent research has demon- betes 2564 years of age who died are
dergo cardiac investigation before strated that this weight gain does not four times more likely to have pneu-
beginning physical activity more intense diminish the substantial CVD benet re- monia and inuenza recorded on their
than that to which they are accustomed. alized from smoking cessation (101).
death certicates than adults without
Nonsmokers should be advised not to diabetes who died at comparable ages
Albuminuria and Nephropathy
use e-cigarettes. (107). In a case-control series, the in-
Physical activity can acutely increase uri-
There are no rigorous studies that have uenza vaccine was shown to reduce
nary protein excretion. However, there
demonstrated that e-cigarettes are a diabetes-related hospital admission
is no evidence that vigorous-intensity
healthier alternative to smoking or that by as much as 79% during u epidemics
exercise increases the rate of progres- e-cigarettes can facilitate smoking cessa-
sion of diabetic kidney disease, and
(108).
tion. More extensive research of their
there appears to be no need for specic short- and long-term effects is needed Pneumococcal Pneumonia
exercise restrictions for people with di-
to determine their safety and their car- Like inuenza, pneumococcal pneumo-
abetic kidney disease (92).
diopulmonary effects in comparison nia is a common, preventable disease.
with smoking and standard approaches People with diabetes may be at in-
SMOKING CESSATION: TOBACCO to smoking cessation (102104). creased risk for the bacteremic form of
AND e-CIGARETTES pneumococcal infection and have been
Recommendations
reported to have a high risk of nosoco-
IMMUNIZATION mial bacteremia, with a mortality rate
c Advise all patients not to use ciga-
as high as 50% (109). All patients with
rettes, other tobacco products, or Recommendations
diabetes 2 years of age and older should
e-cigarettes. A c Provide routine vaccinations for
receive the pneumococcal polysaccha-
c Include smoking cessation coun- children and adults with diabetes
seling and other forms of treat- as for the general population ac- ride vaccine 23 (PPSV23). There is suf-
cient evidence to support that people
ment as a routine component of cording to age-related recommen-
with diabetes have appropriate sero-
diabetes care. B dations. C
logic and clinical responses to these
S30 Foundations of Care and Comprehensive Medical Evaluation Diabetes Care Volume 39, Supplement 1, January 2016

vaccinations. The ADA endorses the appropriate services. A systematic re- with depression without signicant
CDC advisory panel recommendation view and meta-analysis showed that DD, and those with DD without signi-
that both pneumococcal conjugate vac- psychosocial interventions modestly cant depression. Understanding the
cine 13 (PCV13) and PPSV23 should be but signicantly improved A1C (stan- category in which a particular patient
administered routinely in series to all dardized mean difference 20.29%) belongs facilitates a customized care
adults aged $65 years. and mental health outcomes. However, approach that may include DSME,
there was a limited association be- DSMS, cognitive therapy, or treatment
Hepatitis B
tween the effects on A1C and mental for depression (psychotherapy and/
Compared with the general population,
health, and no intervention characteris- or psychotropic medications). The
people with type 1 or type 2 diabetes screening of all patients with diabetes
tics predicted benet on both outcomes
have higher rates of hepatitis B. This with the Patient Health Questionnaire-2
(114).
may be due to contact with infected (PHQ-2) and either the Diabetes Dis-
blood or through improper equipment Screening tress Scale (DDS) or Problem Areas in
use (glucose monitoring devices or in- Key opportunities for psychosocial Diabetes (PAID)-1 scale can help to
fected needles). Because of the higher screening occur at diabetes diagnosis, facilitate this (24,123,124).
likelihood of transmission, hepatitis B during regularly scheduled manage- Other issues known to affect self-
vaccine is recommended for adults ment visits, during hospitalizations, management and health outcomes
with diabetes. with new onset of complications, or include attitudes about the illness, ex-
when problems with glucose control, pectations for medical management and
PSYCHOSOCIAL ISSUES quality of life, or self-management are outcomes, anxiety, general and diabetes-
Recommendations identied. Patients are likely to exhibit related quality of life, resources (nancial,
c The patients psychological and psychological vulnerability at diagnosis, social, and emotional) (125), and psychi-
social situation should be ad- when their medical status changes atric history (126).
dressed in the medical manage- (e.g., end of the honeymoon period),
ment of diabetes. B when the need for intensied treat- Referral to a Mental Health Specialist
c Psychosocial screening and follow- ment is evident, and when complica- Indications for referral to a mental
up may include, but are not lim- tions are discovered. Depression health specialist familiar with diabetes
ited to, attitudes about the illness, affects ;2025% of people with diabe- management may include possibility of
expectations for medical man- tes (115). Individuals with both diabe- self-harm, gross disregard for the med-
agement and outcomes, affect/ tes and major depressive disorder ical regimen (by self or others) (127),
mood, general and diabetes-related have a twofold increased risk for new- depression, overall stress related to
quality of life, resources (nancial, onset myocardial infarction compared work-life balance, debilitating anxiety
social, and emotional), and psy- with either disease state alone (116). (alone or with depression), indications
chiatric history. E There appears to be a bidirectional re- of an eating disorder (128), or cognitive
c Routinely screen for psychoso- lationship between both diabetes (117) functioning that signicantly impairs
cial problems such as depression, and metabolic syndrome (118) and judgment. It is preferable to incorpo-
diabetes-related distress, anxiety, depression. rate psychological assessment and
eating disorders, and cognitive im- treatment into routine care rather
pairment. B Diabetes Distress than waiting for a specic problem or
c Older adults (aged $65 years) Diabetes-related distress (DD) is dis- deterioration in metabolic or psycho-
with diabetes should be consid- tinct from depressive disorders and is logical status (24,119). In the second Di-
ered for evaluation of cognitive very common (119121) in people abetes Attitudes, Wishes and Needs
function and depression screening with diabetes and their family mem- (DAWN2) study, signicant DD was re-
and treatment. B bers (113). DD refers to signicant neg- ported by 45% of the participants, but
c Patients with comorbid diabetes ative psychological reactions related only 24% reported that their health care
and depression should receive a to emotional burdens and worries spe- team asked them how diabetes affected
stepwise collaborative care ap- cic to an individuals experience in their life (119).
proach for the management of de- having to manage a severe, compli- Although the clinician may not feel
pression. A cated, and demanding chronic dis- qualied to treat psychological prob-
ease such as diabetes (120122). Its lems (129), optimizing the patient
Emotional well-being is an important part prevalence is reported to be 1845%, provider relationship as a foundation
of diabetes care and self-management. with an incidence of 3848% over 18 may increase the likelihood of the pa-
Psychological and social problems can months. High levels of distress are tient accepting referral for other ser-
impair the individuals (110112) or signicantly linked to medication non- vices. Collaborative care interventions
familys (113) ability to carry out adherence (122), higher A1C, lower and a team approach have demonstrated
diabetes care tasks and therefore com- self-efcacy, and poorer dietary and ef cacy in diabetes and depression
promise health status. There are oppor- exercise behaviors (15,120). The clini- (130,131). Interventions to enhance
tunities for the clinician to routinely cian needs to understand that individuals self-management and address severe
assess psychosocial status in a timely may fall into one of three categories: distress have demonstrated efcacy
and efcient manner for referral for those with depression and DD, those in DD (15).
care.diabetesjournals.org Foundations of Care and Comprehensive Medical Evaluation S31

COMPREHENSIVE MEDICAL Obstructive Sleep Apnea For patients with type 2 diabetes with
EVALUATION Age-adjusted rates of obstructive sleep fracture risk factors, thiazolidinediones
apnea, a risk factor for CVD, are signi- (148) and sodiumglucose cotransporter
Recommendations cantly higher (4- to 10-fold) with obe- 2 inhibitors should be avoided as their use
A complete medical evaluation should sity, especially with central obesity has been associated with a higher risk of
be performed at the initial visit to
(139). The prevalence of obstructive fractures (149).
c Conrm the diagnosis and classify sleep apnea in the population with
diabetes. B type 2 diabetes may be as high as 23% Low Testosterone in Men
c Detect diabetes complications and (140). In obese participants enrolled in Mean levels of testosterone are lower in
potential comorbid conditions. E the Action for Health in Diabetes (Look men with diabetes compared with age-
c Review previous treatment and AHEAD) trial, it exceeded 80% (141). matched men without diabetes, but
risk factor control in patients Sleep apnea treatment signicantly im- obesity is a major confounder (150).
with established diabetes. E proves quality of life and blood pressure Treatment in asymptomatic men is con-
c Begin patient engagement in the control. The evidence for a treatment troversial. The evidence that testoster-
formulation of a care manage- effect on glycemic control is mixed one replacement affects outcomes is
ment plan. B (142). mixed, and recent guidelines do not rec-
c Develop a plan for continuing care. B ommend testing and treating men with-
Cancer out symptoms (151).
Diabetes (possibly only type 2 diabetes)
Besides assessing diabetes-related is associated with increased risk of Periodontal Disease
complications and comorbidities, clini- cancers of the liver, pancreas, endome- Periodontal disease is more severe, but
cians and their patients need to be trium, colon/rectum, breast, and blad- not necessarily more prevalent, in pa-
aware of other common conditions der (143). The association may result tients with diabetes than in those with-
that affect people with diabetes. Im- from shared risk factors between out (152). Current evidence suggests
proved disease prevention and treat- type 2 diabetes and cancer (older age, that periodontal disease adversely af-
ment mean that people with diabetes obesity, and physical inactivity) but fects diabetes outcomes, although evi-
are living longer and developing heart may also be due to hyperinsulinemia dence for treatment benets remains
failure, fatty liver disease, obstructive or hyperglycemia (144). Patients with controversial (136).
sleep apnea, and arthritisdconditions
diabetes should be encouraged to un-
that affect people with diabetes more dergo recommended age- and sex-ap- Hearing Impairment
often than age-matched people without propriate cancer screenings and to Hearing impairment, both in high-frequency
reduce their modiable cancer risk fac- and low/mid-frequency ranges, is more
diabetes and that may complicate dia-
tors (smoking, obesity, and physical in- common in people with diabetes than
betes management (132136).
activity). in those without, perhaps due to neu-
Adults who develop type 1 diabetes
ropathy and/or vascular disease. In a
may develop additional autoimmune dis- Fractures National Health and Nutrition Examina-
orders including thyroid or adrenal dys-
Age-specic hip fracture risk is signi- tion Survey (NHANES) analysis, hearing
function and celiac disease, although the
cantly increased in both type 1 (relative impairment was about twice as preva-
risk of coexisting autoimmunity is lower in risk 6.3) and type 2 (relative risk 1.7) di-
adults than for youth with type 1 diabe-
lent in people with diabetes compared
abetes in both sexes (145). Type 1 dia- with those without, after adjusting for
tes. For additional details on autoimmune betes is associated with osteoporosis, age and other risk factors for hearing
conditions, see Section 11 Children and but in type 2 diabetes, an increased impairment (153).
Adolescents. risk of hip fracture is seen despite higher
bone mineral density (BMD) (146). In Cognitive Impairment
COMORBIDITIES three large observational studies of Diabetes is associated with a signi-
Fatty Liver Disease older adults, femoral neck BMD T-score cantly increased risk and rate of cogni-
Elevations of hepatic transaminase con- and the World Health Organization Frac- tive decline and an increased risk of
centrations are signicantly associated ture Risk Assessment Tool (FRAX) score dementia (154,155). In a 15-year pro-
with higher BMI, waist circumference, were associated with hip and nonspine spective study of community-dwelling
and triglyceride levels and lower HDL fractures. Fracture risk was higher in people aged .60 years, the presence
cholesterol levels. In a prospective anal- participants with diabetes compared of diabetes at baseline signicantly
ysis, diabetes was signicantly associ- with those without diabetes for a given increased the age- and sex-adjusted
ated with incident nonalcoholic chronic T-score and age for a given FRAX score incidence of all-cause dementia, Alz-
liver disease and with hepatocellular (147). Providers should assess fracture heimer disease, and vascular dementia
carcinoma (137). Interventions that im- history and risk factors in older patients compared with rates in those with
prove metabolic abnormalities in pa- with diabetes and recommend measure- normal glucose tolerance (156). In a
tients with diabetes (weight loss, ment of BMD if appropriate for the pa- substudy of the Action to Control Car-
glycemic control, and treatment with tients age and sex. Fracture prevention diovascular Risk in Diabetes (ACCORD)
specic drugs for hyperglycemia or dys- strategies for people with diabetes are clinical trial, there were no differences
lipidemia) are also benecial for fatty the same as for the general population in cognitive outcomes between the in-
liver disease (138). and include vitamin D supplementation. tensive and standard glycemic control
S32 Foundations of Care and Comprehensive Medical Evaluation Diabetes Care Volume 39, Supplement 1, January 2016

groups, although there was signi- mellitus. Cochrane Database Syst Rev 2005;2: 30. Foster G, Taylor SJ, Eldridge SE, Ramsay J,
cantly less of a decrement in total brain CD003417 Grifths CJ. Self-management education pro-
13. Cochran J, Conn VS. Meta-analysis of qual- grammes by lay leaders for people with chronic
volume, as measured by MRI, in partic-
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S36 Diabetes Care Volume 39, Supplement 1, January 2016

4. Prevention or Delay of Type American Diabetes Association

2
Diabetes
Diabetes Care 2016;39(Suppl. 1):S36S38| DOI: 10.2337/dc16-S007

Recommendations
c Patients with prediabetes should be referred to an intensive diet and physical
activity behavioral counseling program adhering to the tenets of the Diabetes
4. PREVENTION OR DELAY OF TYPE2 DIABETES

Prevention Program (DPP) targeting a loss of 7% of body weight and should


increase their moderate-intensity physical activity (such as brisk walking) to at
least 150 min/week. A
c Follow-up counseling and maintenance programs should be offered for long-
term success in preventing diabetes. B
c Based on the cost-effectiveness of diabetes prevention, such programs should
be covered by third-party payers. B
c Metformin therapy for prevention of type 2 diabetes should be considered in
those with prediabetes, especially in those with BMI .35 kg/m , those aged
2

,60 years, and women with prior gestational diabetes mellitus. A


c At least annual monitoring for the development of diabetes in those with
prediabetes is suggested. E
c Screening for and treatment of modiable risk factors for cardiovascular dis-
ease is suggested. B
c Diabetes self-management education and support programs are appropriate
venues for people with prediabetes to receive education and support to de-
velop and maintain behaviors that can prevent or delay the onset of diabetes. B
c Technology-assisted tools including Internet-based social networks, distance
learning, DVD-based content, and mobile applications can be useful elements
of effective lifestyle modication to prevent diabetes. B
LIFESTYLE MODIFICATION
Randomized controlled trials have shown that individuals at high risk for develop-
ing type 2 diabetes (impaired fasting glucose, impaired glucose tolerance, or both)
can signicantly decrease the rate of diabetes onset with particular interventions
(17). These include intensive lifestyle modication programs that have been
shown to be very effective (;58% reduction after 3 years). Follow-up of all three
large studies of lifestyle intervention has shown sustained reduction in the rate of
conversion to type 2 diabetes: 43% reduction at 20 years in the Da Qing study (8),
43% reduction at 7 years in the Finnish Diabetes Prevention Study (DPS) (9), and
34% reduction at 10 years in the U.S. Diabetes Prevention Program Outcomes Study
(DPPOS) (10).
A cost-effectiveness model suggested that lifestyle interventions in the Diabetes
Prevention Program (DPP) are cost-effective (11). Actual cost data from the DPP and
DPPOS also conrm this (12). Group delivery of DPP content into community
settings has the potential to reduce overall program costs while still producing
weight loss and diabetes risk reduction (13,14). The Centers for Disease Control
and Prevention (CDC) helps to coordinate the National Diabetes Prevention
Program, a resource designed to bring evidence-based lifestyle change programs
for preventing type 2 diabetes to communities (http://www.cdc.gov/diabetes/ Suggested citation: American Diabetes Associa-
prevention/index.htm). tion. Prevention or delay of type 2 diabetes. Sec.
Given the clinical trial results and the known risks of progression from prediabetes 4. In Standards of Medical Care in Diabetesd2016.
to diabetes, people with an A1C 5.76.4% (3946 mmol/mol), impaired glucose Diabetes Care 2016;39(Suppl. 1):S36S38
tolerance, or impaired fasting glucose should be counseled on lifestyle changes 2016 by the American Diabetes Association.
with goals similar to those of the DPP (7% weight loss and moderate-intensity Readers may use this article as long as the work
physical activity of at least 150 min/week). is properly cited, the use is educational and not
for prot, and the work is not altered.
care.diabetesjournals.org Prevention or Delay of Type 2 Diabetes S37

Nutrition health care providers should inform PHARMACOLOGICAL


As for people with diabetes (see Section 3 at-risk patients of these benets in or- INTERVENTIONS
Foundations of Care and Comprehen- der to motivate them to engage Pharmacological agents, such as metfor-
sive Medical Evaluation), evidence sup- in regular moderate-intensity physical min, a-glucosidase inhibitors, orlistat,
ports the importance of maintaining a activity. and thiazolidinediones, have each
healthy diet in order to prevent diabetes Moderate exercise, such as brisk been shown to decrease incident dia-
onset. Unlike past recommendations walking or other activities of equivalent betes to various degrees. Metformin
that focused on simply reducing total di- intensity, has been also observed to im- has the strongest evidence base and
etary fat and cholesterol consumption, prove insulin sensitivity and reduce ab- demonstrated long-term safety as
more recent evidence argues against dominal fat content in children and pharmacological therapy for diabetes
the preventative effects of lowering fat young adults (22,23). The DPP included prevention (34). For other drugs, cost,
and cholesterol intake across the board 150 min/week of moderate-intensity ex- side effects, and durable efcacy re-
and supports instead that the quality of ercise and showed benecial effect on quire consideration.
fats consumed in the diet is more impor- glycemia in those with prediabetes (1). Metformin was less effective than
tant than the total quantity of dietary fat. Both resistance training and endurance lifestyle modication in the DPP and
For example, recent work supports the exercise appear to have benecial ef- DPPOS but may be cost-saving over a
Mediterranean diet, which is relatively fects on waist circumference, insulin 10-year period (12). It was as effective
rich in monounsaturated fats, as a means sensitivity, and thus diabetes risk as lifestyle modication in participants
to help to prevent type 2 diabetes (15). (24,25). The preventative effects of exer- with BMI $35 kg/m but not signi-
2

Studies evaluating glycemic index to cise appear to extend to the prevention cantly better than placebo in those
guide carbohydrate recommendations of gestational diabetes mellitus (GDM) over 60 years of age (1). In the DPP,
have been inconsistent (16,17); however, as well (26). for women with a history of GDM, met-
data suggest that consumption of a diet formin and intensive lifestyle modica-
enriched in whole grains is helpful in pre- Prevention of Cardiovascular Disease tion led to an equivalent 50% reduction
venting type 2 diabetes (18). Finally, in- People with prediabetes often have other in diabetes risk (35), and both inter-
creased consumption of nuts (19) and cardiovascular risk factors, such as obe- ventions remained highly effective
berries (20) in the context of a diet high sity, hypertension, and dyslipidemia during a 10-year follow-up period
in vegetables and whole fruits has been and are at increased risk for cardiovas- (36). Metformin may be recommended
correlated with reduced diabetes risk. In- cular disease events. While treatment for high-risk individuals (e.g., those
dividualized medical nutrition therapy goals for people with prediabetes are with a history of GDM, those who are
(see Section 3 Foundations of Care and the same as for the general population, very obese, and/or those with more
Comprehensive Medical Evaluation for increased vigilance is warranted to severe or progressive hyperglycemia)
more detailed information) has been identify and treat these and other risk and/or those with rising A1C despite
shown to be effective in lowering A1C in factors (e.g., smoking). lifestyle intervention.
individuals diagnosed with prediabetes
(7). This indicates that nutritional inter- Technology Assistance to Deliver
ventions are potentially effective in stav- Lifestyle Modication DIABETES SELF-MANAGEMENT
ing off the progression toward type 2 Technology may be an effective means EDUCATION AND SUPPORT
diabetes (e.g., individuals showing signs to deliver the core components of the As for those with established diabetes, the
of metabolic syndrome). DPP (27,28). Initial studies have vali- standards for diabetes self-management
dated DVD-based content delivery education and support (see Section 3
Physical Activity and Exercise (29). This has been corroborated in a Foundations of Care and Comprehen-
Physical activity and exercise are impor- primary care patient population (30). sive Medical Evaluation) can also apply
tant for those living with diabetes (see Recent studies support content delivery to the education and support of people
Section 3 Foundations of Care and Com- through virtual small groups (31), Internet- with prediabetes. Currently, there are
prehensive Medical Evaluation), but they driven social networks (32,33), cellular signicant barriers to the provision of
have also been evaluated for diabetes pre- phones, and other mobile devices. Mo- education and support to those with pre-
vention. Physical activity is a more general bile applications for weight loss and di- diabetes. However, the strategies for
term that covers all types of activity, abetes prevention have been validated supporting successful behavior change
whereas exercise refers to structured or for their ability to reduce A1C in the and the healthy behaviors recom-
planned activities. Although not well stud- setting of prediabetes (33). The CDCs Di- mended for people with prediabetes
ied in isolation, exercise and physical ac- abetes Prevention Recognition Program are comparable to those for diabetes.
tivity have been validated to prevent or (DPRP) (http://www.cdc.gov/diabetes/ Although reimbursement remains a
delay diabetes development as part of a prevention/recognition/index.htm) has barrier, studies show that providers of
comprehensive approach to lifestyle mod- begun to certify electronic and mobile diabetes self-management education
ication (21). These studies suggest that health-based modalities as effective ve- and support are particularly well equip-
while exercise treatment programs may hicles for DPP-style prevention content ped to assist people with prediabetes in
not reduce body weight, programs of suf- that may be considered alongside more developing and maintaining behaviors
cient intensity have been shown to de- traditional face-to-face and coach-driven that can prevent or delay the onset of
crease diabetes risk (21). Therefore, programs. diabetes (7,37).
S38 Prevention or Delay of Type 2 Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

References 13. Ackermann RT, Finch EA, Brizendine E, in obese adolescent boys: a randomized, con-
1. Knowler WC, Barrett-Connor E, Fowler SE, Zhou H, Marrero DG. Translating the Diabetes trolled trial. Diabetes 2012;61:27872795
et al.; Diabetes Prevention Program Research Prevention Program into the community. The 26. Russo LM, Nobles C, Ertel KA, Chasan-Taber
Group. Reduction in the incidence of type 2 di- DEPLOY Pilot Study. Am J Prev Med 2008;35: L, Whitcomb BW. Physical activity interventions
abetes with lifestyle intervention or metformin. 357363 in pregnancy and risk of gestational diabetes
N Engl J Med 2002;346:393403 14. Balk EM, Earley A, Raman G, Avendano EA, mellitus: a systematic review and meta-analysis.
2. Buchanan TA, Xiang AH, Peters RK, et al. Pittas AG, Remington PL. Combined diet and Obstet Gynecol 2015;125:576582
Preservation of pancreatic b-cell function and
physical activity promotion programs to prevent 27. Levine DM, Savarimuthu S, Squires A,
prevention of type 2 diabetes by pharmacolog- type 2 diabetes among persons at increased risk: Nicholson J, Jay M. Technology-assisted weight
ical treatment of insulin resistance in high-risk a systematic review for the Community Preven- loss interventions in primary care: a systematic
Hispanic women. Diabetes 2002;51:27962803 tive Services Task Force. Ann Intern Med 2015; review. J Gen Intern Med 2015;30:107117
3. Chiasson J-L, Josse RG, Gomis R, Hanefeld M, 163:437451 28. Allen JK, Stephens J, Patel A. Technology-
Karasik A, Laakso M; STOP-NIDDM Trial Re- 15. Salas-Salvad o J, Bull o M, Babio N, et al.; assisted weight management interventions:
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type 2 diabetes mellitus: the STOP-NIDDM the incidence of type 2 diabetes with the Med- Health 2014;20:11031120
randomised trial. Lancet 2002;359:20722077 iterranean diet: results of the PREDIMED-Reus 29. Kramer MK, Kriska AM, Venditti EM, et al. A
nutrition intervention randomized trial. Diabe- novel approach to diabetes prevention: evalua-
4. Lin JS, OConnor E, Evans CV, Senger CA,
Rowland MG, Groom HC. Behavioral counseling tes Care 2011;34:1419 tion of the Group Lifestyle Balance program de-
to promote a healthy lifestyle in persons with 16. Bhupathiraju SN, Tobias DK, Malik VS, et al. livered via DVD. Diabetes Res Clin Pract 2010;
cardiovascular risk factors: a systematic review Glycemic index, glycemic load, and risk of type 2 90:e60e63
for the U.S. Preventive Services Task Force. Ann diabetes: results from 3 large US cohorts and an 30. Ma J, Yank V, Xiao L, et al. Translating the
Intern Med 2014;161:568578 updated meta-analysis. Am J Clin Nutr 2014; Diabetes Prevention Program lifestyle interven-
5. Paulweber B, Valensi P, Lindstrom J, et al. A 100:218232 tion for weight loss into primary care: a random-
European evidence-based guideline for the pre- 17. Sacks FM, Carey VJ, Anderson CAM, et al. ized trial. JAMA Intern Med 2013;173:113 121
vention of type 2 diabetes. Horm Metab Res Effects of high vs low glycemic index of dietary 31. Azar KMJ, Aurora M, Wang EJ, Muzaffar A,
2010;42(Suppl. 1):S3S36 carbohydrate on cardiovascular disease risk fac- Pressman A, Palaniappan LP. Virtual small
6. Diabetes Prevention Program Research tors and insulin sensitivity: the OmniCarb ran- groups for weight management: an innovative
Group. HbA as a predictor of diabetes and as
1c
domized clinical trial. JAMA 2014;312:2531 2541 delivery mechanism for evidence-based lifestyle
an outcome in the Diabetes Prevention Pro- 18. Montonen J, Knekt P, Jarvinen R, Aromaa A, interventions among obese men. Transl Behav
gram: a randomized clinical trial. Diabetes Reunanen A. Whole-grain and ber intake and Med 2015;5:3744
Care 2015;38:5158 the incidence of type 2 diabetes. Am J Clin Nutr 32. Sepah SC, Jiang L, Peters AL. Translating the
7. Parker AR, Byham-Gray L, Denmark R, Winkle 2003;77:622629 Diabetes Prevention Program into an online so-
PJ. The effect of medical nutrition therapy by a 19. Afshin A, Micha R, Khatibzadeh S, cial network: validation against CDC standards.
registered dietitian nutritionist in patients with Mozaffarian D. Consumption of nuts and legumes Diabetes Educ 2014;40:435443
prediabetes participating in a randomized con- and risk of incident ischemic heart disease, stroke, 33. Sepah SC, Jiang L, Peters AL. Long-term out-
trolled clinical research trial. J Acad Nutr Diet and diabetes: a systematic review and meta- comes of a Web-based diabetes prevention pro-
2014;114:17391748 analysis. Am J Clin Nutr 2014;100:278288 gram: 2-year results of a single-arm longitudinal
8. Li G, Zhang P, Wang J, et al. The long-term 20. Mursu J, Virtanen JK, Tuomainen T-P, Nurmi study. J Med Internet Res 2015;17:e92
effect of lifestyle interventions to prevent dia- T, Voutilainen S. Intake of fruit, berries, and 34. Group TDPPR; Diabetes Prevention Pro-
betes in the China Da Qing Diabetes Prevention vegetables and risk of type 2 diabetes in Finnish gram Research Group. Long-term safety, tol-
Study: a 20-year follow-up study. Lancet 2008; men: the Kuopio Ischaemic Heart Disease Risk erability, and weight loss associated with
371:17831789 Factor Study. Am J Clin Nutr 2014;99:328 333 metformin in the Diabetes Prevention Pro-
9. Lindstrom J, Ilanne-Parikka P, Peltonen M, 21. Swift DL, Johannsen NM, Lavie CJ, Earnest gram Outcomes Study. Diabetes Care 2012;
et al.; Finnish Diabetes Prevention Study Group. CP, Church TS. The role of exercise and physical 35:731737
Sustained reduction in the incidence of type 2 activity in weight loss and maintenance. Prog 35. Ratner RE, Christophi CA, Metzger BE, et al.;
diabetes by lifestyle intervention: follow-up of Cardiovasc Dis 2014;56:441447 Diabetes Prevention Program Research Group.
the Finnish Diabetes Prevention Study. Lancet 22. Fedewa MV, Gist NH, Evans EM, Dishman Prevention of diabetes in women with a history
2006;368:16731679 RK. Exercise and insulin resistance in youth: a of gestational diabetes: effects of metformin
10. Knowler WC, Fowler SE, Hamman RF, et al.; meta-analysis. Pediatrics 2014;133:e163e174 and lifestyle interventions. J Clin Endocrinol
Diabetes Prevention Program Research Group. 23. Davis CL, Pollock NK, Waller JL, et al. Exer- Metab 2008;93:47744779
10-year follow-up of diabetes incidence and cise dose and diabetes risk in overweight and 36. Aroda VR, Christophi CA, Edelstein SL, et al.;
weight loss in the Diabetes Prevention Program obese children: a randomized controlled trial. Diabetes Prevention Program Research Group.
Outcomes Study. Lancet 2009;374:16771686 JAMA 2012;308:11031112 The effect of lifestyle intervention and metfor-
11. Herman WH, Hoerger TJ, Brandle M, et al.; 24. Sigal RJ, Alberga AS, Goldeld GS, et al. Ef- min on preventing or delaying diabetes among
Diabetes Prevention Program Research Group. fects of aerobic training, resistance training, or women with and without gestational diabetes:
The cost-effectiveness of lifestyle modication both on percentage body fat and cardiometa- the Diabetes Prevention Program outcomes
or metformin in preventing type 2 diabetes in bolic risk markers in obese adolescents: the study 10-year follow-up. J Clin Endocrinol
adults with impaired glucose tolerance. Ann In- healthy eating aerobic and resistance training Metab 2015;100:16461653
tern Med 2005;142:323332 in youth randomized clinical trial. JAMA Pediatr 37. Butcher MK, Vanderwood KK, Hall TO,
12. Diabetes Prevention Program Research 2014;168:10061014 Gohdes D, Helgerson SD, Harwell TS. Capacity
Group. The 10-year cost-effectiveness of life- 25. Lee S, Bacha F, Hannon T, Kuk JL, Boesch C, of diabetes education programs to provide both
style intervention or metformin for diabetes Arslanian S. Effects of aerobic versus resistance diabetes self-management education and to im-
prevention: an intent-to-treat analysis of the exercise without caloric restriction on abdomi- plement diabetes prevention services. J Public
DPP/DPPOS. Diabetes Care 2012;35:723730 nal fat, intrahepatic lipid, and insulin sensitivity Health Manag Pract 2011;17:242247
Diabetes Care Volume 39, Supplement 1, January 2016 S39

5. Glycemic Targets American Diabetes Association

Diabetes Care 2016;39(Suppl. 1):S39S46 | DOI: 10.2337/dc16-S008

ASSESSMENT OF GLYCEMIC CONTROL


Two primary techniques are available for health providers and patients to assess the
effectiveness of the management plan on glycemic control: patient self-monitoring
of blood glucose (SMBG) and A1C. Continuous glucose monitoring (CGM) or in-
terstitial glucose may be a useful adjunct to SMBG in selected patients.
Recommendations
c When prescribed as part of a broader educational context, self-monitoring of
blood glucose (SMBG) results may help to guide treatment decisions and/or
self-management for patients using less frequent insulin injections B or non-
insulin therapies. E

5. GLYCEMIC TARGETS
c When prescribing SMBG, ensure that patients receive ongoing instruction and
regular evaluation of SMBG technique, SMBG results, and their ability to use
SMBG data to adjust therapy. E
c Most patients on intensive insulin regimens (multiple-dose insulin or insulin
pump therapy) should consider SMBG prior to meals and snacks, occasionally
postprandially, at bedtime, prior to exercise, when they suspect low blood
glucose, after treating low blood glucose until they are normoglycemic, and
prior to critical tasks such as driving. B
c When used properly, continuous glucose monitoring (CGM) in conjunction
with intensive insulin regimens is a useful tool to lower A1C in selected adults
(aged $25 years) with type 1 diabetes. A
c Although the evidence for A1C lowering is less strong in children, teens, and
younger adults, CGM may be helpful in these groups. Success correlates with
adherence to ongoing use of the device. B
c CGM may be a supplemental tool to SMBG in those with hypoglycemia un-
awareness and/or frequent hypoglycemic episodes. C
c Given variable adherence to CGM, assess individual readiness for continuing
CGM use prior to prescribing. E
c When prescribing CGM, robust diabetes education, training, and support are
required for optimal CGM implementation and ongoing use. E
c People who have been successfully using CGM should have continued access
after they turn 65 years of age. E
Self-monitoring of Blood Glucose
Major clinical trials of insulin-treated patients have included SMBG as part of the
multifactorial interventions to demonstrate the benet of intensive glycemic con-
trol on diabetes complications. SMBG is thus an integral component of effective
therapy (1). SMBG allows patients to evaluate their individual response to therapy
and assess whether glycemic targets are being achieved. Integrating SMBG results
into diabetes management can be a useful tool for guiding medical nutrition therapy
and physical activity, preventing hypoglycemia, and adjusting medications (particularly
prandial insulin doses). Among patients with type 1 diabetes, there is a correlation
between greater SMBG frequency and lower A1C (2). The patients specic needs and
goals should dictate SMBG frequency and timing.
Suggested citation: American Diabetes Associa-
Optimization tion. Glycemic targets. Sec. 5. In Standards of
SMBG accuracy is dependent on the instrument and user, so it is important to Medical Care in Diabetesd2016. Diabetes Care
evaluate each patients monitoring technique, both initially and at regular intervals 2016;39(Suppl. 1):S39S46
thereafter. Optimal use of SMBG requires proper review and interpretation of the 2016 by the American Diabetes Association.
data, by both the patient and the provider. Among patients who check their blood Readers may use this article as long as the work
glucose at least once daily, many report taking no action when results are high or is properly cited, the use is educational and not
for prot, and the work is not altered.
S40 Glycemic Targets Diabetes Care Volume 39, Supplement 1, January 2016

low. In a yearlong study of insulin-nave suggested that SMBG reduced A1C by automatic low glucose suspend feature
patients with suboptimal initial glycemic 0.25% at 6 months (13), but the effect washas been approved by the FDA. The Auto-
control, a group trained in structured attenuated at 12 months (14). A key con- mation to Simulate Pancreatic Insulin Re-
SMBG (a paper tool was used at least sideration is that performing SMBG alone sponse (ASPIRE) trial of 247 patients
quarterly to collect and interpret 7-point does not lower blood glucose levels. To beshowed that sensor-augmented insulin
SMBG proles taken on 3 consecutive useful, the information must be integratedpump therapy with a low glucose sus-
days) reduced their A1C by 0.3 percent- into clinical and self-management plans. pend signicantly reduced nocturnal hy-
age points more than the control group poglycemia, without increasing A1C
(3). Patients should be taught how to use Continuous Glucose Monitoring levels for those over 16 years of age
SMBG data to adjust food intake, exer- Real-time CGM measures interstitial (23). These devices may offer the oppor-
cise, or pharmacological therapy to glucose (which correlates well with tunity to reduce severe hypoglycemia for
achieve specic goals. The ongoing need plasma glucose) and includes sophisti- those with a history of nocturnal hypo-
for and frequency of SMBG should be cated alarms for hypo- and hyperglycemic glycemia. Due to variable adherence, op-
reevaluated at each routine visit to avoid excursions, but the U.S. Food and Drug timal CGM use requires an assessment of
overuse (46). SMBG is especially impor- Administration (FDA) has not approved individual readiness for the technology
tant for insulin-treated patients to monitor these devices as a sole agent to monitor as well as initial and ongoing education
for and prevent asymptomatic hypoglyce- glucose. CGMs require calibration with and support (16,24). Additionally, providers
mia and hyperglycemia. SMBG, with the latter still required for need to provide robust diabetes education,
making acute treatment decisions. training, and support for optimal CGM
For Patients on Intensive Insulin Regimens
A 26-week randomized trial of 322 pa- implementation and ongoing use. As
Most patients on intensive insulin regimens
tients with type 1 diabetes showed that people with type 1 or type 2 diabetes
(multiple-dose insulin or insulin pump ther-
adults aged $25 years using intensive in- are living longer healthier lives, individu-
apy) should consider SMBG prior to meals sulin therapy and CGM experienced a 0.5% als who have been successfully using
and snacks, occasionally postprandially, at
reduction in A1C (from ;7.6% to 7.1% CGM should have continued access after
bedtime, prior to exercise, when they sus-
[;60 mmol/mol to 54 mmol/mol]), com- they turn 65 years of age.
pect low blood glucose, after treating low
pared with those using intensive insulin
blood glucose until they are normoglyce- therapy with SMBG (15). Sensor use in A1C TESTING
mic, and prior to critical tasks such as driv-
those aged ,25 years (children, teens, Recommendations
ing. For many patients, this will require
and adults) did not result in signicant c Perform the A1C test at least two
testing 610 (or more) times daily, al-
A1C lowering, and there was no signicant times a year in patients who are
though individual needs may vary. A data-
difference in hypoglycemia in any group. meeting treatment goals (and who
base study of almost 27,000 children and The greatest predictor of A1C lowering have stable glycemic control). E
adolescents with type 1 diabetes showed for all age-groups was frequency of sensor c Perform the A1C test quarterly in
that, after adjustment for multiple con-
use, which was highest in those aged $25 patients whose therapy has changed
founders, increased daily frequency of or who are not meeting glycemic
years and lower in younger age-groups.
SMBG was signicantly associated with A registry study of 17,317 participants goals. E
lower A1C (20.2% per additional test per conrmed that more frequent CGM use is c Point-of-care testing for A1C pro-
day) and with fewer acute complications. associated with lower A1C (16), whereas vides the opportunity for more
For Patients Using Basal Insulin or Oral another study showed that children with timely treatment changes. E
Agents .70% sensor use missed fewer school
The evidence is insufcient regarding days (17). Small randomized controlled A1C reects average glycemia over
when to prescribe SMBG and how often trials in adults and children with baseline several months and has strong predic-
testing is needed for patients who do A1C 7.07.5% (5358 mmol/mol) have tive value for diabetes complications
not use an intensive insulin regimen, conrmed favorable outcomes (A1C and (25,26). Thus, A1C testing should be
such as those with type 2 diabetes using hypoglycemia occurrence) in groups us- performed routinely in all patients with
oral agents or on basal insulin. For patients ing CGM, suggesting that CGM may pro- diabetesdat initial assessment and as
on basal insulin, lowering of A1C has been vide further benet for individuals with part of continuing care. Measurement
demonstrated for those who adjust their type 1 diabetes who already have tight approximately every 3 months deter-
dose to attain a fasting glucose within a control (18,19). mines whether patients glycemic targets
targeted range (7,8). A meta-analysis suggests that, com- have been reached and maintained. The
For individuals with type 2 diabetes on pared with SMBG, CGM is associated frequency of A1C testing should depend
less intensive insulin therapy, more fre- with short-term A1C lowering of ;0.26% on the clinical situation, the treatment
quent SMBG (e.g., fasting, before/after (20). The long-term effectiveness of CGM regimen, and the clinicians judgment. Pa-
meals) may be helpful, as increased fre- needs to be determined. This technology tients with type 2 diabetes with stable
quency has been shown to be inversely may be particularly useful in those with glycemia well within target may do well
correlated with glycemic control (9). hypoglycemia unawareness and/or fre- with testing only twice per year. Unstable or
Several randomized trials have called quent hypoglycemic episodes, although highly intensively managed patients (e.g.,
into question the clinical utility and cost- studies have not shown consistent re- pregnant women with type 1 diabetes)
effectiveness of routine SMBG in noninsulin- ductions in severe hypoglycemia (20 may require testing more frequently than
treated patients (1012). A meta-analysis 22). A CGM device equipped with an every 3 months (27).
care.diabetesjournals.org Glycemic Targets S41

Table 5.1Mean glucose levels for specied A1C levels (24,28)


A1C Mean plasma glucose* Mean fasting glucose Mean premeal glucose Mean postmeal glucose Mean bedtime glucose
% (mmol/mol) mg/dL mmol/L mg/dL mmol/L mg/dL mmol/L mg/dL mmol/L mg/dL mmol/L
6 (42) 126 7.0
,6.5 (48) 122 6.8 118 6.5 144 8.0 136 7.5
6.56.99 (4853) 142 7.9 139 7.7 164 9.1 153 8.5
7 (53) 154 8.6
.7.07.49 (5358) 152 8.4 152 8.4 176 9.8 177 9.8
7.57.99 (5864) 167 9.3 155 8.6 189 10.5 175 9.7
8 (64) 183 10.2
.8.08.5 (6469) 178 9.9 179 9.9 206 11.4 222 12.3
9 (75) 212 11.8
10 (86) 240 13.4
11 (97) 269 14.9
12 (108) 298 16.5
A calculator for converting A1C results into eAG, in either mg/dL or mmol/L, is available at http://professional.diabetes.org/eAG.
*These estimates are based on ADAG data of ;2,700 glucose measurements over 3 months per A1C measurement in 507 adults with type 1, type 2,
and no diabetes. The correlation between A1C and average glucose was 0.92 (28).

A1C Limitations type 2, and no diabetes (28), and an em- A1C GOALS
The A1C test is subject to certain limita- pirical study of the average blood glucose For glycemic goals in children, please refer
tions. Conditions that affect red blood levels at premeal, postmeal, and bedtime
to Section 11 Children and Adolescents.
cell turnover (hemolysis, blood loss) associated with specied A1C levels using For glycemic goals in pregnant women,
and hemoglobin variants must be consid- data from the ADAG trial (24). The Amer-
please refer to Section 12 Management
ered, particularly when the A1C result does ican Diabetes Association (ADA) and the
of Diabetes in Pregnancy.
not correlate with the patients blood glu- American Association for Clinical Chemis-
cose levels. For patients in whom A1C/ try have determined that the correlation Recommendations
estimated average glucose (eAG) and (r 5 0.92) in the ADAG trial is strong c A reasonable A1C goal for many
measured blood glucose appear discrep- enough to justify reporting both the A1C nonpregnant adults is ,7% (53
ant, clinicians should consider the possi- result and the eAG result when a clinician mmol/mol). A
bilities of hemoglobinopathy or altered orders the A1C test. Clinicians should c Providers might reasonably sug-
red blood cell turnover and the options note that the mean plasma glucose num- gest more stringent A1C goals
of more frequent and/or different timing bers in the table are based on ;2,800 (such as ,6.5% [48 mmol/mol])
of SMBG or CGM use. Other measures of readings per A1C in the ADAG trial. for selected individual patients if
chronic glycemia such as fructosamine are this can be achieved without signif-
A1C Differences in Ethnic Populations and
available, but their linkage to average glu- icant hypoglycemia or other adverse
Children
cose and their prognostic signicance are effects of treatment. Appropriate
In the ADAG study, there were no signif-
not as clear as for A1C (see Section 2 Clas- patients might include those with
icant differences among racial and ethnic
sication and Diagnosis of Diabetes). short duration of diabetes, type 2
groups in the regression lines between
A1C does not provide a measure of gly- diabetes treated with lifestyle or
A1C and mean glucose, although there
cemic variability or hypoglycemia. For metformin only, long life expec-
was a trend toward a difference between
patients prone to glycemic variability, es- tancy, or no signicant cardiovascu-
the African/African American and non-
pecially patients with type 1 diabetes or
Hispanic white cohorts. A small study lar disease. C
type 2 diabetes with severe insulin de- c Less stringent A1C goals (such as
comparing A1C to CGM data in children
ciency, glycemic control is best evaluated ,8% [64 mmol/mol]) may be ap-
with type 1 diabetes found a highly sta-
by the combination of results from SMBG propriate for patients with a his-
tistically signicant correlation between
and A1C. A1C may also conrm the accu- tory of severe hypoglycemia,
A1C and mean blood glucose, although
racy of the patients meter (or the patients limited life expectancy, advanced
the correlation (r 5 0.7) was signifi- microvascular or macrovascular
reported SMBG results) and the adequacy
cantly lower than in the ADAG trial (29).
of the SMBG testing schedule. complications, extensive comor-
Whether there are signicant differences bid conditions, or long-standing
A1C and Mean Glucose in how A1C relates to average glucose in
diabetes in whom the general
Table 5.1 shows the correlation between children or in different ethnicities is an
goal is difcult to attain despite
A1C levels and mean glucose levels based area for further study (30,31). For the
diabetes self-management educa-
on two studies: the international A1C- time being, the question has not led to
tion, appropriate glucose monitor-
Derived Average Glucose (ADAG) trial, different recommendations about testing
ing, and effective doses of multiple
which based the correlation with A1C on A1C or to different interpretations of the
glucose-lowering agents including
frequent SMBG and CGM in 507 adults clinical meaning of given levels of A1C in
insulin. B
(83% non-Hispanic whites) with type 1, those populations.
S42 Glycemic Targets Diabetes Care Volume 39, Supplement 1, January 2016

A1C and Microvascular Complications poor control to fair/good control. These events (combined fatal or nonfatal MI
Type 1 Diabetes analyses also suggest that further lower- and sudden death) in the intensive glyce-
Hyperglycemia denes diabetes, and ing of A1C from 7% to 6% [53 mmol/mol mic control arm that did not reach statis-
glycemic control is fundamental to dia- to 42 mmol/mol] is associated with fur- tical signicance (P 5 0.052), and there
betes management. The Diabetes Con- ther reduction in the risk of microvascular was no suggestion of benet on other
trol and Complications Trial (DCCT) (1), a complications, although the absolute risk CVD outcomes (e.g., stroke). However, af-
prospective randomized controlled trial reductions become much smaller. Given ter 10 years of follow-up, those originally
of intensive versus standard glycemic the substantially increased risk of hypo- randomly assigned to intensive glycemic
control in patients with relatively recently glycemia in type 1 diabetes trials and control had signicant long-term reduc-
diagnosed type 1 diabetes, showed den- with polypharmacy in type 2 diabetes, tions in MI (15% with sulfonylurea or in-
itively that improved glycemic control is the risks of lower glycemic targets outweigh sulin as initial pharmacotherapy, 33%
associated with signicantly decreased the potential benets on microvascular with metformin as initial pharmacother-
rates of microvascular (retinopathy [32] complications. apy) and in all-cause mortality (13% and
and diabetic kidney disease) and neuro- The concerning mortality ndings in 27%, respectively) (37).
pathic complications. Follow-up of the the ACCORD trial (42), discussed below, The ACCORD, ADVANCE, and VADT
DCCT cohorts in the Epidemiology of and the relatively intense efforts required suggested no signicant reduction in
Diabetes Interventions and Complications to achieve near-euglycemia should also CVD outcomes with intensive glycemic
(EDIC) study (33) demonstrated persis- be considered when setting glycemic tar- control in participants followed for
tence of these microvascular benets in gets. However, on the basis of physician 3.525.6 years who had more advanced
previously intensively treated subjects, judgment and patient preferences, select type 2 diabetes than UKPDS partici-
even though their glycemic control ap- patients, especially those with little co- pants. All three trials were conducted
proximated that of previous standard morbidity and long life expectancy, may in participants with more long-standing
arm subjects during follow-up. benet from adopting more intensive gly- diabetes (mean duration 811 years)
Type 2 Diabetes cemic targets (e.g., A1C target ,6.5% and either known CVD or multiple car-
[48 mmol/mol]) as long as signicant hy- diovascular risk factors. The target
The Kumamoto Study (34) and UK Pro-
poglycemia does not become a barrier. A1C among intensive control subjects
spective Diabetes Study (UKPDS) (35,36)
was ,6% (42 mmol/mol) in ACCORD,
conrmed that intensive glycemic control A1C and Cardiovascular Disease ,6.5% (48 mmol/mol) in ADVANCE,
was associated with signicantly de- Outcomes and a 1.5% reduction in A1C compared
creased rates of microvascular and neu- Cardiovascular Disease and Type 1 with control subjects in VADT, with
ropathic complications in patients with Diabetes achieved A1C of 6.4% versus 7.5%
type 2 diabetes. Long-term follow-up of Cardiovascular disease (CVD) is a more (46 mmol/mol vs. 58 mmol/mol) in
the UKPDS cohorts showed enduring ef- common cause of death than microvas- ACCORD, 6.5% versus 7.3% (48 mmol/mol
fects of early glycemic control on most cular complications in populations with vs. 56 mmol/mol) in ADVANCE, and
microvascular complications (37). diabetes. There is evidence for a cardio- 6.9% versus 8.4% (52 mmol/mol vs. 68
Therefore, achieving glycemic control vascular benet of intensive glycemic mmol/mol) in VADT. Details of these
of A1C targets of ,7% (53 mmol/mol) control after long-term follow-up of studies are reviewed extensively in the
has been shown to reduce microvascular study cohorts treated early in the course ADA position statement Intensive Glyce-
complications of diabetes and, in patients of type 1 and type 2 diabetes. In the mic Control and the Prevention of Cardio-
with type 1 diabetes, mortality. If imple- DCCT, there was a trend toward lower vascular Events: Implications of the
mented soon after the diagnosis of diabetes, risk of CVD events with intensive control. In ACCORD, ADVANCE, and VA Diabetes
this target is associated with long-term the 9-year post-DCCT follow-up of the EDIC Trials: A Position Statement of the Amer-
reduction in macrovascular disease. cohort, participants previously randomly ican Diabetes Association and a Scientic
ACCORD, ADVANCE, and VADT assigned to the intensive arm had a signif- Statement of the American College of
Three landmark trials (Action to Control icant 57% reduction in the risk of nonfatal Cardiology Foundation and the American
myocardial infarction (MI), stroke, or CVD
Cardiovascular Risk in Diabetes [ACCORD], Heart Association (46).
Action in Diabetes and Vascular Disease: death compared with those previously in The glycemic control comparison in
Preterax and Diamicron MR Controlled the standard arm (43). The benet of in- ACCORD was halted early due to an in-
Evaluation [ADVANCE], and Veterans Af- tensive glycemic control in this cohort with creased mortality rate in the intensive
fairs Diabetes Trial [VADT]) showed that type 1 diabetes has been shown to persist compared with the standard arm
lower A1C levels were associated with for several decades (44) and to be associ- (1.41% vs. 1.14% per year; hazard ratio
reduced onset or progression of micro- ated with a modest reduction in all-cause
1.22 [95% CI 1.011.46]), with a similar
vascular complications (3840). mortality (45). increase in cardiovascular deaths. Anal-
Epidemiological analyses of the DCCT Cardiovascular Disease and Type 2 ysis of the ACCORD data did not identify a
(1) and UKPDS (41) demonstrate a cur- Diabetes clear explanation for the excess mortality
vilinear relationship between A1C and In type 2 diabetes, there is evidence that in the intensive arm (42).
microvascular complications. Such analyses more intensive treatment of glycemia in Longer-term follow-up has shown no
suggest that, on a population level, the newly diagnosed patients may reduce evidence of cardiovascular benet or
greatest number of complications will be long-term CVD rates. During the UKPDS harm in the ADVANCE trial (47), which is
averted by taking patients from very trial, there was a 16% reduction in CVD perhaps not unexpected given the narrow
care.diabetesjournals.org Glycemic Targets S43

separation in A1C between groups. The Table 5.2Summary of glycemic recommendations for nonpregnant adults with
end-stage renal disease rate was lower diabetes
in the intensive group over follow-up. A1C ,7.0% (53 mmol/mol)*
However, 10-year follow-up of the VADT Preprandial capillary plasma glucose 80130 mg/dL* (4.47.2 mmol/L)
cohort (48) showed a reduction in the risk
Peak postprandial capillary plasma glucose ,180 mg/dL* (10.0 mmol/L)
of cardiovascular events (52.7 [control
group] vs. 44.1 [intervention group] *More or less stringent glycemic goals may be appropriate for individual patients. Goals should
be individualized based on duration of diabetes, age/life expectancy, comorbid conditions,
events per 1,000 person-years) with no known CVD or advanced microvascular complications, hypoglycemia unawareness, and
benet in cardiovascular or overall mor- individual patient considerations.
tality. Heterogeneity of mortality effects Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial
across studies was noted, which may re- glucose goals. Postprandial glucose measurements should be made 12 h after the beginning of
the meal, generally peak levels in patients with diabetes.
ect differences in glycemic targets, ther-
apeutic approaches, and population
characteristics (49). of ,7% (53 mmol/mol). The issue of pre- and landmark glycemic control trials
Mortality ndings in ACCORD (42) and prandial versus postprandial SMBG targets such as the DCCT and UKPDS relied
subgroup analyses of VADT (50) suggest is complex (54). Elevated postchallenge (2-h overwhelmingly on preprandial SMBG.
that the potential risks of intensive glyce- oral glucose tolerance test) glucose values Additionally, a randomized controlled
mic control may outweigh its benets in have been associated with increased cardio- trial in patients with known CVD found
higher-risk patients. In all three trials, se- vascular risk independent of fasting plasma no CVD benet of insulin regimens tar-
vere hypoglycemia was signicantly more glucose in some epidemiological studies. In geting postprandial glucose compared
likely in participants who were randomly subjects with diabetes, surrogate measures with those targeting preprandial glucose
assigned to the intensive glycemic control of vascular pathology, such as endothelial (55). Therefore, it is reasonable for post-
arm. Those patients with long duration of dysfunction, are negatively affected by prandial testing to be recommended for
diabetes, a known history of severe hypo- postprandial hyperglycemia. It is clear that individuals who have premeal glucose val-
glycemia, advanced atherosclerosis, or postprandial hyperglycemia, like prepran- ues within target but have A1C values
advanced age/frailty may benet from dial hyperglycemia, contributes to elevated above target. Taking postprandial plasma
less aggressive targets (51,52). A1C levels, with its relative contribution be- glucose measurements 12 h after the
Providers should be vigilant in pre- ing greater at A1C levels that are closer to start of a meal and using treatments aimed
venting severe hypoglycemia in patients 7% (53 mmol/mol). However, outcome at reducing postprandial plasma glucose
with advanced disease and should not studies have clearly shown A1C to be values to ,180 mg/dL (10.0 mmol/L)
aggressively attempt to achieve near- the primary predictor of complications, may help to lower A1C.
normal A1C levels in patients in whom
such targets cannot be safely and rea-
sonably achieved. Severe or frequent
hypoglycemia is an absolute indication
for the modication of treatment regi-
mens, including setting higher glycemic
goals. Many factors, including patient
preferences, should be taken into ac-
count when developing a patients indi-
vidualized goals (Table 5.2).

A1C and Glycemic Targets


Numerous aspects must be considered
when setting glycemic targets. The ADA
proposes optimal targets, but each target
must be individualized to the needs of
each patient and his or her disease factors.
When possible, such decisions should
be made with the patient, reecting his
or her preferences, needs, and values.
Figure 5.1 is not designed to be applied
rigidly but to be used as a broad con-
struct to guide clinical decision making
(53), both in type 1 and type 2 diabetes.
Recommended glycemic targets for
many nonpregnant adults are shown in
Table 5.2. The recommendations in- Figure 5.1Depicted are patient and disease factors used to determine optimal A1C targets.
clude blood glucose levels that appear Characteristics and predicaments toward the left justify more stringent efforts to lower A1C; those
to correlate with achievement of an A1C toward the right suggest less stringent efforts. Adapted with permission from Inzucchi et al. (53).
S44 Glycemic Targets Diabetes Care Volume 39, Supplement 1, January 2016

An analysis of data from 470 partici- (e.g., bedtime snack to prevent overnight
pants of the ADAG study (237 with c Ongoing assessment of cognitive
hypoglycemia), exercise management,
type 1 diabetes and 147 with type 2 dia- function is suggested with in-
betes) found that actual average glucose medication adjustment, glucose monitor-
creased vigilance for hypoglyce-
levels associated with conventional A1C ing, and routine clinical surveillance may
targets were higher than older DCCT and mia by the clinician, patient, and
improve patient outcomes (61). Docu-
caregivers if low cognition or de-
mented symptomatic hypoglycemia and
ADA targets (Table 5.1) (24,28). These nd- clining cognition is found. B asymptomatic hypoglycemia are dened
ings support that premeal glucose targets Hypoglycemia is the major limiting fac- as occurring at a plasma glucose concen-
may be relaxed without undermining over- tration of #70 mg/dL (3.9 mmol/L) (61).
tor in the glycemic management of type
all glycemic control as measured by A1C. This level remains a general threshold for
1 and insulin-treated type 2 diabetes.
These data have prompted a revision in dening hypoglycemia.
Mild hypoglycemia may be inconve-
the ADA-recommended premeal target In 2014, the ADA changed its glycemic
nient or frightening to patients with
to 80130 mg/dL (4.47.2 mmol/L). target to 80130 mg/dL (4.47.2 mmol/L).
diabetes. Severe hypoglycemia is dened
as hypoglycemia requiring assistance This change reects the results of the
HYPOGLYCEMIA ADAG study, which demonstrated that
from another person. It is characterized
Recommendations
higher glycemic targets corresponded to
by cognitive impairment that may be rec-
A1C goals (24). An additional goal of rais-
c Individuals at risk for hypogly- ognized or unrecognized and can prog-
cemia should be asked about ing the lower range of the glycemic tar-
ress to loss of consciousness, seizure,
symptomatic and asymptomatic coma, or death, and it is reversed by ad- get was to limit overtreatment and
hypoglycemia at each encoun- provide a safety margin in patients ti-
ministration of rapid-acting glucose. Se-
trating glucose-lowering drugs such as
ter. C vere hypoglycemia can cause acute insulin to glycemic targets.
c Glucose (1520 g) is the preferred harm to the person with diabetes or
treatment for the conscious in- others, especially if it causes falls, motor Hypoglycemia Treatment
dividual with hypoglycemia, al- vehicle accidents, or other injury. A large Hypoglycemia treatment requires in-
though any form of carbohydrate cohort study suggested that among older gestion of glucose- or carbohydrate-
that contains glucose may be adults with type 2 diabetes, a history of containing foods. The acute glycemic
used. Fifteen minutes after treat- severe hypoglycemia was associated with response correlates better with the glu-
ment, if SMBG shows continued greater risk of dementia (56). Conversely, cose content of food than with the car-
hypoglycemia, the treatment in a substudy of the ACCORD trial, cogni- bohydrate content of food. Pure glucose
should be repeated. Once SMBG tive impairment at baseline or decline in is the preferred treatment, but any form
returns to normal, the individual cognitive function during the trial was sig- of carbohydrate that contains glucose
should consume a meal or snack will raise blood glucose. Added fat may
nicantly associated with subsequent ep-
to prevent recurrence of hypogly- retard and then prolong the acute gly-
isodes of severe hypoglycemia (57).
cemia. E cemic response. Ongoing insulin activity
Evidence from DCCT/EDIC, which in-
c Glucagon should be prescribed for volved younger adults and adolescents or insulin secretagogues may lead to re-
all individuals at increased risk of current hypoglycemia unless further
with type 1 diabetes, found no associa-
severe hypoglycemia, dened as food is ingested after recovery.
tion between frequency of severe hypo-
hypoglycemia requiring assis- Glucagon
glycemia and cognitive decline (58), as
tance, and caregivers, school per- Those in close contact with, or having
discussed in Section 11 Children and
sonnel, or family members of these custodial care of, people with hypoglyce-
Adolescents.
individuals should be instructed in mia-prone diabetes (family members,
Severe hypoglycemia was associated
its administration. Glucagon admin- roommates, school personnel, child care
with mortality in participants in both the
istration is not limited to health providers, correctional institution staff, or
standard and the intensive glycemia
care professionals. E arms of the ACCORD trial, but the relation- coworkers) should be instructed on the use
c Hypoglycemia unawareness or ships between hypoglycemia, achieved of glucagon kits. An individual does not
one or more episodes of severe need to be a health care professional to
A1C, and treatment intensity were not
hypoglycemia should trigger re- safely administer glucagon. Care should
straightforward. An association of severe
evaluation of the treatment regi- be taken to ensure that glucagon kits are
hypoglycemia with mortality was also
men. E
found in the ADVANCE trial (59). An asso- not expired.
c Insulin-treated patients with hy-
ciation between self-reported severe hy- Hypoglycemia Prevention
poglycemia unawareness or an ep-
poglycemia and 5-year mortality has also Hypoglycemia prevention is a critical
isode of severe hypoglycemia
been reported in clinical practice (60). component of diabetes management.
should be advised to raise their
Young children with type 1 diabetes SMBG and, for some patients, CGM are
glycemic targets to strictly avoid
and the elderly are noted as particularly essential tools to assess therapy and de-
further hypoglycemia for at least
vulnerable to severe hypoglycemia be- tect incipient hypoglycemia. Patients
several weeks in order to partially
cause of their reduced ability to recognize should understand situations that in-
reverse hypoglycemia unaware-
hypoglycemic symptoms and effectively crease their risk of hypoglycemia, such
ness and reduce risk of future ep-
communicate their needs. Individualized as fasting for tests or procedures, during
isodes. A
patient education, dietary intervention or after intense exercise, and during
care.diabetesjournals.org Glycemic Targets S45

sleep. Hypoglycemia may increase the hyperglycemic nonketotic hyperosmo- HbA1c by 0.25%. Ann Intern Med 2012;156:JC6
risk of harm to self or others, such as lar state, please refer to the ADA con- JC12
14. Malanda UL, Welschen LM, Riphagen II,
with driving. Teaching people with diabetes sensus report Hyperglycemic Crises in Dekker JM, Nijpels G, Bot SD. Self-monitoring
to balance insulin use and carbohydrate in- Adult Patients With Diabetes (63). of blood glucose in patients with type 2 diabetes
take and exercise are necessary, but these mellitus who are not using insulin. Cochrane
strategies are not always sufcient for Database Syst Rev 2012;1:CD005060
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tional treatment and risk of complications in Diabetes Care 2009;32:187192 severe hypoglycemia. Diabetes Care 2012;35:
patients with type 2 diabetes (UKPDS 33). Lan- 47. Zoungas S, Chalmers J, Neal B, et al.; 18971901
cet 1998;352:837853 ADVANCE-ON Collaborative Group. Follow-up of 61. Seaquist ER, Anderson J, Childs B, et al. Hy-
37. Holman RR, Paul SK, Bethel MA, Matthews blood-pressure lowering and glucose control in poglycemia and diabetes: a report of a work-
DR, Neil HAW. 10-year follow-up of intensive type 2 diabetes. N Engl J Med 2014;371:1392 1406 group of the American Diabetes Association
glucose control in type 2 diabetes. N Engl 48. Hayward RA, Reaven PD, Wiitala WL, et al.; and the Endocrine Society. Diabetes Care
J Med 2008;359:15771589 VADT Investigators. Follow-up of glycemic con- 2013;36:13841395
38. Duckworth W, Abraira C, Moritz T, et al.; trol and cardiovascular outcomes in type 2 62. Cryer PE. Diverse causes of hypoglycemia-
VADT Investigators. Glucose control and vascu- diabetes. N Engl J Med 2015;372:21972206 associated autonomic failure in diabetes. N Engl
lar complications in veterans with type 2 diabetes. 49. Turnbull FM, Abraira C, Anderson RJ, et al. J Med 2004;350:22722279
N Engl J Med 2009;360:129 139 Intensive glucose control and macrovascular 63. Kitabchi AE, Umpierrez GE, Miles JM, Fisher
39. Patel A, MacMahon S, Chalmers J, et al.; outcomes in type 2 diabetes. Diabetologia JN. Hyperglycemic crises in adult patients with
ADVANCE Collaborative Group. Intensive blood 2009;52:22882298 diabetes. Diabetes Care 2009;32:13351343
Diabetes Care Volume 39, Supplement 1, January 2016 S47

6. Obesity Management for the


American Diabetes Association

Treatment of Type 2 Diabetes


Diabetes Care 2016;39(Suppl. 1):S47S51 | DOI: 10.2337/dc16-S009

There is strong and consistent evidence that obesity management can delay pro-
gression from prediabetes to type 2 diabetes (1,2) and may be benecial in the
treatment of type 2 diabetes. In overweight and obese patients with type 2 diabetes,
modest and sustained weight loss has been shown to improve glycemic control and
to reduce the need for glucose-lowering medications (35). Small studies have dem-

6. OBESITY MANAGEMENT IN TYPE 2 DIABETES


onstrated that in obese patients with type 2 diabetes 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 pharmacological
therapy or ongoing procedures (6,7). Weight lossinduced improvements in glycemia
are most likely to occur early in the natural history of type 2 diabetes when obesity-
associated insulin resistance has caused reversible b-cell dysfunction but insulin
secretory capacity remains relatively preserved (5,8). Although the Action for Health
in Diabetes (Look AHEAD) trial did not show that an intensive lifestyle intervention
reduced cardiovascular events in overweight or obese adults with type 2 diabetes (9),
it did show the feasibility of achieving and maintaining long-term weight loss in
patients with type 2 diabetes.

LOOK AHEAD
In the Look AHEAD intensive lifestyle intervention group, mean weight loss was 4.7%
(SE 0.2) at 8 years (10). Approximately 50% of intensive lifestyle intervention par-
ticipants lost $5% and 27% lost $10% of their initial body weight at 8 years (10).
Participants randomly assigned to the intensive lifestyle group achieved equivalent
risk factor control but required fewer glucose-, blood pressure, and lipid-lowering
medications than those randomly assigned to standard care. Secondary analyses of
the Look AHEAD trial and other large cardiovascular outcome studies document
other benets of weight loss in patients with type 2 diabetes, including improve-
ments in mobility, physical and sexual functioning, and health-related quality of life
(11). The goal of this section is to provide evidence-based recommendations for
dietary, pharmacological, and surgical interventions for obesity management as
treatments for hyperglycemia in type 2 diabetes.

ASSESSMENT
Recommendation
c At each patient encounter, BMI should be calculated and documented in the
medical record. B

At each routine patient encounter, BMI should be calculated from the height and
weight. BMI should be classied to determine the presence of overweight or obesity,
discussed with the patient, and documented in the patient record (Table 6.1). In Asian
Americans, the BMI cutoff points to dene overweight and obesity are lower: normal
(,23 kg/m ), overweight (23.027.4 kg/m ), obese (27.537.4 kg/m ), and extremely
2 2 2 Suggested citation: American Diabetes Associa-
obese ($37.5 kg/m ) (12). Providers should advise overweight and obese patients that
2 tion. Obesity management for the treatment of
higher BMIs increase the risk of cardiovascular disease and all-cause mortality. Providers type 2 diabetes. Sec. 6. In Standards of Medical
should assess each patients readiness to achieve weight loss and jointly determine Care in Diabetesd2016. Diabetes Care 2016;
weight loss goals and intervention strategies. Strategies include diet, physical activity, 39(Suppl. 1):S47S51
behavioral therapy, pharmacological therapy, and bariatric surgery (Table 6.1). The latter 2016 by the American Diabetes Association.
two strategies may be prescribed for carefully selected patients as adjuncts to diet, Readers may use this article as long as the work
physical activity, and behavioral therapy. is properly cited, the use is educational and not
for prot, and the work is not altered.
S48 Obesity Management for the Treatment of Type 2 Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

DIET, PHYSICAL ACTIVITY, AND control, and/or other obesity-related consumption of a reduced calorie diet,
BEHAVIORAL THERAPY medical conditions, lifestyle changes and participation in high levels of phys-
Recommendations
that result in modest and sustained ical activity (200300 min/week). Some
weight loss produce clinically meaning- commercial and proprietary weight loss
c Diet, physical activity, and behavioral
ful reductions in blood glucose, A1C, and programs have shown promising weight
therapy designed to achieve 5%
triglycerides (35). Greater weight loss loss results (18).
weight loss should be prescribed
produces even greater benets, including When provided by trained practi-
for overweight and obese patients
reductions in blood pressure, improve- tioners in medical care settings with
with type 2 diabetes ready to
ments in LDL and HDL cholesterol, and close medical monitoring, short-term
achieve weight loss. A reductions in the need for medications (3-month) high-intensity lifestyle inter-
c Such interventions should be high in-
to control blood glucose, blood pressure, ventions that use very low-calorie diets
tensity ($16 sessions in 6 months) and lipids (9,10). (dened as #800 kcal/day) and total
and focus on diet, physical activity,
meal replacements may achieve greater
and behavioral strategies to achieve
short-term weight loss (1015%) than
a 500750 kcal/day energy decit. A Lifestyle Interventions intensive behavioral lifestyle interven-
c Diets that provide the same caloric Weight loss can be attained with life-
tions that typically achieve 5% weight
restriction but differ in protein, style programs that achieve a 500750 loss. Weight regain following the cessation
carbohydrate, and fat content are kcal/day energy decit or provide ap- of high-intensity lifestyle interventions is
equally effective in achieving proximately 1,2001,500 kcal/day for greater than following intensive behavioral
weight loss. A women and 1,5001,800 kcal/day for lifestyle interventions unless a long-term
c For patients who achieve short- men, adjusted for the individuals base- comprehensive weight loss maintenance
term weight loss goals, long-term line body weight. Although benets may program is provided (19,20).
($1-year) comprehensive weight be seen with as little as 5% weight loss,
maintenance programs should be sustained weight loss of $7% is optimal. PHARMACOTHERAPY
prescribed. Such programs should These diets may differ in the types of
Recommendations
provide at least monthly contact foods they restrict (such as high-fat or
high-carbohydrate foods) but are effec- c When choosing glucose-lowering
and encourage ongoing monitoring
medications for overweight or
of body weight (weekly or more fre- tive if they create the necessary energy
obese patients with type 2 diabetes,
quently), continued consumption decit (1316). The diet choice should
of a reduced calorie diet, and par-
consider their effect on weight. E
be based on the patients health status
and preferences. c Whenever possible, minimize the
ticipation in high levels of physical
medications for comorbid condi-
activity (200300 min/week). A Intensive behavioral lifestyle inter-
tions that are associated with weight
c To achieve weight loss of .5%, ventions should include $16 sessions
gain. E
short-term (3-month) high-intensity in 6 months and focus on diet, physical
c Weight loss medications may be
lifestyle interventions that use activity, and behavioral strategies to
effective as adjuncts to diet, physical
very low-calorie diets ( #800 achieve an ;500750 kcal/day energy
activity, and behavioral counseling
kcal/day) and total meal replace- decit. Interventions should be pro-
for selected patients with type 2 di-
ments may be prescribed for vided by trained interventionists in ei-
carefully selected patients by ther individual or group sessions (17). abetes and BMI $27 kg/m . Potential
2

trained practitioners in medical Overweight and obese patients with benets must be weighed against the
care settings with close medical type 2 diabetes who have lost weight potential risks of the medications. A
monitoring. To maintain weight during the 6-month intensive behavioral c If a patients response to weight loss
loss, such programs must incorpo- lifestyle intervention should be enrolled medications is ,5% after 3 months
or if there are any safety or tolerabil-
rate long-term comprehensive in long-term ($1-year) comprehensive
ity issues at any time, the medication
weight maintenance counseling. B weight loss maintenance programs
should be discontinued and alterna-
that provide at least monthly contact
tive medications or treatment ap-
Among overweight or obese patients with a trained interventionist and focus
with type 2 diabetes and inadequate on ongoing monitoring of body weight proaches should be considered. A
glycemic, blood pressure and lipid (weekly or more frequently), continued
When considering pharmacological treat-
ments for overweight or obese patients
with type 2 diabetes, providers should
Table 6.1Treatment for overweight and obesity in type 2 diabetes rst consider their choice of glucose-
BMI category (kg/m )
lowering medications. Whenever possi-
2

Treatment 23.0* or 25.026.9 27.029.9 30.034.9 35.039.9 $40 ble, medications should be chosen to
Diet, physical activity, and
promote weight loss or to be weight neu-
behavioral therapy
tral. Agents associated with weight loss
Pharmacotherapy
Bariatric surgery
include metformin, a-glucosidase inhibi-
tors, glucagon-like peptide 1 agonists,
Treatment may be indicated for selected motivated patients. amylin mimetics, and sodiumglucose
*Cutoff points for Asian American individuals.
cotransporter 2 inhibitors. Dipeptidyl
care.diabetesjournals.org Obesity Management for the Treatment of Type 2 Diabetes S49

peptidase 4 inhibitors appear to be In general, pharmacological treatment education, lifestyle counseling, and
weight neutral. Unlike these agents, insu- of obesity has been limited by low adher- encouragement to participate in Weight
lin secretagogues, thiazolidinediones, and ence, modest efcacy, adverse effects, Watchers) in achieving a target A1C #6%
insulin have often been associated with and weight regain after medication cessa- (42 mmol/mol) at 3 years among obese
weight gain (see Section 7 Approaches tion (21). patients with uncontrolled type 2 diabe-
to Glycemic Treatment). tes (mean A1C 9.3% [78 mmol/mol]). This
BARIATRIC SURGERY A1C target was achieved by 38% (P ,
Concomitant Medications
Recommendations 0.001) in the gastric bypass group, 24%
Providers should carefully review the
c Bariatric surgery may be considered (P 5 0.01) in the sleeve gastrectomy
patients concomitant medications group, and 5% in the group that received
and, whenever possible, minimize or for adults with BMI .35 kg/m and2

type 2 diabetes, especially if diabe- only medical therapy (26). Diabetes re-
provide alternatives for medications mission rates tend to be higher with pro-
that promote weight gain. The latter in- tes or associated comorbidities are
difcult to control with lifestyle and cedures that bypass portions of the small
clude atypical antipsychotics (clozapine,
intestine and lower with procedures that
olanzapine, risperidone, etc.) and an- pharmacological therapy. B
c Patients with type 2 diabetes who only restrict the stomach.
tidepressants (tricyclic antidepressants, Younger age, shorter duration of
have undergone bariatric surgery
selective serotonin reuptake inhibitors, type 2 diabetes, lower A1C, higher
need lifelong lifestyle support
and monoamine oxidase inhibitors), serum insulin levels, and nonuse of
glucocorticoids, oral contraceptives and annual medical monitoring,
at a minimum. B insulin have all been associated with
that contain progestins, anticonvulsants
higher remission rates after bariatric
including gabapentin, and a number of c Although small trials have shown a
surgery (27).
antihistamines and anticholinergics. glycemic benet of bariatric sur-
gery in patients with type 2 dia- Although bariatric surgery has been

betes and BMI 3035 kg/m , shown to improve the metabolic proles
Approved Medications 2

The U.S. Food and Drug Administration of morbidly obese patients with type 1
there is currently insufcient evi-
dence to generally recommend diabetes, the role of bariatric surgery in
(FDA) has approved ve weight loss
medications (or combination medica- surgery in patients with BMI such patients will require larger and
longer studies (28).
tions) for long-term use by patients #35 kg/m . E
2

with BMI $27 kg/m with one or more


2

obesity-associated comorbid conditions Bariatric and metabolic surgeries, either Disadvantages


gastric banding or procedures that involve Bariatric surgery is costly and has asso-
and by patients with BMI $30 kg/m 2

resecting, bypassing, or transposing sec- ciated risks. Morbidity and mortality


who are motivated to lose weight (21
tions of the stomach and small intestine, rates directly related to the surgery
23). Medications approved for long-term
weight loss and weight loss mainte- can be effective weight loss treatments have decreased considerably in recent
nance and their advantages and disad- for severe obesity when performed as years, with 30-day mortality rates
part of a comprehensive weight manage- now 0.2% for laparoscopic procedures,
vantages are summarized in Table 6.2.
The rationale for weight loss medica- ment program with lifelong lifestyle sup- similar to those for laparoscopic cholecys-
tions is to help patients to more consis- port and medical monitoring. In one tectomy, and 2.1% for open procedures
tently adhere to low-calorie diets and to meta-analysis, gastric banding resulted (29,30). Outcomes vary depending on
reinforce lifestyle changes including phys- in less weight loss than sleeve gastrec- the procedure and the experience of
ical activity. Providers should be knowl- tomy and Roux-en-Y gastric bypass the surgeon and center. Longer-term
edgeable about the product label and (1-year excess weight loss ;33% vs. concerns include dumping syndrome
(nausea, colic, diarrhea), vitamin and
should balance the potential benets of ;70%) (24). National guidelines sup-
successful weight loss against the poten- port consideration of bariatric surgery mineral deciencies, osteoporosis, and,
tial risks of the medication for each pa- for people with type 2 diabetes with rarely, severe hypoglycemia from insulin
tient. All medications are FDA pregnancy BMI .35 kg/m . 2 hypersecretion. More recent studies also
category X. These medications are con- suggest that patients who undergo bari-
traindicated in women who are or may Advantages atric surgery may be at increased risk for
become pregnant. Women in their repro- Treatment with bariatric surgery has substance use, including drug and alcohol
ductive years must be cautioned to use a been shown to achieve near or complete use and cigarette smoking (31). Cohort
reliable method of contraception. normalization of glycemia 2 years follow- studies attempting to match surgical
ing surgery in 72% of patients (compared and nonsurgical subjects suggest that
Assessing Efcacy and Safety with 16% in a matched control group the procedure may reduce longer-term
Efcacy and safety should be assessed at treated with lifestyle and pharmacologi- mortality (25).
least monthly for the rst 3 months of treat- cal interventions) (25). A study evaluated In contrast, a propensity score
ment. If a patients response is deemed in- the effectiveness of surgical intervention adjusted analysis of older, severely obese
sufcient (weight loss ,5%) or if there are (Roux-en-Y gastric bypass or sleeve gas- patients in Veterans Affairs Medical Cen-
any safety or tolerability issues at any time, trectomy) and medical therapy compared ters found that bariatric surgery was not
the medication should be discontinued and with medical therapy alone (quarterly associated with decreased mortality com-
alternative medications or treatment ap- visits, pharmacological therapy, self- pared with usual care (mean follow-up
proaches should be considered. monitoring of blood glucose, diabetes 6.7 years) (32). Retrospective analyses
S50

Tabl e 6.2 Medic ations ap prov ed by the FDA for the long -term treatme nt of obe sity
1-Year wei gh t cha nge sta tus2 5
Gene ric drug nam e, % Patient s with $ 5% 12
Adver se effect s2,6
(propr ieta ry name [s ]) and Avera ge wholes ale Avera ge wei ght loss loss of basel ine
dos age str eng th and form Adult dos ing freque ncy price (pe r month)1 relati ve to placeb o weight Common7 Ser ious7
Lipase inh ibitor
Orlistat (Alli) 60 mg ca ps or 60 mg or 120 mg t.i.d . $4182 (60 mg) 2.5 kg (60 mg) 35 73% Abdomina l pain/d iscom fort, oily Liver failure and oxa late
orl istat (Xenical) 120 mg caps (du ring or up to 1 h $615 (120 mg) 3.4 kg (120 mg) spo tti ng/s tool , fecal urge ncy, neph rop ath y
aft er a low-fat meal ) malabs orpt ion of fat -soluble
vitamins (A,D, E, K)and
me dications (e.g., cyclos porine,
thy roid hormon e rep laceme nt, or
anticonvulsa nts ), pote nti ati on of the
eff ects of wa rfarin
T rec epto rag onis t
Sel ecti ve ser ot onin (5-HT) 5-H2C
Lorcaserin (Belviq) 10 mg tab s 10 mg b. i.d. $263 3.2 kg 38 48% Hypoglycemia, hea dache , fat igue Ser oton in syndro me or
NMS-like reac tio ns, hea rt
valve dis ord er ( , 2.4%),
brad ycardia
Sympath omimet ic amine anore ctic/an tiep ileptic com bin ati on
Obesity Management for the Treatment of Type 2 Diabetes

Phen ter mine/t opi ramate ER (Qsymia) Recommen ded dos e: 3.75 mg/ 23 mg $239 (m aximum 6.7 kg (7.5 mg/ 46 mg) 45 70% Pares thes ia, xerostom ia, constipat ion , Topira mate is ter at ogenic and
3.75 mg/ 23 mg cap s, q.d . for 14 day s, the n incre ase to dos e using the 8.9 kg (15 mg/ 92 mg) hea dac he has bee n associate d wit h
7.5 mg/ 46 mg caps, 7.5 mg/ 46 mg q.d. highes t str ength) cleft lip/pa lat e
11.25 mg/ 69 mg caps, Maximum dos e: 15 mg/ 92 mg q.d.
15 mg/ 92 mg caps
Opioid ant ago nist/am ino ket one an tide pr ess antcom bina tion
Naltrexo ne/ bupr opion (Contr ave ) Maximum dos e: two tab lets of Contra ve $239 (maximum dos e) 2.0 4.1 kg 36 57% Nause a, constipa tion , hea dac he, Dep ressio n, pre cipita tion
8 mg/ 90 mg tabs b. i.d. for a tota l dai ly dos age of naltre xone (3 2 mg/ 360 mg) vomiting of man ia
32 mg/ bupr opion 360 mg
Acylated hu man glucagon- like pe ptid e 1 rec epto rago nis t
Liraglutid e (Saxenda ) Mainte nance dos e: 3 mg s.c. q.d. $1,282 5.85.9 kg 51 73% Hypoglycemia, nau sea , vomiting, Pancre ati tis, thy roid C-cell
6 mg/ mL pre lled pen dia rrh ea, con stipation , hea dac he tumo rs in rode nts ,
cont ra ind icated in pat ients
with per son al/fam ily history
of MTCor MEN2, acute ren al
failure

Allmedi cati ons are FDApregnanc ycateg ory X;these medi cati ons are contraindica ted in wome n who are or may become preg nant . Wome n in the ir reprodu ctive years mus t be cau tion ed to use a reliable met hod
of co ntra ception. Caps, capsules ; ER,ex tende d rel ease; MEN2, mult iple endocrin e neop lasia type 2; MTC,medu lla ry thyroid carcinoma; NMS,neur ole pticmalignan t syndrome ; s.c., subcuta neou s; tab s, tab let s.
1
REDBOOKOnline. Micromede x 2.0 (el ectr onic version). Truven Heal th Analytics, Gree nwood Village , CO.
2
Physicians Desk Referenc e. PDRNetwork, LLC(ele ctronic version ). Truven Heal th Analytics, Gree nwood Village , CO.
3
Yanovski SZ,Yanovski JA.Long-ter m drug trea tme nt for obes ity: a system atic and clinical revi ew. JAMA2014;311:74 86.
4
Astrup A,Carraro R,Finer N, et al.; NN8022-1807 Investigat ors. Saf ety ,tole rabi lity and sustaine d weight los s over 2 years with the once -da ily huma n GLP-1 anal og, liraglu tide. Int J Obes (Lond) 2012;36 :843854.
5
Wadd en TA,Holland er P, Klein S, et al.; NN8022-1923 Investigat ors. Wei ght mai ntenanc e and addi tional weight loss with liraglut ide afte r low-cal orie-di et- induced wei ght loss: the SCALE Maintena nce
randomi zed stu dy. Int J Obes (Lond) 201 3;37:14431451.
6
DrugPo ints System (el ectr onic version). Truven Heal th Analytics, Gree nwood Village , CO.
7
Sel ective comm on (de ned as an incidenc e of . 5%) and seri ous adve rse eff ect s are noted. Refer to the medi cation package ins erts for full inform ati on abou t adve rse effe cts, caut ions, and cont rai ndicati ons.
8
Data of commo n adve rse effects for Xenica l were deri ved from seven double-blind, placebo -con trolled clinical tria ls in mixe d-ty pe stud y populations (i.e., pat ient s with or with out type 2 diab etes ), but the
perc ent age of pat ient s with type 2 diab etes was not reported . In clinical trials in obes e pat ient s with diab ete s, hypoglycemi a and abdomin al disten sion were also observe d.
9
Data of comm on adve rse effects for Belviq were deri ved from placebo- cont rolled clinical trials in patien ts with type 2 dia bete s.
10
Data of comm on adve rse effects for Qsymia wer e deri ved from fou r clinical tria ls in mixed -type stud y population s (i.e., pat ient s with or with out type 2 dia bet es); 13% had type 2 diab ete s.
11
Dataof common adverse e ffectsfor Contrave were derived from ve double-blind, placebo-controlled clinical trials in mixed -type stud y populations (i.e., patients withor withou t type 2 diab etes); 13%had type 2d iabe tes.
12
Diabetes Care Volume 39, Supplement 1, January 2016

Da ta ofcommon adve rse e ffectsfor Saxend a were de rived from clinical trials in mix ed-type study populations (i.e., patien ts with or without type 2 diabetes).Percentage of pa tients with type 2 diabet e s was not reported.
care.diabetesjournals.org Obesity Management for the Treatment of Type 2 Diabetes S51

and modeling studies suggest that bariat- intervention: the Look AHEAD study. Obesity 23. Pi-Sunyer X, Astrup A, Fujioka K, et al.;
ric surgery may be cost-effective or even (Silver Spring) 2014;22:513 SCALE Obesity and Prediabetes NN8022-1839
11. Wilding JPH. The importance of weight Study Group. A randomized, controlled trial of
cost-saving for patients with type 2 di-
management in type 2 diabetes mellitus. Int J 3.0 mg of liraglutide in weight management.
abetes, but the results are largely de- Clin Pract 2014;68:682691 N Engl J Med 2015;373:1122
pendent on assumptions about the 12. WHO Expert Consultation. Appropriate 24. Chang S-H, Stoll CRT, Song J, Varela JE,
long-term effectiveness and safety of body-mass index for Asian populations and its Eagon CJ, Colditz GA. The effectiveness and risks
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diabetes, especially those who are not sitions of fat, protein, and carbohydrates. N Engl Association of bariatric surgery with long-term
severely obese, will require well-de- J Med 2009;360:859873 remission of type 2 diabetes and with microvas-
signed clinical trials, with optimal med- 14. de Souza RJ, Bray GA, Carey VJ, et al. Effects cular and macrovascular complications. JAMA
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MJ, Mathers JC, Taylor R. Reversal of type 2 19. Tsai AG, Wadden TA. The evolution of bariatric surgery. JAMA 2011;305:24192426
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association with decreased pancreas and liver tri- analysis. Obesity (Silver Spring) 2006;14: Barker LE, Couper S. Cost-effectiveness of
acylglycerol. Diabetologia 2011;54:2506 2514 12831293 bariatric surgery for severely obese adults
7. Jackness C, Karmally W, Febres G, et al. Very 20. Johansson K, Neovius M, Hemmingsson E. with diabetes. Diabetes Care 2010;33:1933
low-calorie diet mimics the early benecial ef- Effects of anti-obesity drugs, diet, and exercise 1939
fect of Roux-en-Y gastric bypass on insulin sen- on weight-loss maintenance after a very- 34. Keating CL, Dixon JB, Moodie ML, Peeters
sitivity and b-cell function in type 2 diabetic low-calorie diet or low-calorie diet: a systematic A, Playfair J, OBrien PE. Cost-efcacy of sur-
patients. Diabetes 2013;62:30273032 review and meta-analysis of randomized con- gically induced weight loss for the manage-
8. Rothberg AE, McEwen LN, Kraftson AT, trolled trials. Am J Clin Nutr 2014;99:1423 ment of type 2 diabetes: a randomized
Fowler CE, Herman WH. Very-low-energy diet 21. Yanovski SZ, Yanovski JA. Long-term drug controlled trial. Diabetes Care 2009;32:580
for type 2 diabetes: an underutilized therapy? treatment for obesity: a systematic and clinical 584
J Diabetes Complications 2014;28:506510 review. JAMA 2014;311:74 86 35. Wolfe BM, Belle SH. Long-term risks and
9. Wing RR, Bolin P, Brancati FL, et al.; Look 22. Greenway FL, Fujioka K, Plodkowski RA, benets of bariatric surgery: a research chal-
AHEAD Research Group. Cardiovascular effects et al.; COR-I Study Group. Effect of naltrexone lenge. JAMA 2014;312:17921793
of intensive lifestyle intervention in type 2 plus bupropion on weight loss in overweight 36. Courcoulas AP, Goodpaster BH, Eagleton JK,
diabetes. N Engl J Med 2013;369:145154 and obese adults (COR-I): a multicentre, rando- et al. Surgical vs medical treatments for type 2
10. Look AHEAD Research Group. Eight-year mised, double-blind, placebo-controlled, phase diabetes mellitus: a randomized clinical trial.
weight losses with an intensive lifestyle 3 trial. Lancet 2010;376:595605 JAMA Surg 2014;149:707715
S52 Diabetes Care Volume 39, Supplement 1, January 2016

7. Approaches to Glycemic American Diabetes Association

Treatment
Diabetes Care 2016;39(Suppl. 1):S52S59 | DOI: 10.2337/dc16-S010

PHARMACOLOGICAL THERAPY FOR TYPE 1 DIABETES


Recommendations
c Most people with type 1 diabetes should be treated with multiple-dose insulin
injections (three to four injections per day of basal and prandial insulin) or
MENT

continuous subcutaneous insulin infusion. A


ES TO GLYCEMIC TREAT

c Consider educating individuals with type 1 diabetes on matching prandial insulin


dose to carbohydrate intake, premeal blood glucose, and anticipated activity. E
c Most individuals with type 1 diabetes should use insulin analogs to reduce
hypoglycemia risk. A
c Individuals who have been successfully using continuous subcutaneous insulin
infusion should have continued access after they turn 65 years of age. E
7. APPROACH

Insulin Therapy
Insulin is the mainstay of therapy for individuals with type 1 diabetes. There are
excellent reviews to guide the initiation and management of insulin therapy to
achieve desired glycemic goals (1). Although most studies of multiple-dose insulin
versus pump therapy have been small and of short duration, a systematic review and
meta-analysis concluded that there are minimal differences between the two forms
of intensive insulin therapy in A1C (combined mean between-group difference
favoring insulin pump therapy 20.30% [95% CI 20.58 to 20.02]) and severe hypo-
glycemia rates in children and adults (2). A large randomized trial in patients with
type 1 diabetes with nocturnal hypoglycemia reported that sensor-augmented in-
sulin pump therapy with the threshold suspend feature reduced nocturnal hypo-
glycemia, without increasing glycated hemoglobin values (3). Intensive
management through pump therapy/continuous glucose monitoring and active
patient/family participation should be strongly encouraged (46). Selected
individuals who have mastered carbohydrate counting should be educated that fat
increases glucose concentrations and insulin requirements (7).
The Diabetes Control and Complications Trial (DCCT) clearly showed that in-
tensive insulin therapy (three or more injections per day of insulin) or continuous
subcutaneous insulin infusion (CSII) (insulin pump therapy) was a key part of
improved glycemia and better outcomes (8,9). The study was carried out with
short-acting and intermediate-acting human insulins. Despite better microvascular,
macrovascular, and all-cause mortality outcomes, intensive insulin therapy was as-
sociated with a high rate of severe hypoglycemia (62 episodes per 100 patient-years
of therapy). Since the DCCT, a number of rapid-acting and long-acting insulin analogs
have been developed. These analogs are associated with less hypoglycemia in type 1
diabetes, while matching the A1C lowering of human insulins (10,11).
Rapid-acting inhaled insulin used before meals in type 1 diabetes leads to inferior
A1C lowering when compared with aspart insulin, with less hypoglycemia across all
A1C target categories (12). Suggested citation: American Diabetes Associa-
Postprandial glucose excursions can be better controlled by adjusting the timing tion. Approaches to glycemic treatment. Sec. 7.
of prandial (bolus) insulin dose administration. The optimal time to inject prandial In Standards of Medical Care in Diabetesd2016.
insulin varies, based on the type of insulin injected (regular, rapid-acting analog, Diabetes Care 2016;39(Suppl. 1):S52S59
inhaled, etc.), the measured blood glucose level, timing of meals, and carbohydrate 2016 by the American Diabetes Association.
consumption. Recommendations for prandial insulin dose administration should Readers may use this article as long as the work
therefore be individualized. is properly cited, the use is educational and not
for prot, and the work is not altered.
care.diabetesjournals.org Approaches to Glycemic Treatment S53

Recommended therapy for type 1 di- insulin requirements (6.6 units/day, P ,


c A patient-centered approach
abetes consists of the following: 0.001) and led to small reductions in
should be used to guide the choice
weight and total and LDL cholesterol but
of pharmacological agents. Con-
1. Multiple-dose insulin injections (three not to improved glycemic control (abso-
to four injections per day of basal and
siderations include efcacy, cost,
lute A1C reduction 0.11%, P 5 0.42) (14). potential side effects, weight, co-
prandial insulin) or CSII therapy. Incretin-Based Therapies morbidities, hypoglycemia risk,
2. Match prandial insulin to carbohy- Therapies approved for the treatment of
drate intake, premeal blood glucose,
and patient preferences. E
type 2 diabetes are currently being eval- c For patients with type 2 diabetes
and anticipated physical activity. uated in type 1 diabetes. Glucagon-like who are not achieving glycemic
3. For most patients (especially those at peptide 1 (GLP-1) agonists and dipep- goals, insulin therapy should not
elevated risk of hypoglycemia), use tidyl peptidase 4 (DPP-4) inhibitors are
insulin analogs. be delayed. B
not currently FDA approved for those
4. For patients with frequent nocturnal with type 1 diabetes but are being stud- An American Diabetes Association/
hypoglycemia, recurrent severe hy- ied in this population. European Association for the Study of
poglycemia, and/or hypoglycemia
SodiumGlucose Cotransporter 2 Diabetes position statement (17) evalu-
unawareness, a sensor-augmented
Inhibitors ated the data and developed recom-
low glucose threshold suspend pump
Sodiumglucose cotransporter 2 (SGLT2) mendations, including advantages and
may be considered.
inhibitors provide insulin-independent disadvantages, for antihyperglycemic
Pramlintide glucose lowering by blocking glucose re- agents for patients with type 2 diabetes.
Pramlintide, an amylin analog, is an absorption in the proximal renal tubule A patient-centered approach is stressed,
agent that delays gastric emptying, by inhibiting SGLT2. These agents including patient preferences, cost, and
blunts pancreatic secretion of glucagon, provide modest weight loss and blood potential side effects of each class, effects
and enhances satiety. It is a U.S. Food pressure reduction. There are three on body weight, and hypoglycemia risk.
and Drug Administration (FDA)-approved FDA-approved agents for use in patients Lifestyle modications that improve
therapy for use in adults with type 1 di- with type 2 diabetes, but there are in- health (see Section 3 Foundations of
abetes. It has been shown to induce sufcient data to recommend treatment Care and Comprehensive Medical Eval-
weight loss and lower insulin dose. Con- in type 1 diabetes (15). The FDA recently uation) should be emphasized along
current reduction of prandial insulin issued a warning about the risk of keto- with any pharmacological therapy.
dosing is required to reduce the risk of acidosis with SGLT2 inhibitors in individ-
Initial Therapy
severe hypoglycemia. uals with type 1 or type 2 diabetes.
Most patients should begin with life-
Symptoms of ketoacidosis include nau-
Pancreas and Islet Cell Transplantation
style changes, which may include life-
sea, vomiting, abdominal pain, tiredness,
Pancreas and islet cell transplantation style counseling, setting a physical
and dyspnea. Urinary tract infections
have been shown to normalize glucose activity goal of 150 min/week minimum,
leading to urosepsis and pyelonephritis
levels but require lifelong immunosup- and weight loss counseling to lose a min-
may also occur with SGLT2 inhibitors. Pa-
pression to prevent graft rejection and imum of 7% of body weight (for details
tients should stop taking their SGLT2 in-
recurrence of autoimmune islet destruc- on lifestyle therapy, see Section 6 Obe-
hibitor and seek medical attention
tion. Given the potential adverse effects sity Management for the Treatment of
immediately if they have symptoms of
of immunosuppressive therapy, pan- Type 2 Diabetes). When lifestyle efforts
ketoacidosis (16).
creas transplantation should be reserved alone do not achieve or maintain glyce-
for patients with type 1 diabetes under- PHARMACOLOGICAL THERAPY mic goals, metformin monotherapy
going simultaneous renal transplanta- FOR TYPE 2 DIABETES should be added at, or soon after, diag-
tion, following renal transplantation, Recommendations
nosis, unless there are contraindications
or for those with recurrent ketoacidosis or intolerance. Metformin has a long-
c Metformin, if not contraindicated
or severe hypoglycemia despite aggres- standing evidence base for efcacy and
and if tolerated, is the preferred
sive glycemic management (13). Islet safety, is inexpensive, and may reduce
initial pharmacological agent for
cell transplantation remains investiga- risk of cardiovascular events and death
type 2 diabetes. A
tional. Autoislet transplantation may (18). Accumulating observational data
c Consider initiating insulin therapy
be considered for patients requiring to- suggest that metformin may be safely
(with or without additional agents)
tal pancreatectomy who meet eligibility in patients with newly diagnosed continued down to glomerular ltration
criteria. rate (GFR) of 45 mL/min/1.73 m or even
2

type 2 diabetes and markedly symp-


30 mL/min/1.73 m (19). If metformin is
2

tomatic and/or elevated blood glu-


Investigational Agents used in the lower GFR range, the dose
cose levels or A1C. E
Metformin should be reduced and patients should
c If noninsulin monotherapy at max-
Adding metformin to insulin therapy may be advised to stop the medication for nau-
imum tolerated dose does not
reduce insulin requirements and improve sea, vomiting, and dehydration. In patients
achieve or maintain the A1C target
metabolic control in overweight/obese with metformin intolerance or contraindi-
over 3 months, then add a second
patients with poorly controlled type 1 di- cations, consider an initial drug from other
oral agent, a glucagon-like peptide
abetes. In a meta-analysis, metformin in classes depicted in Fig. 7.1 under Dual
type 1 diabetes was found to reduce
1 receptor agonist, or basal insulin. A
therapy and proceed accordingly.
S54 Approaches to Glycemic Treatment Diabetes Care Volume 39, Supplement 1, January 2016

Figure 7.1Antihyperglycemic therapy in type 2 diabetes: general recommendations (17). The order in the chart was determined by historical
availability and the route of administration, with injectables to the right; it is not meant to denote any specic preference. Potential sequences of
antihyperglycemic therapy for patients with type 2 diabetes are displayed, with the usual transition moving vertically from top to bottom (although
horizontal movement within therapy stages is also possible, depending on the circumstances). DPP-4-i, DPP-4 inhibitor; fxs, fractures; GI, gastro-
intestinal; GLP-1-RA, GLP-1 receptor agonist; GU, genitourinary; HF, heart failure; Hypo, hypoglycemia; SGLT2-i, SGLT2 inhibitor; SU, sulfonylurea;
TZD, thiazolidinedione. *See ref. 17 for description of efcacy categorization. Consider starting at this stage when A1C is $9% (75 mmol/mol).
Consider starting at this stage when blood glucose is $300350 mg/dL (16.719.4 mmol/L) and/or A1C is $1012% (86108 mmol/mol), especially
if symptomatic or catabolic features are present, in which case basal insulin 1 mealtime insulin is the preferred initial regimen. Usually a basal
insulin (NPH, glargine, detemir, degludec). Adapted with permission from Inzucchi et al. (17).

Combination Therapy medical, psychosocial, and health eco- may be low-value based on high cost and
Although there are numerous trials nomic outcomes (21). moderate glycemic effect (24).
comparing dual therapy with metformin If the A1C target is not achieved after Rapid-acting secretagogues (megliti-
alone, few directly compare drugs as approximately 3 months, consider a com- nides) may be used instead of sulfonyl-
add-on therapy. A comparative effec- bination of metformin and one of these six ureas in patients with irregular meal
tiveness meta-analysis (20) suggests treatment options: sulfonylurea, thiazolidi- schedules or those who develop late
that overall each new class of noninsulin nedione, DPP-4 inhibitors (22), SGLT2 in- postprandial hypoglycemia on a sulfo-
agents added to initial therapy lowers hibitors, GLP-1 receptor agonists, or basal nylurea. Other drugs not shown in the
A1C around 0.91.1%. A comprehensive insulin (Fig. 7.1). Drug choice is based on gure (e.g., a-glucosidase inhibitors, co-
listing, including the cost, is available in patient preferences (23), as well as various lesevelam, bromocriptine, pramlintide)
Table 7.1. The ongoing Glycemia Reduc- patient, disease, and drug characteristics, may be tried in specic situations, but
tion Approaches in Diabetes: A Compar- with the goal of reducing blood glucose are generally not favored due to modest
ative Effectiveness Study (GRADE) will levels while minimizing side effects, espe- efcacy, the frequency of administra-
compare the effect of four major drug cially hypoglycemia. Figure 7.1 emphasizes tion, and/or side effects.
classes (sulfonylurea, DPP-4 inhibitor, drugs commonly used in the U.S. and/or For all patients, consider initiating
GLP-1 analog, and basal insulin) over Europe. Cost-effectiveness models have therapy with a dual combination when
4 years on glycemic control and other suggested that some of the newer agents A1C is $9% (75 mmol/mol) to more
Table 7.1
Prope rties of availa ble gluc ose-l owering age nts in the U.S. and Europe tha t may gu ide individualiz ed treatme nt ch oices in patien ts wi th type 2 diabe tes (17)
Class Compound (s) Cellular mech ani sm(s) Primary physiological action(s) Advantages Disadva ntages Cost*
Biguani des c Metformin Activa tes AMP-kinase (? othe r) c Hepatic gluc ose pro duction c Extensive experien ce c Gastroi nte stinal side effects Low
c No hypoglycemi a (diarrh ea, abdo minal cra mping)
c CVDeven ts (UKP DS) c Vitamin B 12 de cie ncy
c Contrai ndic ations: CKD , acidosi s,
hypoxia, dehydrat ion, et c.
care.diabetesjournals.org

c Lactic aci dosi s risk (rare)


Sulfon ylureas 2nd Generat ion Closes KATP channel s on b-ce ll c Insulin sec reti on c Extensive experien ce c Hypoglycemi a Low
c Glyburide/ plasma memb ranes c Microva scular risk c Weig ht
glibenc lamide (UKPDS)
c Glipizide
c Gliclazide
c Glimepiride
Meglitinid es (glinides) c Repaglinide Closes KATP channel s on b-ce ll c Insulin sec reti on c Postprandial gluc ose c Hypoglycemi a Moderate
c Nateglinide plasma memb ranes exc ursions c Weig ht
c Dosing exib ility c Frequent dosing schedul e
TZDs c Pioglita zone Activa tes the nuclear c Insulin sen sitivity c No hypoglycemi a c Weig ht Low
c Rosigli tazone tra nsc ription fac tor PPAR- g c Durabil ity c Edema/he art fai lure
c HDL- C c Bone fractu res
c Triglyceri des c LDL-C (rosigl itazone)
(pioglita zone) c ? MI (me ta-a nalyses,
c ? CVDeve nts rosigli tazone)
(PROact ive,
pioglit azone)
a-Glucos idase inhibitors c Acarbose Inhibi ts inte stinal a-glu cosidase c Slows int estinal car boh ydrate c No hypoglycemi a c Generall y mode st A1Cefcacy Low to
c Miglitol dige stion/ab sor ptio n c Post prandial gluc ose c Gastroi nte stinal side effects mod erat e
exc ursions (atulenc e, diarrhea )
c ? CVDeve nts (STOP- c Frequent dosing schedul e
NIDDM)
c Nonsystemic
DPP-4 inhibitors c Sitagliptin Inhibi ts DPP-4 act ivity, incr easing c Insulin sec reti on (gl ucose c No hypoglycemi a c
Angioede ma/u rticaria and othe r High
c Vildagli ptin postpra ndial active increti n depen dent ) c Well tole rate d immune-me diat ed derm atological
c Saxa gliptin (GLP-1, GIP) conc ent rati ons c Glucagon secreti on (glucose effe cts
c Linagli ptin depen dent ) c ? Acute panc reat iti s
c Alogliptin c ? Hear t failure hos pitalization s
Bile aci d sequ est ran ts c Colesevela m Binds bile aci ds in inte stinal trac t, c ? Hepati c gluc ose product ion c No hypoglycemi a c Generall y mode st A1Cef cacy High
increasing hepa tic bile acid c ? Increti n leve ls c LDL -C c Constipat ion
pro duct ion c Triglycerid es
c May abso rption of oth er
medi cati ons
Dopamin e-2 agon ists c Bromocri ptine Activa tes dopaminergi c rec eptor s c Modulates hypothalami c c No hypoglycemi a c Generall y mode st A1Cef cacy High
(quick rele ase) regu lation of meta bolism c ? CVDeve nts (Cyclos et c Dizzine ss/s yncope
c Insulin sen sitivity Saf ety Trial) c Nausea
c Fatigue
c Rhiniti s
Approaches to Glycemic Treatment

Contin ued on p. S56


S55
S56

Tabl e 7.1
Cont inue d
Class Compoun d(s) Cellular mec hani sm(s) Primary physiological action(s) Advantages Disadvantag es Cost*
SGLT2inhibitors c Canagli ozin Inhibits SGLT2in the proxima l c Blocksgluc ose reab sor ptio n by c No hypoglycemi a c Genitou rin ary infecti ons High
c Dapagli ozin neph ron the kidney, increas ing c Wei ght c Polyuria
c Empagli ozin glucosuria c Blood pres sur e c Volume depleti on/ hypo ten sion/
c Effect ive at all stages of dizzine ss
type 2 diab ete s c LDL- C
c Associa ted with lowe r c Creati nine (trans ient)
CVDeven t rat e and c DKA,urinar y trac t infect ions
mor tal ity in pat ient s lea ding to uros epsis, pyelonep hri tis
Approaches to Glycemic Treatment

with CVD(EMPA-REG
OUTCOME)
GLP-1 rec ept or ag onis ts c Exenatide Activates GLP-1 rec ept ors c Insulin secr eti on (glu cose c No hypoglycemi a c Gastroi nte stinal side effects High
c Exenatide extended depe nden t) c Wei ght (nausea/ vomiting/di arrhea)
rele ase c Glucagon secr et ion (glucose c Po stprandi al glu cose c Hear t rate
c Liraglutide depe nden t) ex cursions c ? Acute pancrea titis
c Albiglu tide c Slows gast ric emptying c Som e cardio vascular c C-cell hyperplasia/ medu lla ry
c Lixisenati de c Sati ety risk fac tor s thyroid tumo rs in anim als
c Dulaglu tide c Injectab le
c Training req uire ment s
Amylin mime tics c Pramlintide Activates amylin rece ptor s c Glucagon secr et ion c Po stprandial glu cose c General lymode st A1Cefcacy High
c Slows gastric emptying ex cursions c Gastroi nte stinal side eff ects
c Sati ety c Wei ght (nausea/ vomiting)
c Hypoglycemia unl ess insulin dose is
simulta neou sly redu ced
c Injectab le
c Frequen t dosing schedul e
c Training req uire ment s
Insulins c Ra pid-acting a nalogs Activates insulin rec ept ors c Glucose dis posal c Near ly universal c Hypoglycemia Moderat e to
- Lispro c Hepatic glu cose prod uction res ponse c Weig ht gain hig h#
- Aspart c Theoretical ly unlimited c ? Mitogenic eff ects
- Glulisine c Suppres ses ketogen esi s efcacy c Training req uire ment s
- Inhale d insulin c Microvascular risk c Pati ent relu ctance
c Sho rt-acting (UKPDS) c Injectab le (ex cept inhale d insulin)
- Human Regular c Pulmonar y toxicit y (inhal ed insulin)
c Intermed iate-ac ting
- Human NPH
c Basal insulin anal ogs
- Glargin e
- Dete mir
- Degludec
c Premixe d (several
types)
CKD,chronic kidney dise ase ; CVD,car diovascular diseas e; DKA,diab eti c ket oac idosis; EMPA-REG OUTCOME,BI 10773 (Empagli ozin) Cardiovascula r Outcome Event Trial in Type 2 Diabet es Mellitus Patient s (31);
GIP,glu cose-de pend ent insuli notr opic pep tide; HDL-C, HDLchol esterol ; LDL-C , LDLchol esterol ; MI, myocardial infarc tion; PPAR- g, peroxisome proliferat or activated rece ptor g; PROactive, Pro spective
Pioglita zone Clinical Trial in Macrovascula r Events (32); STOP-NIDDM, Stu dy to Prevent Non-Insulin -Depende nt Diabete s Mellitus (33); TZD,thia zolidinedione; UKPDS , UKPro spective Diabet es Study (34,35).
Cycloset trial of quick-relea se bromocri ptine (36). *Cost is based on lowe st-price d memb er of the class (see ref . 17). Not license d in the U.S. Initia l conc erns rega rding blad der can cer risk are dec reasing after
subseque nt stud y. Not licensed in Eur ope for type 2 diab ete s. #Cost is high ly depe nden t on type/bra nd (analog s . hum an insulins) and dosage. Adapte d with perm ission from Inzucchi et al. (17).
Diabetes Care Volume 39, Supplement 1, January 2016
care.diabetesjournals.org Approaches to Glycemic Treatment S57

Figure 7.2Approach to starting and adjusting insulin in type 2 diabetes (17). FBG, fasting blood glucose; GLP-1-RA, GLP-1 receptor agonist; hypo,
hypoglycemia; mod., moderate; PPG, postprandial glucose; #, number. Adapted with permission from Inzucchi et al. (17).

expeditiously achieve the target A1C elevated blood glucose levels or A1C. control in patients with type 2 diabetes
level. Insulin has the advantage of being Many patients with type 2 diabetes initiating insulin (25).
effective where other agents may not be eventually require and benet from in- Basal Insulin
and should be considered as part of any sulin therapy. Providers may wish to Basal insulin alone is the most conve-
combination regimen when hyperglyce- consider regimen exibility when de nient initial insulin regimen, beginning
mia is severe, especially if symptoms are vising a plan for the initiation and ad-
at 10 units or 0.10.2 units/kg, depend-
present or any catabolic features (weight justment of insulin therapy in people
ing on the degree of hyperglycemia.
loss, ketosis) are present. Consider ini- with type 2 diabetes (Fig. 7.2). The pro-
Basal insulin is usually prescribed in con-
tiating combination insulin injectable gressive nature of type 2 diabetes and
junction with metformin and possibly
therapy when blood glucose is $300 its therapies should be regularly and ob-
one additional noninsulin agent. While
350 mg/dL (16.719.4 mmol/L) and/or jectively explained to patients. For pa-
tients with type 2 diabetes who are not there is evidence for reduced risk of hy-
A1C is $1012% (86108 mmol/mol). As
achieving glycemic goals, providers should poglycemia with newer, longer-acting,
the patients glucose toxicity resolves, the
promptly initiate insulin therapy. basal insulin analogs, people with type
regimen may, potentially, be simplied.
Providers should avoid using insulin
2 diabetes without history of hypogly-
cemia or severe hypoglycemia may use
Insulin Therapy as a threat or describing it as a failure or
Consider initiating insulin therapy (with NPH safely at much lower cost (24,26).
punishment. Equipping patients with an
or without additional agents) in patients algorithm for self-titration of insulin Concentrated preparation of basal in-
with newly diagnosed type 2 diabetes doses based on self-monitoring of blood sulin such as U-500 regular is ve times
and markedly symptomatic and/or glucose (SMBG) improves glycemic as potent per volume of insulin (i.e.,
S58 Approaches to Glycemic Treatment Diabetes Care Volume 39, Supplement 1, January 2016

0.01 mL ;5 units of U-100 regular) and current insulin dose and then providing of hypoglycemia. N Engl J Med 2013;369:224
has a delayed onset and longer one-half of this amount as basal and 232
4. Wood JR, Miller KM, Maahs DM, et al.; T1D
duration of action than U-100 regular. one-half as mealtime insulin, the latter Exchange Clinic Network. Most youth with
U-300 glargine and U-200 degludec are split evenly between three meals. It is crit- type 1 diabetes in the T1D Exchange clinic reg-
three and two times, respectively, as ical that individuals who have been suc- istry do not meet American Diabetes Associa-
potent per volume, have a longer dura- cessfully using CSII should have continued tion or International Society for Pediatric and
Adolescent Diabetes clinical guidelines. Diabe-
tion of action, and may allow higher access after they turn 65 years of age (30).
tes Care 2013;36:20352037
doses of insulin administration in Inhaled Insulin 5. Kmietowicz Z. Insulin pumps improve control
smaller volumes. These concentrated and reduce complications in children with
Inhaled insulin is now available for pran-
preparations may be more comfortable type 1 diabetes. BMJ 2013;347:f5154
dial use with a more limited dosing 6. Phillip M, Battelino T, Atlas E, et al. Nocturnal
for the patient and allow better absorp-
range and may require serial lung func- glucose control with an articial pancreas at a dia-
tion. However, they are more expen-
tion testing prior to and after starting betes camp. N Engl J Med 2013;368:824833
sive, and accurate dosing may be more therapy. 7. Wolpert HA, Atakov-Castillo A, Smith SA,
complicated. Steil GM. Dietary fat acutely increases glucose
Treatment Strategies
If basal insulin has been titrated to an concentrations and insulin requirements in
acceptable fasting blood glucose level, Figure 7.2 focuses solely on sequential patients with type 1 diabetes: implications for
insulin strategies, describing the num- carbohydrate-based bolus dose calculation and
but A1C remains above target, consider
ber of injections and the relative com- intensive diabetes management. Diabetes Care
advancing to combination injectable 2013;36:810816
therapy (Fig. 7.2) to cover postprandial
plexity and exibility of each stage. Once 8. The Diabetes Control and Complications Trial
glucose excursions. Options include an insulin regimen is initiated, dose ti- Research Group. The effect of intensive treat-
adding a GLP-1 receptor agonist (27) or tration is important, with adjustments ment of diabetes on the development and
mealtime insulin, consisting of one to made in both mealtime and basal insu- progression of long-term complications in insulin-
lins based on the prevailing blood glu- dependent diabetes mellitus. N Engl J Med 1993;
three injections of rapid-acting insulin 329:977986
cose levels and an understanding of the
analog (lispro, aspart, or glulisine) ad- 9. Nathan DM, Cleary PA, Backlund J-YC, et al.;
ministered just before eating. A less pharmacodynamic prole of each for- Diabetes Control and Complications Trial/
studied alternative, transitioning from mulation (pattern control). Epidemiology of Diabetes Interventions and
Noninsulin agents may be continued, Complications (DCCT/EDIC) Study Research
basal insulin to twice-daily premixed
although sulfonylureas, DPP-4 inhibi- Group. Intensive diabetes treatment and car-
(or biphasic) insulin analogs (70/30 as- diovascular disease in patients with type 1 di-
tors, and GLP-1 receptor agonists are
part mix, 75/25 or 50/50 lispro mix), abetes. N Engl J Med 2005;353:26432653
could also be considered; pharmacody- typically stopped once more complex in- 10. DeWitt DE, Hirsch IB. Outpatient insulin
sulin regimens beyond basal are used. In therapy in type 1 and type 2 diabetes mellitus:
namic proles make them suboptimal to
cover postprandial glucose excursions. patients with suboptimal blood glucose scientic review. JAMA 2003;289:22542264
control, especially those requiring in- 11. Rosenstock J, Dailey G, Massi-Benedetti M,
Bolus Insulin Fritsche A, Lin Z, Salzman A. Reduced hypoglyce-
creasing insulin doses, adjunctive use mia risk with insulin glargine: a meta-analysis com-
Some individuals with type 2 diabetes of thiazolidinediones (usually pioglita- paring insulin glargine with human NPH insulin in
may require bolus insulin dosing in ad- zone) or SGLT2 inhibitors may be helpful type 2 diabetes. Diabetes Care 2005;28:950955
dition to basal insulin. Rapid-acting an- in improving control and reducing the 12. MannKind Corporation. Brieng Document:
alogs are preferred due to their prompt amount of insulin needed. Comprehen- Endocrinologic and Metabolic Drug Advisory
onset of action after dosing. The FDA Committee. AFREZZA (insulin human [rDNA origin])
sive education regarding SMBG, diet, ex- inhalation powder. An ultra-rapid acting insulin
recently approved a more concentrated ercise, and the avoidance of and response treatment to improve glycemic control in adult
formulation of rapid-acting insulin ana- to hypoglycemia are critically important patients with diabetes mellitus [Internet], 2014.
log, U-200 (200 units/mL), dosed 15 min in any patient using insulin. Available from http://www.fda.gov/downloads/
or immediately prior to a meal. AdvisoryCommittees/CommitteesMeetingMaterials/

Regular human insulin and human BARIATRIC SURGERY Drugs/EndocrinologicandMetabolicDrugsAdvisory


Committee/UCM390865.pdf. Accessed 6 November
NPH-Regular premixed formulations Bariatric surgery also improves glycemic
2015
(70/30) are less costly alternatives to control in type 2 diabetes. Its effects are 13. American Diabetes Association. Pancreas
rapid-acting insulin analogs and pre- discussed in Section 6 Obesity Man- and islet transplantation in type 1 diabetes. Di-
mixed insulin analogs, respectively, agement for the Treatment of Type 2 abetes Care 2006;29:935
Diabetes. 14. Vella S, Buetow L, Royle P, Livingstone S,
but their pharmacodynamic proles
Colhoun HM, Petrie JR. The use of metformin
make them suboptimal to cover post-
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prandial glucose excursions.
1. Wallia A, Molitch ME. Insulin therapy for cacy. Diabetologia 2010;53:809820
Continuous Subcutaneous Insulin Infusion 15. Chiang JL, Kirkman MS, Laffel LM, Peters AL;
type 2 diabetes mellitus. JAMA 2014;311:
A less commonly used and more costly Type 1 Diabetes Sourcebook Authors. Type 1 di-
23152325 abetes through the life span: a position state-
alternative to basalbolus therapy 2. Yeh H-C, Brown TT, Maruthur N, et al. Com- ment of the American Diabetes Association.
with multiple daily injections is CSII (in- parative effectiveness and safety of methods of Diabetes Care 2014;37:20342054
insulin delivery and glucose monitoring for di- 16. U.S. Food and Drug Administration. SGLT2
sulin pump) (28,29). In addition to the
abetes mellitus: a systematic review and meta- inhibitors: drug safety communication labels
suggestions provided for determining
analysis. Ann Intern Med 2012;157:336347 to include warnings about too much acid
the starting dose of mealtime insulin 3. Bergenstal RM, Klonoff DC, Garg SK, et al.; in the blood and serious urinary tract infec-
under a basalbolus regimen, another ASPIRE In-Home Study Group. Threshold- tions [Internet], 4 December 2015. Available
method consists of adding up the total based insulin-pump interruption for reduction from http://www.fda.gov/safety/medwatch/
care.diabetesjournals.org Approaches to Glycemic Treatment S59

safetyinformation/safetyalertsforhumanmedical 24. Institute for Clinical and Economic Review. infusion versus multiple daily injections in older
products/ucm475553.htm. Accessed 7 Decem- Controversies in the management of patients adults with type 2 diabetes. Diabetes Care 2005;
ber 2015 with type 2 diabetes [Internet], 2014. Available 28:15681573
17. Inzucchi SE, Bergenstal RM, Buse JB, et al. from http://cepac.icer-review.org/wp-content/ 31. Zinman B, Wanner C, Lachin JM, et al.;
Management of hyperglycemia in type 2 diabetes, uploads/2014/08/CEPAC-T2D-Final-Report- EMPA-REG OUTCOME Investigators. Empagli-
2015: a patient-centered approach. Update to a December-22.pdf. Accessed 6 November 2015 ozin, cardiovascular outcomes, and mortality
position statement of the American Diabetes As- 25. Blonde L, Merilainen M, Karwe V, Raskin P; in type 2 diabetes. N Engl J Med. 17 September
sociation and the European Association for the TITRATE Study Group. Patient-directed titration 2015 [Epub ahead of print]. DOI: 10.1056/
Study of Diabetes. Diabetes Care 2015;38:140 for achieving glycaemic goals using a once-daily NEJMoa1504720
149 basal insulin analogue: an assessment of two 32. Dormandy JA, Charbonnel B, Eckland DJA, et al.;
18. Holman RR, Paul SK, Bethel MA, Matthews different fasting plasma glucose targetsdthe PROactive Investigators. Secondary prevention
DR, Neil HA. 10-year follow-up of intensive glu- TITRATE study. Diabetes Obes Metab 2009;11: of macrovascular events in patients with type 2
cose control in type 2 diabetes. N Engl J Med 623631 diabetes in the PROactive Study (PROspective
2008;359:15771589 26. Tricco AC, Ashoor HM, Soobiah C, et al. pioglitAzone Clinical Trial In macroVascular Events):
19. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, Safety, effectiveness, and cost of long-acting a randomised controlled trial. Lancet 2005;366:
McGuire DK. Metformin in patients with versus intermediate-acting insulin for type 1 di- 12791289
type 2 diabetes and kidney disease: a systematic abetes: protocol for a systematic review and 33. Chiasson J-L, Josse RG, Gomis R, Hanefeld
review. JAMA 2014;312:26682675 network meta-analysis. Syst Rev 2013;2:73 M, Karasik A, Laakso M; STOP-NIDDM Trial Re-
20. Bennett WL, Maruthur NM, Singh S, et al. 27. Eng C, Kramer CK, Zinman B, Retnakaran R. search Group. Acarbose for prevention of type 2
Comparative effectiveness and safety of medi- Glucagon-like peptide-1 receptor agonist and diabetes mellitus: the STOP-NIDDM randomised
cations for type 2 diabetes: an update including basal insulin combination treatment for the trial. Lancet 2002;359:20722077
new drugs and 2-drug combinations. Ann Intern management of type 2 diabetes: a systematic 34. UK Prospective Diabetes Study (UKPDS) Group.
Med 2011;154:602613 review and meta-analysis. Lancet 2014;384: Intensive blood-glucose control with sulphonylureas
21. Nathan DM, Buse JB, Kahn SE, et al.; GRADE 22282234 or insulin compared with conventional treatment
Study Research Group. Rationale and design of 28. Reznik Y, Cohen O, Aronson R, et al.; OpT2mise and risk of complications in patients with type 2 di-
the glycemia reduction approaches in diabetes: Study Group. Insulin pump treatment compared abetes (UKPDS 33). Lancet 1998;352:837 853
a comparative effectiveness study (GRADE). with multiple daily injections for treatment of 35. UK Prospective Diabetes Study (UKPDS)
Diabetes Care 2013;36:22542261 type 2 diabetes (OpT2mise): a randomised Group. Effect of intensive blood-glucose control
22. Green JB, Bethel MA, Armstrong PW, et al.; open-label controlled trial. Lancet 2014;384: with metformin on complications in overweight
TECOS Study Group. Effect of sitagliptin on car- 12651272 patients with type 2 diabetes (UKPDS 34). Lan-
diovascular outcomes in type 2 diabetes. N Engl 29. Johnson SL, McEwen LN, Newton CA, et al. The cet 1998;352:854865
J Med 2015;373:232242 impact of continuous subcutaneous insulin infusion 36. Gaziano JM, Cincotta AH, OConnor CM,
23. Vijan S, Sussman JB, Yudkin JS, Hayward RA. and multiple daily injections of insulin on glucose et al. Randomized clinical trial of quick-
Effect of patients risks and preferences on variability in older adults with type 2 diabetes. release bromocriptine among patients with
health gains with plasma glucose level lowering J Diabetes Complications 2011;25:211 215 type 2 diabetes on overall safety and cardio-
in type 2 diabetes mellitus. JAMA Intern Med 30. Herman WH, Ilag LL, Johnson SL, et al. A vascular outcomes. Diabetes Care 2010;33:
2014;174:12271234 clinical trial of continuous subcutaneous insulin 15031508
S60 Diabetes Care Volume 39, Supplement 1, January 2016

8. Cardiovascular Disease and Risk American Diabetes Association

Management
Diabetes Care 2016;39(Suppl. 1):S60S71 | DOI: 10.2337/dc16-S011

For prevention and management of diabetes complications in children and adolescents,


please refer to Section 11 Children and Adolescents.
In all patients with diabetes, cardiovascular risk factors should be systematically as-
sessed at least annually. These risk factors include dyslipidemia, hypertension, smoking, a
family history of premature coronary disease, and the presence of albuminuria. Abnor-
mal risk factors should be treated as described elsewhere in these guidelines.
SCULARDISEASE ANDRISK MANAGEMENT

Atherosclerotic cardiovascular disease (ASCVD)ddened as acute coronary


syndromes (ACSs), a history of myocardial infarction (MI), stable or unstable
angina, coronary or other arterial revascularization, stroke, transient ischemic
attack, or peripheral arterial disease presumed to be of atherosclerotic origin dis
the leading cause of morbidity and mortality for individuals with diabetes and is the
largest contributor to the direct and indirect costs of diabetes. The common con-
ditions coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are
clear risk factors for ASCVD, and diabetes itself confers independent risk. Numerous
studies have shown the efcacy of controlling individual cardiovascular risk factors
in preventing or slowing ASCVD in people with diabetes. Large benets are seen
when multiple risk factors are addressed simultaneously. There is evidence that
measures of 10-year coronary heart disease (CHD) risk among U.S. adults with
8. CARDIOVA

diabetes have improved signicantly over the past decade (1) and that ASCVD
morbidity and mortality have decreased (24).
HYPERTENSION/BLOOD PRESSURE CONTROL
Recommendations

Screening and Diagnosis


c Blood pressure should be measured at every routine visit. Patients found to have
elevated blood pressure should have blood pressure conrmed on a separate day. B
Goals
Systolic Targets
c People with diabetes and hypertension should be treated to a systolic blood
pressure goal of ,140 mmHg. A
c Lower systolic targets, such as ,130 mmHg, may be appropriate for certain indi-
viduals with diabetes, such as younger patients, those with albuminuria, and/or
those with hypertension and one or more additional atherosclerotic cardiovascular
disease risk factors, if they can be achieved without undue treatment burden. C
Diastolic Targets
c Individuals with diabetes should be treated to a diastolic blood pressure goal
of ,90 mmHg. A
c Lower diastolic targets, such as ,80 mmHg, may be appropriate for certain indi-
viduals with diabetes, such as younger patients, those with albuminuria, and/or
those with hypertension and one or more additional atherosclerotic cardiovascular
disease risk factors, if they can be achieved without undue treatment burden. B Suggested citation: American Diabetes Associa-

Treatment tion. Cardiovascular disease and risk manage-


ment. Sec. 8. In Standards of Medical Care in
c Patients with blood pressure .120/80 mmHg should be advised on lifestyle
Diabetesd2016. Diabetes Care 2016;39(Suppl. 1):
changes to reduce blood pressure. B
S60S71
c Patients with conrmed ofce-based blood pressure .140/90 mmHg should, 2016 by the American Diabetes Association.
in addition to lifestyle therapy, have prompt initiation and timely subsequent
Readers may use this article as long as the work
titration of pharmacological therapy to achieve blood pressure goals. A is properly cited, the use is educational and not
for prot, and the work is not altered.
care.diabetesjournals.org Cardiovascular Disease and Risk Management S61

arm supported at heart level, after 5 min Diabetes and Vascular Disease: Preterax
c In older adults, pharmacological ther-
of rest. Cuff size should be appropriate for and Diamicron MR Controlled Evalua-
apy to achieve treatment goals of
the upper-arm circumference. Elevated tionBlood Pressure (ADVANCE-BP), ex-
,130/70 mmHg is not recom-
mended; treating to systolic blood values should be conrmed on a separate amined the benet of tighter blood
day. Postural changes in blood pressure pressure control in patients with type 2
pressure ,130 mmHg has not been
and pulse may be evidence of autonomic diabetes.
shown to improve cardiovascular out-
neuropathy and therefore require adjust- ACCORD. The ACCORD trial examined
comes and treating to diastolic blood
ment of blood pressure targets.
pressure ,70 mmHg has been asso- whether a lower SBP of ,120 mmHg in
Home blood pressure self-monitoring
ciated with higher mortality. C patients with type 2 diabetes at high risk
and 24-h ambulatory blood pressure for ASCVD provided greater cardiovascular
c Lifestyle therapy for elevated blood
monitoring may provide evidence of
pressure consists of weight loss, if protection than an SBP of 130140 mmHg
white-coat hypertension, masked hyper-
overweight or obese; a Dietary Ap- (10). The study did not nd a benet in
tension, or other discrepancies between primary end point (nonfatal MI, nonfatal
proaches to Stop Hypertension
(DASH)-style dietary pattern includ- ofce and true blood pressure. Studies stroke, and cardiovascular death) compar-
ing reducing sodium and increasing
in individuals without diabetes found ing intensive blood pressure treatment
that home measurements may better
potassium intake; moderation of al- (goal ,120 mmHg, average blood pres-
correlate with ASCVD risk than ofce
cohol intake; and increased physical sure achieved 5 119/64 mmHg on 3.4
measurements (5,6). However, most of medications) with standard treatment
activity. B
the evidence of benets of hyperten- (average blood pressure achieved 5
c Pharmacological therapy for patients
sion treatment in people with diabetes 143/70 mmHg on 2.1 medications). In
with diabetes and hypertension
should comprise a regimen that in-
is based on ofce measurements. ACCORD, there was no benet of ag-
cludes either an ACE inhibitor or an Treatment Goals gressive blood pressure lowering, de-
angiotensin receptor blocker but not Epidemiological analyses show that spite the extra cost and efforts.
both. B If one class is not tolerated, blood pressure .115/75 mmHg is asso- ADVANCE. In ADVANCE, the active blood
the other should be substituted. C ciated with increased cardiovascular pressure intervention arm (a single-pill,
c Multiple-drug therapy (including a event rates and mortality in individuals xed-dose combination of perindopril
thiazide diuretic and ACE inhibitor/ with diabetes and that systolic blood and indapamide) showed a signicant
angiotensin receptor blocker, at pressure (SBP) .120 mmHg predicts reduction in the risk of the primary com-
maximal doses) is generally required long-term end-stage renal disease. posite end point (major macrovascular
to achieve blood pressure targets. B Randomized clinical trials have dem- or microvascular event) and signicant
c If ACE inhibitors, angiotensin recep- onstrated the benet (reduction of reductions in the risk of death from any
tor blockers, or diuretics are used, CHD events, stroke, and diabetic kidney cause and of death from cardiovascular
serum creatinine/estimated glomer- disease) of lowering blood pressure to causes (11). The baseline blood pres-
ular ltration rate and serum potas- ,140 mmHg systolic and ,90 mmHg sure among the study subjects was
sium levels should be monitored. E diastolic in individuals with diabetes 145/81 mmHg. Compared with the pla-
c In pregnant patients with diabetes (7). There is limited prespecied clinical cebo group, the patients treated with a
and chronic hypertension, blood trial evidence for the benets of lower single-pill, xed-dose combination of
pressure targets of 110129/6579 SBP or diastolic blood pressure (DBP) perindopril and indapamide experienced
mmHg are suggested in the interest targets (8). A meta-analysis of random- an average reduction of 5.6 mmHg in SBP
of optimizing long-term maternal ized trials of adults with type 2 diabetes and 2.2 mmHg in DBP. The nal blood
health and minimizing impaired fetal comparing intensive blood pressure pressure in the treated group was
growth. E targets (upper limit of 130 mmHg systolic 136/73 mmHg, not quite the intensive
and 80 mmHg diastolic) with standard or tight control achieved in ACCORD.
Hypertension is a common diabetes comor- targets (upper limit of 140160 mmHg Recently published 6-year follow-up
bidity that affects many patients, with the systolic and 85100 mmHg diastolic) of the ADVANCEPost-Trial Observational
prevalence depending on type of diabetes, found no signicant reduction in mortal- Study (ADVANCE-ON) reported that the
age, BMI, and ethnicity. Hypertension is a ity or nonfatal MI. There was a statistically reductions in the risk of death from any
major risk factor for both ASCVD and micro- signicant 35% relative risk (RR) reduc- cause and of death from cardiovascular
vascular complications. In type 1 diabetes, tion in stroke with intensive targets, but causes in the intervention group were
hypertension is often the result of under- the absolute risk reduction was only 1%, attenuated, but remained signicant (12).
lying diabetic kidney disease, while in and intensive targets were associated
SPRINT. Systolic Blood Pressure Interven-
type 2 diabetes, it usually coexists with with an increased risk for adverse events
tion Trial (SPRINT) was a multicenter, ran-
other cardiometabolic risk factors. such as hypotension and syncope (9).
domized controlled trial that compared
Screening and Diagnosis ACCORD, ADVANCE, SPRINT, AND HOT two strategies for treating SBP with either
Blood pressure measurement should be Given the epidemiological relationship be- the standard target of ,140 mmHg or an
done by a trained individual and should tween lower blood pressure and better intensive target of ,120 mmHg; primary
follow the guidelines established for the long-term clinical outcomes, two landmark outcomes were MI, ACS, stroke, heart
general population: measurement in the trials, Action to Control Cardiovascular Risk failure, and death due to cardiovascular
seated position, with feet on the oor and in Diabetes (ACCORD) and Action in disease. Of note, patients with diabetes
S62 Cardiovascular Disease and Risk Management Diabetes Care Volume 39, Supplement 1, January 2016

were excluded from participating in this additional ASCVD risk factors such as dysli- antihypertensive agents, including ACE in-
trial, so the results have no direct impli- pidemia, smoking, or obesity (14). The hibitors, angiotensin receptor blockers
cations for blood pressure management 2016 American Diabetes Association (ARBs), b-blockers, diuretics, and calcium
in this population. The National Insti- (ADA) Standards of Care recommendations channel blockers, has been shown to be
tutes of Health halted this study early have been revised to reect the higher- effective in reducing cardiovascular
because intensive therapy with a target quality evidence that exists to support a events. Several studies have suggested
SBP of 120 mmHg demonstrated a risk goal of DBP ,90 mmHg, although lower that ACE inhibitors may be superior to
reduction of cardiovascular events by targets may be appropriate for certain in- dihydropyridine calcium channel blockers
almost a third and the risk of death dividuals. These targets are in harmoniza- in reducing cardiovascular events (1820).
by almost a quarter compared with a tion with a recent publication by the Eighth However, several studies have also shown
target SBP of 140 mmHg (13). Joint National Committee that recom- no specic advantage to ACE inhibitors as
HOT. The results from the ACCORD and mended for individuals over 18 years of an initial treatment of hypertension in the
Hypertension Optimal Treatment (HOT)
age with diabetes a DBP threshold of general hypertensive population, while
(14) trials support the recommendation ,90 mmHg and SBP ,140 mmHg (8). showing an advantage of initial therapy
with low-dose thiazide diuretics on car-
to achieve blood pressure levels ,140/90
Treatment Strategies diovascular outcomes (17,21,22).
mmHg and underscore the important
clinical difference between patients who Lifestyle Modication Angiotensin Receptor Blockers. In people
are able to easily achieve lower blood Although there are no well-controlled with diabetes, inhibitors of the renin-
pressure levels (e.g., as seen in observa- studies of diet and exercise in the treat- angiotensin system (RAS) may have
tional epidemiological studies) and pa- ment of elevated blood pressure or unique advantages for initial or early
tients who require intensive medical hypertension in individuals with diabe- treatment of hypertension. In a trial of
management to achieve lower blood tes, the Dietary Approaches to Stop individuals at high risk for ASCVD,
pressure goals (e.g., the clinical trials). Hypertension (DASH) study evaluated including a large subset with diabetes,
the impact of healthy dietary patterns an ACE inhibitor reduced ASCVD out-
Systolic Blood Pressure
in individuals without diabetes and has comes (23). In patients with congestive
There is strong evidence that SBP .140 shown antihypertensive effects similar to heart failure, including subgroups with
mmHg is harmful, suggesting that clinicians those of pharmacological monotherapy. diabetes, ARBs have been shown to re-
should promptly initiate and titrate ther-
Lifestyle therapy consists of reducing duce major ASCVD outcomes (2427).
apy in an ongoing fashion to achieve and In patients with type 2 diabetes with
excess body weight, restricting sodium
maintain SBP ,140 mmHg in most pa- signicant diabetic kidney disease,
intake (,2,300 mg/day), increasing con-
tients (see Section 10 Older Adults). A ARBs were superior to calcium channel
sumption of fruits and vegetables (810
recent systematic review and meta-anal- blockers for reducing heart failure (28).
servings per day) and low-fat dairy
ysis evaluating SBP lowering in adults with Although evidence for distinct advantages
products (23 servings per day), avoiding
type 2 diabetes showed that each 10-mmHg of RAS inhibitors on ASCVD outcomes in
excessive alcohol consumption (no more
reduction of SBP was associated with signif-
than 2 servings per day in men and no diabetes remains conicting (11,22), the
icantly lower risk of mortality, cardiovascular
more than 1 serving per day in women) high ASCVD risks associated with diabetes
events, CHD, stroke, albuminuria, and reti- (16), and increasing activity levels (17). and the high prevalence of undiagnosed
nopathy. However, when trials were strati- These lifestyle (nonpharmacological) ASCVD may still favor recommendations
ed by mean baseline SBP $140 mmHg or strategies may also positively affect for their use as rst-line antihypertensive
,140 mmHg, blood pressurelowering glycemia and lipid control and should be therapy in people with diabetes (17).
treatment was associated with lower risks
encouraged in those with even mildly ele- However, the use of both ACE inhibitors
of stroke and albuminuria, regardless of vated blood pressure, although the impact and ARBs in combination is not recom-
initial SBP (15). Therefore, individuals in of lifestyle therapy on cardiovascular events mended given the lack of added ASCVD
whom stroke risk is a concern may, as part
has not been established. Nonpharmaco- benet and increased rate of adverse
of shared decision making, have lower
logical therapy is reasonable in individuals eventsdnamely, hyperkalemia, syncope,
systolic targets such as ,130 mmHg. with diabetes and mildly elevated blood
This is especially true if lower blood pres- and renal dysfunction (29).
pressure (SBP .120 mmHg or DBP .80 Other Pharmacological Interventions
sure can be achieved with few drugs and
mmHg). If the blood pressure is conrmed The blood pressure arm of the ADVANCE
without side effects of therapy.
to be $140 mmHg systolic and/or $90 trial demonstrated that routine adminis-
Diastolic Blood Pressure mmHg diastolic, pharmacological therapy tration of a xed combination of the ACE
Similarly, strong evidence from random- should be initiated along with nonpharma- inhibitor perindopril and the diuretic
ized clinical trials supports DBP targets cological therapy (17). To enable long-term indapamide signicantly reduced com-
of ,90 mmHg. Prior recommendations for adherence, lifestyle therapy should be adap- bined microvascular and macrovascular
ted to suit the needs of the patient and outcomes, as well as death from cardio-
lower DBP targets (,80 mmHg) were based
primarily on a post hoc analysis of the HOT discussed as part of diabetes management. vascular causes and total mortality.
trial (14). A DBP of ,80 mmHg may still be The improved outcomes could also
appropriate for patients with long life expec- Pharmacological Interventions have been due to lower achieved blood
tancy, those with chronic kidney disease, ACE Inhibitors. Lowering of blood pres- pressure in the perindoprilindapamide
elevated urinary albumin excretion, and sure with regimens based on a variety of arm (11). Another trial showed a decrease
care.diabetesjournals.org Cardiovascular Disease and Risk Management S63

in morbidity and mortality in those receiv- drugs known to be effective and safe in
c For patients with diabetes aged
ing benazepril and amlodipine versus be- pregnancy include methyldopa, labetalol,
4075 years with additional ath-
nazepril and hydrochlorothiazide (HCTZ) diltiazem, clonidine, and prazosin. Chronic
erosclerotic cardiovascular dis-
(30). The compelling benets of RAS in- diuretic use during pregnancy is not rec-
ease risk factors, consider using
hibitors in patients with diabetes and al- ommended as it has been associated with
high-intensity statin and lifestyle
buminuria or renal insufciency provide restricted maternal plasma volume, which
may reduce uteroplacental perfusion (33). therapy. B
additional rationale for the use of these
c For patients with diabetes aged
agents (see Section 9 Microvascular
LIPID MANAGEMENT .75 years without additional ath-
Complications and Foot Care). If needed erosclerotic cardiovascular dis-
to achieve blood pressure targets, amlo- Recommendations ease risk factors, consider using
dipine, HCTZ, or chlorthalidone can be
c In adults not taking statins, it is moderate-intensity statin therapy
added. If estimated glomerular ltration
reasonable to obtain a lipid prole and lifestyle therapy. B
rate is ,30 mL/min/1.73 m , a loop di-
2
at the time of diabetes diagnosis, at c For patients with diabetes aged
uretic, rather than HCTZ or chlorthali- an initial medical evaluation, and .75 years with additional athero-
done, should be prescribed. Titration of every 5 years thereafter, or more sclerotic cardiovascular disease risk
and/or addition of further blood pressure
frequently if indicated. E factors, consider using moderate-
medications should be made in a timely
c Obtain a lipid prole at initiation intensity or high-intensity statin
fashion to overcome clinical inertia in of statin therapy and periodically therapy and lifestyle therapy. B
achieving blood pressure targets. thereafter as it may help to mon- c In clinical practice, providers may
Bedtime Dosing itor the response to therapy and need to adjust intensity of statin
Growing evidence suggests that there is inform adherence. E therapy based on individual patient
an association between increase in sleep- c Lifestyle modication focusing on response to medication (e.g., side
time blood pressure and incidence of weight loss (if indicated); the reduc- effects, tolerability, LDL cholesterol
ASCVD events. A randomized controlled tion of saturated fat, trans fat, and levels). E
trial of 448 participants with type 2 di- cholesterol intake; increase of c The addition of ezetimibe to
abetes and hypertension demonstrated omega-3 fatty acids, viscous ber, moderate-intensity statin therapy
reduced cardiovascular events and mor- and plant stanols/sterols intake; and has been shown to provide additional
tality with median follow-up of 5.4 years increased physical activity should be cardiovascular benet compared
if at least one antihypertensive medica- recommended to improve the lipid with moderate-intensity statin ther-
tion was given at bedtime (31). Consider prole in patients with diabetes. A apy alone and may be considered
administering one or more antihyper- c Intensify lifestyle therapy and opti- for patients with a recent acute cor-
tensive medications at bedtime (32). mize glycemic control for patients onary syndrome with LDL cholesterol
Other Considerations with elevated triglyceride levels $50 mg/dL (1.3 mmol/L) or for those
An important caveat is that most patients ($150 mg/dL [1.7 mmol/L]) and/or patients who cannot tolerate high-
with diabetes with hypertension require low HDL cholesterol (,40 mg/dL intensity statin therapy. A
multiple-drug therapy to reach treatment [1.0 mmol/L] for men, ,50 mg/dL c Combination therapy (statin/brate)
goals (16). Identifying and addressing [1.3 mmol/L] for women). C has not been shown to improve ath-
barriers to medication adherence (such c For patients with fasting triglyceride erosclerotic cardiovascular disease
as cost and side effects) should rou- levels $500 mg/dL (5.7 mmol/L), outcomes and is generally not rec-
tinely be done. If blood pressure remains evaluate for secondary causes of ommended. A However, therapy
uncontrolled despite conrmed adher- hypertriglyceridemia and consider with statin and fenobrate may be
ence to optimal doses of at least three medical therapy to reduce the risk considered for men with both tri-
antihypertensive agents of different clas- of pancreatitis. C glyceride level $204 mg/dL (2.3
ses, one of which should be a diuretic, c For patients of all ages with diabetes mmol/L) and HDL cholesterol
clinicians should consider an evaluation and atherosclerotic cardiovascular dis- level #34 mg/dL (0.9 mmol/L). B
for secondary causes of hypertension. ease, high-intensity statin therapy c Combination therapy (statin/niacin)
should be added to lifestyle therapy. A has not been shown to provide
Pregnancy and Antihypertensive
c For patients with diabetes aged additional cardiovascular benet
Medications
,40 years with additional athero- above statin therapy alone and
In a pregnancy complicated by diabetes
sclerotic cardiovascular disease risk may increase the risk of stroke and
and chronic hypertension, target blood
factors, consider using moderate- is not generally recommended. A
pressure goals of SBP 110129 mmHg intensity or high-intensity statin c Statin therapy is contraindicated
and DBP 6579 mmHg are reasonable, and lifestyle therapy. C in pregnancy. B
as they contribute to improved long-
c For patients with diabetes aged
term maternal health. Lower blood
4075 years without additional
pressure levels may be associated with Lifestyle Intervention
atherosclerotic cardiovascular dis-
impaired fetal growth. During preg-
ease risk factors, consider using Lifestyle intervention, including weight
nancy, treatment with ACE inhibitors
moderate-intensity statin and life- loss, increased physical activity, and
and ARBs is contraindicated, as they medical nutrition therapy, allows some
style therapy. A
may cause fetal damage. Antihypertensive patients to reduce ASCVD risk factors.
S64 Cardiovascular Disease and Risk Management Diabetes Care Volume 39, Supplement 1, January 2016

Nutrition intervention should be tailored


Table 8.1Recommendations for statin and combination treatment in people
according to each patients age, diabe- with diabetes
tes type, pharmacological treatment, Age Risk factors Recommended statin intensity*
lipid levels, and medical conditions.
,40 years None None
Recommendations should focus on re-
ASCVD risk factor(s)** Moderate or high
ducing saturated fat, cholesterol, and ASCVD High
trans fat intake and increasing plant 4075 None Moderate
stanols/sterols, omega-3 fatty acids, years ASCVD risk factors High
and viscous ber (such as in oats, le- ASCVD High
gumes, and citrus). Glycemic control ACS and LDL cholesterol .50 mg/dL (1.3 mmol/L) Moderate plus ezetimibe
can also benecially modify plasma lipid in patients who cannot tolerate high-dose statins
levels, particularly in patients with very .75 years None Moderate
high triglycerides and poor glycemic ASCVD risk factors Moderate or high
ASCVD High
control.
ACS and LDL cholesterol .50 mg/dL (1.3 mmol/L) in Moderate plus ezetimibe
patients who cannot tolerate high-dose statins
Statin Treatment
*In addition to lifestyle therapy.
Initiating Statin Therapy Based on Risk
Patients with type 2 diabetes have an **ASCVD risk factors include LDL cholesterol $100 mg/dL (2.6 mmol/L), high blood pressure,
smoking, overweight and obesity, and family history of premature ASCVD.
increased prevalence of lipid abnormal-
ities, contributing to their high risk of
ASCVD. Multiple clinical trials have The Risk Calculator. The
American College Age >75 Years
demonstrated the benecial effects of of Cardiology/American Heart Association For adults with diabetes over 75 years of
pharmacological (statin) therapy on ASCVD risk calculator may be a useful tool age, there are limited data regarding the
ASCVD outcomes in subjects with and to estimate 10-year ASCVD (http://my benets and risks of statin therapy.
without CHD (34,35). Subgroup analy- .americanheart.org). As diabetes itself Statin therapy should be individualized
ses of patients with diabetes in larger confers increased risk for ASCVD, the based on risk prole. High-intensity
trials (3640) and trials in patients risk calculator has limited use for statins, if well tolerated, are still appropri-
assessing cardiovascular risk in indi- ate and recommended for older adults
with diabetes (41,42) showed signi-
cant primary and secondary prevention viduals with diabetes. with ASCVD. High-intensity statin therapy
of ASCVD events and CHD death in may also be appropriate in adults with
Age 40 Years
patients with diabetes. Meta-analyses, diabetes .75 years of age with additional
In all patients with diabetes aged $40
including data from over 18,000 patients years, moderate-intensity statin treat- ASCVD risk factors. However, the risk
with diabetes from 14 randomized trials ment should be considered in addition benet prole should be routinely evalu-
of statin therapy (mean follow-up 4.3 ated in this population, with downward
to lifestyle therapy. Clinical trials in high-
years), demonstrate a 9% proportional re- titration (e.g., high to moderate intensity)
risk patients, such as those with ACS or
duction in all-cause mortality and 13% re- performed as needed. See Section 10
previous cardiovascular events (4749),
duction in vascular mortality for each have demonstrated that more aggressive Older Adults for more details on clinical
mmol/L (39 mg/dL) reduction in LDL cho- considerations for this population.
therapy with high doses of statins led to a
lesterol (43). signicant reduction in further events. Age <40 Years and/or Type 1 Diabetes
As in those without diabetes, abso- Therefore, high-dose statins are recom- Very little clinical trial evidence exists
lute reductions in ASCVD outcomes mended in patients with increased car- for patients with type 2 diabetes under
(CHD death and nonfatal MI) are great- diovascular risk (e.g., LDL cholesterol the age of 40 years or for patients with
est in people with high baseline ASCVD $100 mg/dL [2.6 mmol/L], high blood type 1 diabetes of any age. In the Heart
risk (known ASCVD and/or very high LDL pressure, smoking, albuminuria, and Protection Study (lower age limit
cholesterol levels), but the overall ben- family history of premature ASCVD) or 40 years), the subgroup of ;600 patients
ets of statin therapy in people with di- with ASCVD. with type 1 diabetes had a proportionately
abetes at moderate or even low risk for
ASCVD are convincing (44,45). Statins
are the drugs of choice for LDL choles-
terol lowering and cardioprotection. Table 8.2High-intensity and moderate-intensity statin therapy*
Most trials of statins and ASCVD out- High-intensity statin therapy Moderate-intensity statin therapy
comes tested specic doses of statins Lowers LDL cholesterol by $50% Lowers LDL cholesterol by 30% to ,50%
against placebo or other statins rather Atorvastatin 4080 mg Atorvastatin 1020 mg
than aiming for specic LDL cholesterol Rosuvastatin 2040 mg Rosuvastatin 510 mg
goals (46). In light of this fact, the 2016 Simvastatin 2040 mg
ADA Standards of Care position state- Pravastatin 4080 mg
Lovastatin 40 mg
ment was revised to recommend when Fluvastatin XL 80 mg
to initiate and intensify statin therapy Pitavastatin 24 mg
(high vs. moderate intensity) based on
*Once-daily dosing.
risk prole (Table 8.1 and Table 8.2).
care.diabetesjournals.org Cardiovascular Disease and Risk Management S65

similar, although not statistically signi- be considered in adults with heterozygous levels, are the most prevalent pattern
cant, reduction in risk as patients with familial hypercholesterolemia who require of dyslipidemia in individuals with
type 2 diabetes (37). Even though the additional lowering of LDL cholesterol. type 2 diabetes. However, the evidence
data are not denitive, similar statin for the use of drugs that target these
treatment approaches should be consid- Combination Therapy for LDL lipid fractions is substantially less robust
ered for patients with type 1 or type 2 Cholesterol Lowering than that for statin therapy (57). In a
diabetes, particularly in the presence of Statins and Ezetimibe large trial in patients with diabetes,
other cardiovascular risk factors. Please The IMProved Reduction of Outcomes: fenobrate failed to reduce overall
refer to Type 1 Diabetes Mellitus and Vytorin Efcacy International Trial cardiovascular outcomes (58).
Cardiovascular Disease: A Scientic (IMPROVE-IT) was a randomized con- Combination Therapy
Statement From the American Heart As- trolled trial comparing the addition of
Statin and Fibrate
sociation and American Diabetes Associ- ezetimibe to simvastatin therapy versus
Combination therapy (statin and brate)
ation (50) for additional discussion. simvastatin alone. Individuals were
is associated with an increased risk for
High-intensity statin therapy is recom- $50 years of age who experienced an abnormal transaminase levels, myositis,
mended for all patients with diabetes and ACS within the preceding 10 days and and rhabdomyolysis. The risk of rhabdo-
ASCVD. Treatment with a moderate dose had an LDL cholesterol level $50 mg/dL
of statin should be considered if the myolysis is more common with higher
(1.3 mmol/L). In those with diabetes
patient does not have ASCVD but has doses of statins and renal insufciency
(27%), the combination of moderate-
additional ASCVD risk factors. and appears to be higher when statins
intensity simvastatin (40 mg) and ezetimibe
are combined with gem brozil (59)
(10 mg) showed a signicant reduction
Ongoing Therapy and Monitoring (compared with fenobrate).
of major adverse cardiovascular events
In the ACCORD study, in patients with
With Lipid Panel with an absolute risk reduction of
In adults with diabetes, it is reasonable to
type 2 diabetes who were at high risk for
5% (40% vs. 45%) and RR reduction of
obtain a lipid prole (total cholesterol,
ASCVD, the combination of fenobrate
14% (RR 0.86 [95% CI 0.780.94]) over and simvastatin did not reduce the rate
LDL cholesterol, HDL cholesterol, and moderate-intensity simvastatin (40 mg) of fatal cardiovascular events, nonfatal
triglycerides) at the time of diagnosis, alone (53). Therefore, for people meeting
MI, or nonfatal stroke as compared with
at the initial medical evaluation, and at IMPROVE-IT eligibility criteria who can
least every 5 years thereafter. A lipid simvastatin alone. Prespecied subgroup
only tolerate a moderate-dose statin, the
panel should also be obtained immedi-
analyses suggested heterogeneity in
addition of ezetimibe to statin therapy
ately before initiating statin therapy. treatment effects with possible benet
should be considered.
Once a patient is taking a statin, testing
for men with both a triglyceride level
Statins and PCSK9 Inhibitors
for LDL cholesterol may be considered $204 mg/dL (2.3 mmol/L) and an HDL
Placebo-controlled trials evaluating the cholesterol level #34 mg/dL (0.9
on an individual basis (e.g., to monitor
addition of the novel PCSK9 inhibitors, mmol/L) (60).
for adherence and efcacy). In cases
evolocumab and alirocumab, to maxi-
where patients are adherent, but the Statin and Niacin
mally tolerated doses of statin therapy
LDL cholesterol level is not responding, The Atherothrombosis Intervention
in participants who were at high risk for
clinical judgment is recommended to de- in Metabolic Syndrome With Low
ASCVD demonstrated an average reduc-
termine the need for and timing of lipid HDL/High Triglycerides: Impact on
tion in LDL cholesterol ranging from 36%
panels. In individual patients, the highly Global Health Outcomes (AIM-HIGH) tri-
to 59%. These agents may therefore
variable LDL cholesterollowering re- al randomized over 3,000 patients
be considered as adjunctive therapy
sponse seen with statins is poorly under- (about one-third with diabetes) with es-
for patients with diabetes at high risk for
stood (51). When maximally tolerated tablished ASCVD, low LDL cholesterol
ASCVD events who require additional low-
doses of statins fail to substantially lower levels (,180 mg/dL [4.7 mmol/L]), low
ering of LDL cholesterol or who require
LDL cholesterol (,30% reduction from HDL cholesterol levels (men ,40 mg/dL
but are intolerant to high-intensity statin
the patients baseline), there is no strong
therapy (54,55). It is important to note [1.0 mmol/L] and women ,50 mg/dL
evidence that combination therapy [1.3 mmol/L]), and triglyceride levels of
that the effects of this novel class of agents
should be used. Clinicians should attempt 150400 mg/dL (1.74.5 mmol/L) to sta-
on ASCVD outcomes are unknown as
to nd a dose or alternative statin that is tin therapy plus extended-release niacin
phase 4 studies are currently under way.
tolerable, if side effects occur. There is or placebo. The trial was halted early due
evidence for benet from even extremely Treatment of Other Lipoprotein to lack of efcacy on the primary ASCVD
low, less than daily, statin doses (52). Fractions or Targets outcome (rst event of the composite
Increased frequency of LDL cholesterol Hypertriglyceridemia should be addressed of death from CHD, nonfatal MI, ische-
monitoring should be considered for pa- with dietary and lifestyle changes includ- mic stroke, hospitalization for an ACS, or
tients with new-onset ACS. A recent ran- ing abstinence from alcohol (56). Severe symptom-driven coronary or cerebral re-
domized controlled trial evaluated the hypertriglyceridemia (.1,000 mg/dL) vascularization) and a possible increase
addition of ezetimibe to moderate- may warrant immediate pharmacological in ischemic stroke in those on combina-
intensity statin therapy and demon- therapy (bric acid derivatives and/or sh tion therapy (61). Therefore, combina-
strated ASCVD risk benet over statin oil) to reduce the risk of acute pancreatitis. tion therapy with a statin and niacin is
monotherapy (53). Increased frequency Low levels of HDL cholesterol, often not recommended given the lack of
of LDL cholesterol monitoring may also associated with elevated triglyceride efcacy on major ASCVD outcomes,
S66 Cardiovascular Disease and Risk Management Diabetes Care Volume 39, Supplement 1, January 2016

possible increase in risk of ischemic stroke. There was some evidence of a dif-
stroke, and side effects. disease prevention for adults with
ference in aspirin effect by sex: aspirin
diabetes at low atherosclerotic
Diabetes With Statin Use cardiovascular disease risk (10- signicantly reduced ASCVD events in
Several studies have reported an increased year atherosclerotic cardiovascu- men, but not in women. Conversely, as-
risk of incident diabetes with statin use pirin had no effect on stroke in men but
lar disease risk ,5%), such as in
(62,63), which may be limited to those signicantly reduced stroke in women.
men or women with diabetes aged
with diabetes risk factors. An analysis of However, there was no heterogeneity of
,50 years with no major additional
one of the initial studies suggested that effect by sex in the risk of serious vascular
atherosclerotic cardiovascular dis-
although statins were linked to diabetes ease risk factors, as the potential events (P 5 0.9). Sex differences in
risk, the cardiovascular event rate reduc- adverse effects from bleeding likely aspirins effects have not been observed
tion with statins far outweighed the risk of in studies of secondary prevention (66).
offset the potential benets. C
incident diabetes even for patients at high- In the six trials examined by the ATT
c In patients with diabetes ,50 years collaborators, the effects of aspirin on
est risk for diabetes (64). The absolute risk of age with multiple other risk fac-
increase was small (over 5 years of follow- major vascular events were similar for
tors (e.g., 10-year risk 510%), clin-
up, 1.2% of participants on placebo devel- patients with or without diabetes: RR
ical judgment is required. E
oped diabetes and 1.5% on rosuvastatin 0.88 (95% CI 0.671.15) and RR 0.87
c Use aspirin therapy (75162 mg/day)
developed diabetes) (64). A meta-analysis (95% CI 0.790.96), respectively. The con-
as a secondary prevention strat-
of 13 randomized statin trials with 91,140 egy in those with diabetes and a dence interval was wider for those with
participants showed an odds ratio of 1.09 diabetes because of smaller numbers.
history of atherosclerotic cardio-
for a new diagnosis of diabetes, so that Aspirin appears to have a modest effect
vascular disease. A
(on average) treatment of 255 patients on ischemic vascular events with the
c For patients with atherosclerotic
with statins for 4 years resulted in one absolute decrease in events depending
cardiovascular disease and docu-
additional case of diabetes, while simul- on the underlying ASCVD risk. The main
mented aspirin allergy, clopidog-
taneously preventing 5.4 vascular events adverse effects appear to be an increased
rel (75 mg/day) should be used. B
among those 255 patients (63). risk of gastrointestinal bleeding. The excess
c Dual antiplatelet therapy is reason-
able for up to a year after an acute
risk may be as high as 15 per 1,000 per
Statins and Cognitive Function year in real-world settings. In adults with
A recent systematic review of the U.S. coronary syndrome. B
ASCVD risk .1% per year, the number of
Food and Drug Administrations post- ASCVD events prevented will be similar to
marketing surveillance databases, ran- Risk Reduction or greater than the number of episodes of
domized controlled trials, and cohort, Aspirin has been shown to be effective bleeding induced, although these compli-
case-control, and cross-sectional stud- in reducing cardiovascular morbidity cations do not have equal effects on long-
ies evaluating cognition in patients re- and mortality in high-risk patients with term health (72).
ceiving statins found that published
previous MI or stroke (secondary preven-
data do not reveal an adverse effect of Treatment Considerations
tion). Its net benet in primary prevention
statins on cognition. Therefore, a con- In 2010, a position statement of the
among patients with no previous cardio-
cern that statins might cause cognitive ADA, the American Heart Association,
vascular events is more controversial,
dysfunction or dementia should not and the American College of Cardiology
both for patients with diabetes and for
prohibit their use in individuals with Foundation recommended that low-dose
patients without diabetes (66,67). Previ-
diabetes at high risk for ASCVD (65). (75162 mg/day) aspirin for primary
ous randomized controlled trials of aspi-
prevention is reasonable for adults
rin specically in patients with diabetes with diabetes and no previous history
ANTIPLATELET AGENTS failed to consistently show a signicant of vascular disease who are at increased
Recommendations reduction in overall ASCVD end points,
ASCVD risk (10-year risk of ASCVD events
c Consider aspirin therapy (75162 raising questions about the efcacy of over 10%) and who are not at increased
mg/day) as a primary prevention aspirin for primary prevention in people
risk for bleeding. This previous recom-
strategy in those with type 1 or with diabetes, although some sex differ-
mendation included most men over age
type 2 diabetes who are at increased ences were suggested (6871). 50 years and women over age 60 years
cardiovascular risk (10-year risk The Antithrombotic Trialists (ATT) who also have one or more of the follow-
.10%). This includes most men or collaborators published an individual
ing major risk factors: smoking, hyperten-
patient-level meta-analysis of the six
women with diabetes aged $50 sion, dyslipidemia, family history of
years who have at least one addi- large trials of aspirin for primary preven-
premature ASCVD, and albuminuria (73).
tional major risk factor (family his- tion in the general population. These tri-
tory of premature atherosclerotic als collectively enrolled over 95,000 Sex Considerations
cardiovascular disease, hyperten- participants, including almost 4,000 Multiple recent well-conducted studies
sion, smoking, dyslipidemia, or al- with diabetes. Overall, they found that and meta-analyses reported a risk of
buminuria) and are not at increased aspirin reduced the risk of serious vascular heart disease and stroke that is equiva-
events by 12% (RR 0.88 [95% CI 0.82 lent if not higher in women compared
risk of bleeding. C
0.94]). The largest reduction was for non- with men with diabetes, including among
c Aspirin should not be recommended
for atherosclerotic cardiovascular fatal MI, with little effect on CHD death nonelderly adults. Thus, the recommen-
(RR 0.95 [95% CI 0.781.15]) or total dations for using aspirin as primary
care.diabetesjournals.org Cardiovascular Disease and Risk Management S67

prevention are now revised to include Indications for P2Y12 Use the initial test. In adults with diabetes
both men and women aged $50 years A P2Y12 receptor antagonist in combi- $40 years of age, measurement of cor-
with diabetes and one or more major nation with aspirin should be used for at onary artery calcium is also reasonable
risk factors to reect these more recent least 1 year in patients following an ACS. for cardiovascular risk assessment.
ndings (7477). Sex differences in the Evidence supports use of either ticagrelor Pharmacological stress echocardiography
antiplatelet effect of aspirin have been or clopidogrel if no percutaneous cor- or nuclear imaging should be considered
suggested in the general population onary intervention was performed and in individuals with diabetes in whom rest-
(78); however, further studies are needed clopidogrel, ticagrelor, or prasugrel if a ing ECG abnormalities preclude exercise
to investigate the presence of such differ- percutaneous coronary intervention stress testing (e.g., left bundle branch
ences in individuals with diabetes. was performed (82). block or ST-T abnormalities). In addition,
individuals who require stress testing and
Aspirin Use in People <50 Years of Age
CORONARY HEART DISEASE are unable to exercise should undergo
Aspirin is not recommended for those at
Recommendations pharmacological stress echocardiography
low risk of ASCVD (such as men and
or nuclear imaging.
women aged ,50 years with diabetes Screening
with no other major ASCVD risk factors;
c In asymptomatic patients, routine Screening Asymptomatic Patients
10-year ASCVD risk ,5%) as the low screening for coronary artery dis- The screening of asymptomatic patients
benet is likely to be outweighed by ease is not recommended as it with high ASCVD risk is not recommended
the risks of signicant bleeding. Clinical does not improve outcomes as (44), in part because these high-risk
judgment should be used for those at
long as atherosclerotic cardiovascu- patients should already be receiving
intermediate risk (younger patients
lar disease risk factors are treated. A intensive medical therapydan approach
with one or more risk factors or older
c Consider investigations for coro- that provides similar benet as invasive
patients with no risk factors; those
nary artery disease in the presence revascularization (83,84). There is also
with 10-year ASCVD risk of 510%) until of any of the following: atypical car- some evidence that silent MI may reverse
further research is available. Aspirin use
diac symptoms (e.g., unexplained over time, adding to the controversy con-
in patients aged ,21 years is contrain- dyspnea, chest discomfort); signs cerning aggressive screening strategies
dicated due to the associated risk of
or symptoms of associated vascular (85). In prospective trials, coronary artery
Reye syndrome. disease including carotid bruits, calcium has been established as an inde-
Aspirin Dosing transient ischemic attack, stroke, pendent predictor of future ASCVD
Average daily dosages used in most clini- claudication, or peripheral arterial events in patients with diabetes and
cal trials involving patients with diabetes disease; or electrocardiogram ab- is superior to both the UK Prospective
ranged from 50 mg to 650 mg but were normalities (e.g., Q waves). E Diabetes Study (UKPDS) risk engine
mostly in the range of 100325 mg/day. and the Framingham Risk Score in pre-
Treatment
There is little evidence to support any dicting risk in this population (8688).
c In patients with known atheroscle-
specic dose, but using the lowest However, a randomized observational
rotic cardiovascular disease, use as-
possible dose may help to reduce side
pirin and statin therapy (if not trial demonstrated no clinical benet
effects (79). In the U.S., the most com- to routine screening of asymptomatic
contraindicated) A and consider
mon low-dose tablet is 81 mg. Although patients with type 2 diabetes and normal
platelets from patients with diabetes
ACE inhibitor therapy C to reduce ECGs (89). Despite abnormal myocardial
the risk of cardiovascular events.
have altered function, it is unclear what, perfusion imaging in more than one in
c In patients with prior myocardial in-
if any, effect that nding has on the ve patients, cardiac outcomes were
farction, b-blockers should be con-
required dose of aspirin for cardiopro- essentially equal (and very low) in
tinued for at least 2 years after the
tective effects in the patient with dia- screened versus unscreened patients.
event. B
betes. Many alternate pathways for Accordingly, indiscriminate screening
c In patients with symptomatic
platelet activation exist that are inde- is not considered cost-effective. Studies
heart failure, thiazolidinedione
pendent of thromboxane A and thus have found that a risk factorbased
treatment should not be used. A
2

not sensitive to the effects of aspirin approach to the initial diagnostic eval-
c In patients with type 2 diabetes with
(80). Aspirin resistance appears higher uation and subsequent follow-up for
stable congestive heart failure, met-
in patients with diabetes when mea- coronary artery disease fails to identify
formin may be used if renal function
sured by a variety of ex vivo and in vitro which patients with type 2 diabetes will
is normal but should be avoided in
methods (platelet aggregometry, mea- have silent ischemia on screening tests
unstable or hospitalized patients
surement of thromboxane B ) (78). A re- (90,91). Any benet of newer noninva-
with congestive heart failure. B
2

cent trial suggested that more frequent sive coronary artery disease screening
dosing regimens of aspirin may reduce Cardiac Testing methods, such as computed tomography
platelet reactivity in individuals with dia- Candidates for advanced or invasive and computed tomography angiography,
betes (81); however, these observations cardiac testing include those with 1) typ- to identify patient subgroups for different
alone are insufcient to empirically rec- ical or atypical cardiac symptoms and 2) treatment strategies remains unproven.
ommend that higher doses of aspirin be an abnormal resting electrocardiogram Although asymptomatic patients with di-
used in this group at this time. It appears (ECG). Exercise ECG testing without or abetes with higher coronary disease bur-
that 75162 mg/day is optimal. with echocardiography may be used as den have more future cardiac events
S68 Cardiovascular Disease and Risk Management Diabetes Care Volume 39, Supplement 1, January 2016

(86,92,93), the role of these tests beyond Cardiovascular Outcomes with Sitagliptin other glucose-lowering treatments in
risk stratication is not clear. Their routine (TECOS), recent multicenter, randomized, patients with diabetes and congestive
use leads to radiation exposure and may double-blind, noninferiority trials, evalu- heart failure, even in those with reduced
result in unnecessary invasive testing such ated heart failure and mortality outcomes left ventricular ejection fraction or con-
as coronary angiography and revasculari- in patients with type 2 diabetes taking comitant chronic kidney disease; however,
zation procedures. The ultimate balance of different DPP-4 inhibitors, alogliptin metformin should be avoided in hospi-
benet, cost, and risks of such an approach and sitagliptin, respectively, compared talized patients (105).
in asymptomatic patients remains contro- with placebo. EXAMINE reported that
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S72 Diabetes Care Volume 39, Supplement 1, January 2016

9. Microvascular Complications American Diabetes Association

and Foot Care


Diabetes Care 2016;39(Suppl. 1):S72S80 | DOI: 10.2337/dc16-S012

DIABETIC KIDNEY DISEASE


Recommendations

Screening
c At least once a year, assess urinary albumin (e.g., spot urinary albuminto
creatinine ratio) and estimated glomerular ltration rate in patients with
S ANDFOOT CARE

type 1 diabetes with duration of $5 years, in all patients with type 2 diabetes,
and in all patients with comorbid hypertension. B
Treatment
c Optimize glucose control to reduce the risk or slow the progression of diabetic
kidney disease. A
ICATION

c Optimize blood pressure control (,140/90 mmHg) to reduce the risk or slow
the progression of diabetic kidney disease. A
R COMPL

c For people with nondialysis-dependent diabetic kidney disease, dietary pro-


tein intake should be 0.8 g/kg body weight per day (the recommended daily
allowance). For patients on dialysis, higher levels of dietary protein intake
OVASCULA

should be considered. A
c Either an ACE inhibitor or an angiotensin receptor blocker is recommended for
the treatment of nonpregnant patients with diabetes and modestly elevated
9. MICR

urinary albumin excretion (30299 mg/day) B and is strongly recommended


for those with urinary albumin excretion $300 mg/day and/or estimated
glomerular ltration rate ,60 mL/min/1.73 m . A 2

c Periodically monitor serum creatinine and potassium levels for the develop-
ment of increased creatinine or changes in potassium when ACE inhibitors,
angiotensin receptor blockers, or diuretics are used. E
c Continued monitoring of urinary albumintocreatinine ratio in patients with
albuminuria treated with an ACE inhibitor or an angiotensin receptor blocker is
reasonable to assess the response to treatment and progression of diabetic
kidney disease. E
c An ACE inhibitor or an angiotensin receptor blocker is not recommended for
the primary prevention of diabetic kidney disease in patients with diabetes
who have normal blood pressure, normal urinary albumintocreatinine ratio
(,30 mg/g), and normal estimated glomerular ltration rate. B
c When estimated glomerular ltration rate is ,60 mL/min/1.73 m , evaluate
2

and manage potential complications of chronic kidney disease. E


c Patients should be referred for evaluation for renal replacement treatment if
they have estimated glomerular ltration rate ,30 mL/min/1.73 m . A 2

c Promptly refer to a physician experienced in the care of kidney disease for


uncertainty about the etiology of kidney disease, difcult management issues,
and rapidly progressing kidney disease. B
Suggested citation: American Diabetes Associ-
Assessment of Albuminuria and Renal Function ation. Microvascular complications and foot
Diabetic kidney disease, or kidney disease attributed to diabetes, occurs in 2040% care. Sec. 9. In Standards of Medical Care in
of patients with diabetes and is the leading cause of end-stage renal disease Diabetesd2016. Diabetes Care 2016;39(Suppl. 1):
(ESRD) (1). S72S80
Screening for kidney damage (albuminuria) can be most easily performed by 2016 by the American Diabetes Association.
urinary albumintocreatinine ratio (UACR) in a random spot urine collection. Readers may use this article as long as the work
Timed or 24-h collections are more burdensome and add little to prediction or is properly cited, the use is educational and not
for prot, and the work is not altered.
care.diabetesjournals.org Microvascular Complications and Foot Care S73

accuracy (2,3). Measurement of a spot blood pressure control is a subject of not progress to higher levels over 510
urine sample for albumin alone (whether debate. Continued surveillance can as- years of follow-up (5,911). Patients
by immunoassay or by using a sensitive sess both response to therapy and dis- with persistent and severely increased
dipstick test specic for albuminuria) ease progression and may aid in assessing ($300 mg/g Cr) levels of albuminuria
without simultaneously measuring urine adherence to ACE inhibitor or ARB ther- are likely to develop ESRD (12,13).
creatinine (Cr) is less expensive but sus- apy. Some suggest that reducing UACR to The presence of diabetic retinopathy
ceptible to false-negative and false- normal (,30 mg/g Cr) or near normal in patients with UACR $300 mg/g Cr
positive determinations as a result of may improve CKD and cardiovascular strongly suggests diabetic kidney dis-
variation in urine concentration due to disease (CVD) prognosis, but this ap- ease, and its absence in those with re-
hydration. proach has not been formally evaluated duced eGFR and UACR ,300 mg/g Cr
Normal UACR is dened as ,30 mg/g in prospective trials, and evidence suggests nondiabetic CKD. Other causes
Cr, and increased urinary albumin excre- demonstrates spontaneous remission of CKD should be considered in patients
tion is dened as $30 mg/g Cr. Because of albuminuria in up to 40% of patients with diabetes and CKD but without di-
of variability in urinary albumin excretion, with type 1 diabetes. abetic retinopathy and in those with an
two of three specimens of UACR collected Progression of Diabetic Kidney Disease active urine sediment, with rapidly in-
within a 3- to 6-month period should be Conversely, patients with increasing creasing proteinuria or nephrotic syn-
abnormal before considering a patient to UACR, declining eGFR, retinopathy, in- drome with low or rapidly decreasing
have albuminuria. Exercise within 24 h, creasing blood pressure, macrovascular eGFR, with .30% reduction in eGFR
infection, fever, congestive heart failure, disease, elevated lipids and/or uric acid within 23 months of initiating ACE in-
marked hyperglycemia, menstruation, concentrations, or a family history of hibitor or ARB therapy, with refractory
and marked hypertension may elevate CKD are more likely to experience a pro- hypertension, or with signs or symp-
UACR independently of kidney damage. gression of diabetic kidney disease (5). toms of other systemic diseases.
Complications of kidney disease cor-
Estimated Glomerular Filtration Rate Interventions
Serum Cr should be used to estimate relate with level of kidney function. Nutrition
glomerular ltration rate (GFR). Esti-
When eGFR is ,60 mL/min/1.73 m , 2
For people with nondialysis-dependent
mated GFR (eGFR) is commonly report- screening for complications of CKD is in- diabetic kidney disease, dietary protein
ed by laboratories or can be estimated dicated (Table 9.2). Early vaccination intake should be 0.8 g/kg body weight
against hepatitis B virus is indicated in per day (the recommended daily allow-
using formulae such as the Modication
patients likely to progress to ESRD.
of Diet in Renal Disease (MDRD) study ance). Compared with higher levels of
Identifying and monitoring diabetic
equation (4) or the Chronic Kidney dietary protein intake, this level slowed
kidney disease relies on assessments of
Disease Epidemiology Collaboration GFR decline with evidence of a greater
kidney damage (albuminuria) and kid-
(CKD-EPI) equation. The latter is the pre- effect over time. Higher levels of dietary
ferred GFR estimating equation. GFR ney function (eGFR). Persistently in-
protein intake (.20% of daily calories
calculators are available at http:// creased UACR in the range of UACR
from protein or .1.3 g/kg/day) have
www.nkdep.nih.gov. 30299 mg/g Cr is an early indicator of been associated with increased albu-
Abnormal urinary albumin excretion diabetic kidney disease in type 1 diabe- minuria, more rapid kidney function
tes and a marker for development of di-
and eGFR may be used to stage chronic loss, and CVD mortality and therefore
abetic kidney disease in type 2 diabetes.
kidney disease (CKD). The National Kid- should be avoided. Reducing the
It is also a well-established marker of amount of dietary protein below the
ney Foundation classication (Table 9.1)
is based on both kidney damage (UACR increased CVD risk (68). recommended daily allowance of 0.8
Not all people with diabetes, kidney
$30 mg/g Cr) and eGFR. g/kg/day is not recommended because
disease, and reduced eGFR have albumin-
it does not alter glycemic measures, car-
Surveillance uria. In addition, there is increasing evi-
diovascular risk measures, or the course
The need for annual quantitative as- dence that up to 40% of patients with of GFR decline.
sessment of albumin excretion after di- type 1 diabetes and UACR levels 30299
Glycemia
agnosis of albuminuria, institution of mg/g Cr have spontaneous remissions
ACE inhibitor or angiotensin receptor A number of interventions have been
and approximately 3040% remain with
blocker (ARB) therapy, and achieving demonstrated to reduce the risk and
UACR levels of 30299 mg/g Cr and do
slow the progression of diabetic kidney
disease. Intensive diabetes manage-
Table 9.1Stages of CKD ment with the goal of achieving near-
Stage Description GFR (mL/min/1.73 m ) 2
normoglycemia has been shown in large
1 Kidney damage* with normal or increased eGFR $90 prospective randomized studies to delay
2 Kidney damage* with mildly decreased eGFR the onset and progression of increased
6089
3 Moderately decreased eGFR urinary albumin excretion and reduced
3059
4 Severely decreased eGFR
eGFR in patients with type 1 diabetes
1529
5 Kidney failure (13) and type 2 diabetes (1,1417).
,15 or dialysis
Despite prior concerns and published
*Kidney damage is dened as abnormalities on pathological, urine, blood, or imaging tests. case reports, current data indicate that
Adapted from Levey et al. (3).
the overall risk of metformin-associated
S74 Microvascular Complications and Foot Care Diabetes Care Volume 39, Supplement 1, January 2016

Table 9.2Management of CKD in diabetes in hyperkalemic episodes in those on dual


GFR (mL/min/1.73 m ) 2
Recommended management therapy, and larger trials are needed be-
fore recommending such therapy.
All patients Yearly measurement of Cr, UACR, potassium
Diuretics, calcium channel blockers,
4560 Referral to a nephrologist if possibility for nondiabetic kidney
and b-blockers can be used as add-on
disease exists (duration of type 1 diabetes ,10 years, therapy to achieve blood pressure goals
persistent albuminuria, abnormal ndings on renal in patients treated with maximum doses
ultrasound, resistant hypertension, rapid fall in eGFR, or
active urinary sediment on urine microscopic examination) of ACE inhibitors or ARBs (26) or as alter-
Consider the need for dose adjustment of medications nate therapy in the rare individual unable
Monitor eGFR every 6 months to tolerate ACE inhibitors and ARBs.
Monitor electrolytes, bicarbonate, hemoglobin, calcium,
Referral to a Nephrologist
phosphorus, and parathyroid hormone at least yearly
Assure vitamin D sufciency Consider referral to a physician experi-
Consider bone density testing enced in the care of kidney disease when
Referral for dietary counseling there is uncertainty about the etiology of
3044 Monitor eGFR every 3 months kidney disease (absence of retinopathy,
Monitor electrolytes, bicarbonate, calcium, phosphorus, heavy proteinuria, active urine sediment,
parathyroid hormone, hemoglobin, albumin, and weight or rapid decline in GFR). Other triggers for
every 36 months
Consider the need for dose adjustment of medications
referral may include difcult management
issues (anemia, secondary hyperparathy-
,30 Referral to a nephrologist
roidism, metabolic bone disease, resistant
hypertension, or electrolyte disturbances)
lactic acidosis is low (1). GFR may be a ,130 mmHg to avoid diastolic blood or advanced kidney disease. The threshold
more appropriate measure to assess for referral may vary depending on the
pressure levels below 6070 mmHg.
frequency with which a provider en-
continued metformin use than serum The UK Prospective Diabetes Study
counters patients with diabetes and
Cr, considering that the serum Cr level (UKPDS) provided strong evidence that
kidney disease. Consultation with a ne-
can translate into widely varying blood pressure control can reduce the de-
phrologist when stage 4 CKD develops
eGFR levels depending on age, ethnic- velopment of diabetic kidney disease (22).
ity, and muscle mass (18). A review Interruption of the renin-angiotensin- (eGFR #30 mL/min/1.73 m ) has been
2

(19) proposed that metformin use aldosterone system with either ACE found to reduce cost, improve quality of
care, and delay dialysis (27). However,
should be reevaluated at an eGFR inhibitors or ARBs contributes to reduc-
other specialists and providers should
,45 mL/min/1.73 m with a reduction
2 tions of kidney disease events in hy-
also educate their patients about the pro-
in maximum dose to 1,000 mg/day. pertensive patients with diabetes and
Metformin should be discontinued gressive nature of diabetic kidney disease,
eGFR ,60 mL/min/1.73 m and UACR 2

the kidney preservation benets of pro-


when eGFR is ,30 mL/min/1.73 m ; in 2
$300 mg/g Cr.
active treatment of blood pressure and
clinical situations in which there is an ACE inhibitors have been shown to re-
blood glucose, and the potential need for
increased risk of lactic acidosis, such duce major CVD events in patients with
renal replacement therapy.
as sepsis, hypotension, and hypoxia; or diabetes (23), thus further supporting the
when there is a high risk of acute kidney use of these agents in patients with albu-
injury resulting in a worsening of GFR, such minuria, a CVD risk factor. In those with DIABETIC RETINOPATHY
as administration of radiocontrast dye in diabetic kidney disease, some evidence Recommendations
those with eGFR ,60 mL/min/1.73 m . 2 suggests that ARBs compared with ACE
c Optimize glycemic control to re-
Blood Pressure inhibitors are associated with a smaller
duce the risk or slow the progres-
There are no randomized controlled tri- increase in serum potassium levels (24).
sion of diabetic retinopathy. A
als of blood pressure levels in diabetes Combination Therapy
c Optimize blood pressure and se-
that have examined CKD events as out- Two clinical trials studied the combina- rum lipid control to reduce the
comes. Blood pressure levels below tions of ACE inhibitors and ARBs and risk or slow the progression of di-
140/90 mmHg in diabetes are recom- found no benets on CVD or diabetic abetic retinopathy. A
mended to reduce CVD mortality and kidney disease, and the drug combina-
Screening
slow CKD progression. In individuals tion had higher adverse event rates (hy-
c Adults with type 1 diabetes should
with albuminuria, consider lower blood perkalemia and/or acute kidney injury)
have an initial dilated and compre-
pressure targets of ,130/80 mmHg (25). Therefore, the combined use of ACE
hensive eye examination by an oph-
(20,21). Of note, there is an adverse inhibitors and ARBs should be avoided. thalmologist or optometrist within
safety signal in clinical trials of diabetic Mineralocorticoid receptor blockers
kidney disease when diastolic blood pres- (spironolactone) in combination with ACE 5 years after the onset of diabetes. B
c Patients with type 2 diabetes should
sure is treated to below 70 mmHg and inhibitors or ARBs remain an area of great
have an initial dilated and compre-
especially below 60 mmHg in older pop- interest and have been explored in several
hensive eye examination by an oph-
ulations. As a result, clinical judgment short-term studies with a positive effect on
thalmologist or optometrist at the
should be used when attempting to albuminuria reduction in diabetic kidney
achieve systolic blood pressure targets disease. There was, however, an increase time of the diabetes diagnosis. B
care.diabetesjournals.org Microvascular Complications and Foot Care S75

ty p e 2 di a b et e s , w i t h p r e v a l e n c e controlled type 2 diabetes, there was


c If there is no evidence of retinop-
strongly related to both the duration essentially no risk of development of
athy for one or more annual eye
of diabetes and the level of glycemic signicant retinopathy with a 3-year in-
exams, then exams every 2 years
control. Diabetic retinopathy is the terval after a normal examination (35).
may be considered. If any level of
most frequent cause of new cases of Examinations will be required more fre-
diabetic retinopathy is present,
blindness among adults aged 2074 quently by the ophthalmologist if reti-
subsequent dilated retinal exami-
years in developed countries. Glaucoma, nopathy is progressing.
nations for patients with type 1 or
cataracts, and other disorders of the eye Retinal photography, with remote
type 2 diabetes should be re-
occur earlier and more frequently in reading by experts, has great potential
peated at least annually by an
people with diabetes. to provide screening services in areas
ophthalmologist or optometrist.
In addition to diabetes duration, where qualied eye care professionals
If retinopathy is progressing or
factors that increase the risk of, or are are not readily available (36). High-quality
sight-threatening, then examina-
associated with, retinopathy include fundus photographs can detect most
tions will be required more fre-
chronic hyperglycemia (28), nephropa- clinically signicant diabetic retinopathy.
quently. B
thy (29), hypertension (30), and dys- Interpretation of the images should be
c While retinal photography may
lipidemia (31). Intensive diabetes performed by a trained eye care pro-
serve as a screening tool for reti-
management with the goal of achieving vider. Retinal photography may also en-
nopathy, it is not a substitute for a
near-normoglycemia has been shown in hance efciency and reduce costs when
comprehensive eye exam, which
large prospective randomized studies to the expertise of ophthalmologists can be
should be performed at least ini-
prevent and/or delay the onset and pro- used for more complex examinations and
tially and at intervals thereafter as
gression of diabetic retinopathy (15,32). for therapy (37). In-person exams are still
recommended by an eye care pro-
Lowering blood pressure has been necessary when the retinal photos are un-
fessional. E
shown to decrease retinopathy progres- acceptable and for follow-up if abnormal-
c Eye examinations should occur be-
sion, although tight targets (systolic ities are detected. Retinal photos are
fore pregnancy or in the rst tri-
,120 mmHg) do not impart additional not a substitute for a comprehensive
mester, and then patients should
benet (32). In patients with dyslipide- eye exam, which should be performed
be monitored every trimester and
mia, retinopathy progression may be at least initially and at intervals thereafter
for 1 year postpartum as indicated
slowed by the addition of fenobrate, as recommended by an eye care profes-
by the degree of retinopathy. B
particularly with very mild nonprolifer- sional. Results of eye examinations should
Treatment ative diabetic retinopathy (NPDR) at be documented and transmitted to the
c Promptly refer patients with any baseline (31). Several case series and a referring health care professional.
level of macular edema, severe controlled prospective study suggest Type 1 Diabetes
nonproliferative diabetic retinop- that pregnancy in patients with type 1 Because retinopathy is estimated to
athy (a precursor of proliferative diabetes may aggravate retinopathy and take at least 5 years to develop after
diabetic retinopathy), or any pro- threaten vision, especially when glyce- the onset of hyperglycemia, patients
liferative diabetic retinopathy to mic control is poor at the time of con- with type 1 diabetes should have an ini-
an ophthalmologist who is knowl- ception (33,34). Laser photocoagulation tial dilated and comprehensive eye ex-
edgeable and experienced in the surgery can minimize the risk of vision amination within 5 years after the
management and treatment of di- loss (34). diagnosis of diabetes (38).
abetic retinopathy. A
Type 2 Diabetes
c Laser photocoagulation therapy is Screening
indicated to reduce the risk of vision Patients with type 2 diabetes who may
The preventive effects of therapy and
loss in patients with high-risk pro- have had years of undiagnosed diabetes
the fact that patients with proliferative
liferative diabetic retinopathy and, diabetic retinopathy (PDR) or macular and have a signicant risk of prevalent
in some cases, severe nonprolifera- edema may be asymptomatic provide diabetic retinopathy at the time of di-
tive diabetic retinopathy. A agnosis should have an initial dilated
strong support for screening to detect
Intravitreal injections of antivas- and comprehensive eye examination at
c diabetic retinopathy.
cular endothelial growth factor the time of diagnosis.
An ophthalmologist or optometrist
are indicated for center-involved who is knowledgeable and experienced Pregnancy
diabetic macular edema, which oc- in diagnosing diabetic retinopathy Pregnancy is associated with a rapid
curs beneath the foveal center and should perform the examinations. If di- progression of diabetic retinopathy
may threaten reading vision. A abetic retinopathy is present, prompt (39,40). Women with preexisting type
c The presence of retinopathy is referral to an ophthalmologist is recom- 1 or type 2 diabetes who are planning
not a contraindication to aspirin mended. Subsequent examinations for pregnancy or who have become preg-
therapy for cardioprotection, as patients with type 1 or type 2 diabetes nant should be counseled on the risk
aspirin does not increase the risk are generally repeated annually for pa- of development and/or progression of
of retinal hemorrhage. A tients with minimal to no retinopathy. diabetic retinopathy. In addition, rapid
Exams every 2 years may be cost- implementation of tight glycemic con-
Diabetic retinopathy is a highly specic effective after one or more normal eye trol in the setting of retinopathy is asso-
vascular complication of both type 1 and exams, and in a population with well- ciated with worsening of retinopathy
S76 Microvascular Complications and Foot Care Diabetes Care Volume 39, Supplement 1, January 2016

(34). Women who develop gestational di- replaced the need for laser photocoag- 3. Up to 50% of diabetic peripheral
abetes mellitus do not require an eye ulation in the vast majority of patients neuropathy (DPN) may be asymp-
examination during pregnancy and do with diabetic macular edema (47). tomatic. If not recognized and if pre-
not appear to be at increased risk of Most patients require near-monthly ventive foot care is not implemented,
developing diabetic retinopathy during administration of intravitreal therapy patients are at risk for injuries to their
pregnancy (41). with anti-VEGF agents during the rst insensate feet.
12 months of treatment with fewer in- 4. Recognition and treatment of auto-
Treatment
jections needed in subsequent years to nomic neuropathy may improve
Two of the main motivations for screen-
maintain remission from center-involved symptoms, reduce sequelae, and im-
ing for diabetic retinopathy are to pre-
diabetic macular edema. Other emerging prove quality of life.
vent loss of vision and to intervene with
therapies for retinopathy that may use
treatment when vision loss can be pre-
sustained intravitreal delivery of phar- Specic treatment for the underlying
vented or reversed.
macological agents are currently under nerve damage, other than improved gly-
Photocoagulation Surgery cemic control, is currently not available.
investigation.
Two large trials, the Diabetic Retinopathy Glycemic control can effectively prevent
Study (DRS) in patients with PDR and the NEUROPATHY DPN and cardiac autonomic neuropathy
Early Treatment Diabetic Retinopathy (CAN) in type 1 diabetes (48,49) and may
Recommendations
Study (ETDRS) in patients with macular modestly slow their progression in type 2
edema, provide the strongest support Screening diabetes (17) but does not reverse neuro-
for the therapeutic benets of photoco- c All patients should be assessed for nal loss. Therapeutic strategies (pharma-
agulation surgery. The DRS (42) showed diabetic peripheral neuropathy cological and nonpharmacological) for
that panretinal photocoagulation surgery starting at diagnosis of type 2 di- the relief of symptoms related to painful
reduced the risk of severe vision loss from abetes and 5 years after the diag- DPN or autonomic neuropathy can poten-
PDR from 15.9% in untreated eyes to nosis of type 1 diabetes and at tially reduce pain (50) and improve qual-
6.4% in treated eyes, with the greatest least annually thereafter. B ity of life.
riskbenet ratio in those with baseline c Assessment should include a care-
disease (disc neovascularization or vitre- ful history and 10-g monolament Diagnosis
ous hemorrhage). The ETDRS also veried testing and at least one of the fol- Diabetic Peripheral Neuropathy
the benets of panretinal photocoagula- lowing tests: pinprick, tempera- Patients with type 1 diabetes for 5
tion for high-risk PDR and in older-onset ture, or vibration sensation. B or more years and all patients with
patients with severe NPDR or less-than- c Symptoms and signs of autonomic type 2 diabetes should be assessed an-
high-risk PDR. Panretinal laser photoco- neuropathy should be assessed in nually for DPN using medical history
agulation is still commonly used to patients with microvascular and and simple clinical tests. Symptoms
manage complications of diabetic reti- neuropathic complications. E vary according to the class of sensory
nopathy that involve retinal neovasculari-
Treatment bers involved. The most common
zation and its complications. early symptoms are induced by the in-
c Optimize glucose control to pre-
Antivascular Endothelial Growth Factor vent or delay the development of volvement of small bers and include
Treatment neuropathy in patients with type 1 pain and dysesthesias (unpleasant
While the ETDRS (43) established the diabetes A and to slow the pro- sensations of burning and tingling).
benet of focal laser photocoagulation gression of neuropathy in patients The involvement of large bers may
surgery in eyes with clinically signicant with type 2 diabetes. B cause numbness and loss of protective
macular edema (dened as retinal c Assess and treat patients to reduce sensation (LOPS). LOPS indicates the
edema located at or within 500 mm of pain related to diabetic peripheral presence of distal sensorimotor poly-
the center of the macula), current data neuropathy B and symptoms of au- neuropathy and is a risk factor for di-
from multiple well-designed clinical tri- tonomic neuropathy and to im- abetic foot ulceration. The following
als demonstrate that intravitreal anti- prove quality of life. E clinical tests may be used to assess
vascular endothelial growth factor small- and large- ber function and
(anti-VEGF) agents provide a more ef- The diabetic neuropathies are a hetero- protective sensation:
fective treatment regimen for center- geneous group of disorders with diverse
involved diabetic macular edema than clinical manifestations. The early recog- 1. Small-ber function: pinprick and
monotherapy or even combination ther- nition and appropriate management of temperature sensation
apy with laser (4446). neuropathy in the patient with diabetes 2. Large-ber function: vibration per-
Historically, laser photocoagulation is important. ception, 10-g monolament, and an-
surgery in both trials was benecial in kle reexes
reducing the risk of further visual loss 1. Diabetic neuropathy is a diagnosis of 3. Protective sensation: 10-g monolament
in affected patients but generally not exclusion. Nondiabetic neuropathies
benecial in reversing already dimin- may be present in patients with di- These tests not only screen for the pres-
ished acuity. Now, intravitreal therapy abetes and may be treatable. ence of dysfunction but also predict future
with recombinant monoclonal neutralizing 2. Numerous treatment options exist for risk of complications. Electrophysiological
antibody to VEGF improves vision and has symptomatic diabetic neuropathy. testing or referral to a neurologist is rarely
care.diabetesjournals.org Microvascular Complications and Foot Care S77

needed, except in situations where the results are likely to be abnormal in the of painful DPN, may be effective and
clinical features are atypical or the diag- setting of recent uncontrolled hypergly- considered for the treatment of painful
nosis is unclear. cemia or diabetic ketoacidosis and often DPN. Comparative efcacy studies and
In all patients with diabetes and DPN, correlate poorly with symptoms. Con- trials that include quality-of-life out-
causes of neuropathy other than diabe- stipation is the most common lower- comes are rare, so treatment decisions
tes should be considered, including gastrointestinal symptom but can must consider each patients presenta-
toxins (alcohol), neurotoxic medications alternate with episodes of diarrhea. tion and comorbidities and often
(chemotherapy), vitamin B deciency,
12
Genitourinary Disturbances
follow a trial-and-error approach. Given
hypothyroidism, renal disease, malig- the range of partially effective treatment
Diabetic autonomic neuropathy may
nancies (multiple myeloma, broncho- options, a tailored and stepwise pharma-
also cause genitourinary disturbances.
genic carcinoma), infections (HIV), cological strategy with careful attention
In men, diabetic autonomic neuropathy
chronic inammatory demyelinating to relative symptom improvement, med-
may cause erectile dysfunction and/or
neuropathy, inherited neuropathies, ication adherence, and medication side
retrograde ejaculation. Evaluation of
and vasculitis (51). effects is recommended to achieve pain
bladder function should be performed
Diabetic Autonomic Neuropathy reduction and improve quality of life
for individuals with diabetes who have
(50,64,65).
The symptoms and signs of autonomic recurrent urinary tract infections, pyelo-
dysfunction should be elicited carefully nephritis, incontinence, or a palpable Orthostatic Hypotension
during the history and physical exami- bladder. Treating orthostatic hypotension is chal-
nation. Major clinical manifestations of lenging. The therapeutic goal is to min-
diabetic autonomic neuropathy include Treatment imize postural symptoms rather than to
hypoglycemia unawareness, resting Glycemic Control restore normotension. Most patients
tachycardia, orthostatic hypotension, Near-normal glycemic control, imple- require both nonpharmacological mea-
gastroparesis, constipation, diarrhea, mented early in the course of diabetes, sures (e.g., ensuring adequate salt intake,
fecal incontinence, erectile dysfunction, has been shown to effectively delay or avoiding medications that aggravate hypo-
neurogenic bladder, and sudomotor prevent the development of DPN and tension, or using compressive garments
dysfunction with either increased or de- CAN in patients with type 1 diabetes over the legs and abdomen) and pharma-
creased sweating. (5558). Although the evidence for the cological measures. Midodrine is the only
Cardiac Autonomic Neuropathy benet of near-normal glycemic control drug approved by the FDA for the treat-
CAN is associated with mortality inde- is not as strong for type 2 diabetes, some ment of orthostatic hypotension.
pendent of other cardiovascular risk fac- studies have demonstrated a modest Gastroparesis
tors (52,53). In its early stages, CAN may slowing of progression (59,60) without Gastroparesis may improve with a low-
be completely asymptomatic and de- reversal of neuronal loss. Several obser- fat, low-ber diet, optimized glycemic
tected only by decreased heart rate var- vational studies suggest that neuro- control, and prokinetic agents such as
iability with deep breathing. Advanced pathic symptoms improve not only metoclopramide or erythromycin. In
disease may be associated with resting with optimization of glycemic control 2009, the FDA added a boxed warning
tachycardia (.100 bpm) and orthostatic but also with the avoidance of extreme to the metoclopramide label highlighting
hypotension (a fall in systolic or diastolic blood glucose uctuations. the risks of irreversible tardive dyskinesia
blood pressure by .20 mmHg or .10 Diabetic Peripheral Neuropathy after long-term use of metoclopramide.
mmHg, respectively, upon standing DPN symptoms, and especially neuro- The chronic use of metoclopramide
without an appropriate increase in heart pathic pain, can be severe and can im- should be avoided (66). Metoclopramide
rate). CAN treatment is generally fo- pact quality of life, limit mobility, and should be reserved for patients with the
cused on alleviating symptoms. contribute to depression and social dys- most severe symptoms that are unre-
Gastrointestinal Neuropathies function (61). Several medications have sponsive to other therapies. The medica-
Gastrointestinal neuropathies may in- been demonstrated to be effective for tion should be used at the lowest dose
volve any portion of the gastrointestinal the treatment of pain associated with and for the shortest duration possible,
tract with manifestations including DPN, but there is limited clinical evi- generally not to exceed 3 months, and
esophageal dysmotility, gastroparesis, dence regarding which medication is side effects should be closely monitored.
constipation, diarrhea, and fecal incon- most effective for an individual patient Erectile Dysfunction
tinence. Gastroparesis should be sus- (62,63). Treatments for erectile dysfunction may
pected in individuals with erratic The U.S. Food and Drug Administra- include phosphodiesterase type 5 inhib-
glucose control or with upper gastroin- tion (FDA) has approved three medi- itors, intracorporeal or intraurethral
testinal symptoms without another cations (pregabalin, duloxetine, and prostaglandins, vacuum devices, or pe-
identied cause. Evaluation of gastric tapentadol) for the treatment of pain as- nile prostheses. Interventions for other
emptying using the gastric emptying sociated with DPN, but none affords manifestations of autonomic neuropa-
breath test, a new noninvasive test complete relief, even when used in com- thy are described in the American Dia-
that does not use radiation-emitting bination. Tricyclic antidepressants, gaba- betes Association (ADA) statement on
compounds (54), or the double-isotope pentin, venlafaxine, carbamazepine, neuropathy (67). As with DPN treat-
scintigraphy may be performed if symp- tramadol, and topical capsaicin, al- ments, these interventions do not
toms suggest gastroparesis, but test though not approved for the treatment change the underlying pathology and
S78 Microvascular Complications and Foot Care Diabetes Care Volume 39, Supplement 1, January 2016

natural history of the disease process recognition and treatment of patients brachial index testing should be per-
but may improve the patients quality with diabetes and feet at risk for ulcers formed in patients with symptoms or
of life. and amputations can delay or prevent signs of PAD. Due to the high estimated
adverse outcomes. prevalence of PAD in patients with di-
FOOT CARE
The risk of ulcers or amputations is abetes and the fact that many patients
Recommendations increased in people who have the fol- with PAD are asymptomatic, an ADA
c Perform a comprehensive foot eval- lowing risk factors: consensus report on PAD (68) suggested
uation each year to identify risk fac- that ankle-brachial index screening be
tors for ulcers and amputations. B History of foot ulcer performed in patients 50 years of age
c Obtain a prior history of ulceration, Amputation and older and be considered in patients
amputation, Charcot foot, angio- Foot deformities under 50 years of age who have other
plasty or vascular surgery, cigarette Peripheral neuropathy with LOPS PAD risk factors (e.g., smoking, hyper-
smoking, retinopathy, and renal dis- Preulcerative callus or corn tension, dyslipidemia, or duration of di-
ease and assess current symptoms PAD abetes .10 years).
of neuropathy (pain, burning, Poor glycemic control
numbness) and vascular disease Visual impairment Patient Education
(leg fatigue, claudication). B Diabetic nephropathy (especially pa- Patients with diabetes and high-risk foot
c The examination should include in- tients on dialysis) conditions (history of ulcer or amputa-
spection of the skin, assessment of Cigarette smoking tion, deformity, LOPS, or PAD) should be
foot deformities, neurological assess- educated about their risk factors and
ment including 10-g monolament Clinicians are encouraged to review ADA appropriate management. Patients at
testing and pinprick or vibration test- screening recommendations for further risk should understand the implications
ing or assessment of ankle reexes, details and practical descriptions of how of foot deformities, LOPS, and PAD; the
and vascular assessment including to perform components of the compre- proper care of the foot, including nail
pulses in the legs and feet. B hensive foot examination (67). and skin care; and the importance of
c Patients with a history of ulcers or foot monitoring on a daily basis. Pa-
Evaluation for Loss of Protective
amputations, foot deformities, in- tients with LOPS should be educated
Sensation
sensate feet, and peripheral arte- on ways to substitute other sensory mo-
All adults with diabetes should un-
rial disease are at substantially dalities (palpation or visual inspection
dergo a comprehensive foot evaluation
increased risk for ulcers and ampu- using a nonbreakable mirror) for sur-
at least annually to identify high-risk
tations and should have their feet veillance of early foot problems.
conditions. Clinicians should ask about
examined at every visit. C The selection of appropriate foot-
history of foot ulcers or amputation,
c Patients with symptoms of claudi- wear and footwear behaviors at home
neuropathic and peripheral vascular
cation or decreased or absent symptoms, impaired vision, renal dis- should also be discussed. Patients un-
pedal pulses should be referred derstanding of these issues and their
ease, tobacco use, and foot care prac-
for ankle-brachial index and for physical ability to conduct proper foot
tices. A general inspection of skin
further vascular assessment. C surveillance and care should be as-
integrity and musculoskeletal defor-
c A multidisciplinary approach is mities should be performed. Vascular sessed. Patients with visual difculties,
recommended for individuals physical constraints preventing move-
assessment should include inspection
with foot ulcers and high-risk feet ment, or cognitive problems that impair
and assessment of pedal pulses.
(e.g., dialysis patients and those their ability to assess the condition of
The neurological exam performed as
with Charcot foot, prior ulcers, or the foot and to institute appropriate re-
part of the foot examination is designed
amputation). B sponses will need other people, such
to identify LOPS rather than early neu-
c Refer patients who smoke or who as family members, to assist in their care.
ropathy. The 10-g monolament is the
have histories of prior lower- most useful test to diagnose LOPS. Ide-
extremity complications, loss of Treatment
ally, the 10-g monolament test should
protective sensation, structural People with neuropathy or evidence of
be performed with at least one other
abnormalities, or peripheral arte- increased plantar pressures (e.g., ery-
assessment (pinprick, temperature or
rial disease to foot care specialists thema, warmth, or calluses) may be ade-
vibration sensation using a 128-Hz tun-
for ongoing preventive care and quately managed with well-tted walking
ing fork, or ankle reexes). Absent
lifelong surveillance. C shoes or athletic shoes that cushion the
monolament sensation suggests LOPS,
c Provide general foot self-care educa- feet and redistribute pressure. People
while at least two normal tests (and no
tion to all patients with diabetes. B with bony deformities (e.g., hammertoes,
abnormal test) rule out LOPS.
prominent metatarsal heads, bunions)
Foot ulcers and amputation, which are Evaluation for Peripheral Arterial may need extra-wide or -deep shoes. Peo-
consequences of diabetic neuropathy Disease ple with bony deformities, including Char-
and/or peripheral arterial disease Initial screening for PAD should cot foot, who cannot be accommodated
(PAD), are common and represent include a history for decreased walking with commercial therapeutic footwear
major causes of morbidity and mor- speed, leg fatigue, claudication, and an will require custom-molded shoes. Spe-
tality in people with diabetes. Early assessment of the pedal pulses. Ankle- cial consideration and a thorough workup
care.diabetesjournals.org Microvascular Complications and Foot Care S79

should be performed when patients with function, hypertension, and diabetes. Circulation 21. Cushman WC, Evans GW, Byington RP,
neuropathy present with an acute onset 2004;110:3235 et al.; ACCORD Study Group. Effects of intensive
9. de Boer IH, Rue TC, Cleary PA, et al.; Diabetes blood-pressure control in type 2 diabetes melli-
of a red, hot, swollen foot or ankle, and
Control and Complications Trial/Epidemiology tus. N Engl J Med 2010;362:15751585
Charcot neuroarthropathy should be ex- of Diabetes Interventions and Complications 22. UK Prospective Diabetes Study Group. Tight
cluded. Early diagnosis and treatment of Study Research Group. Long-term renal out- blood pressure control and risk of macrovascu-
Charcot neuroarthropathy is the best way comes of patients with type 1 diabetes mellitus lar and microvascular complications in type 2
to prevent deformities that increase the and microalbuminuria: an analysis of the diabetes: UKPDS 38. BMJ 1998;317:703713
Diabetes Control and Complications Trial/ 23. Heart Outcomes Prevention Evaluation
risk of ulceration and amputation. Epidemiology of Diabetes Interventions and Study Investigators. Effects of ramipril on car-
Most diabetic foot infections are poly- Complications cohort. Arch Intern Med 2011; diovascular and microvascular outcomes in peo-
microbial, with aerobic gram-positive 171:412420 ple with diabetes mellitus: results of the HOPE
cocci. Staphylococci are the most com- 10. Molitch ME, Steffes M, Sun W, et al.; Epi- study and MICRO-HOPE substudy. Lancet 2000;
mon causative organisms. Wounds demiology of Diabetes Interventions and Com- 355:253259
plications Study Group. Development and 24. Pepine CJ, Handberg EM, Cooper-DeHoff
without evidence of soft-tissue or bone
progression of renal insufciency with and with- RM, et al.; INVEST Investigators. A calcium an-
infection do not require antibiotic ther- out albuminuria in adults with type 1 diabetes in tagonist vs a non-calcium antagonist hyperten-
apy. Empiric antibiotic therapy can be the Diabetes Control and Complications Trial sion treatment strategy for patients with
narrowly targeted at gram-positive and the Epidemiology of Diabetes Interventions coronary artery disease. The International
cocci in many patients with acute infec- and Complications study. Diabetes Care 2010; Verapamil-Trandolapril Study (INVEST): a ran-
33:15361543 domized controlled trial. JAMA 2003;290:
tions, but those at risk for infection with
11. de Boer IH, Sun W, Cleary PA, et al.; DCCT/ 28052816
antibiotic-resistant organisms or with EDIC Research Group. Intensive diabetes ther- 25. Yusuf S, Teo KK, Pogue J, et al.; ONTARGET
chronic, previously treated, or severe apy and glomerular ltration rate in type 1 di- Investigators. Telmisartan, ramipril, or both in
infections require broader-spectrum abetes. N Engl J Med 2011;365:23662376 patients at high risk for vascular events. N Engl J
regimens and should be referred to spe- 12. Gall M-A, Hougaard P, Borch-Johnsen K, Med 2008;358:15471559
Parving H-H. Risk factors for development of 26. Berl T, Hunsicker LG, Lewis JB, et al.; Irbe-
cialized care centers (69). Foot ulcers
incipient and overt diabetic nephropathy in pa- sartan Diabetic Nephropathy Trial. Collabora-
and wound care may require care by a tients with non-insulin dependent diabetes mel- tive Study Group. Cardiovascular outcomes in
podiatrist, orthopedic or vascular sur- litus: prospective, observational study. BMJ the Irbesartan Diabetic Nephropathy Trial of pa-
geon, or rehabilitation specialist experi- 1997;314:783788 tients with type 2 diabetes and overt nephrop-
enced in the management of individuals 13. The Diabetes Control and Complications athy. Ann Intern Med 2003;138:542549
(DCCT) Research Group. Effect of intensive ther- 27. Smart NA, Dieberg G, Ladhani M, Titus T.
with diabetes (69). apy on the development and progression of di- Early referral to specialist nephrology services
abetic nephropathy in the Diabetes Control and for preventing the progression to end-stage kid-
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8. Klausen K, Borch-Johnsen K, Feldt-Rasmussen 20. Emdin CA, Rahimi K, Neal B, Callender T, complications in the diabetes control and compli-
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vascular lesions in type 2 diabetic subjects with- 49. Martin CL, Albers JW, Pop-Busui R; DCCT/ and Complications study (DCCT/EDIC). Circula-
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37. Ahmed J, Ward TP, Bursell S-E, Aiello LM, ican Academy of Neurology; American Associa- Action to Control Cardiovascular Risk in Diabe-
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specicity of nonmydriatic digital stereoscopic Medicine; American Academy of Physical Med- between A1C and all-cause mortality during a
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38. Hooper P, Boucher MC, Cruess A, et al. report of the American Academy of Neurology, 33:983990
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Diabetes Care Volume 39, Supplement 1, January 2016 S81

10. Older Adults American Diabetes Association

Diabetes Care 2016;39(Suppl. 1):S81S85 | DOI: 10.2337/dc16-S013

Recommendations
c Consider the assessment of medical, functional, mental, and social geriatric
domains for diabetes management in older adults to provide a framework to
determine targets and therapeutic approaches. E
c Screening for geriatric syndromes may be appropriate in older adults experi-
encing limitations in their basic and instrumental activities of daily living, as
they may affect diabetes self-management. E
c Older adults ($65 years of age) with diabetes should be considered a high-
priority population for depression screening and treatment. B
c Hypoglycemia should be avoided in older adults with diabetes. It should be
screened for and managed by adjusting glycemic targets and pharmacological
interventions. B

10.OLDER ADULTS
c Older adults who are functional and cognitively intact and have signicant life
expectancy may receive diabetes care with goals similar to those developed for
younger adults. E
c Glycemic goals for some older adults might reasonably be relaxed, using indi-
vidual criteria, but hyperglycemia leading to symptoms or risk of acute hyper-
glycemic complications should be avoided in all patients. E
c Screening for diabetes complications should be individualized in older adults,
but particular attention should be paid to complications that would lead to
functional impairment. E
c Other cardiovascular risk factors should be treated in older adults with con-
sideration of the time frame of benet and the individual patient. Treatment of
hypertension is indicated in virtually all older adults, and lipid-lowering and
aspirin therapy may benet those with life expectancy at least equal to the
time frame of primary or secondary prevention trials. E
c When palliative care is needed in older adults with diabetes, strict blood
pressure control may not be necessary, and withdrawal of therapy may be
appropriate. Similarly, the intensity of lipid management can be relaxed, and
withdrawal of lipid-lowering therapy may be appropriate. E
c Consider diabetes education for the staff of long-term care facilities to improve
the management of older adults with diabetes. E
c Patients with diabetes residing in long-term care facilities need careful assess-
ment to establish a glycemic goal and to make appropriate choices of glucose-
lowering agents based on their clinical and functional status. E
c Overall comfort, prevention of distressing symptoms, and preservation of quality
of life and dignity are primary goals for diabetes management at the end of life. E

OVERVIEW
Diabetes is an important health condition for the aging population; ;26% of pa-
tients over the age of 65 years have diabetes (1), and this number is expected to
grow rapidly in the coming decades. Older individuals with diabetes have higher
rates of premature death, functional disability, and coexisting illnesses, such as
hypertension, coronary heart disease, and stroke, than those without diabetes. Older Suggested citation: American Diabetes Associa-
adults with diabetes also are at a greater risk than other older adults for several tion. Older adults. Sec. 10. In Standards of Med-
common geriatric syndromes, such as polypharmacy, cognitive impairment, urinary ical Care in Diabetesd2016. Diabetes Care
incontinence, injurious falls, and persistent pain. Screening for diabetes complications 2016;39(Suppl. 1):S81S85
in older adults also should be individualized and periodically revisited, since the results 2016 by the American Diabetes Association.
of screening tests may impact therapeutic approaches and targets. Older adults are at Readers may use this article as long as the work
increased risk for depression and should therefore be screened and treated accordingly is properly cited, the use is educational and not
for prot, and the work is not altered.
S82 Older Adults Diabetes Care Volume 39, Supplement 1, January 2016

(2). Diabetes management may require maintain cognitive function in older no complications. Some older adults
assessment of medical, functional, mental, adults. However, studies examining the with diabetes are frail and have other
and social domains. This may provide a effects of intensive glycemic and blood underlying chronic conditions, substan-
framework to determine targets and pressure control to achieve specic tar- tial diabetes-related comorbidity, or
therapeutic approaches. Particular at- gets have not demonstrated a reduction limited physical or cognitive function-
tention should be paid to complications in brain function decline (12). ing. Other older individuals with diabe-
that can develop over short periods of Older adults with diabetes should be tes have little comorbidity and are
time and/or that would signicantly carefully screened and monitored for cog- active. Life expectancies are highly vari-
impair functional status, such as visual nitive impairment (3). Several organiza- able for this population but are often
and lower-extremity complications. Please tions have released simple assessment longer than clinicians realize. Providers
refer to the American Diabetes Associa- tools, such as the Mini-Mental State Ex- caring for older adults with diabetes
tion (ADA) consensus report Diabetes in amination (MMSE) and the Montreal must take this heterogeneity into con-
Older Adults for details (3). Cognitive Assessment (MoCA), which sideration when setting and prioritizing
may help to identify patients requiring treatment goals (Table 10.1).
NEUROCOGNITIVE FUNCTION neuropsychological evaluation, particu-
Older adults with diabetes are at higher larly those in whom dementia is sus- Healthy Patients With Good
risk of cognitive decline and institution- pected (i.e., experiencing memory loss Functional Status
alization (4,5). The presentation of cog- and decline in their basic and instrumen- There are few long-term studies in
nitive impairment ranges from subtle tal activities of daily living). older adults demonstrating the bene-
executive dysfunction to memory loss ts of intensive glycemic, blood pres-
and overt dementia. Diabetes increases HYPOGLYCEMIA sure, and lipid control. Patients who
the incidence of all-cause dementia, It is important to prevent hypoglycemia can be expected to live long enough
Alzheimer disease, and vascular demen- to reduce the risk of cognitive decline to reap the benets of long-term inten-
tia when compared with rates in people and to carefully assess and reassess pa- sive diabetes management, who have
with normal glucose tolerance (6). The good cognitive and physical function,
tients risk for worsening of glycemic
effects of hyperglycemia and hyperinsu- control and functional decline. Older and who choose to do so via shared de-
linemia on the brain are areas of intense adults are at higher risk of hypoglycemia cision making may be treated using
research interest. Clinical trials of spe- for many reasons, including insulin de- therapeutic interventions and goals
similar to those for younger adults
cic interventionsdincluding cholines- ciency and progressive renal insuf-
terase inhibitors and glutamatergic ciency. In addition, older adults tend to with diabetes. As with all patients
with diabetes, diabetes self-management
antagonistsdhave not shown positive have higher rates of unidentied cogni-
education and ongoing diabetes self-
therapeutic benet in maintaining or tive decits, causing difculty in com-
plex self-care activities (e.g., glucose management support are vital compo-
signicantly improving cognitive func-
monitoring, adjusting insulin doses, nents of diabetes care for older adults
tion or in preventing cognitive decline
(7). Recent pilot studies in patients and their caregivers.
etc.). These decits have been associ-
with mild cognitive impairment evaluat- ated with increased risk of hypoglyce-
Patients With Complications and
ing the potential benets of intranasal mia and with severe hypoglycemia
Reduced Functionality
insulin therapy or metformin therapy linked to increased dementia. There- For patients with advanced diabetes com-
provide insights for future clinical trials fore, it is important to routinely screen plications, life-limiting comorbid illness, or
and mechanistic studies (810). older adults for cognitive dysfunction substantial cognitive or functional impair-
The presence of cognitive impairment and discuss ndings with the caregivers. ment, it is reasonable to set less intensive
can make it challenging for clinicians to Hypoglycemic events should be dili- glycemic target goals. These patients are
help their patients to reach individual- gently monitored and avoided, whereas
less likely to benet from reducing the risk
ized glycemic, blood pressure, and lipid glycemic targets and pharmacological of microvascular complications and more
targets. Cognitive dysfunction makes it interventions may need to be adjusted likely to suffer serious adverse effects
difcult for patients to perform complex to accommodate for the changing needs from hypoglycemia. However, patients
self-care tasks, such as glucose monitor- of the older adult (3). with poorly controlled diabetes may be
ing and adjusting insulin doses. It also
subject to acute complications of diabe-
hinders their ability to appropriately TREATMENT GOALS
tes, including dehydration, poor wound
maintain the timing and content of diet. Rationale healing, and hyperglycemic hyperosmolar
When clinicians are managing these The care of older adults with diabetes is coma. Glycemic goals at a minimum
types of patients, it is critical to simplify complicated by their clinical and func-
should avoid these consequences.
drug regimens and to involve caregivers tional heterogeneity. Some older indi-
in all aspects of care. viduals may have developed diabetes Vulnerable Patients at the End of Life
Poor glycemic control is associated years earlier and have signicant com- For patients receiving palliative care and
with a decline in cognitive function (11), plications, others are newly diagnosed end-of-life care, the focus should be to
and longer duration of diabetes worsens and may have had years of undiagnosed avoid symptoms and complications from
cognitive function. There are ongoing diabetes with resultant complications, glycemic management. Thus, when organ
studies evaluating whether preventing and still other older adults may have failure develops, several agents will have
or delaying diabetes onset may help to truly recent-onset disease with few or to be titrated or discontinued. For the
care.diabetesjournals.org Older Adults S83

Table 10.1Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with
diabetes
Patient Fasting or
characteristics/ Reasonable A1C preprandial
health status Rationale goal glucose Bedtime glucose Blood pressure Lipids
Healthy (few coexisting Longer remaining ,7.5% 90130 mg/dL 90150 mg/dL ,140/90 mmHg Statin unless
chronic illnesses, intact life expectancy (58 mmol/mol) (5.07.2 mmol/L) (5.08.3 mmol/L) contraindicated
cognitive and functional or not tolerated
status)
Complex/intermediate Intermediate ,8.0% 90150 mg/dL 100180 mg/dL ,140/90 mmHg Statin unless
(multiple coexisting remaining life (64 mmol/mol) (5.08.3 mmol/L) (5.610.0 mmol/L) contraindicated
chronic illnesses* or expectancy, high or not tolerated
21 instrumental ADL treatment burden,
impairments or mild-to- hypoglycemia
moderate cognitive vulnerability,
impairment) fall risk
Very complex/poor health Limited remaining ,8.5% 100180 mg/dL 110200 mg/dL ,150/90 mmHg Consider
(LTC or end-stage chronic life expectancy (69 mmol/mol) (5.610.0 mmol/L) (6.111.1 mmol/L) likelihood of
illnesses** or moderate- makes benet benet with
to-severe cognitive uncertain statin (secondary
impairment or 21 ADL prevention more
dependencies) so than primary)
This 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. 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.
A lower A1C goal may be set for an 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. By multiple, we mean at least three, but many patients may have ve or more (27).
**The presence of a single end-stage chronic illness, such as stage 34 congestive heart failure or oxygen-dependent lung disease, chronic kidney disease requiring

dialysis, or uncontrolled metastatic cancer, may cause signi cant symptoms or impairment of functional status and signi cantly 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 they may expose patients to more frequent higher glucose values and the acute risks from glycosuria, dehydration,
hyperglycemic hyperosmolar syndrome, and poor wound healing.

dying patient most agents for type 2 di- Insulin Sensitizers hypoglycemia, and its use requires that
abetes may be removed. There is, how- Metformin is the rst-line agent in older patients or caregivers have good visual
ever, no consensus for the management adults with type 2 diabetes. However, it and motor skills and cognitive ability.
of type 1 diabetes in this scenario (13,14). is contraindicated in patients with renal
insufciency or signicant heart failure. Incretin-Based Therapies
Beyond Glycemic Control Since serum creatinine levels do not ad- Glucagon-like peptide 1 receptor ago-
Although hyperglycemia control may be equately reect renal function in older nists and dipeptidyl peptidase 4 inhibi-
important in older individuals with dia- people (muscle mass losses are associ- tors have few side effects, but their
betes, greater reductions in morbidity ated with chronic conditions and func- costs may be a barrier to some older
and mortality are likely to result from tional decline), a timed urine collection patients. A systematic review concluded
control of other cardiovascular risk fac- to assess creatinine clearance has been that incretin-based agents do not in-
tors rather than from tight glycemic con- recommended, particularly in those crease major adverse cardiovascular
trol alone. There is strong evidence from aged $80 years. Metformin may be events (19). Glucagon-like peptide 1
clinical trials of the value of treating hy- temporarily discontinued before proce- receptor agonists are injectable agents,
pertension in the elderly (15,16). There is dures, during hospitalizations, and which require visual, motor, and cogni-
less evidence for lipid-lowering and aspirin when acute illness may compromise re- tive skills.
therapy, although the benets of these in- nal or liver function. Thiazolidinediones,
SodiumGlucose Cotransporter 2
terventions for primary and secondary if used at all, should be used very cau-
Inhibitors
prevention are likely to apply to older tiously in those with, or at risk for, con-
adults whose life expectancies equal or ex- gestive heart failure and have been Sodiumglucose cotransporter 2 inhibi-
tors offer an oral route, which may be
ceed the time frames seen in clinical trials. associated with fractures.
convenient for older adults with diabe-
tes; however, long-term experience is
PHARMACOLOGICAL THERAPY Insulin Secretagogues limited despite the initial efcacy and
Special care is required in prescribing Sulfonylureas and other insulin secre- safety data reported with these agents.
and monitoring pharmacological ther- tagogues are associated with hypo-
apy in older adults (17). Cost may be a glycemia and should be used with Other Factors to Consider
signicant factor, especially as older caution. Glyburide is contraindicated The needs of older adults with diabetes
adults tend to be on many medications. in older adults (18). Insulin can also cause and their caregivers should be evaluated
S84 Older Adults Diabetes Care Volume 39, Supplement 1, January 2016

to construct a tailored care plan. Social intake and contribute to unintentional END-OF-LIFE CARE
difculties may impair their quality of weight loss and undernutrition. Diets tai- The management of the older adult at
life and increase the risk of functional lored to a patients culture, preferences, the end of life receiving palliative medi-
dependency. The patients living situa- and personal goals might increase qual- cine or hospice is a unique situation.
tion must be considered, as it may affect ity of life, satisfaction with meals, and Overall, palliative medicine promotes
diabetes management and support. nutrition status (22). comfort, symptom control, and preven-
Older adults in assisted living facilities tion (pain, hypoglycemia and hyperglyce-
may not have support to administer Hypoglycemia mia, dehydration) and preservation of
their own medications, whereas those Older adults with diabetes in LTC are dignity and quality of life in patients
living in a nursing home (community liv- especially vulnerable to hypoglycemia. with limited life expectancy (21,24). A pa-
ing centers) may rely completely on the They have a disproportionately high tient has the right to refuse testing and
care plan and nursing support. Those re- number of clinical complications and co- treatment, whereas providers may con-
ceiving palliative care (with or without morbidities that can increase hypogly- sider withdrawing treatment and limiting
hospice) may require an approach that cemia risk: impaired renal function, diagnostic testing, including a reduction
emphasizes comfort and symptom man- slowed hormonal regulation and coun-
in the frequency of nger-stick testing
agement, while deemphasizing strict terregulation, and suboptimal hydra- (25). Glucose targets should aim to pre-
metabolic and blood pressure control. tion, variable appetite and nutritional
vent hypoglycemia and hyperglycemia.
intake, polypharmacy, and slowed intes-
Treatment interventions need to be
TREATMENT IN SKILLED NURSING tinal absorption (23).
FACILITIES AND NURSING HOMES mindful of quality of life. Careful monitor-
Another consideration for the LTC set-
Management of diabetes in the long-
ing of oral intake is warranted. The de-
ting is that unlike the hospital setting,
cision process may need to involve the
term care (LTC) setting (i.e., nursing medical providers are not required to
patient, family, and caregivers, leading
homes and skilled nursing facilities) is evaluate the patients daily. According
unique. Individualization of health care to a care plan that is both convenient
to federal guidelines, assessments
is important in all patients; however, and effective for the goals of care (26).
should be done at least every 30 days
practical guidance is needed for medical The pharmacological therapy may in-
for the rst 90 days after admission
providers as well as the LTC staff and and then at least once every 60 days. clude oral agents as rst line, followed
caregivers. The American Medical Di- Although in practice the patients may by a simplied insulin regimen. If needed,
rectors Association (AMDA) guidelines actually be seen more frequently, the basal insulin can be implemented, ac-
offer a 12-step program for staff (20). concern is that patients may have uncon- companied by oral agents and without
This training includes diabetes detection trolled glucose levels or wide excursions rapid-acting insulin. Agents that can
and institutional quality assessment. It without the practitioner being notied. cause gastrointestinal symptoms such
is also recommended that LTC facilities Providers may make adjustments to as nausea or excess weight loss may not
develop their own policies and proce- treatment regimens by telephone, be good choices in this setting. As symp-
dures for prevention and management fax, or order directly at the LTC facili- toms progress, some agents may be
of hypoglycemia. ties provided they are given timely no- slowly tapered down and discontinued.
Strata have been proposed for diabe-
Resources tication from a standardized alert
system. tes management in those with advanced
Staff of LTC facilities should receive ap- disease (14).
The following alert strategy could be
propriate diabetes education to improve
considered:
the management of older adults with di-
1. A stable patient: continue with the
abetes. Major organizations such as the
1. Call provider immediately: in case patients previous regimen, with a
ADA, the American Geriatrics Society
o f hypoglycemia ( ,7 0 m g / dL focus on the prevention of hypogly-
(AGS), the International Association of cemia and the management of hy-
Gerontology and Geriatrics (IAGG), and [3.9 mmol/L]). Low nger-stick blood
perglycemia, keeping levels below
the European Diabetes Working Party glucose values should be conrmed
by laboratory glucose measurement. the renal threshold of glucose. There
for Older People (EDWPOP) concur with
2. Call as soon as possible: a) glucose is very little role for A1C monitoring
the AMDA on the need to individualize
values between 70 and 100 mg/dL and lowering.
treatments for each patient, the need to
(between 3.9 and 5.6 mmol/L) 2. A patient with organ failure: pre-
avoid both hypoglycemia and the meta-
(regimen may need to be adjusted), venting hypoglycemia is of greater
bolic complications of diabetes, and the
b) glucose values greater than signicance. Dehydration must be pre-
need to provide adequate diabetes train-
250 mg/dL (13.9 mmol/L) within a vented and handled. In people with
ing to LTC staff (3,21).
24-h period, c) glucose values greater type 1 diabetes, insulin administration
Nutrition Considerations than 300 mg/dL (16.7 mmol/L) within may be reduced as the oral intake of
An older adult residing in an LTC facility 2 consecutive days, d) or when any food decreases. For those with type 2
may have irregular and unpredictable reading is too high, e) or the patient diabetes, agents that may cause hypo-
meal consumption, undernutrition, an- is sick, with vomiting or other malady glycemia should be titrated. The main
orexia, and impaired swallowing. Fur- that can reect hyperglycemic crisis, goal is to avoid hypoglycemia, allow-
t h e r m o r e , t h e r a p e u t i c d ie t s m a y may lead to poor oral intake, and thus ing for glucose values in the upper
inadvertently lead to decreased food requires regimen adjustment. level of the desired target range.
care.diabetesjournals.org Older Adults S85

3. A dying patient: for patients with amnestic mild cognitive impairment: a pilot clin- 19. Rotz ME, Ganetsky VS, Sen S, Thomas TF.
type 2 diabetes, the discontinuation ical trial. Arch Neurol 2012;69:2938 Implications of incretin-based therapies on cardio-
9. Freiherr J, Hallschmid M, Frey WH 2nd, et al. vascular disease. Int J Clin Pract 2015;69:531549
of all medications may be a pertinent
Intranasal insulin as a treatment for Alzheimers 20. American Medical Directors Association.
approach, as they are unlikely to have disease: a review of basic research and clinical Diabetes management in the long-term care
any oral intake. In patients with type 1 evidence. CNS Drugs 2013;27:505514 setting [Internet]. Available from http://www
diabetes, there is no consensus, but a 10. Alagiakrishnan K, Sankaralingam S, Ghosh .amda.com/tools/guidelines.cfm#diabetes. Ac-
small amount of basal insulin may M, Mereu L, Senior P. Antidiabetic drugs and cessed 5 October 2015
their potential role in treating mild cognitive 21. Sinclair A, Morley JE, Rodriguez-Ma~nas L,
maintain glucose levels and prevent
impairment and Alzheimers disease. Discov et al. Diabetes mellitus in older people: position
acute hyperglycemic complications. statement on behalf of the International Asso-
Med 2013;16:277286
11. Yaffe K, Falvey C, Hamilton N, et al. Diabe- ciation of Gerontology and Geriatrics (IAGG),
References tes, glucose control, and 9-year cognitive de- the European Diabetes Working Party for Older
cline among older adults without dementia. People (EDWPOP), and the International Task
1. Centers for Disease Control and Prevention.
Arch Neurol 2012;69:11701175 Force of Experts in Diabetes. J Am Med Dir Assoc
National diabetes statistics report: estimates of
diabetes and its burden in the United States, 12. Launer LJ, Miller ME, Williamson JD, et al.; 2012;13:497502
2014 [Internet]. Available from http://www.cdc ACCORD MIND Investigators. Effects of inten- 22. Dorner B, Friedrich EK, Posthauer ME. Prac-
.gov/diabetes/data/statistics/2014statisticsreport sive glucose lowering on brain structure and tice paper of the American Dietetic Association:
.html. Accessed 1 October 2015 function in people with type 2 diabetes individualized nutrition approaches for older
2. Kimbro LB, Mangione CM, Steers WN, et al. (ACCORD MIND): a randomised open-label sub- adults in health care communities. J Am Diet
Depression and all-cause mortality in persons study. Lancet Neurol 2011;10:969977 Assoc 2010;110:15541563
with diabetes mellitus: are older adults at 13. Sinclair A, Dunning T, Colagiuri S. Managing 23. Migdal A, Yarandi SS, Smiley D, Umpierrez
higher risk? Results from the Translating older people with type 2 diabetes: global guide- GE. Update on diabetes in the elderly and in
Research Into Action for Diabetes Study. J Am line. International Diabetes Federation, 2013 nursing home residents. J Am Med Dir Assoc
Geriatr Soc 2014;62:10171022 14. Angelo M, Ruchalski C, Sproge BJ. An ap- 2011;12:627632.e2
3. Kirkman MS, Briscoe VJ, Clark N, et al. Diabe- proach to diabetes mellitus in hospice and pal- 24. Quinn K, Hudson P, Dunning T. Diabetes man-
tes in older adults. Diabetes Care 2012;35: liative medicine. J Palliat Med 2011;14:8387 agement in patients receiving palliative care.
26502664 15. Beckett NS, Peters R, Fletcher AE, et al.; J Pain Symptom Manage 2006;32:275286
4. Cukierman T, Gerstein HC, Williamson JD. HYVET Study Group. Treatment of hypertension 25. Ford-Dunn S, Smith A, Quin J. Management
Cognitive decline and dementia in diabetes: sys- in patients 80 years of age or older. N Engl J Med of diabetes during the last days of life: attitudes
tematic overview of prospective observational 2008;358:18871898 of consultant diabetologists and consultant pal-
studies. Diabetologia 2005;48:24602469 16. James PA, Oparil S, Carter BL, et al. 2014 liative care physicians in the UK. Palliat Med
5. Roberts RO, Knopman DS, Przybelski SA, evidence-based guideline for the management 2006;20:197203
et al. Association of type 2 diabetes with brain of high blood pressure in adults: report from 26. Mallery LH, Ransom T, Steeves B, Cook B,
atrophy and cognitive impairment. Neurology the panel members appointed to the Eighth Dunbar P, Moorhouse P. Evidence-informed
2014;82:11321141 Joint National Committee (JNC 8). JAMA 2014; guidelines for treating frail older adults with
6. Xu WL, von Strauss E, Qiu CX, Winblad B, 311:507520 type 2 diabetes: from the Diabetes Care Pro-
Fratiglioni L. Uncontrolled diabetes increases the 17. Valencia WM, Florez H. Pharmacological gram of Nova Scotia (DCPNS) and the Palliative
risk of Alzheimers disease: a population-based treatment of diabetes in older people. Diabetes and Therapeutic Harmonization (PATH) pro-
cohort study. Diabetologia 2009;52:1031 1039 Obes Metab 2014;16:11921203 gram. J Am Med Dir Assoc 2013;14:801808
7. Ghezzi L, Scarpini E, Galimberti D. Disease- 18. Campanelli CM; American Geriatrics Society 27. Laiteerapong N, Iveniuk J, John PM,
modifying drugs in Alzheimers disease. Drug 2012 Beers Criteria Update Expert Panel. Ameri- Laumann EO, Huang ES. Classication of older
Des Devel Ther 2013;7:14711478 can Geriatrics Society updated Beers Criteria for adults who have diabetes by comorbid condi-
8. Craft S, Baker LD, Montine TJ, et al. Intranasal potentially inappropriate medication use in older tions, United States, 2005-2006. Prev Chronic
insulin therapy for Alzheimer disease and adults. J Am Geriatr Soc 2012;60:616 631 Dis 2012;9:E100
S86 Diabetes Care Volume 39, Supplement 1, January 2016

11. Children and Adolescents American Diabetes Association

Diabetes Care 2016;39(Suppl. 1):S86S93 | DOI: 10.2337/dc16-S014

TYPE 1 DIABETES
Three-quarters of all cases of type 1 diabetes are diagnosed in individuals ,18 years
of age. The provider must consider the unique aspects of care and management of
children and adolescents with type 1 diabetes, such as changes in insulin sensitivity
related to physical growth and sexual maturation, ability to provide self-care, su-
pervision in the child care and school environment, and neurological vulnerability to
hypoglycemia and hyperglycemia in young children, as well as possible adverse
neurocognitive effects of diabetic ketoacidosis (1,2). Attention to family dynamics,
developmental stages, and physiological differences related to sexual maturity are
ESCENTS

all essential in developing and implementing an optimal diabetes regimen (3). Due
to the paucity of clinical research in children, the recommendations for children and
11. CHILDREN ANDADOL

adolescents are less likely to be based on clinical trial evidence. However, expert
opinion and a review of available and relevant experimental data are summarized in
the American Diabetes Association (ADA) position statement Care of Children and
Adolescents With Type 1 Diabetes (4) and have been updated in the ADA position
statement Type 1 Diabetes Through the Life Span (5).
A multidisciplinary team of specialists trained in pediatric diabetes management
and sensitive to the challenges of children and adolescents with type 1 diabetes and
their families should provide care for this population. It is essential that diabetes
self-management education (DSME) and support (DSMS), medical nutrition ther-
apy, and psychosocial support be provided at diagnosis and regularly thereafter by
individuals experienced with the educational, nutritional, behavioral, and emotional
needs of the growing child and family. The appropriate balance between adult
supervision and independent self-care should be dened at the rst interaction
and reevaluated at subsequent clinic visits. The balance between adult supervision
and independent self-care will evolve as the adolescent gradually becomes an
emerging young adult.
Diabetes Self-management Education and Support

Recommendation

c Youth with type 1 diabetes and parents/caregivers (for patients aged ,18
years) should receive culturally sensitive and developmentally appropriate
individualized diabetes self-management education and support according
to national standards at diagnosis and routinely thereafter. B

No matter how sound the medical regimen, it can only be effective if the family and/
or affected individuals are able to implement it. Family involvement is a vital com-
ponent of optimal diabetes management throughout childhood and adolescence.
Health care providers (the diabetes care team) who care for children and adoles-
cents must be capable of evaluating the educational, behavioral, emotional, and
psychosocial factors that impact implementation of a treatment plan and must work
with the individual and family to overcome barriers or redene goals as appropriate.
DSME and DSMS require periodic reassessment, especially as the youth grows,
develops, and acquires the need for greater independent self-care skills. In addition,
Suggested citation: American Diabetes Associa-
it is necessary to assess the educational needs and skills of day care providers, school
tion. Children and adolescents. Sec. 11. In Stan-
nurses, or other school personnel who participate in the care of the young child with
dards of Medical Care in Diabetesd2016.
diabetes (6).
Diabetes Care 2016;39(Suppl. 1):S86S93
School and Child Care 2016 by the American Diabetes Association.
Readers may use this article as long as the work
As a large portion of a childs day is spent in school, close communication with and
the cooperation of school or day care personnel are essential for optimal diabetes is properly cited, the use is educational and not
for prot, and the work is not altered.
care.diabetesjournals.org Children and Adolescents S87

management, safety, and maximal aca- Screening impairment after episodes of severe hypo-
demic opportunities. Refer to the ADA Screening for psychosocial distress and glycemia, current data have not conrmed
position statements Diabetes Care in mental health problems is an important this notion (1820). Furthermore, new
the School Setting (7) and Care of Young component of ongoing care. It is impor- therapeutic modalities, such as rapid-
Children With Diabetes in the Child Care tant to consider the impact of diabetes and long-acting insulin analogs, techno-
Setting (8) for additional details. on quality of life as well as the develop- logical advances (e.g., continuous glucose
ment of mental health problems related monitors, low glucose suspend insulin
Psychosocial Issues
to diabetes distress, fear of hypoglyce- pumps), and education may mitigate the
Recommendations mia (and hyperglycemia), symptoms of incidence of severe hypoglycemia (21).
c At diagnosis and during routine anxiety, disordered eating behaviors as The Diabetes Control and Complica-
follow-up care, assess psychosocial well as eating disorders, and symptoms tions Trial (DCCT) demonstrated that
issues and family stresses that could of depression (15). Consider screening near-normalization of blood glucose levels
impact adherence to diabetes man- for depression and disordered eating was more difcult to achieve in adoles-
agement and provide appropriate behaviors using available screening cents than in adults. Nevertheless, the in-
referrals to trained mental health tools (9,16), and, with respect to disor- creased use of basalbolus regimens,
professionals, preferably experi- dered eating, it is important to recognize insulin pumps, frequent blood glucose
enced in childhood diabetes. E the unique and dangerous disordered monitoring, goal setting, and improved
c Encourage developmentally appro- eating behavior of insulin omission for patient education in youth from infancy
priate family involvement in diabetes weight control in type 1 diabetes (17). through adolescence have been associ-
management tasks for children and The presence of a mental health profes- ated with more children reaching the
adolescents, recognizing that prema- sional on pediatric multidisciplinary blood glucose targets set by the ADA
ture transfer of diabetes care to the teams highlights the importance of at- (7,2225) in those families in which both
child can result in nonadherence and tending to the psychosocial issues of di- the parents and the child with diabetes
deterioration in glycemic control. B abetes. These psychosocial factors are participate jointly to perform the required
c Consider mental health professionals signicantly related to nonadherence, diabetes-related tasks. Furthermore,
as integral members of the pediatric suboptimal glycemic control, reduced studies documenting neurocognitive imag-
diabetes multidisciplinary team. E quality of life, and higher rates of acute ing differences related to hyperglycemia
and chronic diabetes complications. in children provide another compelling
Diabetes management throughout child- motivation for lowering glycemic targets (1).
Glycemic Control
hood and adolescence places substantial In selecting glycemic goals, the long-
burdens on the youth and family, neces- Recommendation
term health benets of achieving a lower
sitating ongoing assessment of psychoso- c An A1C goal of ,7.5% (58 mmol/mol) A1C should be balanced against the risks
cial issues and distress during routine is recommended across all pediatric of hypoglycemia and the developmental
diabetes visits (911). Further, the com- age-groups. E burdens of intensive regimens in children
plexities of diabetes management require and youth. In addition, achieving lower
ongoing parental involvement in care Current standards for diabetes manage- A1C levels is more likely to be related to
throughout childhood with developmen- ment reect the need to lower glucose as setting lower A1C targets (26,27). A1C
tally appropriate family teamwork be- safely as possible. This should be done goals are presented in Table 11.1.
tween the growing child/teen and with stepwise goals. Special consideration
Autoimmune Conditions
parent in order to maintain adherence should be given to the risk of hypoglyce-
and to prevent deterioration in glycemic mia in young children (aged ,6 years) Recommendation
control (12,13). As diabetes-specic fam- who are often unable to recognize, artic- c Assess for the presence of additional
ily conict is related to poorer adherence ulate, and/or manage their hypoglycemic autoimmune conditions soon after the
and glycemic control, it is appropriate to symptoms. This hypoglycemia unaware- diagnosis and if symptoms develop. E
inquire about such conict during visits ness should be considered when estab-
and to either help to negotiate a plan lishing individualized glycemic targets. Because of the increased frequency of
for resolution or refer to an appropriate Although it was previously thought that other autoimmune diseases in type 1
mental health specialist (14). young children were at risk for cognitive diabetes, screening for thyroid dysfunction

Table 11.1Blood glucose and A1C goals for type 1 diabetes across all pediatric age-groups
Blood glucose goal range
Before meals Bedtime/overnight A1C Rationale
90130 mg/dL 90150 mg/dL ,7.5% A lower goal (,7.0% [53 mmol/mol]) is reasonable if it can be
(5.07.2 mmol/L) (5.08.3 mmol/L) (58 mmol/mol) achieved without excessive hypoglycemia
Key concepts in setting glycemic goals:
c Goals should be individualized, and lower goals may be reasonable based on a benetrisk assessment.
c Blood glucose goals should be modied in children with frequent hypoglycemia or hypoglycemia unawareness.
c Postprandial blood glucose values should be measured when there is a discrepancy between preprandial blood glucose values and A1C levels and
to assess preprandial insulin doses in those on basalbolus regimens.
S88 Children and Adolescents Diabetes Care Volume 39, Supplement 1, January 2016

and celiac disease should be considered. Celiac Disease antibody positivity on a separate blood
Periodic screening in asymptomatic indi- Recommendations sample). It is also advisable to check for
viduals has been recommended, but the
c Consider screening children with HLA types in patients who are diagnosed
optimal frequency and benet of screen- type 1 diabetes for celiac disease without a small intestinal biopsy. Asymp-
ing are unclear. tomatic at-risk children should have an in-
by measuring either tissue transglu-
Although much less common than ce- testinal biopsy (37).
taminase or deamidated gliadin an-
liac disease and thyroid dysfunction, In symptomatic children with type 1 di-
tibodies, with documentation of
other autoimmune conditions, such as abetes and conrmed celiac disease,
normal total serum IgA levels, soon
Addison disease (primary adrenal insuf- gluten-free diets reduce symptoms and
after the diagnosis of diabetes. E
ciency), autoimmune hepatitis, auto- rates of hypoglycemia (38). The challeng-
c Consider screening in children who
immune gastritis, dermatomyositis, ing dietary restrictions associated with
have a rst-degree relative with celiac
and myasthenia gravis, occur more com- having both type 1 diabetes and celiac dis-
disease, growth failure, weight loss,
monly in the population with type 1 dia- ease place a signicant burden on individ-
failure to gain weight, diarrhea, atu-
betes than in the general pediatric uals. Therefore, we recommend a biopsy
lence, abdominal pain, or signs of
population and should be assessed and to conrm the diagnosis of celiac disease,
malabsorption or in children with fre-
monitored as clinically indicated. especially in asymptomatic children, be-
quent unexplained hypoglycemia or
fore endorsing signicant dietary changes.
Thyroid Disease deterioration in glycemic control. E
Recommendations
c Children with biopsy-conrmed celiac Management of Cardiovascular Risk
disease should be placed on a gluten-
c Consider testing children with Factors
free diet and have a consultation
type 1 diabetes for antithyroid per- Hypertension
with a dietitian experienced in manag-
oxidase and antithyroglobulin anti- Recommendations
ing both diabetes and celiac disease. B
bodies soon after the diagnosis. E
Screening
c Measure thyroid-stimulating hor- Celiac disease is an immune-mediated dis-
mone concentrations soon after the c Blood pressure should be measured
order that occurs with increased fre- at each routine visit. Children found
diagnosis of type 1 diabetes and after quency in patients with type 1 diabetes to have high-normal blood pressure
glucose control has been estab-
(1.616.4% of individuals compared with (systolic blood pressure or diastolic
lished. If normal, consider rechecking
0.31% in the general population) (3335). blood pressure $90th percentile
every 12 years or sooner if the pa-
Testing. Testing for celiac disease in- for age, sex, and height) or hyper-
tient develops symptoms suggestive
cludes measuring serum levels of IgA tension (systolic blood pressure or
of thyroid dysfunction, thyromegaly,
an abnormal growth rate, or an un- and antitissue transglutaminase anti- diastolic blood pressure $95th per-
bodies, or, with IgA deciency, screening centile for age, sex, and height)
explained glycemic variation. E
can include measuring IgG tissue transglu- should have blood pressure con-
Autoimmune thyroid disease is the taminase antibodies or IgG deamidated rmed on 3 separate days. B
most common autoimmune disorder gliadin peptide antibodies. Because most
associated with diabetes, occurring in cases of celiac disease are diagnosed Treatment
within the rst 5 years after the diagnosis c Initial treatment of high-normal
1730% of patients with type 1 diabe-
of type 1 diabetes, screening should be blood pressure (systolic blood pres-
tes (28). At the time of diagnosis, about
considered at the time of diagnosis and sure or diastolic blood pressure con-
25% of children with type 1 diabetes
have thyroid autoantibodies (29); repeated within 2 and 5 years thereafter. sistently $90th percentile for age,
Although celiac disease can be diag- sex, and height) includes dietary
their presence is predictive of thyroid
nosed more than 10 years after diabe- modication and increased exercise,
dysfunctiondmost commonly hypothy-
tes diagnosis, there are insufcient data if appropriate, aimed at weight con-
roidism, although hyperthyroidism
after 5 years to determine the optimal trol. If target blood pressure is not
occurs in ;0.5% of cases (30,31). Thy-
screening frequency. Testing for antitis- reached with 36 months of initiating
roid function tests may be misleading
sue transglutaminase antibody should lifestyle intervention, pharmacologi-
(euthyroid sick syndrome) if performed
at time of diagnosis owing to the effect be considered at other times in patients cal treatment should be considered. E
of previous hyperglycemia, ketosis or with symptoms suggestive of celiac disease c In addition to lifestyle modication,
(35). A small-bowel biopsy in antibody- pharmacological treatment of hyper-
ketoacidosis, weight loss, etc. There-
tension (systolic blood pressure or
fore, thyroid function tests should be positive children is recommended to
diastolic blood pressure consistently
performed soon after a period of meta- conrm the diagnosis (36). European
bolic stability and good glycemic con- guidelines on screening for celiac dis- $95th percentile for age, sex, and
height) should be considered as
trol. Subclinical hypothyroidism may ease in children (not specic to children
be associated with increased risk of with type 1 diabetes) suggest that bi- soon as hypertension is conrmed. E
opsy may not be necessary in symptom- c ACE inhibitors or angiotensin recep-
symptomatic hypoglycemia (32) and re-
tor blockers should be considered
duced linear growth rate. Hyperthyroid- atic children with high antibody titers
for the initial pharmacological treat-
ism alters glucose metabolism and (i.e., greater than 10 times the upper limit
ment of hypertension, following re-
usually causes deterioration of meta- of normal) provided that further testing is
productive counseling due to the
bolic control. performed (verication of endomysial
care.diabetesjournals.org Children and Adolescents S89

potential teratogenic effects of have two or more cardiovascular disease however, studies have shown short-
both drug classes. E (CVD) risk factors (4042), and the preva- term safety equivalent to that seen in
c The goal of treatment is blood lence of CVD risk factors increases with adults and efcacy in lowering LDL cho-
pressure consistently ,90th per- age (42), with girls having a higher risk lesterol levels in familial hypercholes-
centile for age, sex, and height. E burden than boys (41). terolemia or severe hyperlipidemia,
Pathophysiology. The atherosclerotic improving endothelial function, and
Blood pressure measurements should causing regression of carotid intimal
process begins in childhood, and al-
be determined using the appropriate
though CVD events are not expected thickening (54,55). Statins are not ap-
size cuff with the child seated and re- proved for patients aged ,10 years,
to occur during childhood, observations
laxed. Hypertension should be con- and statin treatment should generally
using a variety of methodologies show
rmed on at least 3 separate days. not be used in children with type 1
that youth with type 1 diabetes may have
Evaluation should proceed as clinically diabetes before this age. Statins are
subclinical CVD abnormalities within the
indicated. Treatment is generally initi- category X in pregnancy; therefore,
rst decade of diagnosis (4345). Studies
ated with an ACE inhibitor, but an angio- pregnancy prevention is of paramount
of carotid intima-media thickness have
tensin receptor blocker can be used if importance for postpubertal girls (see
yielded inconsistent results (39).
the ACE inhibitor is not tolerated (e.g., Section 12 Management of Diabetes in
due to cough). Normal blood pressure Treatment. Pediatric lipid guidelines pro-
Pregnancy for more information).
levels for age, sex, and height and ap- vide some guidance relevant to children
Smoking
propriate methods for measurement with type 1 diabetes (4648); however,
are available online at www.nhlbi.nih there are few studies on modifying lipid Recommendation

.gov/health/prof/heart/hbp/hbp_ped levels in children with type 1 diabetes. A c Elicit a smoking history at initial
.pdf (39). 6-month trial of dietary counseling and follow-up diabetes visits and
produced a signicant improvement in discourage smoking in youth who
Dyslipidemia
lipid levels (49); likewise, a lifestyle do not smoke and encourage
Recommendations intervention trial with 6 months of ex- smoking cessation in those who
ercise in adolescents demonstrated im- do smoke. B
Testing
provement in lipid levels (50).
c Obtain a fasting lipid prole in chil- Although intervention data are sparse, The adverse health effects of smoking
dren $10 years of age soon after the American Heart Association (AHA) cat- are well recognized with respect to fu-
the diagnosis (after glucose con-
egorizes children with type 1 diabetes in ture cancer and CVD risk. In youth with
trol has been established). E diabetes, it is important to avoid addi-
the highest tier for cardiovascular risk and
c If lipids are abnormal, annual
recommends both lifestyle and pharmaco- tional CVD risk factors. Smoking increases
monitoring is reasonable. If LDL
logical treatment for those with elevated the risk of onset of albuminuria; there-
cholesterol values are within the
LDL cholesterol levels (48,51). Initial ther- fore, smoking avoidance is important
accepted risk level (,100 mg/dL to prevent both microvascular and mac-
apy should be with a Step 2 AHA diet,
[2.6 mmol/L]), a lipid prole re- rovascular complications (46,56). Dis-
which restricts saturated fat to 7% of total
peated every 35 years is rea- calories and restricts dietary cholesterol to couraging cigarette smoking, including
sonable. E 200 mg/day. Data from randomized clini- e-cigarettes, is an important part of rou-
Treatment cal trials in children as young as 7 months tine diabetes care. In younger children, it
c Initial therapy should consist of of age indicate that this diet is safe and is important to assess exposure to ciga-
optimizing glucose control and does not interfere with normal growth rette smoke in the home due to the ad-
medical nutrition therapy using a and development (52). verse effects of secondhand smoke and
Step 2 American Heart Association For children with a signicant family to discourage youth from ever smoking
diet to decrease the amount of history of CVD, the National Heart, Lung, if exposed to smokers in childhood.
saturated fat in the diet. B and Blood Institute recommends ob-
c After the age of 10 years, addition taining a fasting lipid panel beginning Microvascular Complications
at 2 years of age (46). Abnormal results Nephropathy
of a statin is suggested in patients
who, despite medical nutrition ther- from a random lipid panel should be Recommendations
apy and lifestyle changes, continue conrmed with a fasting lipid panel.
Screening
to have LDL cholesterol .160 mg/dL Data from the SEARCH for Diabetes in
c Annual screening for albuminuria
(4.1 mmol/L) or LDL cholesterol Youth (SEARCH) study show that im-
with a random spot urine sample
.130 mg/dL (3.4 mmol/L) and one proved glucose control over a 2-year pe-
riod is associated with a more favorable for albumintocreatinine ra-
or more cardiovascular disease risk
tio should be considered once
factors. E lipid prole; however, improved glyce-
the child has had diabetes for
c The goal of therapy is an LDL mic control alone will not normalize lip-
ids in youth with type 1 diabetes and 5 years. B
cholesterol value ,100 mg/dL
dyslipidemia (53). c Estimate glomerular ltration rate
(2.6 mmol/L). E at initial evaluation and then
Neither long-term safety nor cardio-
based on age, diabetes duration,
Population-based studies estimate that vascular outcome efcacy of statin ther-
and treatment. E
1445% of children with type 1 diabetes apy has been established for children;
S90 Children and Adolescents Diabetes Care Volume 39, Supplement 1, January 2016

Treatment
duration of only 12 years. Referrals team, including a physician, diabetes

c Treatment with an ACE inhibitor, should be made to eye care professionals nurse educator, registered dietitian,
titrated to normalization of albumin with expertise in diabetic retinopathy and behavioral specialist or social
excretion, should be considered and experience in counseling the pedi- worker, is essential. In addition to blood
atric patient and family on the importance glucose control, treatment must in-
when elevated urinary albumin
of early prevention and intervention. clude management of comorbidities
tocreatinine ratio (.30 mg/g) is
documented with at least two of Neuropathy such as obesity, dyslipidemia, hyperten-
three urine samples. These should sion, and albumin levels from the outset.
Recommendation
be obtained over a 6-month inter- Presentation with ketosis or ketoacidosis
c Consider an annual comprehensive requires a period of insulin therapy un-
val following efforts to improve
foot exam for the child at the start til fasting and postprandial glycemia
glycemic control and normalize
of puberty or at age $10 years, have been restored to normal or near-
blood pressure. B
whichever is earlier, once the youth normal. Metformin therapy may be
Data from 7,549 participants ,20 years has had type 1 diabetes for 5 years. E used as an adjunct after resolution of
of age in the T1D Exchange clinic registry ketosis/ketoacidosis. Initial treatment
Neuropathy rarely occurs in prepubertal should also be with insulin when the
emphasize the importance of good gly-
cemic and blood pressure control, par-
children or after only 12 years of diabe- distinction between type 1 diabetes
tes (60). A comprehensive foot exam, in- and type 2 diabetes is unclear and
ticularly as diabetes duration increases,
cluding inspection, palpation of dorsalis in patients who have random blood
in order to reduce the risk of nephropa-
pedis and posterior tibial pulses, assess- glucose concentrations $250 mg/dL
thy. The data also underscore the impor-
ment of the patellar and Achilles reexes, ( 1 3 . 9 mm o l / L ) a n d / o r A 1 C . 9 %
tance of routine screening to ensure
and determination of proprioception, vi- (75 mmol/mol) (65).
early diagnosis and timely treatment of
bration, and monolament sensation, Patients and their families must prior-
albuminuria (57). An estimation of glo-
should be performed annually along itize lifestyle modications such as
merular ltration rate (GFR), calculated with assessment of symptoms of neuro- eating a balanced diet, maintaining a
using GFR estimating equations from pathic pain. Foot inspection can be per- healthy weight, and exercising regu-
the serum creatinine, height, age, and formed at each visit to educate youth larly. A family-centered approach to nu-
sex (58), should be determined at base- regarding the importance of foot care.
line and repeated as indicated based on trition and lifestyle modication is
essential in children with type 2 diabe-
clinical status, age, diabetes duration,
TYPE 2 DIABETES tes. Nutrition recommendations should
and therapies. Estimated GFR is calcu-
For information on testing for type 2 be culturally appropriate and sensitive
lated from a serum creatinine measure-
diabetes and prediabetes in children to family resources (see Section 3
ment using an estimating equation. This
and adolescents, please refer to Sec- Foundations of Care and Comprehen-
is not a recommendation to perform a
tion 2 Classication and Diagnosis of sive Medical Evaluation).
measurement of creatinine clearance (in-
When insulin treatment is not re-
volves timed urine collection) every year. Diabetes.
The Centers for Disease Control and quired, initiation of metformin, currently
There are ongoing clinical trials assessing
Prevention recently published projections the only oral hypoglycemic agent speci-
the efcacy of early treatment of persis- cally approved for use in children with
for type 2 diabetes prevalence using the
tent albuminuria with ACE inhibitors (59). type 2 diabetes, is recommended. How-
SEARCH database. Assuming a 2.3% an-
nual increase, the prevalence of type 2 ever, the Treatment Options for type 2 Di-
Retinopathy
diabetes in those under 20 years of age abetes in Adolescents and Youth (TODAY)
Recommendations study found that metformin alone pro-
will quadruple in 40 years (61,62). Given
c An initial dilated and comprehen- the current obesity epidemic, distinguish- vided durable glycemic control (A1C
sive eye examination is recom- ing between type 1 and type 2 diabetes in #8% [64 mmol/mol] for 6 months) in ap-
mended at age $10 years or children can be difcult. For example, ex- proximately half of the subjects (66), sug-
after puberty has started, which- cessive weight is common in children with gesting that many youth with type 2
ever is earlier, once the youth type 1 diabetes (63). Furthermore, diabetes- diabetes are likely to require combination
has had diabetes for 35 years. B associated autoantibodies and ketosis treatment within a few years of diagnosis.
c After the initial examination, an- may be present in patients with features
nual routine follow-up is generally of type 2 diabetes (including obesity and Comorbidities
recommended. Less frequent ex- acanthosis nigricans) (64). Nevertheless, Comorbidities may already be present at
aminations, every 2 years, may accurate diagnosis is critical as treatment the time of diagnosis in youth with
be acceptable on the advice of an regimens, educational approaches, die- type 2 diabetes (67). Therefore, blood
eye care professional. E tary advice, and outcomes differ mark- pressure measurement, a fasting lipid
edly between the two diagnoses. panel, assessment for albumin excre-
Although retinopathy (like albuminuria) tion, and a dilated eye examination
most commonly occurs after the onset Treatment should be performed at diagnosis.
of puberty and after 510 years of dia- The general treatment goals for type 2 Thereafter, screening guidelines and
betes duration (60), it has been reported diabetes are the same as those for type treatment recommendations for hyper-
in prepubertal children and with diabetes 1 diabetes. A multidisciplinary diabetes tension, dyslipidemia, albumin excretion,
care.diabetesjournals.org Children and Adolescents S91

and retinopathy are similar to those for Although scientic evidence is limited, with type 1 diabetes. Pediatrics 2013;132:
youth with type 1 diabetes. Additional it is clear that comprehensive and coordi- e1395e1402
10. Hood KK, Beavers DP, Yi-Frazier J, et al. Psy-
problems that may need to be addressed nated planning that begins in early ado- chosocial burden and glycemic control during
include polycystic ovary disease and lescence, or at least 1 year before the the rst 6 years of diabetes: results from the
other comorbidities associated with pe- date of transition, is necessary to facilitate SEARCH for Diabetes in Youth study. J Adolesc
diatric obesity, such as sleep apnea, a seamless transition from pediatric to Health 2014;55:498504
hepatic steatosis, orthopedic complica- adult health care (71,72). A comprehen- 11. Ducat L, Philipson LH, Anderson BJ. The
mental health comorbidities of diabetes. JAMA
tions, and psychosocial concerns. The sive discussion regarding the challenges
2014;312:691692
ADA consensus report Type 2 Diabetes faced during this period, including specic 12. Katz ML, Volkening LK, Butler DA, Anderson
in Children and Adolescents (68) and a recommendations, is found in the ADA BJ, Laffel LM. Family-based psychoeducation
more recent American Academy of Pe- position statement Diabetes Care for and care ambassador intervention to improve
diatrics clinical practice guideline (69) Emerging Adults: Recommendations for glycemic control in youth with type 1 diabetes: a
randomized trial. Pediatr Diabetes 2014;15:
provide guidance on the prevention, Transition From Pediatric to Adult Diabe-
142150
screening, and treatment of type 2 di- tes Care Systems (72). 13. Laffel LM, Vangsness L, Connell A, Goebel-
abetes and its comorbidities in children The National Diabetes Education Pro- Fabbri A, Butler D, Anderson BJ. Impact of
and adolescents. gram (NDEP) has materials available to ambulatory, family-focused teamwork inter-
facilitate the transition process (http:// vention on glycemic control in youth with
TRANSITION FROM PEDIATRIC TO type 1 diabetes. J Pediatr 2003;142:409416
ndep.nih.gov/transitions), and the En-
ADULT CARE 14. Anderson BJ, Vangsness L, Connell A, Butler
docrine Society in collaboration with D, Goebel-Fabbri A, Laffel LM. Family conict,
Recommendations the ADA and other organizations has de- adherence, and glycaemic control in youth with
c Health care providers and families veloped transition tools for clinicians short duration type 1 diabetes. Diabet Med
should begin to prepare youth in and youth and families (http://www 2002;19:635642
15. Lawrence JM, Yi-Frazier JP, Black MH, et al.;
early to mid-adolescence and, at .endo-society.org/clinicalpractice/ SEARCH for Diabetes in Youth Study Group. De-
the latest, at least 1 year before transition_of_care.cfm). mographic and clinical correlates of diabetes-
the transition to adult health care. E related quality of life among youth with type 1
c Both pediatricians and adult References diabetes. J Pediatr 2012;161:201207.e2
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Antisdel JE, Anderson BJ, Laffel LM. Brief screening
in providing support and links to Diabetes Research in Children Network (DirecNet).
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Alterations in white matter structure in young chil-
resources for the teen and emerg- sistency and external validity in a contemporary
dren with type 1 diabetes. Diabetes Care 2014;37:
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2. Cameron FJ, Scratch SE, Nadebaum C, et al.; Diabetes Care 2010;33:495500
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quences of diabetic ketoacidosis at initial presenta- Dahl-Jrgensen K, R O. Disturbed eating be-
management are increasingly shifted
tion of type 1 diabetes in a prospective cohort study havior and omission of insulin in adolescents
from parents and other adults to the receiving intensied insulin treatment: a na-
of children. Diabetes Care 2014;37:15541562
youth with diabetes throughout child- 3. Markowitz JT, Garvey KC, Laffel LM. Devel- tionwide population-based study. Diabetes
hood and adolescence. The shift from opmental changes in the roles of patients and Care 2013;36:33823387
pediatrics to adult health care providers, families in type 1 diabetes management. Curr 18. Seaquist ER, Anderson J, Childs B, et al. Hy-
Diabetes Rev 2015;11:231238 poglycemia and diabetes: a report of a work-
however, often occurs abruptly as the
4. Silverstein J, Klingensmith G, Copeland K, group of the American Diabetes Association
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young people who have diabetes. During tion. Diabetes Care 2005;28:186212 sence of adverse effects of severe hypoglycemia
5. Chiang JL, Kirkman MS, Laffel LM, Peters AL; on cognitive function in school-aged children
this period of major life transitions, youth
Type 1 Diabetes Sourcebook Authors. Type 1 di- with diabetes over 18 months. Diabetes Care
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and must become fully responsible for ment of the American Diabetes Association. 20. Blasetti A, Chiuri RM, Tocco AM, et al. The
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children with type 1 diabetes safe at school? abetes: a meta-analysis. J Child Neurol 2011;26:
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ents health insurance plan (ongoing 7. Jackson CC, Albanese-ONeill A, Butler KL, severe hypoglycaemia in a contemporary cohort
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S92 Children and Adolescents Diabetes Care Volume 39, Supplement 1, January 2016

Lessons from the Hvidoere International Study Gastroenterology, Hepatology, and Nutrition. structured dietician training to a Mediterranean-
Group on childhood diabetes: be dogmatic European Society for Pediatric Gastroenterol- style diet. J Endocrinol Invest 2012;35:160168
about outcome and exible in approach. Pediatr ogy, Hepatology, and Nutrition guidelines for 50. Salem MA, Aboelasrar MA, Elbarbary NS,
Diabetes 2013;14:473480 the diagnosis of coeliac disease. J Pediatr Gas- Elhilaly RA, Refaat YM. Is exercise a therapeutic
24. Nimri R, Weintrob N, Benzaquen H, Ofan R, troenterol Nutr 2012;54:136160 tool for improvemen