Professional Documents
Culture Documents
Recommendations
1.1 Ensure treatment decisions are timely, rely on evidence-based guidelines,
include social community support, and are made collaboratively with pa-
tients based on individual preferences, prognoses, comorbidities, and in-
formed financial considerations. B
1.2 Align approaches to diabetes management with the Chronic Care Model.
This model emphasizes person-centered team care, integrated long-term
treatment approaches to diabetes and comorbidities, and ongoing collab-
orative communication and goal setting between all team members. A
1.3 Care systems should facilitate in-person and virtual team–based care, in-
cluding those knowledgeable and experienced in diabetes management
as part of the team, and utilization of patient registries, decision support
tools, and community involvement to meet patient needs. B
1.4 Assess diabetes health care maintenance (Table 4.1) using reliable and Disclosure information for each author is
relevant data metrics to improve processes of care and health outcomes, available at https://doi.org/10.2337/dc23-SDIS.
with attention to care costs. B Suggested citation: ElSayed NA, Aleppo G, Aroda
VR, et al., American Diabetes Association. 1.
Improving care and promoting health in po-
Population health is defined as “the health outcomes of a group of individuals, includ- pulations: Standards of Care in Diabetes—2023.
Diabetes Care 2023;46(Suppl. 1):S10–S18
ing the distribution of health outcomes within the group”; these outcomes can be
measured in terms of health outcomes (mortality, morbidity, health, and functional © 2022 by the American Diabetes Association.
status), disease burden (incidence and prevalence), and behavioral and metabolic fac- Readers may use this article as long as the
work is properly cited, the use is educational
tors (physical activity, nutrition, A1C, etc.) (1). Clinical practice recommendations for and not for profit, and the work is not altered.
health care professionals are tools that can ultimately improve health across popula- More information is available at https://www.
tions; however, for optimal outcomes, diabetes care must also be individualized for diabetesjournals.org/journals/pages/license.
diabetesjournals.org/care Improving Care and Promoting Health in Populations S11
each patient. Thus, efforts to improve of the population, such as young adults 6. Health systems (to create a quality-
population health will require a combi- and individuals with complex comorbid- oriented culture)
nation of policy-level, system-level, and ities, financial or other social hardships,
patient-level approaches. With such an and/or limited English proficiency, face A 5-year effectiveness study of the
integrated approach in mind, the Ameri- particular challenges to goal-based care CCM in 53,436 people with type 2 diabe-
can Diabetes Association (ADA) highlights (5–7). Even after adjusting for these tes in the primary care setting suggested
the importance of patient-centered care, patient factors, the persistent variability that the use of this model of care delivery
defined as care that considers individual in the quality of diabetes care across reduced the cumulative incidence of
patient comorbidities and prognoses; is health care professionals and prac- diabetes-related complications and all-
respectful of and responsive to patient tice settings indicates that substan- cause mortality (10). Patients who were
preferences, needs, and values; and en- tial system-level improvements are enrolled in the CCM experienced a re-
sures that patient values guide all clinical still needed. duction in cardiovascular disease risk by
decisions (2). Furthermore, social deter- Diabetes poses a significant financial 56.6%, microvascular complications by
and identifying, developing, and engaging a growing variety of applications and content and skills, behavioral strategies
community resources and public policies services using two-way video, smartphones, (goal setting, problem-solving), and en-
that support healthy lifestyles (29). The wireless tools, and other forms of tele- gagement with psychosocial concerns.
National Diabetes Education Program communications technology (40). Often Increasingly, such support is being ada-
maintains an online resource (cdc.gov/ used interchangeably with telemedicine, pted for online platforms that have the
diabetes/professional-info/training.html) telehealth describes a broader range of potential to promote patient access to
to help health care professionals design digital health services in health care deliv- this important resource. These curricu-
and implement more effective health ery (41). This includes synchronous, asyn- lums need to be tailored to the needs of
care delivery systems for those with dia- chronous, and remote patient monitoring. the intended populations, including ad-
betes. Given the pluralistic needs of peo- Telehealth should be used comple- dressing the “digital divide,” i.e., access
ple with diabetes and that the constant mentary to in-person visits to optimize to the technology required for imple-
challenges they experience vary over the glycemic management in people with mentation (53–56).
course of disease management (complex unmanaged diabetes (42). Increasingly,
Access to Care and Quality Improvement personalized care goals (7,73). (Also see framework for educating health care
The Affordable Care Act and Medicaid COST CONSIDERATIONS FOR MEDICATION-TAKING professionals on the importance of
expansion have increased access to BEHAVIORS, above, regarding cost-related SDOH (84). Furthermore, there are re-
care for many individuals with diabetes, barriers to medication use.) sources available for the inclusion of stan-
emphasizing the protection of people dardized sociodemographic variables in
with preexisting conditions, health pro- TAILORING TREATMENT FOR electronic health records to facilitate the
motion, and disease prevention (60). In SOCIAL CONTEXT measurement of health inequities and
fact, health insurance coverage increased the impact of interventions designed to
from 84.7% in 2009 to 90.1% in 2016 for Recommendations
reduce those inequities (65,84,85).
adults with diabetes aged 18–64 years. 1.5 Assess food insecurity, housing
SDOH are not consistently recognized
Coverage for those aged $65 years re- insecurity/homelessness, financial
and often go undiscussed in the clinical
mained nearly universal (61). Patients barriers, and social capital/social encounter (77). Among people with
who have either private or public in- community support to inform chronic illnesses, two-thirds of those who
headed by single mothers. The food obtain nutritious food more regularly Migrant farmworkers encounter nu-
insecurity rate in individuals with diabe- (98). merous and overlapping barriers to re-
tes may be up to 20% (90). Additionally, ceiving care. Migration, which may occur
the risk for type 2 diabetes is increased Homelessness and Housing Insecurity as frequently as every few weeks for
twofold in those with food insecurity Homelessness/housing insecurity often farmworkers, disrupts care. In addition,
(81) and has been associated with lower accompanies many additional barriers cultural and linguistic barriers, lack of
engagement in self-care behaviors and to diabetes self-management, including transportation and money, lack of avail-
medication use, depression, diabetes food insecurity, literacy and numeracy able work hours, unfamiliarity with new
distress, and worse glycemic manage- deficiencies, lack of insurance, cognitive communities, lack of access to resour-
ment when compared with individuals dysfunction, and mental health issues ces, and other barriers prevent migrant
who are food secure (91–93). Older (99). The prevalence of diabetes in the farmworkers from accessing health care.
adults with food insecurity are more homeless population is estimated to be Without regular care, those with diabetes
around 8% (100). Additionally, people
diabetes care and education specialists be lifelong (112). These factors are rarely 3. Haire-Joshu D, Hill-Briggs F. The next generation
should ensure they provide easy- addressed in routine treatment or disease of diabetes translation: a path to health equity.
Annu Rev Public Health 2019;40:391–410
to-understand information and reduce management but may be underlying 4. Kazemian P, Shebl FM, McCann N, Walensky
unnecessary complexity when develop- reasons for lower engagement in self- RP, Wexler DJ. Evaluation of the cascade of
ing care plans with patients. Interven- care behaviors and medication use. diabetes care in the United States, 2005–2016.
tions addressing low health literacy in Identification or development of com- JAMA Intern Med 2019;179:1376–1385
munity resources to support healthy 5. Kerr EA, Heisler M, Krein SL, et al. Beyond
populations with diabetes seem effec-
comorbidity counts: how do comorbidity type and
tive in improving diabetes outcomes, in- lifestyles is a core element of the CCM severity influence diabetes patients’ treatment
cluding ones focusing primarily on patient (9), with a particular need to incorporate priorities and self-management? J Gen Intern Med
education, self-care training, or disease relevant social support networks. There is 2007;22:1635–1640
management. Combining easily adapted currently a paucity of evidence regarding 6. Fernandez A, Schillinger D, Warton EM, et al.
Language barriers, physician-patient language
materials with formal diabetes education enhancing these resources for those
concordance, and glycemic control among insured
demonstrates effectiveness on clinical most likely to benefit from such interven-
19. Jaffe MG, Lee GA, Young JD, Sidney S, Go AS. compared with current treatment guidelines. 51. Garcia JF, Fogel J, Reid M, Bisno DI, Raymond
Improved blood pressure control associated with Diabetes Educ 2011;37:78–84 JK. Telehealth for young adults with diabetes:
a large-scale hypertension program. JAMA 2013; 35. Tamhane S, Rodriguez-Gutierrez R, Hargraves addressing social determinants of health. Diabetes
310:699–705 I, Montori VM. Shared decision-making in diabetes Spectr 2021;34:357–362
20. Peikes D, Chen A, Schore J, Brown R. Effects care. Curr Diab Rep 2015;15:112 52. Haynes SC, Kompala T, Neinstein A, Rosenthal J,
of care coordination on hospitalization, quality 36. Garg AX, Adhikari NKJ, McDonald H, et al. Crossen S. Disparities in telemedicine use for
of care, and health care expenditures among Effects of computerized clinical decision support subspecialty diabetes care during COVID-19
Medicare beneficiaries: 15 randomized trials. systems on practitioner performance and patient shelter-in-place orders. J Diabetes Sci Technol
JAMA 2009;301:603–618 outcomes: a systematic review. JAMA 2005;293: 2021;15:986–992
21. Raebel MA, Schmittdiel J, Karter AJ, Konieczny 1223–1238 53. Dack C, Ross J, Stevenson F, et al. A digital
JL, Steiner JF. Standardizing terminology and 37. Smith SA, Shah ND, Bryant SC, et al.; Evidens self-management intervention for adults with
definitions of medication adherence and persistence Research Group. Chronic care model and shared type 2 diabetes: combining theory, data and
in research employing electronic databases. Med care in diabetes: randomized trial of an electronic participatory design to develop HeLP-Diabetes.
Care 2013;51(Suppl. 3):S11–S21 decision support system. Mayo Clin Proc 2008; Internet Interv 2019;17:100241
22. Feifer C, Nemeth L, Nietert PJ, et al. Different 83:747–757 54. Lee MK, Lee DY, Ahn HY, Park CY. A novel
from https://www.niddk.nih.gov/health-information/ Objectives for 2020. Phase I report: recom- 99. White BM, Logan A, Magwood GS. Access to
professionals/clinical-tools-patient-management/ mendations for the framework and format of diabetes care for populations experiencing home-
diabetes Healthy People 2020. Accessed 11 October lessness: an integrated review. Curr Diab Rep
68. O’Connor PJ, Sperl-Hillen JM, Fazio CJ, 2022. Available from https://www.healthypeople. 2016;16:112
Averbeck BM, Rank BH, Margolis KL. Outpatient gov/2010/hp2020/advisory/PhaseI/default.htm 100. Bernstein RS, Meurer LN, Plumb EJ, Jackson
diabetes clinical decision support: current status 84. National Academies of Sciences, Engineering, JL. Diabetes and hypertension prevalence in
and future directions. Diabet Med 2016;33: and Medicine. A Framework for Educating Health homeless adults in the United States: a
734–741 Professionals to Address the Social Determinants systematic review and meta-analysis. Am J
69. Institute of Medicine, Committee on Health of Health. Washington, DC, National Academies Public Health 2015;105:e46–e60
Literacy. Health Literacy: A Prescription to End Press, 2016 101. Montgomery AE, Fargo JD, Kane V, Culhane
Confusion. Nielsen-Bohlman L, Panzer AM, Kindig 85. Chin MH, Clarke AR, Nocon RS, et al. A DP. Development and validation of an instrument
DA, Eds. Washington, DC, National Academies roadmap and best practices for organizations to to assess imminent risk of homelessness among
Press, 2004. PMID: 25009856 reduce racial and ethnic disparities in health care. veterans. Public Health Rep 2014;129:428–436
70. Schaffler J, Leung K, Tremblay S, et al. The J Gen Intern Med 2012;27:992–1000 102. Stahre M, VanEenwyk J, Siegel P, Njai R.
effectiveness of self-management interventions 86. Hershey JA, Morone J, Lipman TH, Hawkes Housing Insecurity and the association with
prevention-chronic-care/improve/community/ prevention and disease management with special Qualities. CHW Central, 2016. Available from
index.html reference to diabetes: systematic reviews. Clin https://files.ctctcdn.com/a907c850501/1c1289f0-
114. Egbujie BA, Delobelle PA, Levitt N, Puoane T, Diabetes Endocrinol 2017;3:4 88cc-49c3-a238-66def942c147.pdf
Sanders D, van Wyk B. Role of community 118. Foster G, Taylor SJC, Eldridge SE, Ramsay J, 121. Guide to Community Preventive Services.
health workers in type 2 diabetes mellitus Griffiths CJ. Self-management education pro- Community health workers help patients manage
self-management: a scoping review. PLoS One grammes by lay leaders for people with chronic diabetes. Updated 2018. Accessed 11 October 2022.
2018;13:e0198424 conditions. Cochrane Database Syst Rev 2007(4): Available from https://www.thecommunityguide.
115. Heisler M, Vijan S, Makki F, Piette JD. CD005108 org/content/community-health-workers-help-
Diabetes control with reciprocal peer support 119. Piatt GA, Rodgers EA, Xue L, Zgibor JC. patients-manage-diabetes
versus nurse care management: a randomized Integration and utilization of peer leaders for 122. The Network for Public Health Law. Legal
trial. Ann Intern Med 2010;153:507–515 diabetes self-management support: results from considerations for community health workers
116. Long JA, Jahnle EC, Richardson DM, Project SEED (Support, Education, and Evaluation and their employers. Accessed 11 October 2022.
Loewenstein G, Volpp KG. Peer mentoring in Diabetes). Diabetes Educ 2018;44:373–382 Available from https://www.networkforphl.org/
and financial incentives to improve glucose 120. Rosenthal EL, Rush CH, Allen CG. Under- wp-content/uploads/2020/01/Legal-Considerations-
control in African American veterans: a standing scope and competencies: a contemporary Community-Health-Workers.pdf
25 June 2023. Sections 2 and 3 have been updated based on U.S. Food and Drug Administration approval of a new drug to delay the incidence of
type 1 diabetes. The changes are described in detail in: Addendum. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—
2023. Diabetes Care 2023;46(Suppl. 1):S19–S40 (https://doi.org/10.2337/dc23-ad08) and Addendum. 3. Prevention or Delay of Type 2 Diabetes and
Associated Comorbidities: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S41–S48 (https://doi.org/10.2337/dc23-ad08a).
CLASSIFICATION
Diabetes can be classified into the following general categories:
no longer accurate, as both diseases oc- identification of individualized therapies b-cell destruction are included under
cur in both age groups. Children with for diabetes in the future will be in- the rubric of type 1 diabetes. Use of the
type 1 diabetes often present with the formed by better characterization of the term LADA is common and acceptable
hallmark symptoms of polyuria/poly- many paths to b-cell demise or dysfunc- in clinical practice and has the practical
dipsia, and approximately half present tion (12). Across the globe, many groups impact of heightening awareness of a
with diabetic ketoacidosis (DKA) (2–4). are working on combining clinical, population of adults likely to have pro-
The onset of type 1 diabetes may be pathophysiological, and genetic char- gressive autoimmune b-cell destruction
more variable in adults; they may not acteristics to more precisely define the (16), thus accelerating insulin initiation
present with the classic symptoms subsets of diabetes that are currently prior to deterioration of glucose manage-
seen in children and may experience clustered into the type 1 diabetes versus ment or development of DKA (6,17).
temporary remission from the need for type 2 diabetes nomenclature with the The paths to b-cell demise and dys-
insulin (5–7). The features most useful in goal of optimizing personalized treat- function are less well defined in type 2
discrimination of type 1 diabetes include ment approaches. Many of these stud-
FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; 2-h PG, 2-h plasma glucose.
diabetesjournals.org/care Classification and Diagnosis of Diabetes S21
Table 2.2—Criteria for the diagnosis of diabetes oral glucose tolerance testing
FPG $126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* as a screen for diabetes. A
OR
2-h PG $200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described The A1C test should be performed us-
by WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose ing a method that is certified by the
dissolved in water.*
NGSP (ngsp.org) and standardized or
OR traceable to the Diabetes Control and
A1C $6.5% (48 mmol/mol). The test should be performed in a laboratory using a method Complications Trial (DCCT) reference as-
that is NGSP certified and standardized to the DCCT assay.* say. Point-of-care A1C assays may be
OR NGSP certified and cleared by the U.S.
Food and Drug Administration (FDA)
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random
HIV treatment (34,35), age, race/ethnicity, levels (43). Though conflicting data exist, are both above the diagnostic threshold
genetic background, and anemia/ African American individuals may also when analyzed from the same sample or
hemoglobinopathies. (See OTHER CONDI- have higher levels of fructosamine and in two different test samples, this also
TIONS ALTERING THE RELATIONSHIP OF A 1 C AND glycated albumin and lower levels of confirms the diagnosis. On the other
GLYCEMIA below for more information.) 1,5-anhydroglucitol, suggesting that their hand, if a patient has discordant results
glycemic burden (particularly postprandi- from two different tests, then the test
Age ally) may be higher (44,45). Similarly, result that is above the diagnostic cut
The epidemiologic studies that formed A1C levels may be higher for a given point should be repeated, with careful
the basis for recommending A1C to mean glucose concentration when consideration of the possibility of A1C
diagnose diabetes included only adult measured with continuous glucose assay interference. The diagnosis is made
populations (33). However, recent ADA monitoring (46). A recent report in
on the basis of the confirmatory screen-
clinical guidance concluded that A1C, Afro-Caribbean people demonstrated a
ing test. For example, if a patient meets
FPG, or 2-h PG could be used to test lower A1C than predicted by glucose lev-
TYPE 1 DIABETES increased dramatically over the past (71,72). Fewer than half of these pa-
20 years (2–4). Others have modest tients have autoantibodies that are seen
Recommendations
fasting hyperglycemia that can rapidly in type 1 diabetes, supporting alternate
2.5 Screening for presymptomatic
change to severe hyperglycemia and/ pathobiology. This immune-related adverse
type 1 diabetes may be done or DKA with infection or other stress. event occurs in just under 1% of check-
by detection of autoantibodies Adults may retain sufficient b-cell func- point inhibitor-treated patients but most
to insulin, glutamic acid decar- tion to prevent DKA for many years; commonly occurs with agents that block
boxylase (GAD), islet antigen 2, such individuals may have remission the programmed cell death protein 1/
or zinc transporter 8. B or decreased insulin needs for months programmed cell death ligand 1 pathway
2.6 Multiple confirmed islet autoan- or years and eventually become depen- alone or in combination with other
tibodies is a risk factor for dent on insulin for survival and are at checkpoint inhibitors (73). To date, the
clinical diabetes. Testing for risk for DKA (5–7,67,68). At this later majority of immune checkpoint inhibitor–
dysglycemia may be used to stage of the disease, there is little or related cases of type 1 diabetes occur in
autoantibody positivity in three pediatric (BMI $25 kg/m2 or $23 kg/m2 occurs earlier, in children and
cohorts from Finland, Germany, and the in Asian American individuals) adolescents with overweight
U.S. Of the 585 children who developed who have one or more risk (BMI $85th percentile) or
more than two autoantibodies, nearly factors (Table 2.3). B obesity (BMI $95th percentile)
70% developed type 1 diabetes within 10 2.9 For all people, screening should and who have one or more
years and 84% within 15 years (14). These begin at age 35 years. B risk factors for diabetes. (See
findings are highly significant because 2.10 If tests are normal, repeat Table 2.4 for evidence grad-
while the German group was recruited screening recommended at ing of risk factors.) B
from offspring of parents with type 1 a minimum of 3-year inter- 2.15 People with HIV should be
diabetes, the Finnish and American vals is reasonable, sooner with
groups were recruited from the gen- screened for diabetes and pre-
symptoms or change in risk diabetes with a fasting glucose
eral population. Remarkably, the find- (i.e., weight gain). C
ings in all three groups were the same, test before starting antiretrovi-
American
Diabetes
® Association®
5. Have you ever been diagnosed with high 6’ 0” 184–220 221–293 294+
blood pressure? ..................................................... 6’ 1” 189–226 227–301 302+
Yes (1 point) No (0 points) 6’ 2” 194–232 233–310 311+
6’ 3” 200–239 240–318 319+
6. Are you physically active? ....................................
6’ 4” 205–245 246–327 328+
Yes (0 points) No (1 point)
1 point 2 points 3 points
7. What is your weight category? ............................. If you weigh less than the amount in
See chart at right. the left column: 0 points
which blood glucose levels are higher than normal risk for type 2 diabetes. Small steps make
but not yet high enough to be diagnosed as diabetes. a big difference in helping you live a longer,
Talk to your doctor to see if additional testing is needed. healthier life.
If you are at high risk, your first step is to
Type 2 diabetes is more common in African Americans, visit your doctor to see if additional testing
Hispanics/Latinos, Native Americans, Asian Americans, is needed.
and Native Hawaiians and Pacific Islanders.
Visit diabetes.org or call 1-800-DIABETES
Higher body weight increases diabetes risk for everyone. (800-342-2383) for information, tips on
Asian Americans are at increased diabetes risk at lower getting started, and ideas for simple, small
body weight than the rest of the general public (about 15 steps you can take to help lower your risk.
pounds lower).
increased percentage of body fat dis- in association with the stress of another ill- (90,91). Type 2 diabetes frequently goes
tributed predominantly in the abdomi- ness such as infection or myocardial infarc- undiagnosed for many years because
nal region. tion or with the use of certain drugs (e.g., hyperglycemia develops gradually and,
DKA seldom occurs spontaneously in corticosteroids, atypical antipsychotics, and at earlier stages, is often not severe
type 2 diabetes; when seen, it usually arises sodium–glucose cotransporter 2 inhibitors) enough for the patient to notice the
diabetesjournals.org/care Classification and Diagnosis of Diabetes S27
classic diabetes symptoms caused by hy- conditions in which early detection via A large European randomized con-
perglycemia, such as dehydration or un- screening is appropriate. Both conditions trolled trial compared the impact of
intentional weight loss. Nevertheless, are common and impose significant clin- screening for diabetes and intensive
even undiagnosed people with diabetes ical and public health burdens. There is multifactorial intervention with that of
are at increased risk of developing macro- often a long presymptomatic phase be- screening and routine care (111). Gen-
vascular and microvascular complications. fore the diagnosis of type 2 diabetes. eral practice patients between the ages
People with type 2 diabetes may have Simple tests to detect preclinical disease of 40 and 69 years were screened for
insulin levels that appear normal or ele- are readily available (101). The duration diabetes and randomly assigned by prac-
vated, yet the failure to normalize blood of glycemic burden is a strong predictor tice to intensive treatment of multiple
glucose reflects a relative defect in glu- of adverse outcomes. There are effective risk factors or routine diabetes care.
cose-stimulated insulin secretion. Thus, interventions that prevent progression After 5.3 years of follow-up, CVD risk
insulin secretion is defective in these from prediabetes to diabetes. It is im- factors were modestly but significantly
individuals and insufficient to compensate portant to individualize risk/benefit of improved with intensive treatment com-
of 23 kg/m2 practical. An argument can and ARV-associated hyperglycemia, it may the feasibility, effectiveness, and cost-
be made to push the BMI cut point to be appropriate to consider discontinuing effectiveness of screening in this setting.
lower than 23 kg/m2 in favor of in- the problematic ARV agents if safe and
creased sensitivity; however, this would effective alternatives are available (124). Screening and Testing for Prediabetes
lead to an unacceptably low specificity Before making ARV substitutions, care- and Type 2 Diabetes in Children and
(13.1%). Data from the World Health fully consider the possible effect on Adolescents
Organization also suggest that a BMI of HIV virological control and the poten- In the last decade, the incidence and
$23 kg/m2 should be used to define in- tial adverse effects of new ARV agents. prevalence of type 2 diabetes in chil-
creased risk in Asian American individu- In some cases, antihyperglycemic agents dren and adolescents has increased dra-
als (119). The finding that one-third to may still be necessary. matically, especially in racial and ethnic
one-half of diabetes in Asian American minority populations (75). See Table 2.4
people is undiagnosed suggests that Testing Interval for recommendations on risk-based
testing is not occurring at lower BMI The appropriate interval between screen- screening for type 2 diabetes or pre-
2.17 A1C is not recommended as increase in CFRD with age (increased regimen and in the absence
a screening test for cystic 10% per decade), genotype, decreased of an acute infection. B
fibrosis–related diabetes. B lung function, and female sex (140,141). 2.21 The oral glucose tolerance test
2.18 People with cystic fibrosis– Continuous glucose monitoring or HOMA is the preferred test to make a
related diabetes should be of b-cell function (142) may be more sensi- diagnosis of posttransplanta-
treated with insulin to attain in- tive than OGTT to detect risk for progres- tion diabetes mellitus. B
dividualized glycemic goals. A sion to CFRD; however, evidence linking 2.22 Immunosuppressive regimens
2.19 Beginning 5 years after the these results to long-term outcomes is shown to provide the best out-
diagnosis of cystic fibrosis– lacking, and these tests are not recom- comes for patient and graft
related diabetes, annual mon- mended for screening outside of the re- survival should be used, irre-
itoring for complications of di- search setting (143). spective of posttransplantation
abetes is recommended. E CFRD mortality has significantly de- diabetes mellitus risk. E
creased over time, and the gap in mor-
PTDM at 1 year. Risk factors for PTDM Dipeptidyl peptidase 4 inhibitors do not 6q24, is recurrent in about half of cases,
included elevated BMI, discharge from interact with immunosuppressant drugs and may be treatable with medications
the hospital on insulin, and glucose val- and have demonstrated safety in small other than insulin. Permanent neonatal
ues in the 24 h prior to hospital dis- clinical trials (169,170). Well-designed inter- diabetes is most commonly due to auto-
charge (157). In an Iranian cohort, 19% vention trials examining the efficacy and somal dominant mutations in the genes
had PTDM after heart and lung trans- safety of these and other antihyperglyce- encoding the Kir6.2 subunit (KCNJ11)
plant (158). The OGTT is considered mic agents in people with PTDM are and SUR1 subunit (ABCC8) of the b-cell
the gold-standard test for the diagnosis needed. KATP channel. A recent report details a
of PTDM (1 year posttransplant) (148, de novo mutation in EIF2B1 affecting
149,159,160). Pretransplant elevation MONOGENIC DIABETES SYNDROMES eIF2 signaling associated with permanent
in hs-CRP was associated with PTDM in neonatal diabetes and hepatic dys-
the setting of renal transplant (161,162). Recommendations
function, similar to Wolcott-Rallison
However, screening people with fasting 2.23 Regardless of current age, all
syndrome but with few severe comor-
therapy; in some instances, insulin will increasingly difficult to precisely define plans and delays in diagnosing other
be required over time. Mutations or de- in the absence of a definitive set of tests family members (188). The correct diagno-
letions in HNF1B are associated with re- for either type of diabetes (173–175, sis is especially critical for those with GCK-
nal cysts and uterine malformations (renal 178–184). In most cases, the presence MODY mutations, where multiple stud-
cysts and diabetes [RCAD] syndrome). of autoantibodies for type 1 diabetes ies have shown that no complications
Other extremely rare forms of MODY precludes further testing for mono- ensue in the absence of glucose-lowering
have been reported to involve other genic diabetes, but the presence of auto- therapy (189). The risks of microvascular
transcription factor genes, including PDX1 antibodies in people with monogenic and macrovascular complications with
(IPF1) and NEUROD1. diabetes has been reported (185). Indi- HNFIA- and HNF4A-MODY are similar to
viduals in whom monogenic diabetes is those observed in people with type 1
suspected should be referred to a spe-
Diagnosis of Monogenic Diabetes and type 2 diabetes (190,191). Genetic
A diagnosis of one of the three most cialist for further evaluation if available,
counseling is recommended to ensure
and consultation can be obtained from
common forms of MODY, including HFN1A- that affected individuals understand the
several centers. Readily available com-
MODY, GCK-MODY, and HNF4A-MODY, al- patterns of inheritance and the impor-
mercial genetic testing following the
lows for more cost-effective therapy (no tance of a correct diagnosis and address-
criteria listed below now enables a
therapy for GCK-MODY; sulfonylureas as ing comprehensive cardiovascular risk.
cost-effective (186), often cost-saving, ge-
first-line therapy for HNF1A-MODY and The diagnosis of monogenic diabe-
netic diagnosis that is increasingly sup-
HNF4A-MODY). Additionally, diagnosis ported by health insurance. A biomarker tes should be considered in children
can lead to identification of other af- screening pathway, such as the combina- and adults diagnosed with diabetes in
fected family members. Genetic screen- tion of urinary C-peptide/creatinine ratio early adulthood with the following
ing is increasingly available and cost- and antibody screening, may aid in deter- findings:
effective (176,178). mining who should get genetic testing for
A diagnosis of MODY should be con- MODY (187). It is critical to correctly diag- • Diabetes diagnosed within the first
sidered in individuals who have atypical nose one of the monogenic forms of di- 6 months of life (with occasional cases
diabetes and multiple family members abetes because these individuals may presenting later, mostly INS and ABCC8
with diabetes not characteristic of type 1 be incorrectly diagnosed with type 1 mutations) (172,192)
or type 2 diabetes, although admit- or type 2 diabetes, leading to subopti- • Diabetes without typical features of
tedly, “atypical diabetes” is becoming mal, even potentially harmful, treatment type 1 or type 2 diabetes (negative
S32 Classification and Diagnosis of Diabetes Diabetes Care Volume 46, Supplement 1, January 2023
diabetes by the standard diagnostic crite- gestation or later. See Recommendation GDM diagnosis (Table 2.7) can be ac-
ria used outside of pregnancy should be 2.3 above. complished with either of two strategies:
classified as having diabetes complicat- GDM is often indicative of underlying
ing pregnancy (most often type 2 diabe- b-cell dysfunction (225), which confers 1. The “one-step” 75-g OGTT derived
tes, rarely type 1 diabetes or monogenic marked increased risk for later develop- from the IADPSG criteria, or
diabetes) and managed accordingly. ment of diabetes, generally but not al- 2. The older “two-step” approach with
Early abnormal glucose metabolism, ways type 2 diabetes, in the mother after a 50-g (nonfasting) screen followed
defined as fasting glucose threshold of delivery (226,227). As effective prevention by a 100-g OGTT for those who
110 mg/dL (6.1 mmol/L) or an A1C of interventions are available (228,229), screen positive based on the work
5.9% (39 mmol/mol), may identify in- individuals diagnosed with GDM should of Carpenter-Coustan’s interpretation
dividuals who are at higher risk of ad- receive lifelong screening for prediabetes of the older O’Sullivan and Mahan
verse pregnancy and neonatal outcomes to allow interventions to reduce diabetes (232) criteria.
not two, became sufficient to make the one-step method using IADPSG criteria ver- Two-Step Strategy
diagnosis (233). Many regional studies sus the two-step method using a 1-h 50-g In 2013, the NIH convened a consensus
have investigated the impact of adopting glucose loading test (GLT) and, if posi- development conference to consider
the IADPSG criteria on prevalence and tive, a 3-h OGTT by Carpenter-Coustan diagnostic criteria for diagnosing GDM
have seen a roughly one- to threefold in- criteria identified twice as many individu- (246). The 15-member panel had repre-
crease (234). The anticipated increase als with GDM using the one-step method sentatives from obstetrics and gynecol-
in the incidence of GDM could have a compared with the two-step method. ogy, maternal-fetal medicine, pediatrics,
substantial impact on costs and medical Despite treating more individuals for diabetes research, biostatistics, and other
infrastructure needs and has the po- related fields. The panel recommended a
GDM using the one-step method, there
tential to “medicalize” pregnancies pre- was no difference in pregnancy and peri-
two-step approach to screening that used
viously categorized as normal. A recent a 1-h 50-g GLT followed by a 3-h 100-g
natal complications (239). However, con-
follow-up study of individuals participating OGTT for those who screened positive.
cerns have been raised about sample
in a blinded study of pregnancy OGTTs The American College of Obstetricians
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25 June 2023. Sections 2 and 3 have been updated based on U.S. Food and Drug Administration approval of a new drug to delay the incidence of
type 1 diabetes. The changes are described in detail in: Addendum. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—
2023. Diabetes Care 2023;46(Suppl. 1):S19–S40 (https://doi.org/10.2337/dc23-ad08) and Addendum. 3. Prevention or Delay of Type 2 Diabetes and
Associated Comorbidities: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S41–S48 (https://doi.org/10.2337/dc23-ad08a).
For guidelines related to screening for increased risk for type 1 and type 2 diabetes
(prediabetes), please refer to Section 2, “Classification and Diagnosis of Diabetes.”
For guidelines related to screening, diagnosis, and management of type 2 diabetes
in youth, please refer to Section 14, “Children and Adolescents.”
Recommendation
3.1 Monitor for the development of type 2 diabetes in those with prediabetes
at least annually; modify based on individual risk/benefit assessment. E
Screening for prediabetes and type 2 diabetes risk through an informal assessment
of risk factors (Table 2.3) or with an assessment tool, such as the American Diabetes
Association risk test (Fig. 2.1), is recommended to guide health care professionals on
Disclosure information for each author is
whether performing a diagnostic test for prediabetes (Table 2.5) and previously un- available at https://doi.org/10.2337/dc23-SDIS.
diagnosed type 2 diabetes (Table 2.2) is appropriate (see Section 2, “Classification
Suggested citation: ElSayed NA, Aleppo G,
and Diagnosis of Diabetes”). Testing high-risk adults for prediabetes is warranted be- Aroda VR, et al., American Diabetes Association.
cause the laboratory assessment is safe and reasonable in cost, substantial time ex- 3. Prevention or delay of diabetes and asso-
ists before the development of type 2 diabetes and its complications during which ciated comorbidities: Standards of Care in
one can intervene, and there is an effective means of preventing or delaying type 2 Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):
S41–S48
diabetes in those determined to have prediabetes with an A1C 5.7–6.4% (39–
47 mmol/mol), impaired glucose tolerance, or impaired fasting glucose. The utility of © 2022 by the American Diabetes Association.
A1C screening for prediabetes and diabetes may be limited in the presence of hemoglo- Readers may use this article as long as the
work is properly cited, the use is educational
binopathies and conditions that affect red blood cell turnover. See Section 2, and not for profit, and the work is not altered.
“Classification and Diagnosis of Diabetes,” and Section 6, “Glycemic Targets,” for More information is available at https://www.
additional details on the appropriate use and limitations of A1C testing. diabetesjournals.org/journals/pages/license.
S42 Prevention or Delay of Type 2 Diabetes and Associated Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
LIFESTYLE BEHAVIOR CHANGE type 2 diabetes: 39% reduction at 30 To implement the weight loss and
FOR DIABETES PREVENTION years in the Da Qing study (5), 43% re- physical activity goals, the DPP used an
duction at 7 years in the Finnish DPS (2), individual model of treatment rather than
Recommendations
and 34% reduction at 10 years (6) and a group-based approach. This choice was
3.2 Refer adults with overweight/
27% reduction at 15 years (7) in the U.S. based on a desire to intervene before
obesity at high risk of type 2 di-
Diabetes Prevention Program Outcomes participants had the possibility of devel-
abetes, as typified by the Diabetes
Study (DPPOS). oping diabetes or losing interest in the
Prevention Program (DPP), to an The two major goals of the DPP inten- program. The individual approach also al-
intensive lifestyle behavior change sive lifestyle intervention were to achieve lowed for the tailoring of interventions to
program to achieve and maintain and maintain a minimum of 7% weight reflect the diversity of the population (8).
a weight reduction of at least 7% loss and 150 min moderate-intensity phys- The DPP intervention was adminis-
of initial body weight through ical activity per week, such as brisk walk- tered as a structured core curriculum fol-
healthy reduced-calorie diet and ing. The DPP lifestyle intervention was a lowed by a flexible maintenance program
the case for those with diabetes, individ- locations of CDC-recognized diabetes pre- by third-party payers remains problem-
ualized medical nutrition therapy (see vention lifestyle change programs (cdc. atic. Counseling by a registered dietitian
Section 5, “Facilitating Positive Health gov/diabetes/prevention/find-a-program. nutritionist (RDN) has been shown to
Behaviors and Well-being to Improve html). To be eligible for this program, in- help individuals with prediabetes im-
Health Outcomes,” for more detailed in- dividuals must have a BMI in the over- prove eating habits, increase physical
formation) is effective in lowering A1C weight range and be at risk for diabetes activity, and achieve 7–10% weight loss
in individuals diagnosed with prediabe- based on laboratory testing, a previous (10,46–48). Individualized medical nutri-
tes (23). diagnosis of GDM, or a positive risk test tion therapy (see Section 5, “Facilitating
(cdc.gov/prediabetes/takethetest/). Dur- Positive Health Behaviors and Well-being
Physical Activity ing the first 4 years of implementation of to Improve Health Outcomes,” for more
Just as 150 min/week of moderate- the CDC’s National DPP, 35.5% achieved detailed information) is also effective in
intensity physical activity, such as brisk the 5% weight loss goal (41). The CDC improving glycemia in individuals diag-
walking, showed beneficial effects in has also developed the Diabetes Pre- nosed with prediabetes (23,46). Further-
Program, especially those aged 25– potential benefit in specific populations increases with time (88), with a significantly
59 years with BMI $35 kg/m2, (77–80). Further research is needed to higher risk for vitamin B12 deficiency (<150
higher fasting plasma glucose define characteristics and clinical indica- pmol/L) noted at 4.3 years in the HOME (Hy-
(e.g., $110 mg/dL), and higher tors where vitamin D supplementation perinsulinaemia: the Outcome of its Meta-
may be of benefit (61). bolic Effects) study (88) and significantly
A1C (e.g., $6.0%), and in individ-
No pharmacologic agent has been ap- greater risk of low B12 levels (#203 pg/mL)
uals with prior gestational diabe-
proved by the U.S. Food and Drug Ad- at 5 years in the DPP (87). It has been sug-
tes mellitus. A
ministration for a specific indication of gested that a person who has been on met-
3.7 Long-term use of metformin
type 2 diabetes prevention. The risk ver- formin for more than 4 years or is at risk for
may be associated with bio-
sus benefit of each medication in sup- vitamin B12 deficiency should be monitored
chemical vitamin B12 deficiency;
port of person-centered goals must be for vitamin B12 deficiency annually (89).
consider periodic measurement weighed in addition to cost, side effects,
of vitamin B12 levels in metfor- and efficacy considerations. Metformin PREVENTION OF VASCULAR
Behaviors and Well-being to Improve though risks of weight gain, edema, and glucose 110–125 mg/dL, 2-h postchallenge
Health Outcomes,” for more detailed in- fracture were higher in the pioglitazone glucose 173–199 mg/dL, and A1C $6.0%),
formation. The lifestyle interventions for treatment group (107–109). Lower doses and individuals with a history of gestational
weight loss in study populations at risk may mitigate the adverse effects, though diabetes (1,82,83). In contrast, in the com-
for type 2 diabetes have shown a reduc- further study is needed to confirm the munity-based Atherosclerosis Risk in Com-
tion in cardiovascular risk factors and benefit at lower doses (110). munities (ARIC) study, observational follow-
the need for medications used to treat up of older adults (mean age 75 years)
these cardiovascular risk factors (96,97). PERSON-CENTERED CARE GOALS with laboratory evidence of prediabetes
In longer-term follow-up, lifestyle inter- (based on A1C 5.7–6.4% and/or fasting
ventions for diabetes prevention also Recommendations glucose 100–125 mg/dL), but not meeting
prevented the development of micro- 3.11 In adults with overweight/ specific BMI criteria, found much lower
vascular complications among women obesity at high risk of type 2 progression to diabetes over 6 years: 9%
enrolled in the DPPOS and in the study diabetes, care goals should in- of those with A1C-defined prediabetes,
Disease and Risk Management,” for more 2. Lindstr€ om J, Ilanne-Parikka P, Peltonen M, diabetes risk: a prospective study. Nutr Diabetes
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sidered to support individualized person-- diabetes by lifestyle intervention: follow-up of and diabetes risk: a systematic review and meta-
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mortality, all-cause mortality, and diabetes incidence Association between plant-based dietary patterns
after lifestyle intervention for people with impaired and risk of type 2 diabetes: a systematic review
PHARMACOLOGIC INTERVENTIONS glucose tolerance in the Da Qing Diabetes Pre- and meta-analysis. JAMA Intern Med 2019;179:
FOR TYPE 1 DIABETES vention Study: a 23-year follow-up study. Lancet 1335–1344
Diabetes Endocrinol 2014;2:474–480 19. Esposito K, Chiodini P, Maiorino MI,
Recommendation 4. Nathan DM, Bennett PH, Crandall JP, et al.; Bellastella G, Panagiotakos D, Giugliano D. Which
3.14 Teplizumab-mzwv infusion to DPP Research Group. Does diabetes prevention diet for prevention of type 2 diabetes? A meta-
delay the onset of symptom- translate into reduced long-term vascular analysis of prospective studies. Endocrine 2014;
intensive behavioral counseling program on 46. Raynor HA, Davidson PG, Burns H, et al. for weight loss in patients with prediabetes:
Medicare beneficiaries at risk for diabetes and Medical nutrition therapy and weight loss pragmatic trial. JMIR Diabetes 2019;4:e12985
cardiovascular disease. PLoS One 2016;11: questions for the Evidence Analysis Library 61. Wittert G, Bracken K, Robledo KP, et al.
e0163627 prevention of type 2 diabetes project: systematic Testosterone treatment to prevent or revert
33. Diabetes Prevention Program Research reviews. J Acad Nutr Diet 2017;117:1578–1611 type 2 diabetes in men enrolled in a lifestyle
Group. The 10-year cost-effectiveness of lifestyle 47. Sun Y, You W, Almeida F, Estabrooks P, Davy programme (T4DM): a randomised, double-
intervention or metformin for diabetes pre- B. The effectiveness and cost of lifestyle blind, placebo-controlled, 2-year, phase 3b trial.
vention: an intent-to-treat analysis of the DPP/ interventions including nutrition education for Lancet Diabetes Endocrinol 2021;9:32–45
DPPOS. Diabetes Care 2012;35:723–730 diabetes prevention: a systematic review and 62. Gerstein HC, Bosch J, Dagenais GR, et al.;
34. Alva ML, Hoerger TJ, Jeyaraman R, Amico P, meta-analysis. J Acad Nutr Diet 2017;117: ORIGIN Trial Investigators. Basal insulin and cardio-
Rojas-Smith L. Impact of the YMCA of the USA 404–421.e36 vascular and other outcomes in dysglycemia. N
Diabetes Prevention Program on Medicare 48. Briggs Early K, Stanley K. Position of the Engl J Med 2012;367:319–328
spending and utilization. Health Aff (Millwood) Academy of Nutrition and Dietetics: the role of 63. DeFronzo RA, Tripathy D, Schwenke DC,
2017;36:417–424 medical nutrition therapy and registered dietitian et al.; ACT NOW Study. Pioglitazone for diabetes
35. Zhou X, Siegel KR, Ng BP, et al. Cost- nutritionists in the prevention and treatment of prevention in impaired glucose tolerance. N Engl
therapy with canakinumab for the prevention 88. de Jager J, Kooy A, Lehert P, et al. Long term 102. Crandall JP, Mather K, Rajpathak SN, et al.
and management of diabetes. J Am Coll Cardiol treatment with metformin in patients with type 2 Statin use and risk of developing diabetes: results
2018;71:2392–2401. diabetes and risk of vitamin B-12 deficiency: from the Diabetes Prevention Program. BMJ
76. Ray KK, Colhoun HM, Szarek M, et al.; randomised placebo controlled trial. BMJ 2010; Open Diabetes Res Care 2017;5:e000438
ODYSSEY OUTCOMES Committees and Investi- 340:c2181 103. Preiss D, Seshasai SRK, Welsh P, et al. Risk
gators. Effects of alirocumab on cardiovascular 89. Kidney Disease: Improving Global Outcomes of incident diabetes with intensive-dose com-
and metabolic outcomes after acute coronary (KDIGO) Diabetes Work Group. KDIGO 2020 clinical pared with moderate-dose statin therapy: a
syndrome in patients with or without diabetes: a practice guideline for diabetes management in meta-analysis. JAMA 2011;305:2556–2564
prespecified analysis of the ODYSSEY OUTCOMES chronic kidney disease. Kidney Int 2020;98(4S): 104. Mansi IA, Chansard M, Lingvay I, Zhang S,
randomised controlled trial. Lancet Diabetes S1–S115 Halm EA, Alvarez CA. Association of statin
Endocrinol 2019;7:618–628 90. Ali MK, Bullard KM, Saydah S, Imperatore G, therapy initiation with diabetes progression: a
77. Pittas AG, Dawson-Hughes B, Sheehan P, et al.; Gregg EW. Cardiovascular and renal burdens of retrospective matched-cohort study. JAMA Intern
D2d Research Group. Vitamin D supplementation prediabetes in the USA: analysis of data from Med 2021;181:1562–1574
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2019;381:520–530 Diabetes Endocrinol 2018;6:392–403 Libby P, Glynn RJ. Cardiovascular benefits and
25 June 2023. Section 4 has been updated to reflect the current clinical knowledge and evidence in nonalcoholic fatty liver disease. The
changes are described in detail in: Addendum. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care
in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S49–S67 (https://doi.org/10.2337/dc23-ad09).
Recommendations
4.1 A person-centered communication style that uses person-centered, cul-
turally sensitive, and strength-based language and active listening; elic-
its individual preferences and beliefs; and assesses literacy, numeracy,
and potential barriers to care should be used to optimize health out-
comes and health-related quality of life. B
4.2 People with diabetes can benefit from a coordinated multidisciplinary
team that may include and is not limited to diabetes care and educa-
tion specialists, primary care and subspecialty clinicians, nurses, regis-
tered dietitian nutritionists, exercise specialists, pharmacists, dentists,
podiatrists, and mental health professionals. E Disclosure information for each author is
available at https://doi.org/10.2337/dc23-SDIS.
Suggested citation: ElSayed NA, Aleppo G, Aroda
A successful medical evaluation depends on beneficial interactions between the VR, et al., American Diabetes Association. 4.
person with diabetes and the care team. The Chronic Care Model (1–3) (see Section Comprehensive medical evaluation and assess-
1, “Improving Care and Promoting Health in Populations”) is a person-centered ap- ment of comorbidities: Standards of Care in
proach to care that requires a close working relationship between the person with Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):
S49–S67.2
diabetes and clinicians involved in treatment planning. People with diabetes should
receive health care from a coordinated interdisciplinary team that may include but © 2022 by the American Diabetes Association.
is not limited to diabetes care and education specialists, primary care and subspeci- Readers may use this article as long as the
work is properly cited, the use is educational
alty clinicians, nurses, registered dietitian nutritionists, exercise specialists, pharma- and not for profit, and the work is not altered.
cists, dentists, podiatrists, and mental health professionals. Individuals with dia- More information is available at https://www.
betes must assume an active role in their care. Based on the preferences of the diabetesjournals.org/journals/pages/license.
S50 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
person with diabetes, the family or sup- niques should be used to support the diabetes take in directing the day-to-day
port group and health care team to- person’s self-management efforts, includ- decision-making, planning, monitoring,
gether formulate the management plan, ing providing education on problem- evaluation, and problem-solving involved
which includes lifestyle management (see solving skills for all aspects of diabetes in diabetes self-management. Using a
Section 5, “Facilitating Positive Health management. nonjudgmental approach that normalizes
Behaviors and Well-being to Improve Health care professional communica- periodic lapses in management may help
Health Outcomes”). tion with people with diabetes and fami- minimize the person’s resistance to re-
The goals of treatment for diabetes lies should acknowledge that multiple porting problems with self-management.
are to prevent or delay complications factors impact glycemic management but Empathizing and using active listening
and optimize quality of life (Fig. 4.1). also emphasize that collaboratively devel- techniques, such as open-ended ques-
Treatment goals and plans should be cre- oped treatment plans and a healthy life- tions, reflective statements, and summa-
ated with people with diabetes based on style can significantly improve disease rizing what the person said, can help
their individual preferences, values, and outcomes and well-being (4–8). Thus, the facilitate communication. Perceptions of
goals. This individualized management goal of communication between health people with diabetes about their own
plan should take into account the per- care professionals and people with dia- ability, or self-efficacy, to self-manage
son’s age, cognitive abilities, school/ betes is to establish a collaborative rela- diabetes constitute one important psy-
work schedule and conditions, health tionship and to assess and address self- chosocial factor related to improved dia-
beliefs, support systems, eating patterns, management barriers without blaming betes self-management and treatment
physical activity, social situation, financial people with diabetes for “noncompliance” outcomes in diabetes (10–12) and should
concerns, cultural factors, literacy and nu- or “nonadherence” when the outcomes of be a target of ongoing assessment, edu-
meracy (mathematical literacy), diabetes self-management are not optimal (9). The cation, and treatment planning.
history (duration, complications, current familiar terms “noncompliance” and Language has a strong impact on per-
use of medications), comorbidities, dis- “nonadherence” denote a passive, obe- ceptions and behavior. The use of em-
abilities, health priorities, other medical dient role for a person with diabetes in powering language in diabetes care and
conditions, preferences for care, and life “following doctor’s orders” that is at education can help to inform and moti-
expectancy. Various strategies and tech- odds with the active role people with vate people, yet language that shames
Figure 4.1—Decision cycle for person-centered glycemic management in type 2 diabetes. Adapted from Davies et al. (246). BGM, blood glucose
monitoring; BP, blood pressure; CGM, continuous glucose monitoring; CKD, chronic kidney disease; CVD, atherosclerotic cardiovascular disease;
DSMES, diabetes self-management education and support; HF, heart failure.
diabetesjournals.org/care Comprehensive Medical Evaluation and Assessment of Comorbidities S51
and judges may undermine this effort. comprehensive medical evalua- treatment planning are key components
The American Diabetes Association tion (Table 4.1). A of initial and follow-up visits (Table 4.2).
(ADA) and the Association of Diabetes 4.5 Ongoing management should The risk of atherosclerotic cardiovascu-
Care & Education Specialists (formerly be guided by the assessment lar disease and heart failure (see Sec-
called the American Association of Dia- of overall health status, diabe- tion 10, “Cardiovascular Disease and Risk
betes Educators) joint consensus report, tes complications, cardiovascu- Management”), chronic kidney disease
“The Use of Language in Diabetes Care lar risk, hypoglycemia risk, and staging (see Section 11, “Chronic Kidney
and Education,” provides the authors’ shared decision-making to set Disease and Risk Management”), pres-
expert opinion regarding the use of lan- therapeutic goals. B ence of retinopathy (see Section 12,
guage by health care professionals “Retinopathy, Neuropathy, and Foot
when speaking or writing about dia- Care”), and risk of treatment-associated
betes for people with diabetes or for The comprehensive medical evaluation hypoglycemia (Table 4.3) should be used
professional audiences (13). Although includes the initial and follow-up evalua- to individualize targets for glycemia (see
further research is needed to address tions, assessment of complications, psy- Section 6, “Glycemic Targets”), blood pres-
the impact of language on diabetes out- chosocial assessment, management of sure, and lipids and to select specific glu-
comes, the report includes five key con- comorbid conditions, overall health sta- cose-lowering medication (see Section 9,
sensus recommendations for language tus, and engagement of the person with “Pharmacologic Approaches to Glycemic
use: diabetes throughout the process. While a Treatment”), antihypertension medication,
comprehensive list is provided in Table 4.1, and statin treatment intensity.
• Use language that is neutral, non- in clinical practice the health care pro- Additional referrals should be arranged
judgmental, and based on facts, fessional may need to prioritize the as necessary (Table 4.4). Clinicians should
actions, or physiology/biology. components of the medical evaluation ensure that people with diabetes are
• Use language free from stigma. appropriately screened for complications
given the available resources and time.
• Use language that is strength based, and comorbidities. Discussing and imple-
The goal is to provide the health care
respectful, and inclusive and that im- menting an approach to glycemic man-
team information so it can optimally sup-
parts hope. agement with the person is a part, not
port people with diabetes. In addition to
• Use language that fosters collabora- the sole goal, of the clinical encounter.
the medical history, physical examina-
tion between people with diabetes
tion, and laboratory tests, health care
and health care professionals. IMMUNIZATIONS
professionals should assess diabetes self-
• Use language that is person centered
management behaviors, nutrition, social
(e.g., “person with diabetes” is pre- Recommendation
determinants of health, and psychosocial
ferred over “diabetic”). 4.6 Provide routinely recommended
health (see Section 5, “Facilitating Positive vaccinations for children and
Health Behaviors and Well-being to adults with diabetes as indi-
COMPREHENSIVE MEDICAL Improve Health Outcomes”) and give
EVALUATION cated by age (see Table 4.5 for
guidance on routine immunizations. The highly recommended vaccina-
Recommendations assessment of sleep pattern and duration tions for adults with diabetes). A
4.3 A complete medical evalua- should be considered; a meta-analysis
tion should be performed at found that poor sleep quality, short sleep,
the initial visit to: and long sleep were associated with The importance of routine vaccinations
• Confirm the diagnosis and higher A1C in people with type 2 diabe- for people living with diabetes has been
classify diabetes. A tes (14). Interval follow-up visits should elevated by the coronavirus disease
• Evaluate for diabetes compli- occur at least every 3–6 months individu- 2019 (COVID-19) pandemic. Preventing
cations, potential comorbid alized to the person and then at least avoidable infections not only directly
conditions, and overall health annually. prevents morbidity but also reduces
status. A Lifestyle management and psychosocial hospitalizations, which may additionally
• Review previous treatment care are the cornerstones of diabetes reduce risk of acquiring infections such
and risk factor management management. People with diabetes as COVID-19. Children and adults with
in people with established should be referred for diabetes self- diabetes should receive vaccinations ac-
diabetes. A management education and support, cording to age-appropriate recommen-
• Begin engagement with the medical nutrition therapy, and assess- dations (15,16). The Centers for Disease
person with diabetes in ment of psychosocial/emotional health Control and Prevention (CDC) provides
the formulation of a care concerns if indicated. People with diabe- vaccination schedules specifically for chil-
management plan including tes should receive recommended preven- dren, adolescents, and adults with diabe-
initial goals of care. A tive care services (e.g., immunizations, tes (cdc.gov/vaccines/). The CDC Advisory
• Develop a plan for continuing cancer screening); smoking cessation Committee on Immunization Practices
care. A counseling; and ophthalmological, den- (ACIP) makes recommendations based
4.4 A follow-up visit should include tal, and podiatric referrals, as needed. on its own review and rating of the
most components of the initial The assessment of risk of acute and evidence, provided in Table 4.5 for se-
chronic diabetes complications and lected vaccinations. The ACIP evidence
S52 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
Continued on p. S53
diabetesjournals.org/care Comprehensive Medical Evaluation and Assessment of Comorbidities S53
A1C, if the results are not available within the past 3 months
+May be needed more frequently in people with diabetes with known chronic kidney disease or with changes in medications that affect kidney
function and serum potassium (see Table 11.1).
#May also need to be checked after initiation or dose changes of medications that affect these laboratory values (i.e., diabetes medications,
blood pressure medications, cholesterol medications, or thyroid medications).
^In people without dyslipidemia and not on cholesterol-lowering therapy, testing may be less frequent.
**Should be performed at every visit in people with diabetes with sensory loss, previous foot ulcers, or amputations.
review has evolved over time with the and morbidity in vulnerable populations, influenza vaccination, it is recommended
adoption of Grading of Recommendations including youth, older adults, and peo- for all individuals $6 months of age
Assessment, Development and Evaluation ple with chronic diseases. Influenza vac- who do not have a contraindication. In-
(GRADE) in 2010 and then the Evidence cination in people with diabetes has fluenza vaccination is critically important
to Decision or Evidence to Recommenda- been found to significantly reduce influ- as the severe acute respiratory syn-
tion frameworks in 2018 (17). Here we enza and diabetes-related hospital ad- drome coronavirus 2 (SARS-CoV-2) and
discuss the particular importance of spe- missions (18). In people with diabetes influenza viruses will both be active in
cific vaccines. and cardiovascular disease, influenza the U.S. during the 2022–2023 season
vaccine has been associated with lower (20). The live attenuated influenza vac-
Influenza risk of all-cause mortality, cardiovascular cine, which is delivered by nasal spray, is
Influenza is a common, preventable infec- mortality, and cardiovascular events an option for people who are age 2
tious disease associated with high mortality (19). Given the benefits of the annual years through age 49 years and who are
S54 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
Table 4.5—Highly recommended immunizations for adults with diabetes (Advisory Committee on Immunization Practices,
Centers for Disease Control and Prevention)
Vaccination Age-group recommendations Frequency GRADE evidence type* Reference
Hepatitis B <60 years of age; $60 years Two- or three-dose series 2 Centers for Disease Control and
of age discuss with health Prevention, Use of Hepatitis B
care professionals Vaccination for Adults With
Diabetes Mellitus: Recommendations
of the Advisory Committee on
Immunization Practices (ACIP) (239)
Human papilloma #26 years of age; 27–45 years Three doses over 2 for female individuals, Meites et al., Human Papillomavirus
virus (HPV) of age may also be 6 months 3 for male individuals Vaccination for Adults: Updated
vaccinated against HPV Recommendations of the Advisory
after a discussion with Committee on Immunization Practices
health care professionals (240)
Influenza All people with diabetes advised Annual — Demicheli et al., Vaccines for Preventing
not to receive live attenuated Influenza in the Elderly (241)
influenza vaccine
Pneumonia (PPSV23 19–64 years of age, vaccinate One dose is recommended for those that 2 Centers for Disease Control and
[Pneumovax]) with Pneumovax previously received PCV13. If PCV15 Prevention, Updated Recommendations
used, follow with PPSV23 $1 year for Prevention of Invasive
later. PPSV23 is not indicated after Pneumococcal Disease
PCV20. Adults who received only Among Adults Using the
PPSV23 may receive PCV15 or PCV20 23-Valent Pneumococcal Polysaccaride
$1 year after their last dose. Vaccine (PPSV23) (242)
$65 years of age One dose is recommended for those that 2 Falkenhorst et al., Effectiveness
previously received PCV13. If PCV15 of the 23-Valent Pneumococcal
was used, follow with PPSV23 $1 year Polysaccharide Vaccine (PPV23)
later. PPSV23 is not indicated after Against Pneumococcal Disease
PCV20. Adults who received only in the Elderly: Systematic Review
PPSV23 may receive PCV15 or PCV20 and Meta-analysis (243)
$1 year after their last dose.
PCV20 or PCV15 Adults 19–64 years One dose of PCV15 or PCV20 is 3 Kobayashi et al., Use of 15-Valent
of age, with an recommended by the CDC. Pneumococcal Conjugate Vaccine and
immunocompromising 20-Valent Pneumococcal Conjugate
condition (e.g., chronic Vaccine Among U.S. Adults: Updated
renal failure), cochlear Recommendations of the Advisory
implant, or cerebrospinal Committee on Immunization
fluid leak Practices—United States, 2022 (22)
19–64 years of age, For those who have never received any
immunocompetent pneumococcal vaccine, the CDC
recommends one dose of PCV15 or
PCV20.
$65 years of age, One dose of PCV15 or PCV20. PCSV23
immunocompetent, have may be given $8 weeks after PCV15.
shared decision-making PPSV23 is not indicated after PCV20.
discussion with health
care professionals
Tetanus, diphtheria, All adults; pregnant Booster every 10 years 2 for effectiveness, Havers et al., Use of Tetanus Toxoid,
pertussis (TDAP) individuals should have 3 for safety Reduced Diphtheria Toxoid, and
an extra dose Acellular Pertussis Vaccines: Updated
Recommendations of the Advisory
Committee on Immunization
Practices—United States, 2019 (244)
Zoster $50 years of age Two-dose Shingrix, even if 1 Dooling et al., Recommendations
previously vaccinated of the Advisory Committee on
Immunization Practices for Use
of Herpes Zoster Vaccines (245)
GRADE, Grading of Recommendations Assessment, Development, and Evaluation; PCV13, 13-valent pneumococcal conjugate vaccine; PCV15, 15-valent pneumo-
coccal conjugate vaccine; PCV 20, 20-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine. *Evidence type: 1, ran-
domized controlled trials (RCTs) or overwhelming evidence from observational studies; 2, RCTs with important limitations or exceptionally strong evidence from
observational studies; 3, observational studies or RCTs with notable limitations; 4, clinical experience and observations, observational studies with important limi-
tations, or RCTs with several major limitations. For a comprehensive list, refer to the Centers for Disease Control and Prevention (CDC) at cdc.gov/vaccines/.
S56 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
based on the person’s likelihood of ac- compromised, doses 1 and 2 should be discusses many of the common comor-
quiring hepatitis B infection. at least 3 weeks apart and doses 2 and 3 bidities observed in people with diabetes
at least 4 weeks apart. but is not necessarily inclusive of all the
COVID-19 For most people aged $18 years re- conditions that have been reported.
As of September 2022, the COVID-19 ceiving Novavax vaccine, doses 1 and
vaccines are recommended for all adults 2 should be at least 3–8 weeks apart. Autoimmune Diseases
and some children, including people with For those who are moderately to se- Recommendations
diabetes, under approval from the U.S. verely compromised, doses 1 and 2 4.7 People with type 1 diabetes should
Food and Drug Administration (FDA) (24). should be at least 3 weeks apart. The
be screened for autoimmune
The bivalent booster protecting against the Janssen monovalent vaccine is currently
thyroid disease soon after diagno-
omicron variant and original strain has authorized for use in certain limited sit-
sis and periodically thereafter. B
now replaced the monovalent booster uations due to safety considerations.
4.8 Adults with type 1 diabetes
for many. For most people 12–17 years of age
should be screened for celiac
For people 6 months to 17 years of who received the Moderna vaccine, the
disease in the presence of gas-
age, most can receive the monovalent Pfizer-BioNTech bivalent booster may be
trointestinal symptoms, signs,
Moderna vaccine doses 1 and 2 at least given at least 8 weeks from doses 2 and 3.
laboratory manifestations, or
4–8 weeks apart. For those who are For those moderately or severely compro-
mised, doses 3 and 4 should be at least clinical suspicion suggestive of
moderately or severely immunocompro-
8 weeks apart. celiac disease. B
mised, doses 1 and 2 and doses 2 and 3
should be at least 4 weeks apart. For most people aged 12–17 years
For the Pfizer-BioNTech monovalent who received the Pfizer-BioNTech vac- People with type 1 diabetes are at in-
vaccine for most people aged 6 months cine, the Pifzer-BioNTech bivalent booster creased risk for other autoimmune dis-
to 4 years, doses 1 and 2 should be at may be given at least 8 weeks from eases, with thyroid disease, celiac disease,
least 3–8 weeks apart and doses 2 and 3 doses 2 and 3. For those moderately or and pernicious anemia (vitamin B12 defi-
at least 8 weeks apart. For those aged severely compromised, doses 3 and 4 ciency) being among the most common
6 months to 4 years who are moderately should be at least 8 weeks apart. (30). Other associated conditions include
or severely compromised, doses 1 and 2 For most people aged $12 years re- autoimmune hepatitis, primary adrenal
should be at least 4 weeks apart and ceiving the Novavax vaccine, the Pfizer- insufficiency (Addison disease), collagen
doses 2 and 3 at least 4 weeks apart. BioNTech bivalent booster may be given vascular diseases, and myasthenia gravis
For most people aged 5–11 years, doses 1 as doses 2 and 3 at least 8 weeks apart. (31–34). Type 1 diabetes may also occur
and 2 should be at least 3–8 weeks apart For those moderately to severely immu- with other autoimmune diseases in the
and doses 2 and 3 at least 5 months nocompromised, doses 2 and 3 should context of specific genetic disorders or
apart. For those who are moderately or be given at least 8 weeks apart. polyglandular autoimmune syndromes
severely immunocompromised, doses 1 Those $18 years of age receiving the (35). Given the high prevalence, nonspe-
and 2 should be at least 3 weeks apart Moderna vaccine may be given the cific symptoms, and insidious onset of pri-
and doses 2 and 3 should be at least Moderna bivalent booster 8 weeks after mary hypothyroidism, routine screening
8 weeks apart. For most people aged their last dose. Those $18 years of age for thyroid dysfunction is recommended
12–17 years, doses 1 and 2 should be receiving the Pfizer-BioNTech vaccine for all people with type 1 diabetes. Screen-
at least 3–8 weeks apart. For those who may receive the Pfizer-BioNTech biva- ing for celiac disease should be considered
are moderately to severely immunocom- lent booster 8 weeks after their last in adults with diabetes with suggestive
promised, doses 1 and 2 should be at dose. Those receiving the Janssen vac- symptoms (e.g., diarrhea, malabsorption,
least 3 weeks apart and doses 2 and 3 cine may receive the Moderna or Pfizer- abdominal pain) or signs (e.g., osteoporo-
should be at least 4 weeks apart. BioNTech bivalent booster 8 weeks after sis, vitamin deficiencies, iron deficiency
For the Novavax vaccine, for most peo- their last dose. Those receiving the anemia) (36,37). Measurement of vitamin
ple over 12 years of age, doses 1 and 2 Novavax vaccine aged $12 years may B12 levels should be considered for peo-
should be at least 3–8 weeks apart. For receive either the Moderna or Pfizer- ple with type 1 diabetes and peripheral
those who are moderately to severely im- BioNTech bivalent booster 8 weeks neuropathy or unexplained anemia.
munocompromised, doses 1 and 2 should after their last dose.
be at least 3 weeks apart. For most peo- Cancer
ple aged $18 years receiving the Mod- ASSESSMENT OF COMORBIDITIES Diabetes is associated with increased risk
erna vaccine, doses 1 and 2 should be at Besides assessing diabetes-related com- of cancers of the liver, pancreas, endo-
least 4–8 weeks apart. For those who are plications, clinicians and people with dia- metrium, colon/rectum, breast, and
moderately or severely compromised, betes need to be aware of common bladder (38). The association may result
doses 1 and 2 should be at least 4 weeks comorbidities that affect people with di- from shared risk factors between type 2
apart and doses 2 and 3 at least 4 weeks abetes and that may complicate man- diabetes and cancer (older age, obesity,
apart. For most people receiving the agement (25–29). Diabetes comorbidities and physical inactivity) but may also be
Pfizer-BioNTech vaccine, doses 1 and 2 are conditions that affect people with di- due to diabetes-related factors (39),
should be at least 3–8 weeks apart. For abetes more often than age-matched such as underlying disease physiology
those who are moderately or severely people without diabetes. This section or diabetes treatments, although
diabetesjournals.org/care Comprehensive Medical Evaluation and Assessment of Comorbidities S57
evidence for these links is scarce. Peo- Cardiovascular Risk in Diabetes (ACCORD) Hepatitis C Infection
ple with diabetes should be encouraged study found that each 1% higher A1C Infection with hepatitis C virus (HCV) is
to undergo recommended age- and sex- level was associated with lower cogni- associated with a higher prevalence of
appropriate cancer screenings and to re- tive function in individuals with type 2 type 2 diabetes, which is present in up
duce their modifiable cancer risk factors diabetes (45). However, the ACCORD to one-third of individuals with chronic
(obesity, physical inactivity, and smok- study found no difference in cognitive HCV infection. HCV may impair glucose
ing). New onset of atypical diabetes outcomes in participants randomly as- metabolism by several mechanisms, in-
(lean body habitus, negative family his- signed to intensive and standard glycemic cluding directly via viral proteins and
tory) in a middle-aged or older person management, supporting the recommen- indirectly by altering proinflammatory
may precede the diagnosis of pancreatic dation that intensive glucose manage- cytokine levels (53). The use of newer
adenocarcinoma (40). However, in the ment should not be advised for the direct-acting antiviral drugs produces a
absence of other symptoms (e.g., weight improvement of cognitive function in sustained virological response (cure) in
loss, abdominal pain), routine screening individuals with type 2 diabetes (46). nearly all cases and has been reported to
of all such individuals is not currently improve glucose metabolism in individuals
recommended. Hypoglycemia with diabetes (54). A meta-analysis of
In type 2 diabetes, severe hypoglycemia mostly observational studies found a
Cognitive Impairment/Dementia is associated with reduced cognitive func- mean reduction in A1C levels of 0.45%
tion, and those with poor cognitive func- (95% CI 0.60 to 0.30) and reduced
Recommendation requirement for glucose-lowering medi-
tion have more severe hypoglycemia. In a
4.9 In the presence of cognitive long-term study of older people with cation use following successful eradica-
impairment, diabetes treat- type 2 diabetes, individuals with one tion of HCV infection (55).
ment plans should be simpli- or more recorded episodes of severe
fied as much as possible and hypoglycemia had a stepwise increase Pancreatitis
tailored to minimize the risk of in risk of dementia (47). Likewise, the Diabetes is linked to diseases of the exo-
hypoglycemia. B ACCORD trial found that as cognitive crine pancreas such as pancreatitis, which
function decreased, the risk of severe may disrupt the global architecture or
hypoglycemia increased (48). This has physiology of the pancreas, often resulting
Diabetes is associated with a significantly in both exocrine and endocrine dysfunc-
also been demonstrated in people with
increased risk and rate of cognitive de- type 1 diabetes. Tailoring glycemic ther- tion. Up to half of patients with diabetes
cline and an increased risk of dementia apy may help to prevent hypoglycemia may have some degree of impaired exo-
(41,42). A recent meta-analysis of pro- in individuals with cognitive dysfunction crine pancreas function (56). People with
spective observational studies in people (49). See Section 13, “Older Adults,” for diabetes are at an approximately twofold
with diabetes showed 73% increased risk more detailed discussion of hypoglyce- higher risk of developing acute pancreati-
of all types of dementia, 56% increased mia in older people with type 1 and tis (57).
risk of Alzheimer dementia, and 127% in- type 2 diabetes. Conversely, prediabetes and/or diabetes
creased risk of vascular dementia com- has been found to develop in approxi-
pared with individuals without diabetes Nutrition mately one-third of patients after an epi-
(43). The reverse is also true: people In one study, following the Mediterranean sode of acute pancreatitis (58); thus, the
with Alzheimer dementia are more likely diet correlated with improved cognitive relationship is likely bidirectional. Postpan-
to develop diabetes than people without function (50). However, a Cochrane re- creatitis diabetes may include either new-
Alzheimer dementia. In a 15-year pro- view found insufficient evidence to rec- onset disease or previously unrecognized
spective study of community-dwelling ommend any specific dietary change for diabetes (59). Studies of patients treated
people >60 years of age, the presence the prevention or treatment of cognitive with incretin-based therapies for diabetes
of diabetes at baseline significantly in- dysfunction (51). have also reported that pancreatitis may
creased the age- and sex-adjusted inci- occur more frequently with these medica-
dence of all-cause dementia, Alzheimer Statins tions, but results have been mixed and cau-
dementia, and vascular dementia com- A systematic review has reported that sality has not been established (60–62).
pared with rates in those with normal data do not support an adverse effect of Islet autotransplantation should be
glucose tolerance (44). See Section 13, statins on cognition (52). The FDA post- considered for patients requiring total
“Older Adults,” for a more detailed dis- marketing surveillance databases have pancreatectomy for medically refractory
cussion regarding screening for cognitive also revealed a low reporting rate for chronic pancreatitis to prevent postsurgi-
impairment. cognitive function–related adverse events, cal diabetes. Approximately one-third of
including cognitive dysfunction or de- patients undergoing total pancreatectomy
Hyperglycemia mentia, with statin therapy, similar to with islet autotransplantation are insulin
In those with type 2 diabetes, the de- rates seen with other commonly pre- free 1 year postoperatively, and observa-
gree and duration of hyperglycemia are scribed cardiovascular medications (52). tional studies from different centers have
related to dementia. More rapid cogni- Therefore, fear of cognitive decline demonstrated islet graft function up to a
tive decline is associated with both in- should not be a barrier to statin use in decade after the surgery in some patients
creased A1C and longer duration of people with diabetes and a high risk for (63–67). Both patient and disease factors
diabetes (43). The Action to Control cardiovascular disease. should be carefully considered when
S58 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
deciding the indications and timing of this observed (76). In the Diabetes Control and with obesity, especially with central obesity
surgery. Surgeries should be performed in Complications Trial/Epidemiology of Diabe- (83). The prevalence of obstructive sleep
skilled facilities that have demonstrated tes Interventions and Complications (DCCT/ apnea in the population with type 2 diabe-
expertise in islet autotransplantation. EDIC) cohort, time-weighted mean A1C was tes may be as high as 23%, and the preva-
associated with increased risk of hearing lence of any sleep-disordered breathing
Fractures impairment when tested after long-term may be as high as 58% (84,85). In partici-
Age-specific hip fracture risk is signifi- (>20 years) follow-up (77). Impairment in pants with obesity enrolled in the Action
cantly increased in both people with smell, but not taste, has also been reported for Health in Diabetes (Look AHEAD) trial,
type 1 diabetes (relative risk 6.3) and in individuals with diabetes (78). it exceeded 80% (86). Individuals with
those with type 2 diabetes (relative risk symptoms suggestive of obstructive sleep
1.7) in both sexes (68). Type 1 diabetes Low Testosterone in Men apnea (e.g., excessive daytime sleepiness,
is associated with osteoporosis, but in snoring, witnessed apnea) should be con-
Recommendation
type 2 diabetes, an increased risk of hip sidered for screening (87). Sleep apnea
4.10 In men with diabetes who have
fracture is seen despite higher bone treatment (lifestyle modification, continu-
symptoms or signs of hypogo-
mineral density (BMD) (69). In three ous positive airway pressure, oral applian-
nadism, such as decreased sex-
large observational studies of older ces, and surgery) significantly improves
ual desire (libido) or activity, or quality of life and blood pressure man-
adults, femoral neck BMD T-score and
erectile dysfunction, consider agement. The evidence for a treatment
the World Health Organization Fracture
screening with a morning se- effect on glycemic control is mixed (88).
Risk Assessment Tool (FRAX) score were
rum testosterone level. B
associated with hip and nonspine frac-
tures. Fracture risk was higher in partici- Periodontal Disease
pants with diabetes compared with those Periodontal disease is more severe, and
Mean levels of testosterone are lower
without diabetes for a given T-score and may be more prevalent, in people with
in men with diabetes compared with
age or for a given FRAX score (70). Pro- diabetes than in those without and has
age-matched men without diabetes, but been associated with higher A1C levels
viders should assess fracture history and
obesity is a major confounder (79,80). (89–91). Longitudinal studies suggest
risk factors in older patients with diabetes
Testosterone replacement in men with that people with periodontal disease
and recommend measurement of BMD if
symptomatic hypogonadism may have have higher rates of incident diabetes.
appropriate for the patient’s age and sex.
benefits including improved sexual func- Current evidence suggests that periodon-
Fracture prevention strategies for people
tion, well-being, muscle mass and strength, tal disease adversely affects diabetes out-
with diabetes are the same as for the gen-
eral population and may include vitamin D and bone density (81). In men with diabe- comes, although evidence for treatment
supplementation. For patients with type 2 tes who have symptoms or signs of low benefits remains controversial (29,92). In
diabetes with fracture risk factors, thiazolidi- testosterone (hypogonadism), a morning an RCT, intensive periodontal treatment
nediones (71) and sodium–glucose cotrans- total testosterone level should be mea- was associated with better glycemic
porter 2 inhibitors (72) should be used with sured using an accurate and reliable assay outcomes (A1C 8.3% vs. 7.8% in control
caution. (82). In men who have total testosterone subjects and the intensive-treatment
levels close to the lower limit, it is reason- group, respectively) and reduction in in-
Sensory Impairment able to determine free testosterone con- flammatory markers after 12 months of
Hearing impairment, both in high-frequency centrations either directly from equilibrium follow-up (93).
and low- to midfrequency ranges, is more dialysis assays or by calculations that use
common in people with diabetes than in total testosterone, sex hormone binding Nonalcoholic Fatty Liver Disease
those without, with stronger associations globulin, and albumin concentrations (82). Screening
found in studies of younger people (73). Please see the Endocrine Society clinical
Recommendations
Proposed pathophysiologic mechanisms in- practice guideline for detailed recom-
4.11a Adults with type 2 diabetes or
clude the combined contributions of hyper- mendations (82). Further tests (such as
prediabetes, particularly those
glycemia and oxidative stress to cochlear luteinizing hormone and follicle-stimulat-
with obesity or cardiometabolic
microangiopathy and auditory neuropathy ing hormone levels) may be needed to
risk factors/established cardio-
(74). In a National Health and Nutrition further evaluate the patient. Testoster-
vascular disease, should be
Examination Survey (NHANES) analysis, one replacement in older men with hy-
screened/risk stratified for non-
hearing impairment was about twice as pogonadism has been associated with
alcoholic fatty liver disease
prevalent in people with diabetes com- increased coronary artery plaque vol-
with clinically significant fibrosis
pared with those without, after adjusting ume, with no conclusive evidence that
(defined as moderate fibrosis
for age and other risk factors for hearing im- testosterone supplementation is associ-
to cirrhosis) using a calculated
pairment (75). Low HDL cholesterol, coro- ated with increased cardiovascular risk in
fibrosis-4 index (derived from
nary heart disease, peripheral neuropathy, hypogonadal men (82).
age, ALT, AST, and platelets
and general poor health have been re-
[mdcalc.com/calc/2200/fibrosis-
ported as risk factors for hearing impair- Obstructive Sleep Apnea
4-fib-4-index-liver-fibrosis]),
ment for people with diabetes, but an Age-adjusted rates of obstructive sleep
even if they have normal liver
association of hearing loss with blood apnea, a risk factor for cardiovascular dis-
enzymes. B
glucose levels has not been consistently ease, are significantly higher (4- to 10-fold)
diabetesjournals.org/care Comprehensive Medical Evaluation and Assessment of Comorbidities S59
4.11b Adults with diabetes or predia- stages are classified histologically as the alter hepatocyte triglyceride metabo-
betes with persistently ele- following: F0, no fibrosis; F1, mild; F2, lism may also increase the risk of NASH
vated plasma aminotransferase moderate (significant); F3, severe (ad- progression and cirrhosis (108,109), am-
levels for >6 months and low vanced); and F4, cirrhosis. In the U.S., plifying the impact of obesity, but the role
fibrosis-4 index should be eval- between 12% and 20% of people with of genetic testing in clinical practice re-
uated for other causes of liver type 2 diabetes have clinically signifi- mains to be established.
disease. B cant fibrosis ($F2) (95,96,100), with Individuals with clinically significant fi-
4.12 Adults with type 2 diabetes or similar prevalence worldwide (94,98). brosis ($F2), especially those with type 2
prediabetes with an indetermi- NASH is a leading cause of hepatocellular diabetes, have a greater risk of cirrhosis
nate or high fibrosis-4 index carcinoma (HCC) (101,102) and of liver with liver decompensation, HCC, liver
should have additional risk strati- transplantation in the U.S., with trans- transplantation, and all-cause mortality
plant waiting lists being overrepre- (110–113). Increased mortality associ-
fication by liver stiffness measure-
sented by people with type 2 diabetes ated with NAFLD is attributable not only
ment with transient elastography,
(103). Clinicians underestimate its prev- to cirrhosis and HCC but also to extrahe-
or the blood biomarker en-
alence and do not consistently imple- patic cancer (102), type 2 diabetes (114),
hanced liver fibrosis. B
ment appropriate screening strategies, and cardiovascular disease (115,116). The
4.13 Adults with type 2 diabetes or
thus missing the diagnosis of the poten- estimated relative impact depends on
prediabetes with indeterminate
tially progressive form of NAFLD in high- length of follow-up and population stud-
results or at high risk for signifi-
risk groups, such as those having obesity ied, among other factors. Emerging evi-
cant liver fibrosis (i.e., by fibrosis-
or type 2 diabetes. This pattern of un- dence suggests that NAFLD increases the
4 index, liver stiffness measure-
derdiagnosis is compounded by sparse risk of chronic kidney disease, particularly
ment, or enhanced liver fibrosis)
referral to specialists and inadequate when liver fibrosis is present (117,118), al-
should be referred to a gastroen-
prescription of medications with proven though the association of NAFLD with dia-
terologist or hepatologist for fur-
efficacy in NASH (104,105). betic retinopathy is less clear (119). Early
ther workup. Multidisciplinary
The goal of screening for NAFLD is diagnosis is essential to prevent future cir-
care is recommended for long-
to identify patients at risk for adverse rhosis and complications.
term management. B
health outcomes associated with NASH A recent meta-analysis reported a preva-
such as cirrhosis, HCC, and death from lence of NAFLD of 22% in people with
Nonalcoholic fatty liver disease (NAFLD) liver disease. This risk is higher in people type 1 diabetes (120). This risk may be
is the term used to identify the broad who have central obesity and cardiometa- linked to the fact that about one-third of
spectrum of disease ranging from nonal- bolic risk factors or insulin resistance, are people with type 1 diabetes in the U.S.
coholic fatty liver with macrovesicular >50 years of age, and/or have persistently have obesity (121). However, there is large
hepatic steatosis (or with mild inflam- elevated plasma aminotransferases (AST variability in NAFLD prevalence across stud-
mation) to steatohepatitis (nonalcoholic and/or ALT >30 units/L for >6 months) ies, and most measured liver fat by ultra-
steatohepatitis [NASH]) to cirrhosis. This (106,107). Some genetic variants that sound. In one of the few studies using
is in the absence of ongoing or recent
consumption of significant amounts of
alcohol (defined as ingestion of >21
standard drinks per week in men and
>14 standard drinks per week in
women over a 2-year period preceding
evaluation) or other secondary causes
of fatty liver disease. Diabetes is a major
risk factor for developing NASH, disease
progression, and worse liver outcomes
(94). Recent studies in adults in the U.S.
estimate that NAFLD is prevalent in
>70% of people with type 2 diabetes
(95–97). This is consistent with studies
from other countries (98). NASH is defined
histologically as having $5% hepatic
steatosis and associated with inflam-
mation and hepatocyte injury (hepato-
cyte ballooning), with or without
evidence of liver fibrosis (99). Steatohe-
patitis is estimated to affect more than
half of people with type 2 diabetes with Figure 4.2—A proposed algorithm for risk stratification in individuals with nonalcoholic fatty
NAFLD (100) and appears to be a driver liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). ELF, enhanced liver fibrosis; FIB-4,
for the development of fibrosis. Fibrosis fibrosis-4 index. Adapted from Kanwal et al. (105).
S60 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
the gold-standard MRI technique to value to rule out advanced fibrosis but associated with MRE are barriers to its use.
quantify liver fat, the prevalence of lacks adequate sensitivity and positive While, liver biopsy remains the gold stan-
steatosis in a population with type 1 di- predictive value to establish presence dard for the diagnosis of NASH, its indica-
abetes with low prevalence of obesity of advanced fibrosis in many cases, tion is reserved to the discretion of the
was only 8.8% compared with 68% in which is the reason why people with dia- specialist within a multidisciplinary team ap-
people with type 2 diabetes (122). The betes often fall in the “indeterminate” proach due to high costs and potential for
prevalence of fibrosis was not established (or intermediate) risk group for ad- morbidity associated with this procedure.
in that study. Therefore, screening for fi- vanced fibrosis and adverse liver out- In 2020, an expert panel convened by
brosis in people with type 1 diabetes comes (when FIB-4 is between 1.3 and the American Gastroenterological Associ-
should only be considered in the pres- 2.67). However, its low cost, simplicity, ation that included representatives of the
ence of additional risk factors for NAFLD, and good specificity make it the initial ADA reviewed the published literature
such as obesity, incidental hepatic stea- test of choice (Fig. 4.2). Performance is on the burden, screening, risk stratifica-
tosis on imaging, or elevated plasma better in a population with higher preva- tion, diagnosis, and management of
aminotransferases. lence of significant fibrosis (i.e., hepatol- individuals with NAFLD (105). See Fig.
There is consensus that the fibrosis-4 ogy clinics) compared with primary care 4.2, which is adapted from this special
index (FIB-4) is the most cost-effective settings. FIB-4 has not been well vali- report (105). A Clinical Care Pathway
strategy for the initial screening of peo- dated in pediatric populations and summarized the diagnosis and manage-
ple with prediabetes and cardiometa- does not perform as well in those aged ment of NAFLD in a subsequent publica-
bolic risk factors or with type 2 diabetes <35 years. In people with diabetes tion (107). Consensus has emerged to
in primary care and diabetes clinical set- $65 years of age, higher cutoffs for start screening with FIB-4 followed by
tings (99,105–107,123–125). See the pro- FIB-4 have been recommended (1.9–2.0 LSM or ELF and patented biomarkers as
posed diagnostic algorithm by an expert rather than >1.3) (137,138). needed for the noninvasive fibrosis risk
group that included ADA representatives In people with an indeterminate or stratification of individuals with NAFLD
in Fig. 4.2 (105). A screening strategy high FIB-4, additional risk stratification is in primary care and diabetes clinics (99,
based on elevated plasma aminotrans- required with a liver stiffness measure- 105–107,123–125,146).
ferases >40 units/L would miss most in- ment (LSM) by transient elastography After initial risk stratification (i.e., FIB-4,
dividuals with NASH in these settings, as (Fig. 4.2) or, if unavailable, by commer- LSM, and/or patented biomarkers), peo-
clinically significant fibrosis ($F2) is cial blood fibrosis biomarkers such as ple with diabetes at indeterminate or high
frequently observed with plasma ami- the enhanced liver fibrosis (ELF) test risk of fibrosis should be referred, based on
notransferases below the commonly (139) or others. Use of a second non- practice setting, to a gastroenterologist or
used cutoff of 40 units/L (95–97,100, proprietary diagnostic panel is not rec- hepatologist for further workup within
126,127). The American College of Gastro- ommended (i.e., NAFLD fibrosis score, the framework of a multidisciplinary team
enterology considers the upper limit of others), as they generally do not perform (105,147,148).
normal ALT levels to be 29–33 units/L for better than FIB-4 (97,133). Transient elas-
male individuals and 19–25 units/L for tography (LSM) is the best-validated Management
female individuals (128), as higher lev- imaging technique for fibrosis risk strati- Recommendations
els are associated with increased liver- fication, and it predicts future cirrhosis 4.14 Adults with type 2 diabetes or
related mortality, even in the absence and all-cause mortality in NAFLD prediabetes particularly with
of identifiable risk factors. The FIB-4 esti- (99,106,140). An LSM value of <8.0 kPa overweight or obesity with non-
mates the risk of hepatic cirrhosis and is has a good negative predictive value to alcoholic fatty liver disease
calculated from the computation of age, exclude advanced fibrosis ($F3–F4) should be recommended lifestyle
plasma aminotransferases (AST and ALT), (141–143) and indicates low risk for clini- changes that promote weight
and platelet count (mdcalc.com/calc/ cally significant fibrosis. Such individuals loss, ideally within a structured
2200/fibrosis-4-fib-4-index-liver-fibrosis). with diabetes can be followed in nonspe- nutrition plan and physical activ-
A value of <1.3 is considered low risk of cialty clinics with repeat surveillance ity program for cardiometabolic
having advanced fibrosis (F3–F4) and for testing every $2 years, although the benefits B and histological im-
developing adverse liver outcomes, while precise time interval remains to be es- provement. C
>2.67 is considered as having a high tablished. If the LSM is >12 kPa, the 4.15 For adults with type 2 diabetes
probability of advanced fibrosis (F3–F4) risk for advanced fibrosis is high and particularly with overweight or
and increased risk of adverse liver out- people with diabetes should be referred obesity with nonalcoholic fatty
comes. FIB-4 predicts changes over to the hepatologist (100). FIB-4 followed
liver disease, consider using a
time in hepatic fibrosis (129,130) and al- by LSM helps stratify people with diabe-
glucagon-like peptide 1 recep-
lows risk stratification of individuals in tes by risk level and minimize specialty
tor agonist with demonstrated
terms of future liver-related morbidity referrals (132,135,140,144,145) (Fig. 4.2).
benefits in nonalcoholic steato-
and mortality (131,132). FIB-4 has rea- Specialists may order additional tests for
hepatitis as an adjunctive ther-
sonable specificity but low sensitivity, fibrosis risk stratification (105–107,125,
apy to lifestyle interventions
hence a negative result rules out fibrosis 140), with magnetic resonance elastogra-
for weight loss. B
while a positive result requires confirma- phy (MRE) having the best overall perfor-
4.16 Pioglitazone or glucagon-like
tory testing. (130,133–136). It has a reason- mance (particularly for early fibrosis
peptide 1 receptor agonists are
able specificity and negative predictive stages). However, the accessibility and costs
diabetesjournals.org/care Comprehensive Medical Evaluation and Assessment of Comorbidities S61
the preferred agents for the predisposition, insulin resistance, and (168). Therefore, early diagnosis and
treatment of hyperglycemia in environmental factors (149–151), there treatment of NAFLD offers the best op-
adults with type 2 diabetes with is ample evidence to implicate excess portunity for cirrhosis prevention. Piogli-
biopsy-proven nonalcoholic stea- visceral and overall adiposity in people tazone and some glucagon-like peptide 1
tohepatitis, or those at high risk with overweight and obesity in the path- receptor agonists (GLP-1 RAs) have been
for nonalcoholic fatty liver disease ogenesis of the disease (152,153). Obe- shown to be effective to treat steatohe-
with clinically significant liver fi- sity in the setting of type 2 diabetes patitis (105,106,169–171) and may slow fi-
brosis using noninvasive tests. A worsens insulin resistance and steatohepa- brosis progression (172–174) and decrease
4.17a In adults with type 2 diabetes titis, promoting the development of cirrho- cardiovascular disease (106,170), which
and nonalcoholic steatohepati- sis (154). Therefore, clinicians should enact is the number one cause of death in peo-
tis, use of glucose-lowering ther- evidence-based interventions (as discussed ple with type 2 diabetes and NAFLD
apies other than pioglitazone or in Section 5, “Facilitating Positive Health (115).
glucagon-like peptide 1 receptor Behaviors and Well-being to Improve Pioglitazone improves glucose and lipid
agonists may be continued as Health Outcomes”) to promote healthy metabolism and reverses steatohepatitis
lifestyle change and weight loss for people in people with prediabetes, type 2 diabe-
clinically indicated, but these
with overweight or obesity and NAFLD. A tes (175,176), or even without diabetes
therapies lack evidence of bene-
minimum weight loss goal of 5%, prefera- (177–179). Fibrosis also improved in some
fit in nonalcoholic steatohepati-
bly $10% (155,156), is needed to improve trials (176,178). A meta-analysis (172) con-
tis. B
liver histology, with fibrosis requiring the cluded that pioglitazone treatment results
4.17b Insulin therapy is the preferred
larger weight reduction to change (156– in resolution of NASH and may improve
agent for the treatment of hy-
158). Individualized, structured weight loss fibrosis. Pioglitazone may halt the accel-
perglycemia in adults with type 2
and exercise programs offer greater bene- erated pace of fibrosis progression ob-
diabetes with decompensated
fit than standard counseling in people with served in people with type 2 diabetes
cirrhosis. C
NAFLD (149,159). (173) and is overall cost-effective for the
4.18a Adults with type 2 diabetes and
Dietary recommendations to induce an treatment of NASH (180,181). Vitamin E
nonalcoholic fatty liver disease
energy deficit are not different than those may be beneficial for the treatment of
are at increased cardiovascular
for people with diabetes with obesity NASH in people without diabetes (177).
risk; therefore, comprehensive
without NAFLD and should include a re- However, in people with type 2 diabetes,
management of cardiovascular
duction of macronutrient content, limiting Vitamin E monotherapy was found to be
risk factors is recommended. B
saturated fat, starch, and added sugar, negative in a small randomized controlled
4.18b Statin therapy is safe in adults
with adoption of healthier eating pat- trial (RCT) (173), and it did not seem to
with type 2 diabetes and com-
terns. The Mediterranean diet has the enhance pioglitazone’s efficacy when used
pensated cirrhosis from nonalco-
best evidence for improving liver and in combination as reported in an earlier
holic fatty liver disease and
cardiometabolic health (99,106,123,124, trial in this population (176). Pioglitazone
should be initiated or continued
159–163). Both aerobic and resistance causes dose-dependent weight gain (15
for cardiovascular risk reduction
training improve NAFLD in proportion to mg/day, mean of 1–2%; 45 mg/day, 3–5%),
as clinically indicated. B Statin
treatment engagement and intensity of increases fracture risk, may promote heart
therapy should be used with cau- the program (164–166). failure if used in individuals with preexisting
tion and close monitoring in Obesity pharmacotherapy may assist congestive heart failure, and may increase
people with decompensated cir- with weight loss in the context of life- the risk of bladder cancer, although this
rhosis, given limited safety and style modification if not achieved by life- remains controversial (105,106,170,171).
efficacy data. B style modification alone (see Section 8, GLP-1 RAs are effective in inducing
4.19a Consider metabolic surgery in “Obesity and Weight Management for weight loss and ameliorating elevated
appropriate candidates as an op- the Prevention and Treatment of Type 2 plasma aminotransferases and steatosis
tion to treat nonalcoholic steato- Diabetes”). (169). However, there are only two RCTs
hepatitis in adults with type 2 At present, there are no FDA-approved of GLP-1 RAs in biopsy-proven individu-
diabetes and nonalcoholic stea- drugs for the treatment of NASH. There- als with NASH. A small RCT reported
tohepatitis B and improve car- fore, treatment for people with type 2 di- that liraglutide improved some features
diovascular outcomes. B abetes and NASH is centered on the dual of NASH and, of particular relevance,
4.19b Metabolic surgery should be purpose of treating hyperglycemia and delayed the progression of fibrosis
used with caution in adults obesity, especially if clinically significant fi- (182). More recently, once-daily subcu-
with type 2 diabetes with com- brosis ($F2) is present. The rationale for taneous semaglutide in 320 people with
pensated cirrhosis from nonal- the treatment of people with type 2 dia- biopsy-proven NASH (62% having type 2
coholic fatty liver disease B and betes is based on their high prevalence diabetes) reported resolution of steatohe-
is not recommended in decom- of NASH with significant fibrosis (10–15% patitis in 59% at the higher dose (equivalent
pensated cirrhosis. B of people with type 2 diabetes) (95, to 2.4 mg/week semaglutide) compared
96,98), their higher risk of disease progres- with 17% in the placebo group (P <
While steatohepatitis and cirrhosis oc- sion and liver-related mortality (94,113, 0.001) (174). Cumulatively, semaglutide
cur in lean people with diabetes and 167), and the lack of pharmacological did not significantly affect the stage of
are believed to be linked to genetic treatments once cirrhosis is established liver fibrosis in this group of people (70%
S62 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
of whom had F2 or F3 at baseline), but it (99,105–107). Within a multidisciplinary 4.26 Health care systems need to en-
significantly slowed over 72 weeks the approach, statin therapy should be initi- sure that the vulnerable popula-
progression of liver fibrosis (4.9% with the ated or continued for cardiovascular risk tions are not disproportionately
GLP-1 RA at the highest dose compared reduction as clinically indicated. Overall,
disadvantaged by use of tech-
with 18.8% on placebo). Tirzepatide (183), its use appears to be safe in adults with
nological methods of consulta-
sodium–glucose cotransporter inhibitors type 2 diabetes and NASH, including in
tions. E
(184–186), and insulin (171) reduce he- the presence of compensated cirrhosis
4.27 There is no clear indication to
patic steatosis, but their effects on steato- (Child-Pugh class A or B cirrhosis) from
change prescribing of glucose-
hepatitis remain unknown. The use of NAFLD. Some studies even suggest that
their use in people with chronic liver dis- lowering therapies in people
glucose-lowering agents other than piogli-
tazone or GLP-1 RAs may be continued in ease may reduce episodes of hepatic de- with diabetes infected by the
patients with type 2 diabetes and NAFLD compensation and/or overall mortality SARS-CoV-2 virus. B
for glycemic control, as clinically indi- (192,193). Statin therapy is not recom- 4.28 People with diabetes should be
cated. However, they have either failed to mended in decompensated cirrhosis prioritized and offered SARS-
improve steatohepatitis in paired-biopsy given limited safety and efficacy data CoV-2 vaccines. B
studies (metformin) or have no RCTs with (99,106,107).
liver histological end points (i.e., sulfony- SARS-CoV-2, the virus that causes the
lureas, glitinides, dipeptidyl peptidase 4 DIABETES AND COVID-19 clinical disease COVID-19, was first re-
inhibitors, or acarbose). Recommendations ported in December 2019 in China and
Insulin is the preferred glucose-lowering 4.20 Health care professionals should has disproportionately impacted certain
agent for the treatment of hyperglycemia help people with diabetes aim groups, including men, older people, eth-
in adults with type 2 diabetes with de- to achieve individualized targeted nic minority populations, and people
compensated cirrhosis given the lack of glycemic control to reduce the with certain chronic conditions, including
robust evidence about the safety and effi- risk of macrovascular and micro- diabetes, cardiovascular disease, kidney
cacy of oral agents and noninsulin inject- vascular risk as well as reduce disease, and certain respiratory diseases.
ables (i.e., GLP-1 RA, GLP-1/GIP RA) (187), the risk of COVID-19 and its COVID-19 has now been recognized as a
although a recent 48-week study sug- complications. B complex multisystem disease including
gested that a GLP-1 RAs may be safe in 4.21 As we move into the recovery widespread insulin resistance, endothelial
patients with NASH and compensated cir- phase, diabetes health care dysfunction, hematological disorders, and
rhosis (188). services and practitioners should hyperimmune responses (194). There is
Metabolic surgery improves NASH and address the impact of the now evidence of not only direct but also
cardiometabolic health, altering the nat- pandemic in higher-risk groups, indirect adverse effects of COVID-19 in
ural history of the disease (189). Meta- including ethnic minority, de-
analyses report that 70–80% of people people with diabetes. Many people with
prived, and older populations. B multiple long-term conditions have diabe-
have improvement in hepatic steatosis,
4.22 People who have been infected tes, which has also been associated with
50–75% in inflammation and hepatocyte
with SARS-CoV-2 should be fol- worse outcomes in people with COVID-19
ballooning (necrosis), and 30–40% in fi-
lowed up in the longer term to (195). The association with BMI and
brosis (190,191). It may also reduce the
assess for complications and COVID-19 mortality is U-shaped in both
risk of HCC (191). Metabolic surgery
symptoms of long COVID. E type 1 and type 2 diabetes (196).
should be used with caution in individu-
4.23 People with new-onset diabetes COVID-19 has disproportionately af-
als with compensated cirrhosis (i.e.,
need to be followed up regu- fected certain groups, such as older
asymptomatic stage of cirrhosis without
larly in routine clinical practice people and those from some ethnic
associated liver complications), but with
to determine if diabetes is populations who are known to have
experienced surgeons the risk of hepatic
transient. B high prevalence of chronic conditions
decompensation is similar to that for
4.24 Health care professionals need such as diabetes, cardiovascular disease,
those with less advanced liver disease.
to carefully monitor people with kidney disease, and certain respiratory
Because of the paucity of safety and out-
diabetes for diabetic ketoacidosis diseases (197). People with chronic con-
come data, metabolic surgery is not recom-
during the COVID-19 pan- ditions have experienced some of the
mended in individuals with decompensated
demic. C worst COVID-19 outcomes, including
cirrhosis (i.e., cirrhosis stage with complica-
4.25 People with diabetes and their hospital admission and mortality (198).
tions such as variceal hemorrhage, ascites,
families/caregivers should be
hepatic encephalopathy, or jaundice), who In people with diabetes, higher blood
monitored for psychological
also have a much higher risk of postopera- glucose levels both prior to and during
well-being and offered support
tive development of these liver-related COVID-19 admission have been associ-
or referrals as needed, includ-
complications (99,106,107). ated with poor outcomes, including mor-
ing mental/behavioral health
A number of studies now recognize that tality (199). Type 1 diabetes has been
care, self-management edu-
adults with type 2 diabetes and NAFLD associated with higher risk of COVID-19
cation and support, and re-
are at an increased risk of cardiovascular mortality than type 2 diabetes (200).
sources to address related risk
disease and require a comprehensive One whole-population-level study of over
factors. E
management of cardiovascular risk factors 61 million people in England in the first
diabetesjournals.org/care Comprehensive Medical Evaluation and Assessment of Comorbidities S63
wave of the pandemic reported that after on long COVID specifically in people There is also evidence of adverse ef-
adjustment for age, sex, ethnicity, depri- with diabetes are lacking, and people fects of COVID-19 on mental health (210)
vation, and geographical region, the odds who have been infected with SARS-CoV-2 and health-promoting lifestyles during the
ratios for in-hospital COVID-19–related should be followed up in the longer pandemic. Some small studies in people
deaths were 3.51 (95% CI 3.16–3.90) term. with diabetes have reported longer-term
in people with type 1 diabetes and There have also been recent reports psychological impact of SARS-CoV-2 in-
2.03 (1.97–2.09) in people with type 2 of development of new-onset diabetes fection in people with diabetes, including
diabetes compared with the general in people who have had COVID-19. There fatigue and risk of suicide (211). Longitu-
population (201). There were also ex- are conflicting reports of new-onset dia- dinal follow-up of the Look AHEAD study
cess deaths in the first wave by 59.1% betes, with publications from a number of older adults with type 2 diabetes re-
in people with type 1 diabetes and of countries. The precise mechanisms ported a 1.6-fold higher prevalence for
64.3% in people with type 2 diabetes for new-onset diabetes in people with depressive symptoms and 1.8-fold higher
compared with death rates in the same COVID-19 are not known but may in- prevalence for loneliness during the
time period for the previous 3 years clude previously undiagnosed diabetes pandemic compared with prepandemic
(196). The largest study of people with presenting early or later in the disease levels (212). Furthermore, people with
diabetes to date, using whole-population trajectory, stress hyperglycemia, steroid- diabetes remain fearful of attending face-
data from England with over 3 million induced hyperglycemia, and possibly di- to-face contact due to the possible
people, reported a higher association for rect or indirect effects of SARS-CoV-2 on threat from mutant strains of corona-
mortality in people with type 1 diabetes the b-cell (205). Whether new-onset di- virus (213). Negative emotions due to
than type 2 diabetes (196). Male sex, abetes is likely to remain permanent or the pandemic, including lockdowns, have
older age, renal impairment, non-White is more aggressive is not known, and it been associated with reduced motiva-
ethnicity, socioeconomic deprivation, will be important for health care profes- tion, physical inactivity, and sedentary
and previous stroke and heart failure sionals to monitor these people in the behavior (214). Higher levels of pandemic-
were associated with increased COVID-19– longer term. One large U.S. retrospective related distress have been linked to higher
related mortality in both type 1 and type 2 study of over 27 million people reported A1C (215). Greater pandemic-related life
diabetes (196). that COVID-19 was associated with sig- disruptions have been related to higher
Much of the evidence for recommen- nificantly increased risk of new-onset distress in parents of youth with diabe-
dations is from a recent systematic re- type 1 diabetes and a disproportionately tes, which may have impacted families
view that was commissioned by the higher risk in ethnic minority people from racial and ethnic minority groups
World Health Organization on the latest (206). Another recent cross-sectional to a greater degree than non-Hispanic
research evidence on the impact of population–based Canadian study ob- White families (216). On the other hand,
COVID-19 on people with diabetes served a slightly higher but nonsignifi- for some youth with type 1 diabetes,
(200). Data were summarized from 112 cant increase in diabetes incidence in increased time at home during the early
systematic reviews that were narratively children during the pandemic, suggesting phases of the COVID-19 pandemic pro-
synthesized. The review reported that this resulted from delays in diagnosis vided opportunities for enhanced family
there are no appropriate data to deter- early during the pandemic with a catch- support for diabetes self-management
mine whether diabetes is a risk factor up effect (207). Whether COVID-19 leads and reduced diabetes-related distress
for acquiring SARS-CoV-2 infection. Dia- to new-onset diabetes is not known. (217).
betes is a risk factor for severe disease There have been several publications Recurrent lockdowns and other public
and death from COVID-19. on the risk of diabetic ketoacidosis (DKA) health measures due to the pandemic
Reasons for the higher rates of during the pandemic. A German diabetes have restricted access to routine diabetes
COVID-19 and severity in minority ethnic prospective study using registry data care and have affected self-management,
groups are complex and could be due to of children and adolescents found an care-seeking behavior, and access to
higher prevalence of comorbid conditions increase in type 1 diabetes in the first medications (218). This has resulted in
(e.g., diabetes), differences in exposure 3 months of the first wave, and the fre- compromised routine care and manage-
risk (e.g., overcrowded living conditions, quency of DKA at presentation was sig- ment of risk factors (219,220). There
essential worker jobs), and access to nificantly higher than those for 2019 have been reductions in diagnosis of
treatment (e.g., health insurance status, (44.7% vs. 24.5%, adjusted risk ratio type 2 diabetes and reductions in new
specialist services, and medications), which 1.84) and 2018 (vs. 24.1%, adjusted prescriptions of metformin during the
all relate to long-standing structural in- risk ratio 1.85) as well as the propor- pandemic (221). Due to unemployment
equities that vary by ethnicity (202). tion with severe DKA (208). A larger or lost income during the pandemic,
There is now overwhelming evidence study using national data in England people living with diabetes have expe-
that approximately 30–40% of people during the first two waves found that rienced financial hardships that may
who are infected with COVID-19 get per- rates of DKA were higher than those for have reduced their affordability for medi-
sistent and sometimes relapsing and re- preceding years across all pandemic pe- cations in countries where costs for medi-
mitting symptoms 4 weeks after infection, riods studied (209). The study reported cations are out of pocket (219). Many
which has been termed post-acute se- lower DKA hospital admissions in people individuals with diabetes have avoided
quelae of COVID-19, post-COVID-19 con- with type 1 diabetes but higher rates of or delayed seeking medical attention
dition, post-acute COVID-19 syndrome, DKA in people with type 1 diabetes and for routine non-COVID-19–related prob-
or long COVID (203,204). Currently, data those newly diagnosed with diabetes. lems due to fear of infection and/or to
S64 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023
reduce strain on health care services in the risks have been small, and these 6. Lachin JM, Genuth S, Nathan DM, Zinman B;
(222). Disruptions in care delivery and findings could be due to confounding by DCCT/EDIC Research Group. Effect of glycemic
exposure on the risk of microvascular complications
completion of care processes have been indication (230). The gold standard for as- in the diabetes control and complications trial–
associated with an increased risk of non- sessing the effects of therapies is by RCT, revisited. Diabetes 2008;57:995–1001
COVID-19–related deaths in people with and only one RCT, the Dapagliflozin in Pa- 7. White NH, Cleary PA, Dahms W, Goldstein D,
diabetes (223). tients with Cardiometabolic Risk Factors Malone J; Diabetes Control and Complications Trial
Direct contact will still be necessary if Hospitalized with COVID-19 (DARE-19), a (DCCT)/Epidemiology of Diabetes Interventions
and Complications (EDIC) Research Group. Beneficial
blood tests or physical examinations are double-blind, placebo-controlled RCT in effects of intensive therapy of diabetes during
required. However, it will be important people with and without type 2 diabetes adolescence: outcomes after the conclusion of
to ensure that disparities are not wid- with at least one cardiovascular risk fac- the Diabetes Control and Complications Trial
ened for vulnerable groups such as the tor, has been reported (231). In this (DCCT). J Pediatr 2001;139:804–812
elderly and socieconomically challenged 8. Rodriguez K, Ryan D, Dickinson JK, Phan V.
study, dapagliflozin was well tolerated
and ethnic minority groups due to ac- Improving quality outcomes: the value of diabetes
and resulted in fewer events of organ care and education specialists. Clin Diabetes 2022;
cess to literacy. dysfunction, but results were not statis- 40:356–365
As we recover from the pandemic, it tically significant for the dual primary 9. Anderson RM, Funnell MM. Compliance and
is essential that we prioritize the highest- outcome of prevention (time to new or adherence are dysfunctional concepts in diabetes
risk groups for their routine review and worsening organ dysfunction or death) care. Diabetes Educ 2000;26:597–604
assessment as well as management of 10. Sarkar U, Fisher L, Schillinger D. Is self-efficacy
and the hierarchical composite out- associated with diabetes self-management across
their mental/behavioral health and risk come of recovery by 30 days. race/ethnicity and health literacy? Diabetes Care
factors. Diabetes professional bodies in Great progress has been made glob- 2006;29:823–829
some countries have published guidance ally to develop vaccines against SARS- 11. King DK, Glasgow RE, Toobert DJ, et al. Self-
on risk stratification and who to prioritize CoV-2, and RCT data and real-world data efficacy, problem solving, and social-environmental
for diabetes review (224,225). Factors to support are associated with diabetes self-
show that vaccines have led to reduced management behaviors. Diabetes Care 2010;33:
consider for prioritization should include
infections, transmission, hospitalization, 751–753
demographics, socioeconomical status, 12. Nouwen A, Urquhart Law G, Hussain S,
and mortality. It is therefore important
education levels, established complica- McGovern S, Napier H. Comparison of the role of
that people with diabetes have regular
tions, comorbidities, and modifiable risk self-efficacy and illness representations in
SARS-CoV-2 vaccines (see IMMUNIZATIONS,
factors, which are associated with high relation to dietary self-care and diabetes distress
above, for detailed information on in adolescents with type 1 diabetes. Psychol Health
risk of progression of diabetes-related
COVID-19 vaccines). 2009;24:1071–1084
complications.
It is unclear currently how often people 13. Dickinson JK, Guzman SJ, Maryniuk MD, et al.
In many countries, health care profes- The use of language in diabetes care and
with diabetes will require booster vac-
sionals have reduced face-to-face contact education. Diabetes Care 2017;40:1790–1799
cines. Though limited data are available
and adapted technological methods of de- 14. Lee SWH, Ng KY, Chin WK. The impact of sleep
livering routine diabetes care. One small on COVID-19 vaccination attitudes or up- amount and sleep quality on glycemic control in
RCT in adults with type 2 diabetes with take in people with diabetes in the U.S. type 2 diabetes: a systematic review and meta-
(232), diabetes health care professionals analysis. Sleep Med Rev 2017;31:91–101
follow-up to 16 weeks showed that remote 15. Robinson CL, Bernstein H, Poehling K, Romero
consultations during the pandemic re- may be in a position to address ques-
JR, Szilagyi P. Advisory Committee on Immunization
duced the prevalence of mental health- tions and concerns among people with Practices recommended immunization schedule
and diabetes-related emotional distress diabetes and encourage vaccination. for children and adolescents aged 18 years or
(226). The number of face-to-face ap- younger—United States, 2020. MMWR Morb
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the UK: a cross-sectional national survey of views hypoglycemia-related emergency department or 246. Davies MJ, Aroda VR, Collins BS, et al.
of health professionals delivering diabetes care. hospital use. JAMA Intern Med 2017;177:1461–1470 Management of hyperglycemia in type 2 diabetes,
Prim Care Diabetes 2022;16:257–263 234. Lipska KJ, Ross JS,Wang Y, et al. National trends 2022. A consensus report by the American
221. Carr MJ, Wright AK, Leelarathna L, et al. in US hospital admissions for hyperglycemia and Diabetes Association (ADA) and the European
Impact of COVID-19 restrictions on diabetes hypoglycemia among Medicare beneficiaries, 1999 to Association for the Study of Diabetes (EASD).
health checks and prescribing for people with 2011. JAMA Intern Med 2014;174:1116–1124 Diabetes Care 2022;45:2753–2786
S68 Diabetes Care Volume 46, Supplement 1, January 2023
and/or when not meeting treat- needs, goals, and life experiences of the 4. When transitions in life and care
ment targets, when complicating person with diabetes. Health care profes- occur
factors develop (medical, physi- sionals are encouraged to consider the
cal, psychosocial), and when tran- burden of treatment (9) and the person’s DSMES focuses on empowering indi-
sitions in life and care occur. E level of confidence and self-efficacy for viduals with diabetes by providing people
5.3 Clinical outcomes, health status, management behaviors as well as the with diabetes the tools to make informed
level of social and family support when self-management decisions (15). DSMES
and well-being are key goals of
providing DSMES. An individual’s engage- should be person-centered. This is an
diabetes self-management edu-
ment in self-management behaviors and approach that places the person with dia-
cation and support that should
the effects on clinical outcomes, health betes and their family and/or support
be measured as part of routine
status, and quality of life, as well as the system at the center of the care model,
care. C
psychosocial factors impacting the per- working in collaboration with health care
5.4 Diabetes self-management educa-
professionals. Person-centered care is re-
increased patient engagement (62), al- to include social determinants of health to be instrumental for improving out-
though data from trials are consider- (SDOH) of the target population in guid- comes when it is implemented after the
ably heterogeneous. ing design and delivery of DSMES. The completion of education services. DSMES
Technology-enabled diabetes self- DSMES team should take into account is frequently reimbursed when performed
management solutions improve A1C demographic characteristics such as race, in person. However, although DSMES can
most effectively when there is two-way ethnic/cultural background, sex/gender, also be provided via phone calls and tele-
communication between the person with age, geographic location, technology ac- health, these remote versions may not
diabetes and the health care team, cess, education, literacy, and numeracy always be reimbursed (13). Medicare re-
individualized feedback, use of person- (43,79). imburses remote physiologic monitoring
generated health data, and education Despite the benefits of DSMES, reports for glucose and other cardiometabolic
(46). Continuous glucose monitoring, indicate that only 5–7% of individuals eli- data if certain conditions are met (83).
when combined with individualized diabe- gible for DSMES through Medicare or a Changes in reimbursement policies that
tes education or behavioral interventions, private insurance plan actually receive it increase DSMES access and utilization will
with type 1 diabetes (97) and 0.3–2.0% weight and improve clinical indicators. (105,116) but has long-term benefits;
for people with type 2 diabetes (97). There is strong and consistent evidence maintaining weight loss for 5 years is
See Table 5.1 for specific nutrition rec- that modest, sustained weight loss can associated with sustained improvements
ommendations. Because of the progres- delay the progression from prediabetes in A1C and lipid levels (117). MNT guid-
sive nature of type 2 diabetes, behavior to type 2 diabetes (97–99) (see Section 3, ance from an RDN with expertise in
modification alone may not be adequate “Prevention or Delay of Type 2 Diabetes diabetes and weight management through-
to maintain euglycemia over time. How- and Associated Comorbidities”) and is out the course of a structured weight
ever, after medication is initiated, nutrition beneficial for the management of type 2 loss plan is strongly recommended.
therapy continues to be an important diabetes (see Section 8, “Obesity and Along with routine medical manage-
component, and RDNs providing MNT in Weight Management for the Prevention ment visits, people with diabetes and
diabetes care should assess and monitor and Treatment of Type 2 Diabetes”). prediabetes should be screened during
medication changes in relation to the In prediabetes, the weight loss goal is DSMES and MNT encounters for a history
nutrition care plan (70,94). 7–10% for preventing progression to of dieting and past or current disordered
desired energy deficit (126–129). Any ap- Referral to an RDN is essential to as- carbohydrate counting) were effective
proach to meal planning should be indi- sess the overall nutrition status of, and in helping achieve improved A1C (145).
vidualized, considering the health status, to work collaboratively with, the person The diabetes plate method is a com-
personal preferences, and ability of the with diabetes to create a personalized monly used visual approach for provid-
person with diabetes to sustain the rec- meal plan that coordinates and aligns ing basic meal planning guidance. This
ommendations in the plan. with the overall treatment plan, includ- simple graphic (featuring a 9-inch plate)
ing physical activity and medication use. shows how to portion foods (1/2 of the
Eating Patterns and Meal Planning The Mediterranean (130,134–136), low- plate for nonstarchy vegetables, 1/4 of
Evidence suggests that there is not an carbohydrate (137–139), and vegetarian the plate for protein, and 1/4 of the
ideal percentage of calories from carbo- or plant-based (135,136,140,141) eating plate for carbohydrates). Carbohydrate
hydrate, protein, and fat for people patterns are all examples of healthful eat- counting is a more advanced skill that
with diabetes. Therefore, macronutrient ing patterns that have shown positive re- helps plan for and track how much carbo-
distribution should be based on an indi- sults in research for individuals with type 2 hydrate is consumed at meals and snacks.
(156,157). The literature concerning gly- studies, which further complicates evalu- minimize intake of refined carbohydrates
cemic index and glycemic load in indi- ating the distinct contribution of the eat- with added sugars, fat, and sodium and
viduals with diabetes is complex, often ing pattern (47,121,125,167). instead focus on carbohydrates from veg-
with varying definitions of low- and high- The quality of carbohydrate and/or etables, legumes, fruits, dairy (milk and
glycemic-index foods (158,159). The gly- what is absent from the diet may contrib- yogurt), and whole grains. People with di-
cemic index ranks carbohydrate foods on ute to confounding results. However, abetes and those at risk for diabetes are
their postprandial glycemic response, and when core dimensions of the comparative encouraged to consume a minimum of
glycemic load takes into account both diets are similar, there is little difference 14 g of fiber/1,000 kcal, with at least half
the glycemic index of foods and the in outcome measures. When Gardner et of grain consumption being whole, intact
amount of carbohydrate eaten. Studies al. (168) tested a low-carbohydrate keto- grains, according to the Dietary Guidelines
have found mixed results regarding the genic diet and a low-carbohydrate Medi- for Americans (172). Regular intake of suf-
effect of glycemic index and glycemic terranean diet, in a randomized crossover ficient dietary fiber is associated with
load on fasting glucose levels and A1C, design, metabolic improvements were lower all-cause mortality in people with
better insulin coverage for high-fat and/or In individuals with type 2 diabetes, compared with placebo, supplementation
high-protein mixed meals (185,192). protein intake may enhance or increase with n-3 fatty acids at the dose of
The effectiveness of insulin dosing the insulin response to dietary carbohy- 1 g/day did not lead to cardiovascular
decisions should be confirmed with a drates (199). Therefore, use of carbohy- benefit in people with diabetes without
structured approach to blood glucose drate sources high in protein (e.g., nuts) evidence of CVD (212). However, results
monitoring or continuous glucose moni- to treat or prevent hypoglycemia should from the Reduction of Cardiovascular
toring to evaluate individual responses be avoided due to the potential concur- Events With Icosapent Ethyl–Interven-
and guide insulin dose adjustments. rent rise in endogenous insulin. Health tion Trial (REDUCE-IT) found that supple-
Checking glucose 3 h after eating may care professionals should counsel pa- mentation with 4 g/day of pure EPA
help to determine if additional insulin tients to treat hypoglycemia with pure significantly lowered the risk of adverse
adjustments are required (i.e., increas- glucose (i.e., glucose tablets) or carbo- cardiovascular events. This trial of 8,179
ing or stopping bolus) (185,192,193). hydrate-containing foods at the hypogly- participants, in which over 50% had dia-
Refining insulin doses to account for cemia alert value of <70 mg/dL. See betes, found a 5% absolute reduction in
concern related to long-term safety. Based public, including people with diabetes over at least 3 days/week, with
on the recent U.S. Preventative Services (70,227). For some people with diabetes no more than 2 consecutive
Task Force statement, the harms of who are accustomed to regularly consum- days without activity. Shorter du-
b-carotene outweigh the benefits for the ing sugar-sweetened products, nonnutri- rations (minimum 75 min/week)
prevention of CVD or cancer. b-Carotene tive sweeteners (containing few or no
of vigorous-intensity or interval
was significantly associated with increased calories) may be an acceptable substitute
training may be sufficient for
lung cancer and cardiovascular mortality for nutritive sweeteners (those containing
younger and more physically fit
risk (219). calories, such as sugar, honey, and agave
individuals.
In addition, there is insufficient evidence syrup) when consumed in moderation
5.30 Adults with type 1 diabetes C
to support the routine use of herbal sup- (228,229). Nonnutritive sweeteners do
and type 2 diabetes B should
plements and micronutrients, such as cin- not appear to have a significant effect on
glycemic management (97,230,231), and engage in 2–3 sessions/week of
namon (220), curcumin, vitamin D (221), resistance exercise on noncon-
aloe vera, or chromium, to improve glyce- they can reduce overall calorie and carbo-
Objective measurement by accelerome- with diabetes (251). The ADA position ketoacidosis, retinopathy, and microalbu-
ter in 871 individuals with type 2 diabe- statement “Physical Activity/Exercise and minuria (260). Over time, activities should
tes showed that 44.2%, 42.6%, and Diabetes” reviews the evidence for the progress in intensity, frequency, and/
65.1% of White, African American, and benefits of exercise in people with type 1 or duration to at least 150 min/week
Hispanic individuals, respectively, met and type 2 diabetes and offers specific rec- of moderate-intensity exercise. Adults
the recommended threshold of exercise ommendations (252). Increased physical able to run at 6 miles/h (9.7 km/h) for at
(241). An RCT in 1,366 individuals with activity (soccer training) has also been least 25 min can benefit sufficiently from
prediabetes combined a physical activity shown to be beneficial for improving shorter-intensity activity (75 min/week)
intervention with text messaging and tele- overall fitness in Latino men with obe- (252). Many adults, including most with
phone support, which showed improve- sity, demonstrating feasible methods to type 2 diabetes, may be unable or un-
ment in daily step count at 12 months increase physical activity in an often willing to participate in such intense ex-
compared with the control group. Un- hard-to-engage population (253). Physical ercise and should engage in moderate
fortunately, this was not sustained at activity and exercise should be recom-
Physical Activity and Glycemic injury, such as uncontrolled hyperten- contraindicated because of the risk of
Management sion, untreated proliferative retinopathy, triggering vitreous hemorrhage or reti-
Clinical trials have provided strong evi- autonomic neuropathy, peripheral neu- nal detachment (274). Consultation
dence for the A1C-lowering value of resis- ropathy, and a history of foot ulcers or with an ophthalmologist prior to engag-
tance training in older adults with type 2 Charcot foot. Age and previous physical ing in an intense exercise plan may be
diabetes (252) and for an additive benefit activity level should be considered when appropriate.
of combined aerobic and resistance exer- customizing the exercise plan to the indi-
cise in adults with type 2 diabetes (271). vidual’s needs. Those with complications Peripheral Neuropathy
If not contraindicated, people with type 2 may need a more thorough evaluation Decreased pain sensation and a higher
diabetes should be encouraged to do at prior to starting an exercise program pain threshold in the extremities can
least two weekly sessions of resistance (247). result in an increased risk of skin break-
exercise (exercise with free weights or down, infection, and Charcot joint de-
weight machines), with each session con- Hypoglycemia struction with some forms of exercise.
SMOKING CESSATION: TOBACCO was associated with amelioration of meta- planning (305,307–309), problem-solving
AND E-CIGARETTES bolic parameters and reduced blood pres- (308,310), tracking or self-monitoring
sure and albuminuria at 1 year (293). health behaviors with or without feedback
Recommendations
In recent years, e-cigarettes have from a health care professional (305,307–
5.34 Advise all individuals not to use
gained public awareness and popularity 309), and facilitating opportunities for so-
cigarettes and other tobacco
because of perceptions that e-cigarette cial support (305,308,309). Multicompo-
products or e-cigarettes. A nent intervention packages have the
use is less harmful than regular cigarette
5.35 After identification of tobacco or highest efficacy for behavioral and glyce-
smoking (294,295). However, in light of
e-cigarette use, include smoking mic outcomes (300,309,311). For youth
recent Centers for Disease Control and
cessation counseling and other with diabetes, family-based behavioral
Prevention evidence (296) of deaths re-
forms of treatment as a routine intervention packages and multisystem
lated to e-cigarette use, no individuals
component of diabetes care. A interventions that facilitate health be-
should be advised to use e-cigarettes, ei-
5.36 Address smoking cessation as havior change demonstrate benefit for
ther as a way to stop smoking tobacco or
treatment for symptoms of dia- referral to appropriate services (324,325). problems with achieving A1C goals, quality
betes distress, depression, suici- Various health care professionals working of life, or self-management are identified.
dality, anxiety, treatment-related with people with diabetes may contrib- People with diabetes are likely to exhibit
fear of hypoglycemia, disordered ute to psychosocial care in different ways psychological vulnerability at diagnosis,
based on training, experience, need, and when their medical status changes (e.g.,
eating, and/or cognitive capaci-
availability (313,326,327). Ideally, quali- end of the honeymoon period), when the
ties. Such specialized psycho-
social care should use age- fied mental health professionals with need for intensified treatment is evident,
specialized training and experience in and when complications are discovered.
appropriate standardized and
diabetes should be integrated with or Significant changes in life circumstances
validated tools and treatment
provide collaborative care as part of dia- and SDOH are known to considerably af-
approaches. B
betes care teams (328–331), or referrals fect a person’s ability to self-manage their
5.41 Consider screening older adults
for in-depth assessment and treatment condition. Thus, screening for SDOH (e.g.,
(aged $65 years) with diabetes loss of employment, birth of a child, or
for psychosocial concerns should be
Table 5.2—Situations that warrant referral of a person with diabetes to a qualified behavioral or mental health professional
for evaluation and treatment
A positive screen on a validated screening tool for depressive symptoms, diabetes distress, anxiety, fear of hypoglycemia, or cognitive
impairment
The presence of symptoms or suspicions of disordered eating behavior, an eating disorder, or disrupted patterns of eating
Intentional omission of insulin or oral medication to cause weight loss is identified
A serious mental illness is suspected
In youth and families with behavioral self-care difficulties, repeated hospitalizations for diabetic ketoacidosis, failure to achieve expected
developmental milestones, or significant distress
Declining or impaired ability to perform diabetes self-care behaviors
Before undergoing bariatric or metabolic surgery and after surgery, if assessment reveals an ongoing need for adjustment support
distress is identified, it should be ac- compared with diabetes education (353) diabetes-specific concern is fears related
knowledged and addressed. If indicated, in teens with type 1 diabetes showed to hypoglycemia (375,376), which may
the person should be referred for follow- that diabetes distress and depressive explain avoidance of behaviors associ-
up care (333). This may include specific symptoms were significantly reduced for ated with lowering glucose, such as in-
diabetes education to address areas of up to 3 years post-intervention, though creasing insulin doses or frequency of
diabetes self-care causing distress and neither A1C nor self-management behav- monitoring. Other common sources of
impacting clinical management and/or iors improved over time. These recent diabetes-related anxiety include not meet-
behavioral intervention from a qualified studies support that a combination of ed- ing blood glucose targets (373), insulin in-
mental health professional, ideally with ucational, behavioral, and psychological jections or infusion (377), and onset of
expertise in diabetes, or from another intervention approaches is needed to ad- complications (1). People with diabetes
trained health care professional. Several dress distress, depression, and A1C. who exhibit excessive diabetes self-man-
educational and behavioral intervention As with treatment of other diabetes- agement behaviors well beyond what is
strategies have demonstrated benefits for associated behavioral and psychosocial prescribed or needed to achieve glyce-
all people with diabetes, espe- have been shown to improve both de- disease physiology, treatments for
cially those with a self-reported pression and medical outcomes (392). diabetes and disordered eating
history of depression. Use age- Depressive symptoms may also be a man- behaviors, and weight-related
appropriate, validated depression ifestation of reduced quality of life sec- and psychological risk factors for
ondary to disease burden (also see DIABETES disordered eating behaviors. B
screening measures, recognizing
DISTRESS, above) and resultant changes in
that further evaluation will be
resource allocation impacting the person
necessary for individuals who
and their family. When depressive symp- Estimated prevalence of disordered eat-
have a positive screen. B
toms are identified, it is important to ing behavior and diagnosable eating dis-
5.46 Beginning at diagnosis of compli-
query origins, both diabetes-specific and orders in people with diabetes varies
cations or when there are signif-
due to other life circumstances (363,393). (399–401). For people with type 1 dia-
icant changes in medical status, Trials have shown consistent evidence betes, insulin omission causing glycos-
consider assessment for depres- of improvements in depressive symptoms uria in order to lose weight is the most
needed (410). Health care teams may 5.51 In people who are prescribed Serious mental illness is often associated
consider the appropriateness of technol- atypical antipsychotic medica- with the inability to evaluate and utilize
ogy use among people with diabetes and information to make judgments about
tions, screen for prediabetes
disordered eating behaviors, although treatment options. When a person has
and diabetes 4 months after an established diagnosis of a mental ill-
more research on the risks and benefits is medication initiation and sooner ness that impacts judgment, activities of
needed (411). Caution should be taken in if clinically indicated, at least daily living, and ability to establish a col-
labeling individuals with diabetes as hav- annually. B laborative relationship with care profes-
ing a diagnosable psychiatric disorder, 5.52 If a second-generation antipsy- sionals, it is wise to include a nonmedical
i.e., an eating disorder, when disordered chotic medication is prescribed caretaker in decision-making regarding
or disrupted eating patterns are found to for adolescents or adults with the medical treatment plan. This person
be associated with the disease and its diabetes, changes in weight, can help improve the patient’s ability to
treatment. In other words, patterns of glycemia, and cholesterol levels follow the agreed-upon treatment plan
through both monitoring and caretaking
Figure 5.1—Importance of 24-h physical behaviors for type 2 diabetes. Reprinted from Davies et al. (88).
whether the person can collaborate with When this ability is shown to be altered, day-to-day monitoring as well as a liaison
the care team to achieve optimal meta- declining, or absent, a lay care profes- with the rest of the care team (1). Cogni-
bolic outcomes and prevent complica- sional should be introduced into the care tive capacity also contributes to ability
tions, both short and long term (416). team who serves in the capacities of to benefit from diabetes education and
S86 Facilitating Positive Health Behaviors and Well-being Diabetes Care Volume 46, Supplement 1, January 2023
may indicate the need for alternative type 2 diabetes (430,431) and possibly 3. Rutten GEHM, Alzaid A. Person-centred type 2
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6. GLYCEMIC TARGETS
cludes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guide-
lines, and tools to evaluate quality of care. Members of the ADA Professional
Practice Committee, a multidisciplinary expert committee, are responsible for up-
dating the Standards of Care annually, or more frequently as warranted. For a de-
tailed description of ADA standards, statements, and reports, as well as the
evidence-grading system for ADA’s clinical practice recommendations and a full
list of Professional Practice Committee members, please refer to Introduction
and Methodology. Readers who wish to comment on the Standards of Care are
invited to do so at professional.diabetes.org/SOC.
Glycemic Assessment
Recommendations
6.1 Assess glycemic status (A1C or other glycemic measurement such as time Disclosure information for each author is
in range or glucose management indicator) at least two times a year in available at https://doi.org/10.2337/dc23-SDIS.
patients who are meeting treatment goals (and who have stable glycemic Suggested citation: ElSayed NA, Aleppo G, Aroda
control). E VR, et al., American Diabetes Association. 6.
6.2 Assess glycemic status at least quarterly and as needed in patients whose Glycemic targets: Standards of Care in Diabetes—
2023. Diabetes Care 2023;46(Suppl. 1):S97–S110
therapy has recently changed and/or who are not meeting glycemic
goals. E © 2022 by the American Diabetes Association.
Readers may use this article as long as the
work is properly cited, the use is educational
and not for profit, and the work is not altered.
A1C reflects average glycemia over approximately 3 months. The performance of the More information is available at https://www.
test is generally excellent for National Glycohemoglobin Standardization Program diabetesjournals.org/journals/pages/license.
S98 Glycemic Targets Diabetes Care Volume 46, Supplement 1, January 2023
(NGSP)-certified assays (ngsp.org). The most assays in use in the U.S. are accu-
Table 6.1—Estimated average glucose
test is the primary tool for assessing gly- rate in individuals who are heterozygous (eAG)
cemic control and has a strong predictive for the most common variants (ngsp.
A1C (%) mg/dL* mmol/L
value for diabetes complications (2–4). org/interf.asp). Other measures of aver-
5 97 (76–120) 5.4 (4.2–6.7)
Thus, A1C testing should be performed age glycemia such as fructosamine and
routinely in all people with diabetes at 1,5-anhydroglucitol are available, but 6 126 (100–152) 7.0 (5.5–8.5)
initial assessment and as part of continu- their translation into average glucose 7 154 (123–185) 8.6 (6.8–10.3)
ing care. Measurement approximately levels and their prognostic significance 8 183 (147–217) 10.2 (8.1–12.1)
every 3 months determines whether pa- are not as clear as for A1C and CGM.
tients’ glycemic targets have been reached Though some variability in the relation- 9 212 (170–249) 11.8 (9.4–13.9)
and maintained. A 14-day CGM assess- ship between average glucose levels 10 240 (193–282) 13.4 (10.7–15.7)
ment of TIR and GMI can serve as a and A1C exists among different individ- 11 269 (217–314) 14.9 (12.0–17.5)
surrogate for A1C for use in clinical uals, in general the association between
70 Low 5%
54
10% Goal: <4% Glucose Variability ............................................ 45.5%
Very Low 5%
Goal: <36%
Goal: <1% Each 1% time in range = ~15 minutes
AGP is a summary of glucose values from the report period, with median (50%) and other percentiles shown as if they occurred in a single day.
350
mg/dL
95%
75%
250
50%
25%
180
Target
Range
70 5%
54
0
12am 3am 6am 9am 12pm 3pm 6pm 9pm 12am
180
70
180
70
Figure 6.1—Key points included in standard ambulatory glucose profile (AGP) report. Reprinted from Holt et al. (34).
diabetesjournals.org/care Glycemic Targets S101
assess hypoglycemia, hyperglycemia, and parallel goal for many nonpreg- glycemic separation between the treat-
glycemic variability. As discussed in a re- nant adults is time in range of ment groups diminished and disap-
cent consensus document, a report for- peared during follow-up.
>70% with time below range
matted as shown in Fig. 6.1 can be The Kumamoto Study (44) and UK
<4% and time <54 mg/dL
generated (35). Published data from two Prospective Diabetes Study (UKPDS)
<1%. For those with frailty or
retrospective studies suggest a strong cor- (45,46) confirmed that intensive gly-
at high risk of hypoglycemia, a
relation between TIR and A1C, with a cemic control significantly decreased
target of >50% time in range
goal of 70% TIR aligning with an A1C of rates of microvascular complications
with <1% time below range
7% (8,26). Note the goals of therapy in people with short-duration type 2
is recommended. (See Fig. 6.1
next to each metric in Fig. 6.1 (e.g., low, diabetes. Long-term follow-up of the
and Table 6.2.) B
<4%; very low, <1%) as values to guide UKPDS cohorts showed enduring ef-
changes in therapy. 6.6 On the basis of health care
fects of early glycemic control on most
professional judgment and pa- microvascular complications (47).
Potentially modifiable
Patient preference betes being diagnosed at <40 years of
highly motivated, excellent preference for less
self-care capabilities burdensome therapy
age and a demonstrably increased bur-
den of heart disease and years of life
Resources and support
system
lost in people diagnosed at a younger
readily available limited age (57–60). Thus, to prevent both mi-
crovascular and macrovascular compli-
Figure 6.2—Patient and disease factors used to determine optimal glycemic targets. Character- cations of diabetes, there is a major call
istics and predicaments toward the left justify more stringent efforts to lower A1C; those to-
ward the right suggest less stringent efforts. A1C 7% = 53 mmol/mol. Adapted with permission to overcome therapeutic inertia and
from Inzucchi et al. (71). treat to target for an individual patient
(60,61). During the UKPDS, there was a
16% reduction in CVD events (combined
risk. These trials showed that lower higher versus lower A1C; therefore, fatal or nonfatal MI and sudden death)
A1C levels were associated with reduced beyond post hoc analysis of these tri- in the intensive glycemic control arm
onset or progression of some micro- als, we do not have evidence that it is that did not reach statistical significance
vascular complications (50–52). the glucose lowering by these agents that (P = 0.052), and there was no sugges-
The concerning mortality findings confers the CVD and renal benefit (53). tion of benefit on other CVD outcomes
in the ACCORD trial discussed below As such, based on clinician judgment and (e.g., stroke). Similar to the DCCT/EDIC,
and the relatively intense efforts re- patient preferences, select patients, espe- after 10 years of observational follow-
quired to achieve near euglycemia should cially those with little comorbidity and a up, those originally randomized to in-
also be considered when setting gly- long life expectancy, may benefit from tensive glycemic control had significant
cemic targets for individuals with long- adopting more intensive glycemic targets long-term reductions in MI (15% with
standing diabetes, such as those popula- if they can achieve them safely and with- sulfonylurea or insulin as initial pharma-
tions studied in ACCORD, ADVANCE, and out hypoglycemia or significant thera- cotherapy, 33% with metformin as ini-
VADT. Findings from these studies sug- peutic burden. tial pharmacotherapy) and in all-cause
gest caution is needed in treating diabe- mortality (13% and 27%, respectively)
tes to near-normal A1C goals in people A1C and Cardiovascular Disease (47).
with long-standing type 2 diabetes with Outcomes ACCORD, ADVANCE, and VADT sug-
or at significant risk of CVD. Cardiovascular Disease and Type 1 Diabetes gested no significant reduction in CVD
These landmark studies need to be CVD is a more common cause of death outcomes with intensive glycemic control
considered with an important caveat; than microvascular complications in pop- in participants followed for shorter dura-
glucagon-like peptide 1 (GLP-1) receptor ulations with diabetes. There is evidence tions (3.5–5.6 years) and who had more
agonists and sodium–glucose cotrans- for a cardiovascular benefit of intensive advanced type 2 diabetes and CVD risk
porter 2 (SGLT2) inhibitors were not ap- glycemic control after long-term follow- than the UKPDS participants. All three tri-
proved at the time of these trials. As up of cohorts treated early in the course als were conducted in relatively older par-
such, these agents with established car- of type 1 diabetes. In the DCCT, there ticipants with a longer known duration
diovascular and renal benefits appear to was a trend toward lower risk of CVD of diabetes (mean duration 8–11 years)
be safe and beneficial in this group of events with intensive control. In the and either CVD or multiple cardio-
individuals at high risk for cardiorenal 9-year post-DCCT follow-up of the vascular risk factors. The target A1C
complications. Randomized clinical trials EDIC cohort, participants previously among intensive-control participants
examining these agents for cardiovas- randomized to the intensive arm had was <6% (42 mmol/mol) in ACCORD,
cular safety were not designed to test a significant 57% reduction in the risk <6.5% (48 mmol/mol) in ADVANCE,
diabetesjournals.org/care Glycemic Targets S103
and a 1.5% reduction in A1C compared and mortality (69). Therefore, health engage people with type 1 and type 2 di-
with control participants in VADT, care professionals should be vigilant abetes in shared decision-making. More
with achieved A1C of 6.4% vs. 7.5% in preventing hypoglycemia and should aggressive targets may be recommended
(46 mmol/mol vs. 58 mmol/mol) in not aggressively attempt to achieve if they can be achieved safely and
ACCORD, 6.5% vs. 7.3% (48 mmol/mol near-normal A1C levels in people in with an acceptable burden of therapy
vs. 56 mmol/mol) in ADVANCE, and 6.9% whom such targets cannot be safely and if life expectancy is sufficient to
vs. 8.4% (52 mmol/mol vs. 68 mmol/mol) and reasonably achieved. As discussed reap the benefits of stringent targets.
in VADT. Details of these studies are in Section 9, “Pharmacologic Approaches Less stringent targets (A1C up to 8%
reviewed extensively in the joint ADA to Glycemic Treatment,” addition of spe- [64 mmol/mol]) may be recommended
position statement “Intensive Glycemic cific SGLT2 inhibitors or GLP-1 receptor if the patient’s life expectancy is such
Control and the Prevention of Cardio- agonists that have demonstrated CVD that the benefits of an intensive goal
vascular Events: Implications of the benefit is recommended in patients may not be realized, or if the risks and
ACCORD, ADVANCE, and VA Diabetes with established CVD, chronic kidney burdens outweigh the potential bene-
Table 6.3—Summary of glycemic recommendations for many nonpregnant hypoglycemia avoidance educa-
adults with diabetes tion and reevaluation and ad-
A1C <7.0% (53 mmol/mol)*# justment of the treatment plan
Preprandial capillary plasma glucose 80–130 mg/dL* (4.4–7.2 mmol/L) to decrease hypoglycemia. E
6.14 Insulin-treated patients with hy-
Peak postprandial capillary plasma glucose† <180 mg/dL* (10.0 mmol/L)
poglycemia unawareness, one
*More or less stringent glycemic goals may be appropriate for individual patients. #CGM level 3 hypoglycemic event, or a
may be used to assess glycemic target as noted in Recommendation 6.5b and Fig. 6.1. pattern of unexplained level 2
Goals should be individualized based on duration of diabetes, age/life expectancy, comorbid
hypoglycemia should be advised
conditions, known CVD or advanced microvascular complications, hypoglycemia unaware-
ness, and individual patient considerations (as per Fig. 6.2). †Postprandial glucose may be to raise their glycemic targets
targeted if A1C goals are not met despite reaching preprandial glucose goals. Postprandial to strictly avoid hypoglycemia
glucose measurements should be made 1–2 h after the beginning of the meal, generally for at least several weeks in or-
administer glucagon. In addition to tra- diabetes (106). Hence, individuals with insulin dosing can improve A1C with
ditional glucagon injection powder that one or more episodes of clinically signifi- minimal hypoglycemia (133,134).
requires reconstitution prior to injec- cant hypoglycemia may benefit from at
tion, intranasal glucagon and ready-to- least short-term relaxation of glycemic INTERCURRENT ILLNESS
inject glucagon preparations for sub- targets and availability of glucagon (107).
For further information on management
cutaneous injection are available and Any person with recurrent hypoglycemia
may be beneficial in view of safety, ef- or hypoglycemia unawareness should of individuals with hyperglycemia in the
ficacy, and ease of use. Care should be have their glucose management treat- hospital, see Section 16, “Diabetes Care
taken to ensure that glucagon products ment plan adjusted. in the Hospital.”
are not expired (102). Stressful events (e.g., illness, trauma,
Use of CGM Technology in Hypoglycemia surgery) may worsen glycemic control and
Hypoglycemia Prevention Prevention precipitate diabetic ketoacidosis or nonke-
Hypoglycemia prevention is a critical With the advent of sensor-augmented totic hyperglycemic hyperosmolar state,
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sensor: a randomized controlled trial. Diabetes Level Awareness in Diabetes Study (GLADIS). diabetes: a multicentre, randomised controlled
Care 2006;29:44–50 Diabet Med 2015;32:609–617 trial. Lancet 2019;393:1138–1148
132. New JP, Ajjan R, Pfeiffer AFH, Freckmann G. 133. Bergenstal RM, Johnson M, Passi R, et al. 134. Kitabchi AE, Umpierrez GE, Miles JM, Fisher
Continuous glucose monitoring in people with Automated insulin dosing guidance to optimise JN. Hyperglycemic crises in adult patients with
diabetes: the randomized controlled Glucose insulin management in patients with type 2 diabetes. Diabetes Care 2009;32:1335–1343
7. DIABETES TECHNOLOGY
cludes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guide-
lines, and tools to evaluate quality of care. Members of the ADA Professional
Practice Committee, a multidisciplinary expert committee, are responsible for up-
dating the Standards of Care annually, or more frequently as warranted. For a de-
tailed description of ADA standards, statements, and reports, as well as the
evidence-grading system for ADA’s clinical practice recommendations and a full
list of Professional Practice Committee members, please refer to Introduction
and Methodology. Readers who wish to comment on the Standards of Care are
invited to do so at professional.diabetes.org/SOC.
Diabetes technology is the term used to describe the hardware, devices, and soft-
ware that people with diabetes use to assist with self-management, ranging from
lifestyle modifications to glucose monitoring and therapy adjustments. Historically,
diabetes technology has been divided into two main categories: insulin adminis-
tered by syringe, pen, or pump (also called continuous subcutaneous insulin infu-
sion), and glucose as assessed by blood glucose monitoring (BGM) or continuous
glucose monitoring (CGM). Diabetes technology has expanded to include automated
insulin delivery (AID) systems, where CGM-informed algorithms modulate insulin de-
livery, as well as diabetes self-management support software serving as medical devi-
ces. Diabetes technology, when coupled with education, follow-up, and support, can
improve the lives and health of people with diabetes; however, the complexity and
rapid evolution of the diabetes technology landscape can also be a barrier to imple-
mentation for both people with diabetes and the health care team.
Recommendations
7.1 The type(s) and selection of devices should be individualized based on a Disclosure information for each author is
available at https://doi.org/10.2337/dc23-SDIS.
person’s specific needs, preferences, and skill level. In the setting of an
individual whose diabetes is partially or wholly managed by someone else Suggested citation: ElSayed NA, Aleppo G,
Aroda VR, et al., American Diabetes Association.
(e.g., a young child or a person with cognitive impairment or dexterity, psy- 7. Diabetes technology: Standards of Care in
chosocial, and/or physical limitations), the caregiver’s skills and preferences Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):
are integral to the decision-making process. E S111–S127
7.2 When prescribing a device, ensure that people with diabetes/caregivers © 2022 by the American Diabetes Association.
receive initial and ongoing education and training, either in-person or Readers may use this article as long as the
remotely, and ongoing evaluation of technique, results, and their ability work is properly cited, the use is educational
to utilize data, including uploading/sharing data (if applicable), to moni- and not for profit, and the work is not altered.
tor and adjust therapy. C More information is available at https://www.
diabetesjournals.org/journals/pages/license.
S112 Diabetes Technology Diabetes Care Volume 46, Supplement 1, January 2023
7.3 People with diabetes who have assessed, particularly if outcomes are not snacks, after meals, at bedtime,
been using continuous glucose being met. prior to exercise, when hypo-
monitoring, continuous sub- glycemia is suspected, after
cutaneous insulin infusion, and/ Use in Schools treating low blood glucose
or automated insulin delivery Instructions for device use should be levels until they are normo-
for diabetes management should outlined in the student’s diabetes medi- glycemic, when hyperglycemia
have continued access across cal management plan (DMMP). A backup
is suspected, and prior to and
plan should be included in the DMMP
third-party payers, regardless while performing critical tasks
for potential device failure (e.g., BGM,
of age or A1C levels. E such as driving. B
CGM, and/or insulin delivery devices).
7.4 Students should be supported 7.8 Health care professionals should
School nurses and designees should
at school in the use of diabetes be aware of the differences in
complete training to stay up to date on
technology, such as continuous accuracy among blood glucose
diabetes technologies prescribed for use
prandial insulin doses). The specific needs Surveillance Program provides information platforms (19). People with diabetes
and goals of the person with diabetes on the performance of devices used for should be taught how to use BGM data
should dictate BGM frequency and timing BGM (diabetestechnology.org/surveillance/). to adjust food intake, physical activity,
or the consideration of CGM use. As rec- In one analysis, 6 of the top 18 glucose or pharmacologic therapy to achieve
ommended by the device manufacturers meters met the accuracy standard (12). specific goals. The ongoing need for and
and the U.S. Food and Drug Administra- In a subsequent analysis with updated frequency of BGM should be reevaluated
tion (FDA), people with diabetes using glucose meters, 14 of 18 glucose meters at each routine visit to ensure its effec-
CGM must have access to BGM for mul- met the minimum accuracy requirements tive use (17,20,21).
tiple reasons, including whenever there (13). There are single-meter studies in
is suspicion that the CGM is inaccurate, which benefits have been found with People With Diabetes on Intensive Insulin
while waiting for warm-up, for calibration individual meter systems, but few studies Therapies
(some sensors) or if a warning mes- have compared meters head-to-head. BGM is especially important for people
Table 7.1—Comparison of ISO 15197:2013 and FDA blood glucose meter accuracy standards
Setting FDA (248,254) ISO 15197:2013 (255)
Home use 95% within 15% for all BG in the usable BG range† 95% within 15% for BG $100 mg/dL
99% within 20% for all BG in the usable BG range† 95% within 15 mg/dL for BG <100 mg/dL
Hospital use 95% within 12% for BG $75 mg/dL 99% in A or B region of consensus error grid‡
95% within 12 mg/dL for BG <75 mg/dL
98% within 15% for BG $75 mg/dL
98% within 15 mg/dL for BG <75 mg/dL
BG, blood glucose; FDA, U.S. Food and Drug Administration; ISO, International Organization for Standardization. To convert mg/dL to mmol/L,
see endmemo.com/medical/unitconvert/Glucose.php. †The range of blood glucose values for which the meter has been proven accurate and
will provide readings (other than low, high, or error). ‡Values outside of the “clinically acceptable” A and B regions are considered “outlier”
readings and may be dangerous to use for therapeutic decisions (256).
S114 Diabetes Technology Diabetes Care Volume 46, Supplement 1, January 2023
with type 2 diabetes taking basal insulin care professionals in intensive care unit
Table 7.2—Interfering substances for
with or without oral agents and/or non- settings need to be particularly aware of glucose meter readings
insulin injectables. However, for those the potential for abnormal meter readings Glucose oxidase monitors
taking basal insulin, assessing fasting glu- during critical illness, and laboratory-based Uric acid
cose with BGM to inform dose adjust- values should be used if there is any Galactose
ments to achieve blood glucose targets doubt. Xylose
results in lower A1C (23,24). Some meters give error messages if Acetaminophen
L-DOPA
In people with type 2 diabetes not meter readings are likely to be false (33).
taking insulin, routine glucose monitor- Ascorbic acid
ing may be of limited additional clinical Oxygen. Currently available glucose mon- Glucose dehydrogenase monitors
benefit. By itself, even when combined itors utilize an enzymatic reaction linked Icodextrin (used in peritoneal dialysis)
with education, it has shown limited im- to an electrochemical reaction, either
See Table 7.3 for definitions of types of
provement in outcomes (25–28). However, glucose oxidase or glucose dehydrogenase
7.15 In people with diabetes on levels are rising or falling rapidly). There with iCGM designation and FDA approval
multiple daily injections or are two basic types of CGM devices: for use with AID systems.
continuous subcutaneous insulin those that are owned by the user, un-
infusion, real-time continuous blinded, and intended for frequent/con- Benefits of Continuous Glucose
tinuous use, including real-time CGM Monitoring
glucose monitoring devices
should be used as close to (rtCGM) and intermittently scanned CGM Data From Randomized Controlled Trials
daily as possible for maximal (isCGM), and professional CGM devices Multiple randomized controlled trials (RCTs)
benefit. A Intermittently scanned that are owned and applied in the clinic, have been performed using rtCGM devices,
which provide data that are blinded or and the results have largely been positive
continuous glucose monitor-
unblinded for a discrete period of time. in terms of reducing A1C levels and/or
ing devices should be scanned
The types of sensors currently available episodes of hypoglycemia as long as
frequently, at a minimum once
are either disposable (rtCGM and isCGM) participants regularly wore the devices
every 8 h. A People with dia-
CGM, continuous glucose monitoring; isCGM, intermittently scanned CGM; rtCGM, real-time CGM.
S116 Diabetes Technology Diabetes Care Volume 46, Supplement 1, January 2023
type 1 diabetes and met its primary In an observational study in youth with births, length of stay, and neonatal hypo-
outcome of a reduction in rates of hy- type 1 diabetes, a slight increase in A1C glycemia (97). An observational cohort
poglycemia (49). In adults with type 2 di- and weight was seen, but the device was study that evaluated the glycemic vari-
abetes on insulin, two studies were associated with a high user satisfaction ables reported using rtCGM and isCGM
done; one study did not meet its pri- rate (82). found that lower mean glucose, lower
mary end point of A1C reduction (76) Retrospective data from rtCGM use in standard deviation, and a higher percentage
but achieved a secondary end point of a Veterans Affairs population (90) with of time in target range were associated
a reduction in hypoglycemia, and the type 1 and type 2 diabetes treated with with lower risk of large-for-gestational-age
other study met its primary end point insulin showed that the use of rtCGM births and other adverse neonatal out-
of an improvement in Diabetes Treat- significantly lowered A1C and reduced comes (98). Use of the rtCGM-reported
ment Satisfaction Questionnaire score rates of emergency department visits or mean glucose is superior to use of glu-
as well as a secondary end point of hospitalizations for hypoglycemia but did cose management indicator (GMI) and
A1C reduction (77). In a study of indi- not significantly lower overall rates of other calculations to estimate A1C given
pens and assist with calculating insulin 7.25 Insulin pump therapy alone with and adults (155). There is no consensus
doses. Some connected insulin pens and or without sensor-augmented to guide choosing which form of insulin
pen caps can be programmed to calculate pump low glucose suspend administration is best for a given individ-
insulin doses and provide downloadable feature and/or automated insu- ual, and research to guide this decision-
data reports. These pens and pen caps lin delivery systems should be making process is needed (155). Thus, the
are useful to people with diabetes for choice of MDI or an insulin pump is often
offered for diabetes manage-
real-time insulin dosing and allow clini- based upon the characteristics of the per-
ment to youth and adults on
cians to retrospectively review the insu- son with diabetes and which method is
multiple daily injections with
lin delivery times and in some cases most likely to benefit them. DiabetesWise
type 1 diabetes A or other
doses and glucose data in order to (DiabetesWise.org) and the PANTHER
types of insulin-deficient dia-
make informed insulin dose adjustments Program (pantherprogram.org) have help-
betes E who are capable of
(148). ful websites to assist health care profes-
Needle thickness (gauge) and length using the device safely (either
sionals and people with diabetes in
Complications of the pump can be quality of life, and preventing long-term systems eventually may be truly auto-
caused by issues with infusion sets (dis- complications. Based on shared decision- mated, currently used hybrid closed-
lodgement, occlusion), which place indi- making by people with diabetes and loop systems require the manual entry
viduals at risk for ketosis and DKA and health care professionals, insulin pumps of carbohydrates consumed to calcu-
thus must be recognized and managed may be considered in all children and late prandial doses, and adjustments for
early (165). Other pump skin issues adolescents with type 1 diabetes. In partic- physical activity must be announced. Mul-
included lipohypertrophy or, less fre- ular, pump therapy may be the preferred tiple studies using various systems with
quently, lipoatrophy (166,167) and pump mode of insulin delivery for children under varying algorithms, pumps, and sensors
site infection (168). Discontinuation of 7 years of age (185). Because of a paucity have been performed in adults and chil-
pump therapy is relatively uncommon of data in adolescents and youth with dren (191–200). Evidence suggests AID sys-
today; the frequency has decreased over type 2 diabetes, there is insufficient ev- tems may reduce A1C levels and improve
the past few decades, and its causes idence to make recommendations. TIR (201–205). They may also lower the
Do-It-Yourself Closed-Loop Systems diabetes clinic have been published (224). programs, which vary in terms of their
Recommendation The FDA approves and monitors clinically effectiveness (236,237). There are lim-
7.28 Individuals with diabetes may validated, digital, and usually online ited RCT data for many of these inter-
be using systems not approved health technologies intended to treat a ventions, and long-term follow-up is
by the U.S. Food and Drug medical or psychological condition; these lacking. However, for an individual with
Administration, such as do-it- are known as digital therapeutics or diabetes, opting into one of these pro-
“digiceuticals” (fda.gov/medical-devices/ grams can be helpful in providing support
yourself closed-loop systems
digital-health-center-excellence/device- and, for many, is an attractive option.
and others; health care profes-
software-functions-including-mobile-medical-
sionals cannot prescribe these
applications) (225). Other applications, Inpatient Care
systems but should assist in
such as those that assist in displaying or
diabetes management to en- Recommendation
storing data, encourage a healthy life-
sure the safety of people with 7.30 People with diabetes who are
style or provide limited clinical data sup-
are underway to assess the effectiveness glycemic outcomes: 7-year follow-up study. unused testing results. Am J Manag Care 2015;
of this approach, which may ultimately Diabetes Care 2022;45:750–753 21:e119–e129
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lead to the approved use of CGM for Clements MA. Early initiation of diabetes devices Patient satisfaction with a new, high accuracy
monitoring hospitalized individuals (247– relates to improved glycemic control in children blood glucose meter that provides personalized
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as during a shortage of personal protec- control in newly diagnosed type 1 diabetes: the devices. J Am Med Inform Assoc 2020;27:667–
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used to manage hospitalized individuals 107:998–1008 20. Gellad WF, Zhao X, Thorpe CT, Mor MK,
6. Tanenbaum ML, Zaharieva DP, Addala A, et al. Good CB, Fine MJ. Dual use of Department of
in conjunction with BGM. Point-of-care ‘I was ready for it at the beginning’: parent Veterans Affairs and Medicare benefits and use
BGM remains the approved method for experiences with early introduction of continuous of test strips in veterans with type 2 diabetes
32. Mannucci E, Antenore A, Giorgino F, Scavini 45. Beck RW, Riddlesworth T, Ruedy K, et al.; Monitoring Study Group. The effect of continuous
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Technol 2022;16:1136–1143
Obesity is a chronic and often progressive disease with numerous medical, physical,
and psychosocial complications, including a substantially increased risk for type 2
diabetes (1). There is strong and consistent evidence that obesity management can
delay the progression from prediabetes to type 2 diabetes (2–6) and is highly bene-
ficial in treating type 2 diabetes (7–18). In people with type 2 diabetes and over-
weight or obesity, modest weight loss improves glycemia and reduces the need for
glucose-lowering medications (7–9), and larger weight loss substantially reduces A1C
and fasting glucose and has been shown to promote sustained diabetes remission
through at least 2 years (11,19–23). Several modalities, including intensive behavioral
counseling, obesity pharmacotherapy, and bariatric surgery, may aid in achieving and Disclosure information for each author is
maintaining meaningful weight loss and reducing obesity-associated health risks. available at https://doi.org/10.2337/dc23-SDIS.
Metabolic surgery strongly improves glycemia and often leads to remission of diabe- Suggested citation: ElSayed NA, Aleppo G, Aroda
VR, et al., American Diabetes Association. 8.
tes, improved quality of life, improved cardiovascular outcomes, and reduced mortal- Obesity and weight management for the pre-
ity. The importance of addressing obesity is further heightened by numerous studies vention and treatment of type 2 diabetes:
showing that both obesity and diabetes increase the risk for more severe coronavirus Standards of Care in Diabetes—2023. Diabetes
disease 2019 (COVID-19) infections (24–27). This section aims to provide evidence- Care 2023;46(Suppl. 1):S128–S139
based recommendations for obesity management, including behavioral, pharmaco- © 2022 by the American Diabetes Association.
logic, and surgical interventions, in people with type 2 diabetes and in those at risk. Readers may use this article as long as the
work is properly cited, the use is educational
This section focuses on obesity management in adults; further discussion on obesity
and not for profit, and the work is not altered.
in older individuals and children can be found in Section 13, “Older Adults,” and Sec- More information is available at https://www.
tion 14, “Children and Adolescents,” respectively. diabetesjournals.org/journals/pages/license.
diabetesjournals.org/care Obesity and Weight Management for Type 2 Diabetes S129
ASSESSMENT Height and weight should be measured counseling, pharmacologic therapy, medical
to calculate BMI annually or more fre- devices, and metabolic surgery (Table 8.1).
Recommendations
quently when appropriate (20). BMI, calcu- The latter three strategies may be consid-
8.1 Use person-centered, nonjudg- ered for carefully selected individuals as
lated as weight in kilograms divided by the
mental language that fosters
square of height in meters (kg/m2), is calcu- adjuncts to nutrition changes, physical ac-
collaboration between individ- lated automatically by most electronic med- tivity, and behavioral counseling.
uals and health care professio- ical records. Use BMI to document weight Among people with type 2 diabetes
nals, including person-first lan- status (overweight: BMI 25–29.9 kg/m2; and overweight or obesity who have in-
guage (e.g., “person with obesity” obesity class I: BMI 30–34.9 kg/m2; obesity adequate glycemic, blood pressure, and
rather than “obese person”). E class II: BMI 35–39.9 kg/m2; obesity class lipid control and/or other obesity-related
8.2 Measure height and weight III: BMI $40 kg/m2) but note that misclassi- medical conditions, modest and sustained
and calculate BMI at annual fication can occur, particularly in very mus- weight loss improves glycemia, blood
visits or more frequently. As- cular or frail individuals. In some groups, pressure, and lipids and may reduce the
*Recommended cut points for Asian American individuals (expert opinion). †Treatment may be indicated for select motivated individuals.
8.7 Such interventions should in- practitioners in medical set- sexual function, and health-related quality
of life (32). Moreover, several subgroups
by trained interventionists in either indi- little or no weight loss benefits. In contrast, discontinuation of the medi-
vidual or group sessions (51). Assessing vitamin/mineral (e.g., iron, vitamin B12, vi- cation and evaluate alterna-
an individual’s motivation level, life cir- tamin D) supplementation may be indicated tive medications or treatment
cumstances, and willingness to implement in cases of documented deficiency, and pro- approaches. A
behavioral changes to achieve weight loss tein supplements may be indicated as ad-
should be considered along with medical juncts to medically supervised weight loss
status when weight loss interventions are therapies. Glucose-Lowering Therapy
recommended and initiated (37,56). Health disparities adversely affect peo- A meta-analysis of 227 randomized con-
People with type 2 diabetes and over- ple who have systematically experienced trolled trials of glucose-lowering treat-
weight or obesity who have lost weight greater obstacles to health based on their ments in type 2 diabetes found that A1C
should be offered long-term ($1 year) race or ethnicity, socioeconomic status, changes were not associated with base-
comprehensive weight loss maintenance gender, disability, or other factors. Over- line BMI, indicating that people with obe-
programs that provide at least monthly whelming research shows that these dis-
FDA-approved obesity medications have continue the medication. When early use with BMI 30.0–34.9 kg/m2
been shown to improve glycemia in peo- appears ineffective (typically <5% weight (27.5–32.4 kg/m 2 in Asian
ple with type 2 diabetes and delay pro- loss after 3 months’ use), it is unlikely that American individuals) who do
gression to type 2 diabetes in at-risk continued use will improve weight out- not achieve durable weight loss
individuals (23). Phentermine and other comes; as such, it should be recom-
and improvement in comorbid-
older adrenergic agents are indicated for mended to discontinue the medication
ities (including hyperglycemia)
short-term (#12 weeks) treatment (68). and consider other treatment options.
with nonsurgical methods. A
Five medications are FDA approved for
8.20 Metabolic surgery should
long-term use (>12 weeks) in adults with MEDICAL DEVICES FOR WEIGHT LOSS
BMI $27 kg/m2 with one or more obe- be performed in high-volume
While gastric banding devices have fallen centers with multidisciplinary
sity-associated comorbid conditions (e.g.,
out of favor in recent years, since 2015, teams knowledgeable about
type 2 diabetes, hypertension, and/or
several minimally invasive medical devices and experienced in managing
dyslipidemia) who are motivated to lose
Table 8.2—Continued
1-Year (52- or 56-week)
mean weight loss (% loss from baseline)
National Average
Typical adult Average wholesale Drug Acquisition Weight loss
maintenance price (30-day Cost (30-day (% loss from Common side effects Possible safety concerns/
Medication name dose supply) (128) supply) (129) Treatment arms baseline) (130–134) considerations (130–134)
Glucagon-like peptide 1 receptor agonist
Liraglutide (17)** 3 mg q.d. $1,619 $1,295 3.0 mg q.d. 6.0 Gastrointestinal side effects Pancreatitis has been reported in
1.8 mg q.d. 4.7 (nausea, vomiting, diarrhea, clinical trials, but causality has not
PBO 2.0 esophageal reflux), injection been established. Discontinue if
site reactions, elevated heart pancreatitis is suspected.
rate, hypoglycemia Use caution in people with kidney
Obesity and Weight Management for Type 2 Diabetes
Postbariatric hypoglycemia (PBH) can mental health conditions until these condi- phentermine and topiramate extended release.
Diabetes Care 2014;37:3309–3316
occur with RYGB, VSG, and other gastro- tions have been sufficiently addressed. In-
15. O’Neil PM, Smith SR, Weissman NJ, et al.
intestinal procedures and may severely dividuals with preoperative or new-onset Randomized placebo-controlled clinical trial of
impact quality of life (116–118). PBH is psychopathology should be assessed regu- lorcaserin for weight loss in type 2 diabetes
driven in part by altered gastric empty- larly following surgery to optimize mental mellitus: the BLOOM-DM study. Obesity (Silver
Spring) 2012;20:1426–1436
ing of ingested nutrients, leading to rapid health and postsurgical outcomes. 16. Hollander P, Gupta AK, Plodkowski R, et al.;
intestinal glucose absorption and exces- COR-Diabetes Study Group. Effects of naltrexone
sive postprandial secretion of glucagon- References sustained-release/bupropion sustained-release
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Recommendations
9.1 Most individuals with type 1 diabetes should be treated with multiple daily
injections of prandial and basal insulin, or continuous subcutaneous insulin
infusion. A
9.2 Most individuals with type 1 diabetes should use rapid-acting insulin analogs
to reduce hypoglycemia risk. A
9.3 Individuals with type 1 diabetes should receive education on how to match
mealtime insulin doses to carbohydrate intake, fat and protein content, and
anticipated physical activity. B
Insulin Therapy
Because the hallmark of type 1 diabetes is absent or near-absent b-cell function,
insulin treatment is essential for individuals with type 1 diabetes. In addition to hy- Disclosure information for each author is
perglycemia, insulinopenia can contribute to other metabolic disturbances like hy- available at https://doi.org/10.2337/dc23-SDIS.
pertriglyceridemia and ketoacidosis as well as tissue catabolism that can be life Suggested citation: ElSayed NA, Aleppo G,
threatening. Severe metabolic decompensation can be, and was, mostly prevented Aroda VR, et al., American Diabetes Association.
with once- or twice-daily injections for the six or seven decades after the discovery 9. Pharmacologic approaches to glycemic treat-
of insulin. However, over the past three decades, evidence has accumulated sup- ment: Standards of Care in Diabetes—2023.
Diabetes Care 2023;46(Suppl. 1):S140–S157
porting more intensive insulin replacement, using multiple daily injections of insulin
or continuous subcutaneous administration through an insulin pump, as providing © 2022 by the American Diabetes Association.
the best combination of effectiveness and safety for people with type 1 diabetes. Readers may use this article as long as the
work is properly cited, the use is educational
The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive and not for profit, and the work is not altered.
therapy with multiple daily injections or continuous subcutaneous insulin infusion More information is available at https://www.
(CSII) reduced A1C and was associated with improved long-term outcomes (1–3). diabetesjournals.org/journals/pages/license.
diabetesjournals.org/care Pharmacologic Approaches to Glycemic Treatment S141
The study was carried out with short- to the individual to keep them safe and monitoring should be considered in most
acting (regular) and intermediate-acting out of diabetic ketoacidosis and to avoid individuals with type 1 diabetes. AID sys-
(NPH) human insulins. In this landmark significant hypoglycemia, with every ef- tems may be considered in individuals
trial, lower A1C with intensive control fort made to reach the individual’s gly- with type 1 diabetes who are capable of
(7%) led to 50% reductions in micro- cemic targets. using the device safely (either by them-
vascular complications over 6 years of Most studies comparing multiple daily selves or with a caregiver) in order to
treatment. However, intensive therapy injections with CSII have been relatively improve time in range and reduce A1C
was associated with a higher rate of se- small and of short duration. However, a and hypoglycemia (22). See Section 7,
vere hypoglycemia than conventional systematic review and meta-analysis con- “Diabetes Technology,” for a full discus-
treatment (62 compared with 19 epi- cluded that CSII via pump therapy has sion of insulin delivery devices.
sodes per 100 patient-years of therapy). modest advantages for lowering A1C In general, individuals with type 1 dia-
Follow-up of subjects from the DCCT ( 0.30% [95% CI 0.58 to 0.02]) and betes require 50% of their daily insulin
as basal and 50% as prandial, but this is
adjust prandial insulin to account for car- the adipogenic actions of insulin at a site SURGICAL TREATMENT FOR TYPE 1
bohydrate intake, premeal glucose levels, of multiple injections. Lipohypertrophy ap- DIABETES
and anticipated activity can be effective pears as soft, smooth raised areas several Pancreas and Islet Transplantation
and should be offered to most individuals centimeters in breadth and can contribute Successful pancreas and islet transplan-
(25,26). For individuals in whom carbohy- to erratic insulin absorption, increased tation can normalize glucose levels and
drate counting is effective, estimates of glycemic variability, and unexplained mitigate microvascular complications of
the fat and protein content of meals can hypoglycemic episodes. People treated type 1 diabetes. However, people receiving
be incorporated into their prandial dos- with insulin and/or caregivers should these treatments require lifelong immuno-
ing for added benefit (27) (see Section 5, receive education about proper injec- suppression to prevent graft rejection and/
“Facilitating Positive Health Behaviors and tion site rotation and how to recognize or recurrence of autoimmune islet destruc-
Well-being to Improve Health Outcomes”). and avoid areas of lipohypertrophy. As tion. Given the potential adverse effects
of immunosuppressive therapy, pancreas
The 2021 ADA/European Association noted in Table 4.1, examination of insu-
transplantation should be reserved for
TIR % highest and TBR % lowest numeracy or literacy skills). glucose outside of activity of
with: hybrid closed-loop > low- URAA/RAA bolus.
glucose suspend > CGM-
augmented open-loop > BGM-
augmented open-loop.
MDI: LAA 1 flexible doses of URAA LAA once daily (insulin detemir or Can use pens for all components. At least four daily injections. Mealtime insulin: if carbohydrate
or RAA at meals insulin glargine may require twice- Flexibility in meal timing and Most costly insulins. counting is accurate, change ICR if
daily dosing); generally 50% of content. Smallest increment of insulin is glucose after meal consistently out
TDD. Insulin analogs cause less 1 unit (0.5 unit with some pens). of target.
Mealtime and correction: URAA or hypoglycemia than human insulins. LAAs may not cover strong dawn Correction insulin: adjust ISF and/or
RAA based on ICR and/or ISF and phenomenon (rise in glucose in target glucose if correction does
target glucose. early morning hours) as well as not consistently bring glucose into
pump therapy. range.
LAA: based on overnight or fasting
glucose or daytime glucose
outside of activity time course, or
URAA or RAA injections.
MDI regimens with less flexibility
Four injections daily with fixed Pre-breakfast: RAA 20% of TDD. May be feasible if unable to Shorter duration RAA may lead to Pre-breakfast RAA: based on BGM
doses of N and RAA Pre-lunch: RAA 10% of TDD. carbohydrate count. basal deficit during day; may need after breakfast or before lunch.
Pre-dinner: RAA 10% of TDD. All meals have RAA coverage. twice-daily N. Pre-lunch RAA: based on BGM after
Bedtime: N 50% of TDD. N is less expensive than LAAs. Greater risk of nocturnal hypoglycemia lunch or before dinner.
with N. Pre-dinner RAA: based on BGM after
Requires relatively consistent mealtimes dinner or at bedtime.
and carbohydrate intake. Evening N: based on fasting or
overnight BGM.
Continued on p. S145
Diabetes Care Volume 46, Supplement 1, January 2023
BGM, blood glucose monitoring; CGM, continuous glucose monitoring; ICR, insulin-to-carbohydrate ratio; ISF, insulin sensitivity factor; LAA, long-acting analog; MDI, multiple daily injections; N, NPH
insulin; R, short-acting (regular) insulin; RAA, rapid-acting analog; TDD, total daily insulin dose; URAA, ultra-rapid-acting analog. Reprinted from Holt et al. (5).
Pharmacologic Approaches to Glycemic Treatment
S145
modifications and health behaviors that cologic approaches that provide the ef- Weight management is an impactful com-
improve health (see Section 5, “Facilitating ficacy to achieve treatment goals should ponent of glucose-lowering management
Positive Health Behaviors and Well-being be considered, such as metformin or other in type 2 diabetes (45,46). The glucose-
to Improve Health Outcomes”) should be agents, including combination therapy, that lowering treatment regimen should con-
emphasized along with any pharmacologic provide adequate efficacy to achieve and sider approaches that support weight
therapy. Section 13, “Older Adults,” and maintain treatment goals (45). In adults management goals, with very high ef-
Section 14, “Children and Adolescents,” with type 2 diabetes and established/high ficacy for weight loss seen with sema-
have recommendations specific for older risk of atherosclerotic cardiovascular disease glutide and tirzepatide (Fig. 9.3 and
adults and for children and adolescents (ASCVD), heart failure (HF), and/or chronic Table 9.2) (45).
with type 2 diabetes, respectively. Sec- kidney disease (CKD), the treatment regi- Metformin is effective and safe, is inex-
tion 10, “Cardiovascular Disease and Risk men should include agents that reduce cardi- pensive, and may reduce risk of cardiovas-
Management,” and Section 11, “Chronic orenal risk (see Fig. 9.3, Table 9.2, Section cular events and death (47). Metformin is
Kidney Disease and Risk Management,” 10, “Cardiovascular Disease and Risk available in an immediate-release form for
have recommendations for the use of glucose- Management,” and Section 11, “Chronic twice-daily dosing or as an extended-
lowering drugs in the management of cardio- Kidney Disease and Risk Management”). release form that can be given once daily.
vascular and renal disease, respectively. Pharmacologic approaches that provide the Compared with sulfonylureas, metformin
efficacy to achieve treatment goals should as first-line therapy has beneficial effects
Choice of Glucose-Lowering Therapy be considered, specified as metformin or on A1C, weight, and cardiovascular mor-
Healthy lifestyle behaviors, diabetes self- agent(s), including combination therapy, tality (48).
management, education, and support, that provide adequate efficacy to achieve The principal side effects of metfor-
avoidance of clinical inertia, and social and maintain treatment goals (Fig. 9.3 and min are gastrointestinal intolerance due
determinants of health should be consid- Table 9.2). In general, higher-efficacy ap- to bloating, abdominal discomfort, and
ered in the glucose-lowering manage- proaches have greater likelihood of achiev- diarrhea; these can be mitigated by grad-
ment of type 2 diabetes. Pharmacologic ing glycemic goals, with the following ual dose titration. The drug is cleared by
therapy should be guided by person- considered to have very high efficacy for renal filtration, and very high circulating
centered treatment factors, including glucose lowering: the GLP-1 RAs dulaglutide levels (e.g., as a result of overdose or
comorbidities and treatment goals. Phar- (high dose) and semaglutide, the gastric in- acute renal failure) have been associated
macotherapy should be started at the hibitory peptide (GIP) and GLP-1 RA tirze- with lactic acidosis. However, the occur-
time type 2 diabetes is diagnosed unless patide, insulin, combination oral therapy, rence of this complication is now known
there are contraindications. Pharma- and combination injectable therapy. to be very rare, and metformin may be
diabetesjournals.org/care
Figure 9.3—Use of glucose-lowering medications in the management of type 2 diabetes. ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin-to-creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardio-
vascular disease; CGM, continuous glucose monitoring; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; DPP-4i, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomeru-
lar filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; MACE,
Pharmacologic Approaches to Glycemic Treatment
major adverse cardiovascular events; MI, myocardial infarction; SDOH, social determinants of health; SGLT2i, sodium-glucose cotransporter 2 inhibitor; T2D, type 2 diabetes; TZD, thiazolidinedione. Adapted from Davies et al. (45).
S147
CV, cardiovascular; CVOT, cardiovascular outcomes trial; DKA, diabetic ketoacidosis; DKD, diabetic kidney disease; DPP-4, dipeptidyl peptidase 4; eGFR, estimated glomerular filtration rate; FDA,
U.S. Food and Drug Administration; GI, gastrointestinal; GIP, gastric inhibitory polypeptide; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; NASH, nonalcoholic steatohepatitis;
MACE, major adverse cardiovascular events; SGLT2, sodium–glucose cotransporter 2; SQ, subcutaneous; T2DM, type 2 diabetes mellitus. *For agent-specific dosing recommendations, please refer
Diabetes Care Volume 46, Supplement 1, January 2023
to manufacturers’ prescribing information. 1Tsapas et al. (62). 2Tsapas et al. (114). Reprinted from Davies et al. (45).
safely used in people with reduced esti- durability of glycemic effect (57). The Table 10.3C, and Section 10, “Cardiovascular
mated glomerular filtration rates (eGFR); VERIFY (Vildagliptin Efficacy in combina- Disease and Risk Management”) is recom-
the FDA has revised the label for metfor- tion with metfoRmln For earlY treatment mended as part of the glucose-lowering
min to reflect its safety in people with of type 2 diabetes) trial demonstrated regimen independent of A1C, independent
eGFR $30 mL/min/1.73 m2 (49). A ran- that initial combination therapy is supe- of metformin use and in consideration of
domized trial confirmed previous obser- rior to sequential addition of medications person-specific factors (Fig. 9.3). For peo-
vations that metformin use is associated for extending primary and secondary fail- ple without established ASCVD, indica-
with vitamin B12 deficiency and worsen- ure (58). In the VERIFY trial, participants tors of high ASCVD risk, HF, or CKD,
ing of symptoms of neuropathy (50). This receiving the initial combination of met- medication choice is guided by efficacy
is compatible with a report from the Di- formin and the dipeptidyl peptidase 4 in support of individualized glycemic and
abetes Prevention Program Outcomes (DPP-4) inhibitor vildagliptin had a slower weight management goals, avoidance of
Study (DPPOS) suggesting periodic test- decline of glycemic control compared with side effects (particularly hypoglycemia
metformin alone and with vildagliptin and weight gain), cost/access, and indi-
TO AVOID
THERAPEUTIC
Use principles in Figure 9.3, including reinforcement of behavioral INERTIA
REASSESS AND
interventions (weight management and physical activity) and provision MODIFY TREATMENT
of DSMES, to meet individualized treatment goals REGULARLY
(3–6 MONTHS)
Consider GLP-1 RA or GIP/GLP-1 RA in most individuals prior to insulin2 If already on GLP-1 RA or dual GIP
INITIATION: Initiate appropriate starting dose for agent selected (varies within class) and GLP-1 RA or if these are not
TITRATION: Titrate to maintenance dose (varies within class) appropriate OR insulin is preferred
If above A1C target and not already on a GLP-1 RA or dual GIP and GLP-1 RA,
consider these classes, either in free combination or fixed-ratio combination, with insulin.
If A1C remains above target:
1. Consider insulin as the first injectable if evidence of ongoing catabolism, symptoms of hyperglycemia are present, when A1C levels (>10% [86 mmol/mol]) or blood glucose levels
( 300 mg/dL [16.7 mmol/L]) are very high, or a diagnosis of type 1 diabetes is a possibility.
2. When selecting GLP-1 RA, consider individual preference, A1C lowering, weight-lowering effect, or fequency of injection. If CVD is present, consider GLP-1 RA with proven CVD benefit. Oral or
injectable GLP-1 RA are appropriate.
3. For people on GLP-1 RA and basal insulin combination, consider use of a fixed-ratio combination product (IDegLira or iGlarLixi).
4. Consider switching from evening NPH to a basal analog if the individual develops hypoglycemia and/or frequently forgets to administer NPH in the evening and would be better managed
with an A.M. dose of a long-acting basal insulin.
5. If adding prandial insulin to NPH, consider initiation of a self-mixed or premixed insulin regimen to decrease the number of injections required.
Figure 9.4—Intensifying to injectable therapies in type 2 diabetes. DSMES, diabetes self-management education and support; FPG, fasting plasma
glucose; GLP-1 RA, glucagon-like peptide 1 receptor agonist; max, maximum; PPG, postprandial glucose. Adapted from Davies et al. (43).
diabetesjournals.org/care Pharmacologic Approaches to Glycemic Treatment S151
who are intensified to insulin therapy, provide the complementary outcomes analogs (U-100 glargine or detemir) have
combination therapy with a GLP-1 RA benefits associated with these classes been demonstrated to reduce the risk of
has been shown to have greater efficacy of medication (76). In cardiovascular symptomatic and nocturnal hypoglycemia
and durability of glycemic treatment ef- outcomes trials, empagliflozin, canagli- compared with NPH insulin (80–85), al-
fect, as well as weight and hypoglycemia flozin, dapagliflozin, liraglutide, semaglu- though these advantages are modest and
benefit, than treatment intensification tide, and dulaglutide all had beneficial may not persist (86). Longer-acting basal
with insulin alone (45). However, cost effects on indices of CKD, while dedicated analogs (U-300 glargine or degludec) may
and tolerability issues are important renal outcomes studies have demonstrated convey a lower hypoglycemia risk com-
considerations in GLP-1 RA use. benefit of specific SGLT2 inhibitors. See pared with U-100 glargine when used in
Costs for diabetes medications have Section 11, “Chronic Kidney Disease and combination with oral agents (87–93).
increased dramatically over the past two Risk Management,” for discussion of how Clinicians should be aware of the poten-
decades, and an increasing proportion is tial for overbasalization with insulin ther-
CKD may impact treatment choices. Ad-
apy. Clinical signals that may prompt
Table 9.3—Median monthly (30-day) AWP and NADAC of maximum approved daily dose of noninsulin glucose-lowering
agents in the U.S.
Dosage strength/ Median AWP Median NADAC Maximum approved
Class Compound(s) product (if applicable) (min, max)† (min, max)† daily dose*
Biguanides Metformin 850 mg (IR) $106 ($5, $189) $2 2,550 mg
1,000 mg (IR) $87 ($3, $144) $2 2,000 mg
1,000 mg (ER) $242 ($242, $7,214) $32 ($32, $160) 2,000 mg
Sulfonylureas (2nd Glimepiride 4 mg $74 ($71, $198) $3 8 mg
generation) Glipizide 10 mg (IR) $70 ($67, $91) $6 40 mg
10 mg (XL/ER) $48 ($46, $48) $11 20 mg
Glyburide 6 mg (micronized) $52 ($48, $71) $12 12 mg
5 mg $79 ($63, $93) $9 20 mg
Thiazolidinedione Pioglitazone 45 mg $345 ($7, $349) $4 45 mg
AWP, average wholesale price; DPP-4, dipeptidyl peptidase 4; ER and XL, extended release; GIP, glucose-dependent insulinotropic polypeptide; GLP-1 RA,
glucagon-like peptide 1 receptor agonist; IR, immediate release; max, maximum; min, minimum; NA, data not available; NADAC, National Average Drug
Acquisition Cost; SGLT2, sodium-glucose cotransporter 2. †Calculated for 30-day supply (AWP [72] or NADAC [73] unit price × number of doses re-
quired to provide maximum approved daily dose × 30 days); median AWP or NADAC listed alone when only one product and/or price.
*Utilized to calculate median AWP and NADAC (min, max); generic prices used, if available commercially. **Administered once weekly. ††AWP and
NADAC calculated based on 120 mg three times daily.
address prandial control and to minimize with type 1 diabetes, require higher Concentrated Insulins
the risks of hypoglycemia and weight gain daily doses (1 unit/kg), and have lower Several concentrated insulin preparations
associated with insulin therapy (45). For rates of hypoglycemia (97). Titration can are currently available. U-500 regular
individuals who advance to prandial in- be based on home glucose monitoring or insulin is, by definition, five times more
sulin, a prandial insulin dose of 4 units or A1C. With significant additions to the pran- concentrated than U-100 regular insulin.
10% of the amount of basal insulin at the dial insulin dose, particularly with the eve- U-500 regular insulin has distinct phar-
largest meal or the meal with the great- ning meal, consideration should be macokinetics with delayed onset and
est postprandial excursion is a safe esti- given to decreasing basal insulin. Meta- longer duration of action, has charac-
mate for initiating therapy. The prandial analyses of trials comparing rapid-acting teristics more like an intermediate-acting
insulin regimen can then be intensified insulin analogs with human regular insu- (NPH) insulin, and can be used as two or
based on individual needs (Fig. 9.4). In- lin in type 2 diabetes have not reported three daily injections (100). U-300 glar-
dividuals with type 2 diabetes are gen- important differences in A1C or hypogly- gine and U-200 degludec are three and
erally more insulin resistant than those cemia (98,99). two times as concentrated as their U-100
diabetesjournals.org/care Pharmacologic Approaches to Glycemic Treatment S153
Table 9.4—Median cost of insulin products in the U.S. calculated as AWP (72) and NADAC (73) per 1,000 units of specified
dosage form/product
Median AWP Median
Insulins Compounds Dosage form/product (min, max)* NADAC*
Rapid-acting Lispro follow-on product U-100 vial $118 ($118, $157) $94
U-100 prefilled pen $151 $121
Lispro U-100 vial $99† $79†
U-100 cartridge $408 $326
U-100 prefilled pen $127† $102†
U-200 prefilled pen $424 $339
Lispro-aabc U-100 vial $330 $261
U-100 prefilled pen $424 $339
U-200 prefilled pen $424 NA
Glulisine U-100 vial $341 $272
formulations, respectively, and allow who require large doses of insulin. While pharmacokinetics (8). Studies comparing
higher doses of basal insulin adminis- U-500 regular insulin is available in both inhaled insulin with injectable insulin
tration per volume used. U-300 glargine prefilled pens and vials, other concen- have demonstrated its faster onset and
has a longer duration of action than trated insulins are available only in pre- shorter duration compared with rapid-
U-100 glargine but modestly lower efficacy filled pens to minimize the risk of dosing acting insulin lispro as well as clinically
per unit administered (101,102). The errors. meaningful A1C reductions and weight
FDA has also approved a concentrated reductions compared with insulin aspart
formulation of rapid-acting insulin lispro, Alternative Insulin Routes over 24 weeks (103–105). Use of in-
U-200 (200 units/mL), and insulin lispro- Insulins with different routes of admin- haled insulin may result in a decline in
aabc (U-200). These concentrated prepa- istration (inhaled, bolus-only insulin de- lung function (reduced forced expiratory
rations may be more convenient and livery patch pump) are also available volume in 1 s [FEV1]). Inhaled insulin is
comfortable for individuals to inject and (45). Inhaled insulin is available as a contraindicated in individuals with chronic
may improve treatment plan engage- rapid-acting insulin; studies in individu- lung disease, such as asthma and chronic
ment in those with insulin resistance als with type 1 diabetes suggest rapid obstructive pulmonary disease, and is not
S154 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 46, Supplement 1, January 2023
recommended in individuals who smoke options as well as recommendations for fur- 7. Bartley PC, Bogoev M, Larsen J, Philotheou A.
or who recently stopped smoking. All ther intensification, if needed, to achieve Long-term efficacy and safety of insulin detemir
compared to neutral protamine Hagedorn insulin
individuals require spirometry (FEV1) glycemic goals. When initiating combination in patients with type 1 diabetes using a treat-
testing to identify potential lung disease injectable therapy, metformin therapy to-target basal-bolus regimen with insulin aspart
prior to and after starting inhaled insulin should be maintained, while sulfonylureas at meals: a 2-year, randomized, controlled trial.
therapy. and DPP-4 inhibitors are typically weaned Diabet Med 2008;25:442–449
8. DeWitt DE, Hirsch IB. Outpatient insulin
or discontinued. In individuals with sub- therapy in type 1 and type 2 diabetes mellitus:
Combination Injectable Therapy optimal blood glucose control, especially scientific review. JAMA 2003;289:2254–2264
If basal insulin has been titrated to an those requiring large insulin doses, ad- 9. Bode BW, McGill JB, Lorber DL, Gross JL, Chang
acceptable fasting blood glucose level junctive use of a thiazolidinedione or an PC; Affinity 1 Study Group. Inhaled technosphere
(or if the dose is >0.5 units/kg/day with SGLT2 inhibitor may help to improve con- insulin compared with injected prandial insulin
in type 1 diabetes: a randomized 24-week trial.
indications of need for other therapy) trol and reduce the amount of insulin Diabetes Care 2015;38:2266–2273
multicentre, 12-week randomised trial. Lancet controlled trial. Lancet Diabetes Endocrinol www.fda.gov/drugs/drug-safety-and-availability/fda-
2018;392:1321–1329 2017;5:597–609 drug-safety-communication-fda-revises-warnings-
22. Brown SA, Kovatchev BP, Raghinaru D, et al.; 36. Mathieu C, Zinman B, Hemmingsson JU, regarding-use-diabetes-medicine-metformin-certain
iDCL Trial Research Group. Six-month randomized, et al.; ADJUNCT ONE Investigators. Efficacy and 50. Out M, Kooy A, Lehert P, Schalkwijk CA,
multicenter trial of closed-loop control in type 1 safety of liraglutide added to insulin treatment in Stehouwer CDA. Long-term treatment with
diabetes. N Engl J Med 2019;381:1707–1717 type 1 diabetes: the ADJUNCT ONE treat-to-target metformin in type 2 diabetes and methylmalonic
23. Peters AL, Laffel L (Eds.). American Diabetes randomized trial. Diabetes Care 2016;39:1702– acid: post hoc analysis of a randomized controlled
Association/JDRF Type 1 Diabetes Sourcebook. 1710 4.3-year trial. J Diabetes Complications 2018;32:
Alexandria, VA, American Diabetes Association, 37. Ahren B, Hirsch IB, Pieber TR, et al.; ADJUNCT 171–178
2013 TWO Investigators. Efficacy and safety of liraglutide 51. Aroda VR, Edelstein SL, Goldberg RB, et al.;
24. Chiang JL, Kirkman MS, Laffel LMB; Type 1 added to capped insulin treatment in subjects with Diabetes Prevention Program Research Group.
Diabetes Sourcebook Authors. Type 1 diabetes type 1 diabetes: the ADJUNCT TWO randomized Long-term metformin use and vitamin B12 deficiency
through the life span: a position statement of the trial. Diabetes Care 2016;39:1693–1701 in the Diabetes Prevention Program Outcomes Study.
American Diabetes Association. Diabetes Care 38. Dandona P, Mathieu C, Phillip M, et al.; DEPICT-1 J Clin Endocrinol Metab 2016;101:1754–1761
2014;37:2034–2054 Investigators. Efficacy and safety of dapagliflozin in 52. Henry RR, Murray AV, Marmolejo MH,
and network meta-analysis. Ann Intern Med 77. Blonde L, Merilainen M, Karwe V; TITRATE 90. Marso SP, McGuire DK, Zinman B, et al.;
2020;173:278–286 Study Group. Patient-directed titration for achieving DEVOTE Study Group. Efficacy and safety of
63. Pratley R, Amod A, Hoff ST, et al.; PIONEER 4 glycaemic goals using a once-daily basal insulin degludec versus glargine in type 2 diabetes. N
investigators. Oral semaglutide versus subcutaneous analogue: an assessment of two different fasting Engl J Med 2017;377:723–732
liraglutide and placebo in type 2 diabetes (PIONEER plasma glucose targets–the TITRATE study. Diabetes 91. Rodbard HW, Cariou B, Zinman B, et al.; BEGIN
4): a randomised, double-blind, phase 3a trial. Lancet Obes Metab 2009;11:623–631 Once Long Trial Investigators. Comparison of insulin
2019;394:39–50 78. Porcellati F, Lucidi P, Cioli P, et al. Pharma- degludec with insulin glargine in insulin-naive
64. Singh S, Wright EE Jr, Kwan AYM, et al. cokinetics and pharmacodynamics of insulin subjects with type 2 diabetes: a 2-year randomized,
Glucagon-like peptide-1 receptor agonists compared glargine given in the evening as compared with treat-to-target trial. Diabet Med 2013;30:1298–
with basal insulins for the treatment of type 2 in the morning in type 2 diabetes. Diabetes Care 1304
diabetes mellitus: a systematic review and meta- 2015;38:503–512 92. Wysham C, Bhargava A, Chaykin L, et al. Effect
analysis. Diabetes Obes Metab 2017;19:228–238 79. Wang Z, Hedrington MS, Gogitidze Joy N, et al. of insulin degludec vs insulin glargine u100 on
65. Levin PA, Nguyen H, Wittbrodt ET, Kim SC. Dose-response effects of insulin glargine in type 2 hypoglycemia in patients with type 2 diabetes: the
Glucagon-like peptide-1 receptor agonists: a diabetes. Diabetes Care 2010;33:1555–1560 SWITCH 2 randomized clinical trial. JAMA 2017;
systematic review of comparative effectiveness 80. Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett 318:45–56
injections: the STAT study. Diabetes Technol Ther 108. Maiorino MI, Chiodini P, Bellastella G, Capuano to titrated insulin glargine on glycemic control in
2018;20:639–647 A, Esposito K, Giugliano D. Insulin and glucagon-like patients with type 2 diabetes: the SURPASS-5
104. Hoogwerf BJ, Pantalone KM, Basina M, Jones peptide 1 receptor agonist combination therapy in randomized clinical trial. JAMA 2022;327:534–
MC, Grant M, Kendall DM. Results of a 24-week type 2 diabetes: a systematic review and meta- 545
trial of technosphere insulin versus insulin aspart in analysis of randomized controlled trials. Diabetes 112. Taybani Z, B otyik B, Katk
o M, Gyimesi A,
type 2 diabetes. Endocr Pract 2021;27:38–43 Care 2017;40:614–624 Varkonyi T. Simplifying complex insulin regimens
105. Grant M, Heise T, Baughman R. Comparison 109. Aroda VR, Rosenstock J, Wysham C, et al.; while preserving good glycemic control in type 2
of pharmacokinetics and pharmacodynamics of LixiLan-L Trial Investigators. Efficacy and safety of diabetes. Diabetes Ther 2019;10:1869–1878
inhaled technosphere insulin and subcutaneous LixiLan, a titratable fixed-ratio combination of 113. Rodbard HW, Visco VE, Andersen H, Hiort LC,
insulin lispro in the treatment of type 1 diabetes insulin glargine plus lixisenatide in type 2 diabetes Shu DHW. Treatment intensification with
mellitus. Clin Pharmacokinet 2022;61:413–422 inadequately controlled on basal insulin and metformin: stepwise addition of prandial insulin aspart
106. Diamant M, Nauck MA, Shaginian R, et al.; the LixiLan-L randomized trial. Diabetes Care 2016; boluses compared with full basal-bolus therapy
4B Study Group. Glucagon-like peptide 1 receptor 39:1972–1980 (FullSTEP Study): a randomised, treat-to-target
agonist or bolus insulin with optimized basal 110. Lingvay I, Perez Manghi F, Garcıa-Hernandez clinical trial. Lancet Diabetes Endocrinol 2014;2:
insulin in type 2 diabetes. Diabetes Care 2014; P, et al.; DUAL V Investigators. Effect of insulin 30–37
A recent meta-analysis indicated that and are similar to those for people with such as albuminuria. Although some vari-
SGLT2 inhibitors reduce the risk of heart type 2 diabetes. ability in calibration exists in various sub-
failure hospitalization, cardiovascular mor- As depicted in Fig. 10.1, a comprehen- groups, including by sex, race, and diabetes,
tality, and all-cause mortality in people sive approach to the reduction in risk of the overall risk prediction does not differ
with (secondary prevention) and without diabetes-related complications is recom- in those with or without diabetes (13–16),
(primary prevention) cardiovascular dis- mended. Therapy that includes multiple, validating the use of risk calculators in
ease (12). concurrent evidence-based approaches to people with diabetes. The 10-year risk of
For prevention and management of care will provide complementary reduc- a first ASCVD event should be assessed to
both ASCVD and heart failure, cardio- tion in the risks of microvascular, kidney, better stratify ASCVD risk and help guide
vascular risk factors should be systemat- neurologic, and cardiovascular complica- therapy, as described below.
ically assessed at least annually in all tions. Management of glycemia, blood Recently, risk scores and other cardio-
people with diabetes. These risk factors pressure, and lipids and the incorpora- vascular biomarkers have been devel-
oped for risk stratification of secondary
Recommendations
10.1 Blood pressure should be
measured at every routine
clinical visit. When possible,
individuals found to have ele-
vated blood pressure (systolic
blood pressure 120–129 mmHg
and diastolic <80 mmHg)
should have blood pressure
confirmed using multiple read-
Figure 10.1—Multifactorial approach to reduction in risk of diabetes complications. *Risk re- ings, including measurements
duction interventions to be applied as individually appropriate.
S160 Cardiovascular Disease and Risk Management Diabetes Care Volume 46, Supplement 1, January 2023
on a separate day, to diag- targets should be individual- of <130/80 mmHg derives primarily from
nose hypertension. A Hyper- ized through a shared decision- the collective evidence of the following
tension is defined as a systolic making process that addresses randomized controlled trials. The Systolic
blood pressure $130 mmHg cardiovascular risk, potential ad- Blood Pressure Intervention Trial (SPRINT)
or a diastolic blood pressure verse effects of antihypertensive demonstrated that treatment to a target
$80 mmHg based on an medications, and patient prefer- systolic blood pressure of <120 mmHg
average of $2 measurements ences. B decreases cardiovascular event rates
obtained on $2 occasions. A 10.4 People with diabetes and by 25% in high-risk patients, although
Individuals with blood pres- hypertension qualify for anti- people with diabetes were excluded from
sure $180/110 mmHg and hypertensive drug therapy when this trial (33). The recently completed
cardiovascular disease could the blood pressure is persistently Strategy of Blood Pressure Intervention in
be diagnosed with hyperten- elevated $130/80 mmHg. The the Elderly Hypertensive Patients (STEP)
$130 mmHg and increased cardiovascu- hypertension to a systolic blood pres- significantly reduced the risk of stroke by
lar risk and treated to a systolic blood sure target of 110 to <130 mmHg (in- 31% but did not reduce the risk of MI
pressure target of <120 mmHg (in- tensive treatment) or a target of 130 to (38). Another meta-analysis of 19 trials in-
tensive treatment) versus a target of <150 mmHg (34). In this trial, the pri- cluding 44,989 patients showed that a
<140 mmHg (standard treatment). The mary composite outcome of stroke, mean blood pressure of 133/76 mmHg is
primary composite outcome of myocar- acute coronary syndrome, acute decom- associated with a 14% risk reduction for
dial infarction (MI), coronary syndromes, pensated heart failure, coronary revas- major cardiovascular events compared with
stroke, heart failure, or death from cardio- cularization, atrial fibrillation, or death a mean blood pressure of 140/81 mmHg
vascular causes was reduced by 25% in from cardiovascular causes was reduced (32). This benefit was greatest in people
the intensive treatment group. The by 26% in the intensive treatment with diabetes. An analysis of trials includ-
achieved systolic blood pressures in the group. In this trial, 18.9% of patients in ing people with type 2 diabetes and im-
trial were 121 mmHg and 136 mmHg in the intensive treatment arm and 19.4% paired glucose tolerance with achieved
the intensive versus standard treatment systolic blood pressures of <135 mmHg
Table 10.1—Randomized controlled trials of intensive versus standard hypertension treatment strategies
Clinical trial Population Intensive Standard Outcomes
ACCORD BP (35) 4,733 participants with SBP target: SBP target: No benefit in primary end point:
T2D aged 40–79 <120 mmHg 130–140 mmHg composite of nonfatal MI, nonfatal
years with prior Achieved (mean) Achieved (mean) stroke, and CVD death
evidence of CVD or SBP/DBP: SBP/DBP: Stroke risk reduced 41% with
multiple 119.3/64.4 mmHg 135/70.5 mmHg intensive control, not sustained
cardiovascular risk through follow-up beyond the
factors period of active treatment
Adverse events more common in
intensive group, particularly
elevated serum creatinine and
electrolyte abnormalities
ACCORD BP, Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial; ACS, acute coronary syndrome; ADVANCE, Action in Diabe-
tes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AKI, acute kidney injury; CVD, cardiovascular disease; DBP, dia-
stolic blood pressure; HOT, Hypertension Optimal Treatment trial; MI, myocardial infarction; SBP, systolic blood pressure; SPRINT, Systolic
Blood Pressure Intervention Trial; STEP, Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients; T2D, type 2 diabetes.
pressure control when they have high ab- Potential adverse effects of antihyper- pressure control (43). In addition, individ-
solute cardiovascular risk. This approach is tensive therapy (e.g., hypotension, syn- uals with orthostatic hypotension, sub-
consistent with guidelines from the Ameri- cope, falls, acute kidney injury, and stantial comorbidity, functional limitations,
can College of Cardiology and Ameri- electrolyte abnormalities) should also or polypharmacy may be at high risk of
can Heart Association, which also advocate be taken into account (33,35,42,43). adverse effects, and some patients may
a blood pressure target of <130/80 mmHg Individuals with older age, CKD, and frailty prefer higher blood pressure targets
for all people, with or without diabetes have been shown to be at higher risk to enhance quality of life. However, in
(20). of adverse effects of intensive blood ACCORD BP, it was found that intensive
diabetesjournals.org/care Cardiovascular Disease and Risk Management S163
blood pressure lowering decreased the medically indicated preterm birth at increasing potassium intake,
risk of cardiovascular events irrespective <35 weeks of gestation, placental abrup- moderation of alcohol in-
of baseline diastolic blood pressure in tion, or fetal/neonatal death, occurred in take, and increased physi-
patients who also received standard gly- 30.2% of female participants in the ac- cal activity. A
cemic control (44). Therefore, the pres- tive treatment group vs. 37.0% in the
ence of low diastolic blood pressure is control group (P < 0.001). The mean
not necessarily a contraindication to systolic blood pressure between ran- Lifestyle management is an important
more intensive blood pressure man- domization and delivery was 129.5 mmHg component of hypertension treatment
agement in the context of otherwise in the active treatment group and because it lowers blood pressure, enhan-
standard care. 132.6 mmHg in the control group. ces the effectiveness of some antihyper-
Current evidence supports controlling tensive medications, promotes other
Pregnancy and Antihypertensive Medications blood pressure to 110–135/85 mmHg to aspects of metabolic and vascular health,
reduce the risk of accelerated maternal
No Yes No Yes
Figure 10.2—Recommendations for the treatment of confirmed hypertension in people with diabetes. *An ACE inhibitor (ACEi) or angiotensin receptor
blocker (ARB) is suggested to treat hypertension for people with coronary artery disease (CAD) or urine albumin-to-creatinine ratio 30–299 mg/g creati-
nine and strongly recommended for individuals with urine albumin-to-creatinine ratio $300 mg/g creatinine. **Thiazide-like diuretic; long-acting agents
shown to reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred. ***Dihydropyridine calcium channel blocker (CCB). BP,
blood pressure. Adapted from de Boer et al. (20).
the recommended blood pres- or a single-pill combination with diabetes. A ACE inhibi-
sure goal of <130/80 mmHg. A of drugs demonstrated to re- tors or angiotensin receptor
10.8 Individuals with confirmed duce cardiovascular events in blockers are recommended
office-based blood pressure people with diabetes. A first-line therapy for hyperten-
$160/100 mmHg should, in 10.9 Treatment for hypertension sion in people with diabetes
addition to lifestyle therapy, should include drug classes and coronary artery disease. A
have prompt initiation and demonstrated to reduce car- 10.10 Multiple-drug therapy is gener-
timely titration of two drugs diovascular events in people ally required to achieve blood
diabetesjournals.org/care Cardiovascular Disease and Risk Management S165
pressure targets. However, reduce the risk of progressive kidney dis- among patients with reduced glomerular
combinations of ACE inhibi- ease (20) (Fig. 10.2). In patients receiving filtration who are at increased risk of hy-
tors and angiotensin receptor ACE inhibitor or ARB therapy, continua- perkalemia and AKI (77,78,80).
blockers and combinations of tion of those medications as kidney func-
tion declines to estimated glomerular Resistant Hypertension
ACE inhibitors or angiotensin
receptor blockers with direct filtration rate (eGFR) <30 mL/min/1.73 m2
Recommendation
renin inhibitors should not be may provide cardiovascular benefit with-
10.13 Individuals with hypertension
used. A out significantly increasing the risk of
who are not meeting blood
10.11 An ACE inhibitor or angiotensin end-stage kidney disease (67). In the ab-
sence of albuminuria, risk of progressive pressure targets on three clas-
receptor blocker, at the ses of antihypertensive medi-
maximum tolerated dose in- kidney disease is low, and ACE inhibitors
and ARBs have not been found to afford cations (including a diuretic)
dicated for blood pressure should be considered for min-
application of a Mediterranean 40 years, or more frequently 10.20 For people with diabetes aged
or Dietary Approaches to Stop if indicated. E 40–75 at higher cardiovascular
Hypertension (DASH) eating 10.17 Obtain a lipid profile at initia- risk, including those with one or
pattern; reduction of saturated tion of statins or other lipid- more atherosclerotic cardiovas-
fat and trans fat; increase of di- lowering therapy, 4–12 weeks cular disease risk factors, it is
etary n-3 fatty acids, viscous fi- after initiation or a change in recommended to use high-
ber, and plant stanols/sterols dose, and annually thereafter intensity statin therapy to reduce
intake; and increased physical as it may help to monitor the LDL cholesterol by $50% of
activity should be recom- response to therapy and in- baseline and to target an LDL
mended to improve the lipid form medication taking. E cholesterol goal of <70 mg/dL. B
profile and reduce the risk of 10.21 For people with diabetes aged
developing atherosclerotic car- 40–75 years at higher cardio-
established ASCVD, intensive therapy is therapy versus simvastatin alone (105). preference) versus placebo. Evolocumab
indicated and has been shown to be of Individuals were $50 years of age, had reduced LDL cholesterol by 59% from a
benefit in multiple large meta-analyses experienced a recent acute coronary syn- median of 92 to 30 mg/dL in the treat-
and randomized cardiovascular out- drome (ACS) and were treated for an av- ment arm.
comes trials (91,99,105,107,108). High- erage of 6 years. Overall, the addition of During the median follow-up of 2.2 years,
intensity statin therapy is recommended ezetimibe led to a 6.4% relative benefit the composite outcome of cardiovascu-
for all people with diabetes and ASCVD and a 2% absolute reduction in major ad- lar death, MI, stroke, hospitalization for
to target an LDL cholesterol reduction of verse cardiovascular events (atheroscle- angina, or revascularization occurred in
$50% from baseline and an LDL choles- rotic cardiovascular events), with the 11.3% vs. 9.8% of the placebo and evo-
terol goal of <55 mg/dL. Based on the degree of benefit being directly propor- locumab groups, respectively, represent-
evidence discussed below, addition of tional to the change in LDL cholesterol, ing a 15% relative risk reduction (P <
ezetimibe or a PCSK9 inhibitor is recom- which was 70 mg/dL in the statin group 0.001). The combined end point of car-
mended if this goal is not achieved on on average and 54 mg/dL in the combi-
Participants With Atherosclerotic Cardio- Treatment of Other Lipoprotein factor (primary prevention cohort) (121).
vascular Disease and Elevated Low-density Fractions or Targets Patients were randomized to icosapent
Lipoprotein Cholesterol (ORION-10) and ethyl 4 g/day (2 g twice daily with food)
Recommendations
Inclisiran for Subjects With ASCVD or versus placebo. The trial met its primary
ASCVD-Risk Equivalents and Elevated 10.28 For individuals with fasting tri- end point, demonstrating a 25% relative
Low-density Lipoprotein Cholesterol glyceride levels $500 mg/dL, risk reduction (P < 0.001) for the primary
(ORION-11) trials (116), individuals with evaluate for secondary causes end point composite of cardiovascular
established cardiovascular disease or of hypertriglyceridemia and death, nonfatal MI, nonfatal stroke, coro-
ASCVD risk equivalent were random- consider medical therapy to re- nary revascularization, or unstable angina.
ized to receive inclisiran or placebo. Incli- duce the risk of pancreatitis. C This reduction in risk was seen in people
siran allows less frequent administration 10.29 In adults with moderate hyper- with or without diabetes at baseline. The
compared with monoclonal antibodies triglyceridemia (fasting or non- composite of cardiovascular death, nonfa-
and was administered on day 1, on fasting triglycerides 175–499 tal MI, or nonfatal stroke was reduced by
to provide additional cardio- therapy (128). A total of 25,673 individ- several lines of evidence point against
vascular benefit above statin uals with prior vascular disease were this association, as detailed in a 2018
therapy alone, may increase randomized to receive 2 g of extended- European Atherosclerosis Society Consensus
the risk of stroke with addi- release niacin and 40 mg of laropiprant Panel statement (132). First, there are three
tional side effects, and is gen- (an antagonist of the prostaglandin D2 large randomized trials of statin versus pla-
erally not recommended. A receptor DP1 that has been shown to cebo where specific cognitive tests were
improve participation in niacin therapy) performed, and no differences were seen
versus a matching placebo daily and fol- between statin and placebo (133–136). In
Statin and Fibrate Combination Therapy lowed for a median follow-up period of addition, no change in cognitive function
Combination therapy (statin and fibrate) 3.9 years. There was no significant dif- has been reported in studies with the addi-
is associated with an increased risk for ference in the rate of coronary death, tion of ezetimibe (105) or PCSK9 inhibitors
abnormal transaminase levels, myositis, MI, stroke, or coronary revascularization (108,137) to statin therapy, including
with the addition of niacin–laropiprant among patients treated to very low
should be considered for indi- bleeding, or other serious bleeding). factor (family history of premature
viduals with stable coronary During a mean follow-up of 7.4 years, ASCVD, hypertension, dyslipidemia, smok-
and/or peripheral artery dis- there was a significant 12% reduction ing, or CKD/albuminuria) who are not at
ease and low bleeding risk to in the primary efficacy end point (8.5% increased risk of bleeding (e.g., older age,
prevent major adverse limb vs. 9.6%; P = 0.01). In contrast, major anemia, renal disease) (148–151). Nonin-
and cardiovascular events. A bleeding was significantly increased from vasive imaging techniques such as coro-
10.38 Aspirin therapy (75–162 mg/day) 3.2 to 4.1% in the aspirin group (rate ra- nary calcium scoring may potentially help
may be considered as a primary tio 1.29; P = 0.003), with most of the ex- further tailor aspirin therapy, particularly
prevention strategy in those cess being gastrointestinal bleeding and in those at low risk (152,153). For people
with diabetes who are at in- other extracranial bleeding. There were >70 years of age (with or without diabe-
creased cardiovascular risk, af- no significant differences by sex, weight, tes), the balance appears to have greater
ter a comprehensive discussion or duration of diabetes or other baseline risk than benefit (144,146). Thus, for pri-
factors including ASCVD risk score. mary prevention, the use of aspirin needs
diabetes, there were no significant dif- including intracranial hemorrhage, was with rivaroxaban added to aspirin treatment
ferences in cardiovascular events or ma- noted with dual antiplatelet therapy. in both COMPASS and VOYAGER PAD.
jor bleeding between patients assigned The net clinical benefit (ischemic benefit The risks and benefits of dual antiplate-
to 81 mg and those assigned to 325 mg vs. bleeding risk) was improved with ti- let or antiplatelet plus anticoagulant treat-
of aspirin daily (156). In the U.S., the cagrelor therapy in the large prespeci- ment strategies should be thoroughly
most common low-dose tablet is 81 mg. fied subgroup of patients with history discussed with eligible patients, and
Although platelets from people with di- of percutaneous coronary intervention, shared decision-making should be used
abetes have altered function, it is un- while no net benefit was seen in pa- to determine an individually appropriate
clear what, if any, effect that finding has tients without prior percutaneous coro- treatment approach. This field of cardio-
on the required dose of aspirin for car- nary intervention (165). However, early vascular risk reduction is evolving rapidly,
dioprotective effects in people with dia- aspirin discontinuation compared with as are the definitions of optimal care for
betes. Many alternate pathways for continued dual antiplatelet therapy af- patients with differing types and circum-
platelet activation exist that are inde- stances of cardiovascular complications.
Table 10.3A—Cardiovascular and cardiorenal outcomes trials of available antihyperglycemic medications completed after
the issuance of the FDA 2008 guidelines: DPP-4 inhibitors
SAVOR-TIMI 53 (224) EXAMINE (235) TECOS (226) CARMELINA (193,236) CAROLINA (193,237)
(n = 16,492) (n = 5,380) (n = 14,671) (n = 6,979) (n = 6,042)
Intervention Saxagliptin/placebo Alogliptin/placebo Sitagliptin/placebo Linagliptin/placebo Linagliptin/
glimepiride
Main inclusion Type 2 diabetes and Type 2 diabetes and Type 2 diabetes and Type 2 diabetes and Type 2 diabetes and
criteria history of or ACS within 15–90 preexisting CVD high CV and renal high CV risk
multiple risk days before risk
factors for CVD randomization
A1C inclusion $6.5 6.5–11.0 6.5–8.0 6.5–10.0 6.5–8.5
criteria (%)
—, not assessed/reported; ACS, acute coronary syndrome; CHF, congestive heart failure; CV, cardiovascular; CVD, cardiovascular disease;
DPP-4, dipeptidyl peptidase 4; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GLP-1, glucagon-like peptide 1; HF,
heart failure; MACE, major adverse cardiovascular event; MI, myocardial infarction; UL, upper limit. Data from this table was adapted from
Cefalu et al. (238) in the January 2018 issue of Diabetes Care. †Age was reported as means in all trials except EXAMINE, which reported me-
dians; diabetes duration was reported as means in all trials except SAVOR-TIMI 53 and EXAMINE, which reported medians. ‡Significant differ-
ence in A1C between groups (P < 0.05). §Outcomes reported as hazard ratio (95% CI). jjWorsening nephropathy is defined as a doubling of
creatinine level, initiation of dialysis, renal transplantation, or creatinine >6.0 mg/dL (530 mmol/L) in SAVOR-TIMI 53. Worsening nephropathy
was a prespecified exploratory adjudicated outcome in SAVOR-TIMI 53.
S174
Table 10.3B—Cardiovascular and cardiorenal outcomes trials of available antihyperglycemic medications completed after the issuance of the FDA 2008 guidelines: GLP-1
receptor agonists
ELIXA (208) LEADER (203) SUSTAIN-6 (204)* EXSCEL (209) REWIND (207) PIONEER-6 (205)
(n = 6,068) (n = 9,340) (n = 3,297) (n = 14,752) (n = 9,901) (n = 3,183)
Intervention Lixisenatide/placebo Liraglutide/placebo Semaglutide s.c. Exenatide QW/ Dulaglutide/ Semaglutide oral/
injection/placebo placebo placebo placebo
Main inclusion criteria Type 2 diabetes and Type 2 diabetes and Type 2 diabetes and Type 2 diabetes Type 2 diabetes and Type 2 diabetes and high
history of ACS preexisting CVD, preexisting CVD, with or without prior ASCVD CV risk (age of $50
Cardiovascular Disease and Risk Management
(<180 days) CKD, or HF at HF, or CKD at preexisting CVD event or risk years with established
$50 years of age $50 years of age factors for ASCVD CVD or CKD, or age of
or CV risk at $60 or CV risk at $60 $60 years with CV
years of age years of age risk factors only)
A1C inclusion criteria (%) 5.5–11.0 $7.0 $7.0 6.5–10.0 #9.5 None
Age (years)† 60.3 64.3 64.6 62 66.2 66
Race (% White) 75.2 77.5 83.0 75.8 75.7 72.3
Sex (% male) 69.3 64.3 60.7 62 53.7 68.4
Diabetes duration (years)† 9.3 12.8 13.9 12 10.5 14.9
Median follow-up (years) 2.1 3.8 2.1 3.2 5.4 1.3
Statin use (%) 93 72 73 74 66 85.2 (all lipid-lowering)
Metformin use (%) 66 76 73 77 81 77.4
Prior CVD/CHF (%) 100/22 81/18 60/24 73.1/16.2 32/9 84.7/12.2
Mean baseline A1C (%) 7.7 8.7 8.7 8.0 7.4 8.2
Mean difference in A1C 0.3‡^ 0.4‡ 0.7 or 1.0^ 0.53‡^ 0.61‡ 0.7
between groups at end of
treatment (%)
Year started/reported 2010/2015 2010/2016 2013/2016 2010/2017 2011/2019 2017/2019
Primary outcome§ 4-point MACE 1.02 3-point MACE 0.87 3-point MACE 0.74 3-point MACE 0.91 3-point MACE 0.88 3-point MACE 0.79
(0.89–1.17) (0.78–0.97) (0.58–0.95) (0.83–1.00) (0.79–0.99) (0.57–1.11)
Continued o
Diabetes Care Volume 46, Supplement 1, January 2023
0.87 (0.79–0.95)
Cardiovascular death§ 0.98 (0.78–1.22) 0.78 (0.66–0.93) 0.98 (0.65–1.48) 0.88 (0.76–1.02) 0.91 (0.78–1.06) 0.49 (0.27–0.92)
Ml§ 1.03 (0.87–1.22) 0.86 (0.73–1.00) 0.74 (0.51–1.08) 0.97 (0.85–1.10) 0.96 (0.79–1.15) 1.18 (0.73–1.90)
Stroke§ 1.12 (0.79–1.58) 0.86 (0.71–1.06) 0.61 (0.38–0.99) 0.85 (0.70–1.03) 0.76 (0.61–0.95) 0.74 (0.35–1.57)
HF hospitalization§ 0.96 (0.75–1.23) 0.87 (0.73–1.05) 1.11 (0.77–1.61) 0.94 (0.78–1.13) 0.93 (0.77–1.12) 0.86 (0.48–1.55)
Unstable angina hospitalization§ 1.11 (0.47–2.62) 0.98 (0.76–1.26) 0.82 (0.47–1.44) 1.05 (0.94–1.18) 1.14 (0.84–1.54) 1.56 (0.60–4.01)
All-cause mortality§ 0.94 (0.78–1.13) 0.85 (0.74–0.97) 1.05 (0.74–1.50) 0.86 (0.77–0.97) 0.90 (0.80–1.01) 0.51 (0.31–0.84)
Worsening nephropathy§jj — 0.78 (0.67–0.92) 0.64 (0.46–0.88) — 0.85 (0.77–0.93) —
—, not assessed/reported; ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CHF, congestive heart failure; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovas-
cular disease; GLP-1, glucagon-like peptide 1; HF, heart failure; MACE, major adverse cardiovascular event; Ml, myocardial infarction. Data from this table was adapted from Cefalu et al. (238) in the
January 2018 issue of Diabetes Care. *Powered to rule out a hazard ratio of 1.8; superiority hypothesis not prespecified. †Age was reported as means in all trials; diabetes duration was reported as
means in all trials except EXSCEL, which reported medians. ‡Significant difference in A1C between groups (P < 0.05). ^AIC change of 0.66% with 0.5 mg and 1.05% with 1 mg dose of semaglutide.
§Outcomes reported as hazard ratio (95% Cl). jjWorsening nephropathy is defined as the new onset of urine albumin-to-creatinine ratio >300 mg/g creatinine or a doubling of the serum creatinine
level and an estimated glomerular filtration rate of <45 mL/min/1.73 m2, the need for continuous renal replacement therapy, or death from renal disease in LEADER and SUSTAIN-6 and as new macro-
albuminuria, a sustained decline in estimated glomerular filtration rate of 30% or more from baseline, or chronic renal replacement therapy in REWIND. Worsening nephropathy was a prespecified ex-
ploratory adjudicated outcome in LEADER, SUSTAIN-6, and REWIND.
lar events. A
cular death. A
hospitalization. A
kidney events. A
Cardiovascular Disease and Risk Management
is recommended to improve
reduced ejection fraction, a
symptoms, physical limita- testing and are unable to exercise should cardiovascular risk assessment in people
tions, and quality of life. A undergo pharmacologic stress echocardi- with type 2 diabetes (183), their routine
10.43 For people with type 2 diabe- ography or nuclear imaging. use leads to radiation exposure and may
tes and chronic kidney disease result in unnecessary invasive testing such
with albuminuria treated with Screening Asymptomatic Patients as coronary angiography and revasculariza-
maximum tolerated doses of The screening of asymptomatic patients tion procedures. The ultimate balance of
ACE inhibitor or angiotensin with high ASCVD risk is not recom- benefit, cost, and risks of such an ap-
receptor blocker, addition of mended (171), in part because these proach in asymptomatic patients re-
finerenone is recommended high-risk patients should already be re- mains controversial, particularly in the
to improve cardiovascular out- ceiving intensive medical therapy—an modern setting of aggressive ASCVD
comes and reduce the risk of approach that provides benefit similar risk factor control.
chronic kidney disease pro- to invasive revascularization (172,173).
in people with CKD is included in trials, 10,142 participants with type 2 dia- in the canagliflozin and placebo groups, re-
Section 11, “Chronic Kidney Disease betes were randomized to canagliflozin or spectively (HR 10.80 [95% CI 1.39–83.65])
and Risk Management.” placebo and were followed for an average (194).
Cardiovascular outcomes trials of di- 3.6 years. The mean age of patients was The Dapagliflozin Effect on Cardiovas-
peptidyl peptidase 4 (DPP-4) inhibitors 63 years, and 66% had a history of cardio- cular Events-Thrombosis in Myocardial In-
have all, so far, not shown cardiovascular vascular disease. The combined analysis of farction 58 (DECLARE-TIMI 58) trial was
benefits relative to placebo. In addition, the two trials found that canagliflozin sig- another randomized, double-blind trial
the CAROLINA (Cardiovascular Outcome nificantly reduced the composite outcome that assessed the effects of dapagliflozin
Study of Linagliptin Versus Glimepiride in of cardiovascular death, MI, or stroke ver- versus placebo on cardiovascular and
Type 2 Diabetes) study demonstrated sus placebo (occurring in 26.9 vs. 31.5 par- renal outcomes in 17,160 people with
noninferiority between a DPP-4 inhibitor, ticipants per 1,000 patient-years; HR 0.86 type 2 diabetes and established ASCVD
linagliptin, and a sulfonylurea, glimepir- [95% CI 0.75–0.97]). The specific estimates or multiple risk factors for ASCVD (196).
ide, on cardiovascular outcomes despite for canagliflozin versus placebo on the pri- Study participants had a mean age of
Table 10.3C—Cardiovascular and cardiorenal outcomes trials of available antihyperglycemic medications completed after the issuance of the FDA 2008 guidelines: SGLT2
inhibitors
DAPA-CKD EMPEROR-Reduced EMPEROR-Preserved
EMPA-REG CANVAS DECLARE-TIMI 58 (197,239) DAPA-HF (11) (200) (189,241) DELIVER (199)
OUTCOME (8) Program (9) (196) CREDENCE (194) (n = 4,304; 2,906 VERTIS CV (201,240) (n = 4,744; 1,983 (n = 3,730; 1,856 (n = 5,988; 2,938 with (n = 6,263; 2,807
(n = 7,020) (n = 10,142) (n = 17,160) (n = 4,401) with diabetes) (n = 8,246) with diabetes) with diabetes) diabetes) with diabetes)
Intervention Empagliflozin/placebo Canagliflozin/placebo Dapagliflozin/placebo Canagliflozin/placebo Dapagliflozin/placebo Ertugliflozin/placebo Dapagliflozin/placebo Empagliflozin/placebo* Empagliflozin/placebo Dapagliflozin/placebo
Main inclusion Type 2 diabetes and Type 2 diabetes and Type 2 diabetes and Type 2 diabetes Albuminuric kidney Type 2 diabetes and NYHA class II, III, or NYHA class II, III, or NYHA class II, III, or IV NYHA class II, III, or IV
criteria preexisting CVD preexisting CVD at established ASCVD and albuminuric disease, with or ASCVD IV heart failure IV heart failure heart failure and an heart failure and an
$30 years of age or multiple risk kidney disease without diabetes and an ejection and an ejection ejection fraction ejection fraction
or $2 CV risk factors for ASCVD fraction #40%, fraction #40%, >40% >40% with or
Cardiovascular Disease and Risk Management
Age (years)† 63.1 63.3 64.0 63 61.8 64.4 66 67.2, 66.5 71.8, 71.9 71.7
Race (% White) 72.4 78.3 79.6 66.6 53.2 87.8 70.3 71.1, 69.8 76.3, 75.4 71.2
Sex (% male) 71.5 64.2 62.6 66.1 66.9 70 76.6 76.5, 75.6 55.4, 55.3 56.1
Median follow-up 3.1 3.6 4.2 2.6 2.4 3.5 1.5 1.3 2.2 2.3
(years)
Prior CVD/CHF (%) 99/10 65.6/14.4 40/10 50.4/14.8 37.4/10.9 99.9/23.1 100% with CHF 100% with CHF 100% with CHF 100% with CHF
Mean baseline 8.1 8.2 8.3 8.3 7.1% (7.8% in those 8.2 — — — 6.6
A1C (%) with diabetes)
Year started/reported 2010/2015 2009/2017 2013/2018 2017/2019 2017/2020 2013/2020 2017/2019 2017/2020 2017/2020 2018/2022
Continued on p. S179
Diabetes Care Volume 46, Supplement 1, January 2023
CV death or HF death from renal death from renal from CV causes 0.75 (0.65–0.86) (0.69–0.90) (0.73–0.92)
hospitalization or CV cause 0.70 or CV cause 0.61 0.74 (0.65–0.85)
0.83 (0.73–0.95) (0.59–0.82) (0.51–0.72) Results did not differ
by diabetes status
Key secondary 4-point MACE 0.89 All-cause and CV Death from any cause CV death or HF $50% decline in CV death or HF CV death or HF Total HF All HF hospitalizations Total number
outcome§ (0.78–1.01) mortality (see 0.93 (0.82–1.04) hospitalization eGFR, ESKD, or hospitalization hospitalization hospitalizations (first and recurrent) worsening HF and
below) Renal composite 0.69 (0.57–0.83) death from renal 0.88 (0.75–1.03) 0.75 (0.65–0.85) 0.70 (0.58–0.85) 0.73 (0.61–0.88) CV deaths 0.77
($40% decrease in 3-point MACE 0.80 cause 0.56 CV death 0.92 Mean slope of Rate of decline in eGFR (0.67–0.89)
eGFR rate to <60 (0.67–0.95) (0.45–0.68) (0.77–1.11) change in eGFR (1.25 vs. 2.62 Change in KCCQ TSS
mL/min/1.73 m2, CV death or HF Renal death, renal 1.73 (1.10–2.37) mL/min/1.73 m2; at month 8 1.11
new ESRD, or hospitalization replacement P < 0.001) (1.03–1.21)
death from renal 0.71 (0.55–0.92) therapy, or Mean change in
or CV causes 0.76 Death from any doubling of KCCQ TSS 2.4
(0.67–0.87) cause 0.69 creatinine 0.81 (1.5–3.4)
(0.53–0.88) (0.63–1.04) All-cause mortality
0.94 (0.83–1.07)
Cardiovascular death§ 0.62 (0.49–0.77) 0.87 (0.72–1.06) 0.98 (0.82–1.17) 0.78 (0.61–1.00) 0.81 (0.58–1.12) 0.92 (0.77–1.11) 0.82 (0.69–0.98) 0.92 (0.75–1.12) 0.91 (0.76–1.09) 0.88 (0.74–1.05)
HF hospitalization§ 0.65 (0.50–0.85) 67 (0.52–0.87) 0.73 (0.61–0.88) 0.61 (0.47–0.80) — 0.70 (0.54–0.90) 0.70 (0.59–0.83) 0.69 (0.59–0.81) 0.73 (0.61–0.88) 0.77 (0.67–0.89)
All-cause mortality§ 0.68 (0.57–0.82) 87 (0.74–1.01) 0.93 (0.82–1.04) 0.83 (0.68–1.02) 0.69 (0.53–0.88) 0.93 (0.80–1.08) 0.83 (0.71–0.97) 0.92 (0.77–1.10) 1.00 (0.87–1.15) 0.94 (0.83–1.07)
Worsening 0.61 (0.53–0.70) 0.60 (0.47–0.77) 0.53 (0.43–0.66) (See primary (See primary (See secondary 0.71 (0.44–1.16) Composite renal Composite renal —
nephropathy§jj outcome) outcome) outcomes) outcome 0.50 outcome** 0.95
(0.32–0.77) (0.73–1.24)
—, not assessed/reported; CHF, congestive heart failure; CV, cardiovascular; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; HF, heart failure;
KCCQ TSS, Kansas City Cardiomyopathy Questionnaire Total Symptom Score; MACE, major adverse cardiovascular event; Ml, myocardial infarction; SGLT2, sodium–glucose cotransporter 2; NYFIA, New
York Fleart Association. Data from this table was adapted from Cefalu et al. (238) in the January 2018 issue of Diabetes Care. *Baseline characteristics for EMPEROR-Reduced displayed as empagliflozin,
placebo. †Age was reported as means in all trials; diabetes duration was reported as means in all trials except EMPA-REG OUTCOME, which reported as percentage of population with diabetes duration
>10 years, and DECLARE-TIMI 58, which reported median. ‡Significant difference in A1C between groups (P < 0.05). ^AIC change of 0.30 in EMPA-REG OUTCOME is based on pooled results for both
doses (i.e., 0.24% for 10 mg and 0.36% for 25 mg of empagliflozin). §Outcomes reported as hazard ratio (95% Cl). jjDefinitions of worsening nephropathy differed between trials. **Composite outcome
in EMPEROR-Preserved: time to first occurrence of chronic dialysis, renal transplantation; sustained reduction of $40% in eGFR, sustained eGFR <15 mL/min/1.73 m2 for individuals with baseline eGFR
$30 mL/min/1.73 m2.
Cardiovascular Disease and Risk Management
S179
or hospitalization for heart failure (HR Sotagliflozin, an SGLT1 and SGLT2 in- people with type 2 diabetes at high risk
0.71 [95% CI 0.55–0.92]). The effects of hibitor not currently approved by the for cardiovascular disease or with cardio-
dapagliflozin therapy were similar in FDA in the U.S., lowers glucose via de- vascular disease (203). Study participants
individuals with and without type 2 layed glucose absorption in the gut in had a mean age of 64 years and a mean
diabetes. addition to increasing urinary glucose duration of diabetes of nearly 13 years.
Results of the Dapagliflozin and Pre- excretion and has been evaluated in the Over 80% of study participants had estab-
vention of Adverse Outcomes in Heart Effect of Sotagliflozin on Cardiovascular lished cardiovascular disease. After a
Failure (DAPA-HF) trial, the Empagliflozin and Renal Events in Patients With median follow-up of 3.8 years, LEADER
Outcome Trial in Patients With Chronic Type 2 Diabetes and Moderate Renal Im- showed that the primary composite out-
Heart Failure and a Reduced Ejection pairment Who Are at Cardiovascular Risk come (MI, stroke, or cardiovascular death)
Fraction (EMPEROR-Reduced), Empagli- (SCORED) trial (202). A total of 10,584 occurred in fewer participants in the
flozin Outcome Trial in Patients With people with type 2 diabetes, CKD, and ad- treatment group (13.0%) when com-
Chronic Heart Failure With Preserved ditional cardiovascular risk were enrolled
for noninferiority) (205). The cardiovascu- outcome of cardiovascular death, MI, diabetes and established ASCVD (210,211).
lar effects of this formulation of sema- stroke, or hospitalization for unstable SGLT2 inhibitors also reduce risk of heart
glutide will be further tested in a large, angina occurred in 406 patients (13.4%) failure hospitalization and progression of
longer-term outcomes trial. in the lixisenatide group vs. 399 (13.2%) kidney disease in people with established
The Harmony Outcomes trial random- in the placebo group (HR 1.2 [95% CI ASCVD, multiple risk factors for ASCVD, or
ized 9,463 people with type 2 diabetes 0.89–1.17]), which demonstrated the albuminuric kidney disease (212,213). In
and cardiovascular disease to once-weekly noninferiority of lixisenatide to placebo people with type 2 diabetes and estab-
subcutaneous albiglutide or matching pla- (P < 0.001) but did not show superior- lished ASCVD, multiple ASCVD risk factors,
cebo, in addition to their standard care ity (P = 0.81). or diabetic kidney disease, an SGLT2 inhibi-
(206). Over a median duration of 1.6 The Exenatide Study of Cardiovascular tor with demonstrated cardiovascular ben-
years, the GLP-1 receptor agonist reduced Event Lowering (EXSCEL) trial also reported efit is recommended to reduce the risk of
the risk of cardiovascular death, MI, or results with the once-weekly GLP-1 recep- major adverse cardiovascular events and/
stroke to an incidence rate of 4.6 events tor agonist extended-release exenatide or heart failure hospitalization. In people
associated with increased morbidity and agonists lixisenatide, liraglutide, sema- placebo on a primary composite outcome
mortality, commonly coincide, and inde- glutide, exenatide once-weekly, albi- of cardiovascular death or hospitalization
pendently contribute to adverse out- glutide, or dulaglutide compared with for worsening heart failure in a population
comes (217). Strategies to mitigate these placebo (Table 10.3B) (203,204,207–209). of 3,730 patients with NYHA class II, III, or
risks are needed, and the heart failure- Reduced incidence of heart failure IV heart failure and an ejection fraction of
related risks and benefits of glucose- has been observed with the use of 40% or less (200). At baseline, 49.8% of
lowering medications should be considered SGLT2 inhibitors (8,194,196). In EMPA- participants had a history of diabetes.
carefully when determining a regimen of REG OUTCOME, the addition of empagli- Over a median follow-up of 16 months,
care for people with diabetes and either flozin to standard care led to a signifi- those in the empagliflozin-treated group
established heart failure or high risk for cant 35% reduction in hospitalization for had a reduced risk of the primary outcome
the development of heart failure. heart failure compared with placebo (8). (HR 0.75 [95% CI 0.65–0.86]; P < 0.001)
Data on the effects of glucose-lowering Although the majority of patients in the and fewer total hospitalizations for heart
agents on heart failure outcomes have study did not have heart failure at base- failure (HR 0.70 [95% CI 0.58–0.85]; P <
Post Worsening Heart Failure (SOLOIST- vs. 3.4%) and severe hypoglycemia of worsening heart failure and cardiovas-
WHF) included 21,947 patients and dem- (1.5% vs. 0.3%) were more common cular death. In addition, an SGLT2 inhibitor
onstrated reduced risk for the composite with sotagliflozin than with placebo. The is recommended in this patient population
of cardiovascular death or hospitalization trial was originally also intended to to improve symptoms, physical limitations,
for heart failure, cardiovascular death, first evaluate the effects of SGLT inhibition and quality of life. The benefits seen in
hospitalization for heart failure, and all- in people with HFpEF, and ultimately no this patient population likely represent a
cause mortality. The findings on the stud- evidence of heterogeneity of treatment class effect, and they appear unrelated to
ied end points were consistent in both tri- effect by ejection fraction was noted. glucose lowering given comparable out-
als of heart failure with mildly reduced or However, the relatively small percent- comes in people with heart failure with
preserved ejection fraction and in all five age of such patients enrolled (only 21% and without diabetes.
trials combined. Collectively, these studies of participants had ejection fraction
indicate that SGLT2 inhibitors reduce the >50%) and the early termination of the Finerenone in People With Type 2 Diabetes
risk for heart failure hospitalization and trial limited the ability to determine the
inhibitor or ARB, addition of finernone College of Cardiology “2020 Expert Con- individuals with more long-standing dia-
should be considered to improve car- sensus Decision Pathway on Novel betes may be more challenging, particu-
diovascular outcomes and reduce the Therapies for Cardiovascular Risk Re- larly if patients are using an already
risk of CKD progression. duction in Patients With Type 2 Dia- complex glucose-lowering regimen. In
betes” (234). Figure 10.3, reproduced such patients, SGLT2 inhibitor or GLP-1
Clinical Approach from that decision pathway, outlines receptor agonist therapy may need to
As has been carefully outlined in Fig. 9.3 the approach to risk reduction with replace some or all of their existing med-
in the preceding Section 9, “Pharmacologic SGLT2 inhibitor or GLP-1 receptor ago- ications to minimize risks of hypoglyce-
Approaches to Glycemic Treatment,” peo- nist therapy in conjunction with other mia and adverse side effects, and
ple with type 2 diabetes with or at high traditional, guideline-based preventive potentially to minimize medication
risk for ASCVD, heart failure, or CKD medical therapies for blood pressure, costs. Close collaboration between pri-
should be treated with a cardioprotective lipids, and glycemia and antiplatelet mary and specialty care professionals
SGLT2 inhibitor and/or GLP-1 receptor ago- therapy. can help to facilitate these transitions in
nist as part of the comprehensive ap- Adoption of these agents should be clinical care and, in turn, improve out-
proach to cardiovascular and kidney risk reasonably straightforward in people with comes for highrisk people with type 2
reduction. Importantly, these agents established cardiovascular or kidney dis- diabetes.
should be included in the regimen of care ease who are later diagnosed with dia-
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393:31–39 availability/fda-drug-safety-communication- EXAMINE Investigators. Alogliptin after acute
with severely increased al- normal urinary albumin-to- 11.5b For people with type 2 diabe-
buminuria (urinary albumin- creatinine ratio (<30 mg/g tes and diabetic kidney dis-
to-creatinine ratio $300 mg/g creatinine), and normal esti- ease, use of a sodium–glucose
creatinine) and/or estimated mated glomerular filtration cotransporter 2 inhibitor is rec-
glomerular filtration rate rate. A ommended to reduce chronic
<60 mL/min/1.73 m2 . A 11.4d Do not discontinue renin- kidney disease progression
11.4b Periodically monitor serum cre- angiotensin system blockade and cardiovascular events in
atinine and potassium levels for increases in serum creati- patients with an estimated
for the development of in- nine (#30%) in the absence glomerular filtration rate $20
creased creatinine and hyper- of volume depletion. A mL/min/1.73 m2 and urinary
kalemia when ACE inhibitors, 11.5a For people with type 2 diabe- albumin ranging from normal
angiotensin receptor blockers, tes and diabetic kidney dis- to 200 mg/g creatinine. B
and mineralocorticoid receptor ease, use of a sodium–glucose 11.5c In people with type 2 diabetes
antagonists are used, or hypo- cotransporter 2 inhibitor is rec- and diabetic kidney disease,
kalemia when diuretics are ommended to reduce chronic consider use of sodium–glucose
used. B kidney disease progression cotransporter 2 inhibitors (if
11.4c An ACE inhibitor or an angio- and cardiovascular events in estimated glomerular filtration
tensin receptor blocker is not patients with an estimated rate is $20 mL/min/1.73 m2),
recommended for the primary glomerular filtration rate a glucagon-like peptide 1 ago-
prevention of chronic kidney $20 mL/min/1.73 m2 and nist, or a nonsteroidal mineralo-
disease in people with diabetes urinary albumin $200 mg/g corticoid receptor antagonist
who have normal blood pressure, creatinine. A (if estimated glomerular filtration
diabetesjournals.org/care Chronic Kidney Disease and Risk Management S193
rate is $25 mL/min/1.73 m2) (diabetic kidney disease) in adults, >20% between measurements in uri-
additionally for cardiovascular which occurs in 20–40% of people with nary albumin excretion, two of three
risk reduction. A diabetes (1,3–5). Diabetic kidney disease specimens of UACR collected within a
11.5d In people with chronic kidney typically develops after a diabetes dura- 3- to 6-month period should be abnormal
disease and albuminuria who tion of 10 years in type 1 diabetes (the before considering a patient to have
are at increased risk for cardio- most common presentation is 5–15 years moderately or severely elevated albu-
vascular events or chronic kidney after the diagnosis of type 1 diabetes) minuria (1,2,13,14). Exercise within 24 h,
disease progression, a nonsteroi- but may be present at diagnosis of type 2 infection, fever, congestive heart failure,
dal mineralocorticoid receptor diabetes. CKD can progress to end-stage marked hyperglycemia, menstruation,
antagonist shown to be effective renal disease (ESRD) requiring dialysis or and marked hypertension may elevate
kidney transplantation and is the leading UACR independently of kidney damage
in clinical trials is recommended
cause of ESRD in the U.S. (6). In addition, (15).
to reduce chronic kidney disease
Traditionally, eGFR is calculated from
diabetic kidney disease may be present possible causes other than diabetes) Lastly, it should be noted that ACE
at diagnosis or without retinopathy in may also affect these decisions (24). inhibitors and ARBs are commonly not
type 2 diabetes. Reduced eGFR without dosed at maximum tolerated doses
albuminuria has been frequently re- ACUTE KIDNEY INJURY because of fear that serum creatinine
ported in type 1 and type 2 diabetes will rise. As noted above, this is an error.
Acute kidney injury (AKI) is diagnosed by
and is becoming more common over Note that in all clinical trials demonstrat-
time as the prevalence of diabetes in- a 50% or greater sustained increase in se-
rum creatinine over a short period of ing efficacy of ACE inhibitors and ARBs in
creases in the U.S. (3,4,18,19). slowing kidney disease progression, the
An active urinary sediment (containing time, which is also reflected as a rapid
decrease in eGFR (25,26). People with di- maximum tolerated doses were used—
red or white blood cells or cellular casts), not very low doses that do not provide
rapidly increasing albuminuria or total abetes are at higher risk of AKI than
benefit. Moreover, there are now studies
proteinuria, the presence of nephrotic those without diabetes (27). Other risk
demonstrating outcome benefits on both
syndrome, rapidly decreasing eGFR, or factors for AKI include preexisting CKD,
mortality and slowed CKD progression in
kidney function may be detected by in- Assessment of Comorbidities,” for further Glycemic Targets
information on immunization). Intensive lowering of blood glucose with
creases in albuminuria before changes
the goal of achieving near-normoglycemia
in eGFR (43), and this also significantly
Prevention has been shown in large randomized
affects cardiovascular risk. Moreover, an
The only proven primary prevention inter- studies to delay the onset and pro-
initial reduction of >30% from baseline,
ventions for CKD are blood glucose and gression of albuminuria and reduce
subsequently maintained over at least 2 eGFR in people with type 1 diabetes
blood pressure control. There is no evi-
years, is considered a valid surrogate for (51,52) and type 2 diabetes (1,53–58).
dence that renin-angiotensin-aldosterone
renal benefit by the Division of Cardiology Insulin alone was used to lower blood
system (RAAS) inhibitors or any other
and Nephrology of the U.S. Food and glucose in the Diabetes Control and
interventions prevent the development
Drug Administration (FDA) (10). Contin- of diabetic kidney disease. Thus, the Complications Trial (DCCT)/Epidemiology
ued surveillance can assess both response American Diabetes Association does of Diabetes Interventions and Complica-
to therapy and disease progression and not recommend routine use of these tions (EDIC) study of type 1 diabetes,
may aid in assessing participation in ACE medications solely for the purpose of while a variety of agents were used
inhibitor or ARB therapy. In addition, in prevention of the development of di- in clinical trials of type 2 diabetes,
clinical trials of ACE inhibitors or ARB abetic kidney disease. supporting the conclusion that lower-
therapy in type 2 diabetes, reducing albu- ing blood glucose itself helps prevent
minuria to levels <300 mg/g creatinine INTERVENTIONS CKD and its progression. The effects
or by >30% from baseline has been asso- Nutrition of glucose-lowering therapies on CKD
ciated with improved renal and cardiovas- For people with non-dialysis-dependent have helped define A1C targets (see
CKD, dietary protein intake should be Table 6.2).
cular outcomes, leading some to suggest
0.8 g/kg body weight per day (the rec- The presence of CKD affects the risks
that medications should be titrated to
ommended daily allowance) (1). Com- and benefits of intensive lowering of
maximize reduction in UACR. Data from
pared with higher levels of dietary protein blood glucose and a number of specific
post hoc analyses demonstrate less ben- glucose-lowering medications. In the Ac-
intake, this level slowed GFR decline with
efit on cardiorenal outcomes at half tion to Control Cardiovascular Risk in Dia-
evidence of a greater effect over time.
doses of RAS blockade (44). In type 1 di- betes (ACCORD) trial of type 2 diabetes,
Higher levels of dietary protein intake
abetes, remission of albuminuria may (>20% of daily calories from protein or adverse effects of intensive management
occur spontaneously, and cohort studies >1.3 g/kg/day) have been associated of blood glucose levels (hypoglycemia
evaluating associations of change in al- with increased albuminuria, more rapid and mortality) were increased among
buminuria with clinical outcomes have kidney function loss, and CVD mortality people with kidney disease at baseline
reported inconsistent results (45,46). and therefore should be avoided. Reduc- (59,60). Moreover, there is a lag time
The prevalence of CKD complications ing the amount of dietary protein below of at least 2 years in type 2 diabetes to
correlates with eGFR (42). When eGFR is the recommended daily allowance of over 10 years in type 1 diabetes for the
<60 mL/min/1.73 m2, screening for 0.8 g/kg/day is not recommended be- effects of intensive glucose control to
complications of CKD is indicated (Table cause it does not alter blood glucose manifest as improved eGFR outcomes
11.1). Early vaccination against hepatitis levels, cardiovascular risk measures, or (56,60,61). Therefore, in some people
B virus is indicated in individuals likely the course of GFR decline (47). with prevalent CKD and substantial co-
to progress to ESRD (see Section 4, Restriction of dietary sodium (to <2,300 morbidity, target A1C levels may be less
“Comprehensive Medical Evaluation and mg/day) may be useful to control blood intensive (1,62).
S196 Chronic Kidney Disease and Risk Management Diabetes Care Volume 46, Supplement 1, January 2023
Blood Pressure and Use of RAAS moderately increased albuminuria with- selecting antihyperglycemia agents (see
Inhibitors out hypertension, outcome trials have Section 9, “Pharmacologic Approaches to
RAAS inhibition remains a mainstay of not been performed in this setting to Glycemic Treatment”).
management for people with diabetic determine whether they improve renal
kidney disease with albuminuria and for outcomes. Moreover, two long-term, dou- Selection of Glucose-Lowering
the treatment of hypertension in people ble-blind studies demonstrated no reno- Medications for People With Chronic
with diabetes (with or without diabetic protective effect of either ACE inhibitors Kidney Disease
kidney disease). Indeed, all the trials or ARBs in type 1 and type 2 diabetes For people with type 2 diabetes and es-
that evaluated the benefits of SGLT2 in- among those who were normotensive tablished CKD, special considerations for
hibition or nonsteroidal mineralocorti- with or without high albuminuria (for- the selection of glucose-lowering medica-
coid receptor antagonist effects were merly microalbuminuria) (78,79). tions include limitations to available med-
done in individuals who were being Absent kidney disease, ACE inhibitors ications when eGFR is diminished and a
treated with an ACE inhibitor or ARB, in or ARBs are useful to manage blood desire to mitigate risks of CKD progres-
A number of large cardiovascular out- (28). Additionally, the development of 0.55–0.92; P 5 0.009). Finally, all-cause
comes trials in people with type 2 dia- the primary end point, which included mortality was decreased in the dapagli-
betes at high risk for CVD or with chronic dialysis for $30 days, kidney flozin group compared with the placebo
existing CVD examined kidney effects as transplantation or eGFR <15 mL/min/ group (P < 0.004).
secondary outcomes. These trials in- 1.73 m2 sustained for $30 days by cen- In addition to renal effects, while
clude EMPA-REG OUTCOME [BI 10773 tral laboratory assessment, doubling SGLT2 inhibitors demonstrated reduced
(Empagliflozin) Cardiovascular Outcome from the baseline serum creatinine aver- risk of heart failure hospitalizations,
Event Trial in Type 2 Diabetes Mellitus age sustained for $30 days by central some also demonstrated cardiovascular
Patients], CANVAS (Canagliflozin Cardio- laboratory assessment, or renal death or risk reduction. GLP-1 RAs clearly demon-
vascular Assessment Study), LEADER (Lira- cardiovascular death, was reduced by strated cardiovascular benefits. Namely,
glutide Effect and Action in Diabetes: 30%. This benefit was on background in the EMPA-REG OUTCOME, CANVAS,
Evaluation of Cardiovascular Outcome Re- ACE inhibitor or ARB therapy in >99% of Dapagliflozin Effect on Cardiovascular
sults), and SUSTAIN-6 (Trial to Evaluate the patients (28). Moreover, in this ad- Events–Thrombolysis in Myocardial In-
event information, for these agents. Addi- in people with an eGFR $20 mL/min/ and the mean albuminuria was 852 mg/g
tional clinical trials focusing on CKD and 1.73 m2. (interquartile range 446–1,634 mg/g).
cardiovascular outcomes in people with Of note, GLP-1 RAs may also be used The primary end point was reduced
CKD are ongoing and will be reported in at low eGFR for cardiovascular protection with finerenone compared with pla-
the next few years. but may require dose adjustment (113). cebo (HR 0.82 [95% CI 0.73–0.93]; P 5
For people with type 2 diabetes and 0.001), as was the key secondary com-
CKD, the selection of specific agents may Renal and Cardiovascular Outcomes posite of cardiovascular outcome (HR
depend on comorbidity and CKD stage. of Mineralocorticoid Receptor 0.86 [95% CI 0.75–0.99]; P 5 0.03).
SGLT2 inhibitors may be more useful for Antagonists in Chronic Kidney Hyperkalemia resulted in 2.3% discontin-
individuals at high risk of CKD progres- Disease uation in the study group compared
sion (i.e., with albuminuria or a history of MRAs historically have not been well with 0.9% in the placebo group. How-
documented eGFR loss) (Fig. 9.3) due to studied in diabetic kidney disease ever, the study was completed, and
because of the risk of hyperkalemia there were no deaths related to hy-
the placebo group (HR 0.64 [95% CI found to reduce cost, improve quality of 13. Gomes MB, Gonçalves MF. Is there a
0.41–0.995]). There was a higher inci- care, and delay dialysis (120). However, physiological variability for albumin excretion
rate? Study in patients with diabetes type 1 and
dence of hyperkalemia in the finerenone other specialists and health care professio- non-diabetic individuals. Clin Chim Acta 2001;304:
group, 10.8% vs. 5.3%, although only 1.2% nals should also educate their patients 117–123
of the 3,686 individuals on finerenone about the progressive nature of CKD, the 14. Naresh CN, Hayen A, Weening A, Craig JC,
stopped the study due to hyperkalemia kidney preservation benefits of proactive Chadban SJ. Day-to-day variability in spot urine
treatment of blood pressure and blood albumin-creatinine ratio. Am J Kidney Dis 2013;
(0.6% vs. 0.4% of the placebo group).
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DIABETIC RETINOPATHY
Recommendations
12.1 Optimize glycemic control to reduce the risk or slow the progression of
diabetic retinopathy. A
12.2 Optimize blood pressure and serum lipid control to reduce the risk or
slow the progression of diabetic retinopathy. A
in these trials. Retinopathy status should trimester and should be moni- photography may also enhance efficiency
be assessed when intensifying glucose- tored every trimester and for and reduce costs when the expertise of
lowering therapies such as those using 1 year postpartum as indicated ophthalmologists can be used for more
GLP-1 RAs, since rapid reductions in A1C by the degree of retinopathy. B complex examinations and for therapy
can be associated with initial worsening (15,18,19). In-person exams are still nec-
of retinopathy (11). essary when the retinal photos are of
The preventive effects of therapy and unacceptable quality and for follow-up if
Screening the fact that individuals with prolifera- abnormalities are detected. Retinal pho-
Recommendations tive diabetic retinopathy (PDR) or macu- tos are not a substitute for dilated com-
12.3 Adults with type 1 diabetes lar edema may be asymptomatic provide prehensive eye exams, which should be
should have an initial dilated strong support for screening to detect performed at least initially and at yearly
diabetic retinopathy. Prompt diagnosis intervals thereafter or more frequently
and comprehensive eye exami-
as recommended by an eye care profes-
type 1 or type 2 diabetes, the prevalence 12.11 Intravitreous injections of anti– nonproliferative diabetic retinopathy
of any diabetic retinopathy and PDR in vascular endothelial growth or less-than-high-risk PDR. Panretinal
early pregnancy was 52.3% and 6.1%, re- factor are a reasonable alter- laser photocoagulation is still commonly
spectively. The pooled progression rate per native to traditional panretinal used to manage complications of dia-
100 pregnancies for new diabetic reti- betic retinopathy that involve retinal
laser photocoagulation for
nopathy development was 15.0 (95% CI neovascularization and its complications.
some individuals with prolifer-
9.9–20.8), worsened nonproliferative A more gentle, macular focal/grid laser
ative diabetic retinopathy and
diabetic retinopathy was 31.0 (95% CI photocoagulation technique was shown
also reduce the risk of vision
23.2–39.2), pooled sight-threatening pro- in the ETDRS to be effective in treating
loss in these individuals. A
gression rate from nonproliferative dia- eyes with clinically significant macular
12.12 Intravitreous injections of anti–
betic retinopathy to PDR was 6.3 (95% CI edema from diabetes (26), but this is
vascular endothelial growth
3.3–10.0), and worsened PDR was 37.0 now largely considered to be second-line
(95% CI 21.2–54.0), demonstrating that factor are indicated as first-
located at or threatening the macular and 5 years after the diagnosis symptoms, reduce sequelae, and im-
center), current data from well-designed of type 1 diabetes and at least prove quality of life.
clinical trials demonstrate that intravi- annually thereafter. B
treal anti-VEGF agents provide a more 12.16 Assessment for distal symmet- Specific treatment to reverse the un-
effective treatment plan for center- ric polyneuropathy should in- derlying nerve damage is currently not
involved diabetic macular edema than clude a careful history and available. Glycemic control can effec-
monotherapy with laser (30,31). Most tively prevent diabetic peripheral neu-
assessment of either tem-
patients require near-monthly adminis- ropathy (DPN) and cardiac autonomic
perature or pinprick sensation
tration of intravitreal therapy with anti- neuropathy (CAN) in type 1 diabetes
(small-fiber function) and vibra-
VEGF agents during the first 12 months (36,37) and may modestly slow their
tion sensation using a 128-Hz
of treatment, with fewer injections needed progression in type 2 diabetes (38), but
tuning fork (for large-fiber func-
in subsequent years to maintain remission
tion). All people with diabetes it does not reverse neuronal loss. Treat-
from central-involved diabetic macular
where the clinical features are atypical pressure by >20 mmHg or >10 mmHg, neuropathy in people with
or the diagnosis is unclear. respectively, upon standing without an type 2 diabetes. C Optimize
In all people with diabetes and appropriate increase in heart rate). CAN blood pressure and serum lipid
DPN, causes of neuropathy other than treatment is generally focused on allevi- control to reduce the risk or
diabetes should be considered, including ating symptoms.
slow the progression of dia-
toxins (e.g., alcohol), neurotoxic medica-
betic neuropathy. B
tions (e.g., chemotherapy), vitamin B12 Gastrointestinal Neuropathies. Gastrointes-
12.19 Assess and treat pain related
deficiency, hypothyroidism, renal disease, tinal neuropathies may involve any por-
to diabetic peripheral neu-
malignancies (e.g., multiple myeloma, tion of the gastrointestinal tract, with
ropathy B and symptoms of
bronchogenic carcinoma), infections (e.g., manifestations including esophageal
autonomic neuropathy to im-
HIV), chronic inflammatory demyelinating dysmotility, gastroparesis, constipation,
diarrhea, and fecal incontinence. Gastro- prove quality of life. E
neuropathy, inherited neuropathies, and
paresis should be suspected in individu- 12.20 Gabapentinoids, serotonin-
vasculitis (43). See the American Diabetes
and neuropathy development has be- some areas of disagreement exist, particu- of sodium channel blockers in treating
come increasingly clear in type 2 diabe- larly around SNRI/opioid dual-mechanism pain in DPN (60).
tes, the optimal therapeutic intervention agents (61). A recent head-to-head trial Capsaicin. Capsaicin has received FDA ap-
has not been identified. Positive effects suggested therapeutic equivalency for proval for treatment of pain in DPN using
of physical activity, weight loss, and bar- TCAs, SNRIs, and gabapentinoids in the an 8% patch, with one high-quality study
iatric surgery have been reported in indi- treatment of pain in DPN (62). The trial reported. One medium-quality study of
viduals with DPN, but use of conventional also supported the role of combination 0.075% capsaicin cream has been re-
lipid-lowering pharmacotherapy (such as therapy over monotherapy for the treat- ported. In patients with contraindica-
statins or fenofibrates) does not appear ment of pain in DPN. tions to oral pharmacotherapy or who
to be effective in treating or preventing Gabapentinoids. Gabapentinoids include prefer topical treatments, the use of
DPN development (56). several calcium channel a2-d subunit li- topical capsaicin can be considered.
gands. Eight high-quality studies and seven Carbamazepine and a-Lipoic Acid. Carba-
medium-quality studies support the role of mazepine and a-lipoic acid, although not
gastrointestinal motility, including opioids, pinprick, temperature, vibra- 12.29 The use of specialized ther-
anticholinergics, tricyclic antidepressants, tion), and vascular assess- apeutic footwear is recom-
GLP-1 RAs, and pramlintide, may also ment, including pulses in the mended for people with
improve intestinal motility (67,71). How- legs and feet. B diabetes at high risk for ul-
ever, the risk of removal of GLP-1 RAs 12.23 Individuals with evidence of ceration, including those with
should be balanced against their potential sensory loss or prior ulceration loss of protective sensation,
benefits. In cases of severe gastroparesis, or amputation should have foot deformities, ulcers, cal-
pharmacologic interventions are needed. their feet inspected at every
Only metoclopramide, a prokinetic agent, lous formation, poor periph-
visit. A eral circulation, or history of
is approved by the FDA for the treatment 12.24 Obtain a prior history of ul-
of gastroparesis. However, the level of amputation. B
ceration, amputation, Charcot 12.30 For chronic diabetic foot ul-
evidence regarding the benefits of meto-
foot, angioplasty or vascular cers that have failed to heal
clopramide for the management of gas-
Identifying the at-risk foot begins with more frequently for those in higher-risk noncompressible vessels. Toe systolic blood
a detailed history documenting diabetes categories (75,76). pressure tends to be more accurate. Toe
control, smoking history, exercise toler- LOPS is vital to risk assessment. One systolic blood pressures <30 mmHg are
ance, history of claudication or rest pain, of the most useful tests to determine suggestive of PAD and an inability to
and prior ulcerations or amputations. A LOPS is the 10-g monofilament test. heal foot ulcerations (80). Individuals with
thorough examination of the feet should Studies have shown that clinical exami- abnormal pulse volume recording tracings
be performed annually in all people with nation and the 10-g monofilament test and toe pressures <30 mmHg with foot
diabetes and more frequently in at-risk are the two most sensitive tests in iden- ulcers should be referred for immediate
individuals (75). The examination should tifying the foot at risk for ulceration vascular evaluation. Due to the high
include assessment of skin integrity, as- (78). The monofilament test should be prevalence of PAD in people with dia-
sessment for LOPS using the 10-g mono- performed with at least one other neu- betes, it has been recommended by the
filament along with at least one other rologic assessment tool (e.g., pinprick, Society for Vascular Surgery and the
Table 12.1—International Working Group on the Diabetic Foot risk stratification system and corresponding foot screening
frequency
Category Ulcer risk Characteristics Examination frequency*
0 Very low No LOPS and No PAD Annually
1 Low LOPS or PAD Every 6–12 months
2 Moderate LOPS 1 PAD, or Every 3–6 months
LOPS 1 foot deformity, or
PAD 1 foot deformity
3 High LOPS or PAD and one or more of the following: Every 1–3 months
History of foot ulcer
Amputation (minor or major)
End-stage renal disease
Adapted with permission from Schaper et al. (76). LOPS, loss of protective sensation; PAD, peripheral artery disease. *Examination frequency
suggestions are based on expert opinion and patient-centered requirements.
diabetesjournals.org/care Retinopathy, Neuropathy, and Foot Care S211
Individuals considered at risk should education and self-care. People in the include the following five basic prin-
understand the implications of foot de- moderate- to high-risk category should ciples of ulcer treatment:
formities, LOPS, and PAD; the proper be referred to foot care specialists for
care of the foot, including nail and skin further evaluation and regular surveil- • Offloading of plantar ulcerations
care; and the importance of foot inspec- lance as outlined in Table 12.1. This in- • Debridement of necrotic, nonviable
tions on a daily basis. Individuals with cludes individuals with LOPS, PAD, and/ tissue
LOPS should be educated on appropriate or structural foot deformities, such as • Revascularization of ischemic wounds
ways to examine their feet (palpation or Charcot foot, bunions, or hammertoes. when necessary
visual inspection with an unbreakable Individuals with any open ulceration or • Management of infection: soft tissue
mirror) for daily surveillance of early unexplained swelling, erythema, or in- or bone
foot problems. Patients should also be creased skin temperature should be re- • Use of physiologic, topical dressings
ferred urgently to a foot care specialist
educated on the importance of refer-
or multidisciplinary team.
2. Diabetes Control and Complications Trial retinopathy: a meta-analysis. Arch Ophthalmol diabetic retinopathy: the Protocol W randomized
Research Group; Nathan DM, Genuth S, Lachin J, 2011;129:435–444 clinical trial. JAMA Ophthalmol 2021;139:701–712
et al. The effect of intensive treatment of diabetes 17. Walton OB 4th, Garoon RB, Weng CY, et al. 30. Elman MJ, Bressler NM, Qin H, et al.;
on the development and progression of long- Evaluation of automated teleretinal screening Diabetic Retinopathy Clinical Research Network.
term complications in insulin-dependent diabetes program for diabetic retinopathy. JAMA Ophthalmol Expanded 2-year follow-up of ranibizumab plus
mellitus. N Engl J Med 1993;329:977–986 2016;134:204–209 prompt or deferred laser or triamcinolone plus
3. Stratton IM, Kohner EM, Aldington SJ, et al. 18. Daskivich LP, Vasquez C, Martinez C Jr, Tseng prompt laser for diabetic macular edema.
UKPDS 50: risk factors for incidence and progression CH, Mangione CM. Implementation and evaluation Ophthalmology 2011;118:609–614
of retinopathy in type II diabetes over 6 years of a large-scale teleretinal diabetic retinopathy 31. Mitchell P, Bandello F, Schmidt-Erfurth U,
from diagnosis. Diabetologia 2001;44:156–163 screening program in the Los Angeles County et al.; RESTORE study group. The RESTORE study:
4. Estacio RO, McFarling E, Biggerstaff S, Jeffers Department of Health Services. JAMA Intern ranibizumab monotherapy or combined with
BW, Johnson D, Schrier RW. Overt albuminuria Med 2017;177:642–649 laser versus laser monotherapy for diabetic
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NIDDM. Am J Kidney Dis 1998;31:947–953 evolution of teleophthalmology programs in the 32. Wells JA, Glassman AR, Ayala AR, et al.;
5. Yau JWY, Rogers SL, Kawasaki R, et al.; Meta- United Kingdom: beyond diabetic retinopathy Diabetic Retinopathy Clinical Research Network.
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44. Pop-Busui R, Evans GW, Gerstein HC, et al.; et al. Serum lipidomic determinants of human Mellitus and Related Disorders. 6th ed. Arlington,
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Study Group. Effects of cardiac autonomic Transl Neurol 2022;9:1392–1404 72. Sugumar A, Singh A, Pasricha PJ. A sys-
dysfunction on mortality risk in the Action to 57. Lu Y, Xing P, Cai X, et al. Prevalence and risk tematic review of the efficacy of domperidone for
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Diabetes Interventions and Complications). J Am US: results from a retrospective chart review and Parkman HP, Nowak T. Gastric electrical
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provide the components of diabetes care, general treatment goals and guide-
lines, and tools to evaluate quality of care. Members of the ADA Professional
Practice Committee, a multidisciplinary expert committee, are responsible for up-
dating the Standards of Care annually, or more frequently as warranted. For a de-
tailed description of ADA standards, statements, and reports, as well as the
evidence-grading system for ADA’s clinical practice recommendations and a full
list of Professional Practice Committee members, please refer to Introduction
and Methodology. Readers who wish to comment on the Standards of Care are
invited to do so at professional.diabetes.org/SOC.
Recommendations
13.1 Consider the assessment of medical, psychological, functional (self-
management abilities), and social domains in older adults to provide
a framework to determine targets and therapeutic approaches for dia-
betes management. B
13.2 Screen for geriatric syndromes (i.e., polypharmacy, cognitive impairment,
depression, urinary incontinence, falls, persistent pain, and frailty) in older
adults, as they may affect diabetes self-management and diminish quality
of life. B
Diabetes is a highly prevalent health condition in the aging population. Over one-
quarter of people over the age of 65 years have diabetes, and one-half of older
adults have prediabetes (1,2), and the number of older adults living with these con-
ditions is expected to increase rapidly in the coming decades. Diabetes in older
adults is also a highly heterogeneous condition. While type 2 diabetes predomi-
nates in the older population as much as in the younger population, improvements
in insulin delivery, technology, and care over the last few decades have led to in-
creasing numbers of people with childhood and adult-onset type 1 diabetes surviv- Disclosure information for each author is
ing and thriving into their later decades. Diabetes management in older adults available at https://doi.org/10.2337/dc23-SDIS.
requires regular assessment of medical, psychological, functional, and social do- Suggested citation: ElSayed NA, Aleppo G, Aroda
mains. When assessing older adults with diabetes, it is important to accurately cat- VR, et al., American Diabetes Association. 13.
egorize the type of diabetes as well as other factors, including diabetes duration, Older adults: Standards of Care in Diabetes—
2023. Diabetes Care 2023;46(Suppl. 1):S216–S229
the presence of complications, and treatment-related concerns, such as fear of hy-
poglycemia. Screening for diabetes complications in older adults should be individu- © 2022 by the American Diabetes Association.
alized and periodically revisited, as the results of screening tests may impact Readers may use this article as long as the
work is properly cited, the use is educational
targets and therapeutic approaches (3–5). Older adults with diabetes have higher and not for profit, and the work is not altered.
rates of premature death, functional disability, accelerated muscle loss, and coexist- More information is available at https://www.
ing illnesses, such as hypertension, coronary heart disease, and stroke, than those diabetesjournals.org/journals/pages/license.
diabetesjournals.org/care Older Adults S217
without diabetes. At the same time, is associated with a decline in cognitive mild cognitive impairment or dementia
older adults with diabetes are also at function (15,16), and longer duration of (4,29). Screening for cognitive impairment
greater risk than other older adults for diabetes is associated with worsening cog- should additionally be considered when
several common geriatric syndromes, nitive function. There are ongoing studies an individual presents with a significant
such as polypharmacy, cognitive impair- evaluating whether preventing or delay- decline in clinical status due to increased
ment, depression, urinary incontinence, ing diabetes onset may help to maintain problems with self-care activities, such as
injurious falls, persistent pain, and frailty cognitive function in older adults. How- errors in calculating insulin dose, difficulty
(1). These conditions may impact older ever, studies examining the effects of counting carbohydrates, skipped meals,
adults’ diabetes self-management abili- intensive glycemic and blood pressure con- skipped insulin doses, and difficulty rec-
ties and quality of life if left unaddressed trol to achieve specific targets have not ognizing, preventing, or treating hypo-
(2,6,7). See Section 4, “Comprehensive demonstrated a reduction in brain function glycemia. People who screen positive
Medical Evaluation and Assessment of decline (17,18). for cognitive impairment should receive
Clinical trials of specific interventions—
education is appropriate (when compli- ing the potential benefits of intranasal 13.4 Because older adults with di-
cating factors arise or when transitions insulin therapy and metformin therapy abetes have a greater risk of
in care occur) or whether the current provide insights for future clinical trials hypoglycemia than younger
plan is too complex for the individual’s and mechanistic studies (20–23). adults, episodes of hypogly-
self-management ability or the care- Despite the paucity of therapies to cemia should be ascertained
givers providing care (11). Particular atten- prevent or remedy cognitive decline, and addressed at routine
tion should be paid to complications that identifying cognitive impairment early visits. B
can develop over short periods of time has important implications for diabetes 13.5 For older adults with type 1
and/or would significantly impair func- care. The presence of cognitive impair- diabetes, continuous glucose
tional status, such as visual and lower- ment can make it challenging for clinicians monitoring is recommended to
extremity complications. Please refer to the to help their patients reach individualized reduce hypoglycemia. A
American Diabetes Association (ADA) con- glycemic, blood pressure, and lipid tar- 13.6 For older adults with type 2
sensus report “Diabetes in Older Adults” gets. Cognitive dysfunction makes it diffi- diabetes on multiple daily
for details (3). cult for individuals to perform complex doses of insulin, continuous
self-care tasks (24), such as monitoring glucose monitoring should be
NEUROCOGNITIVE FUNCTION glucose and adjusting insulin doses. It considered to improve glyce-
also hinders their ability to appropriately mic outcomes and decrease
Recommendation maintain the timing of meals and content glucose variability. B
13.3 Screening for early detection of the diet. When clinicians are providing 13.7 For older adults with type 1 dia-
of mild cognitive impairment care for people with cognitive dysfunc- betes, consider the use of auto-
or dementia should be per- tion, it is critical to simplify care plans and mated insulin delivery systems
formed for adults 65 years to facilitate and engage the appropriate B and other advanced insulin
of age or older at the ini- support structure to assist individuals in delivery devices such as con-
tial visit, annually, and as all aspects of care. nected pens E to reduce risk
appropriate. B Older adults with diabetes should be of hypoglycemia, based on
carefully screened and monitored for individual ability.
cognitive impairment (2). Several simple
Older adults with diabetes are at higher assessment tools are available to screen
risk of cognitive decline and institution- for cognitive impairment (24,25), such Older adults are at higher risk of hypo-
alization (12,13). The presentation of as the Mini-Mental State Examination glycemia for many reasons, including
cognitive impairment ranges from sub- (26), Mini-Cog (27), and the Montreal insulin deficiency necessitating insulin
tle executive dysfunction to memory Cognitive Assessment (28), which may therapy and progressive renal insuffi-
loss and overt dementia. People with di- help to identify individuals requiring ciency (31). As described above, older
abetes have higher incidences of all- neuropsychological evaluation, particu- adults have higher rates of unidenti-
cause dementia, Alzheimer disease, and larly those in whom dementia is sus- fied cognitive impairment and demen-
vascular dementia than people with nor- pected (i.e., experiencing memory loss tia, leading to difficulties in adhering to
mal glucose tolerance (14). The effects and decline in their basic and instru- complex self-care activities (e.g., glucose
of hypoglycemia, hyperglycemia, and hy- mental activities of daily living). Annual monitoring, insulin dose adjustment).
perinsulinemia on the brain are areas of screening is indicated for adults 65 years Cognitive decline has been associated
intense research. Poor glycemic control of age or older for early detection of with increased risk of hypoglycemia,
S218 Older Adults Diabetes Care Volume 46, Supplement 1, January 2023
and conversely, severe hypoglycemia has 8% (95% CI 6.0–11.5) increase in time improvements in time in range compared
been linked to increased risk of de- spent in range between 70 and 180 mg/dL. with sensor-augmented pump therapy
mentia (32,33). Therefore, as dis- A 6-month extension of the trial demon- (46). Moreover, they found small but sig-
cussed in Recommendation 13.3, it is strated that these benefits were sustained nificant decreases in hypoglycemia with
important to routinely screen older for up to a year (42). These and other the hybrid closed-loop strategy. Boughton
adults for cognitive impairment and short-term trials are supported by obser- et al. (47) reported results of an open-
dementia and discuss findings with vational data from the Diabetes Control label, crossover design clinical trial in
the patients and their caregivers. and Complications Trial/Epidemiology of 37 older adults ($60 years) in which
People with diabetes and their care- Diabetes Interventions and Complications 16 weeks of treatment with a hybrid
givers should be routinely queried about (DCCT/EDIC) study indicating that among closed-loop advanced insulin delivery
hypoglycemia (e.g., selected questions older adults (mean age 58 years) with system was compared with sensor-
from the Diabetes Care Profile) (34) and long-standing type 1 diabetes, routine augmented pump therapy. They found
hypoglycemia unawareness (35). Older CGM and insulin pump use was associ- that hybrid closed-loop insulin delivery
13.10 Screening for diabetes compli- determining individualized glycemic Based on concepts of competing mortal-
cations should be individualized targets. ity and time to benefit, people with ad-
in older adults. Particular atten- A1C may have limitations in those vanced diabetes complications are less
tion should be paid to compli- who have medical conditions that im- likely to benefit from reducing the risk of
cations that would lead to pact red blood cell turnover (see Sec- microvascular complications (55). In addi-
functional impairment. C tion 2, “Classification and Diagnosis of tion, they are more likely to suffer seri-
13.11 Treatment of hypertension to Diabetes,” for additional details on the ous adverse effects of therapeutics, such
individualized target levels is in- limitations of A1C) (54). Many condi- as hypoglycemia (56). However, those
dicated in most older adults. C tions associated with increased red with poorly managed diabetes may be
13.12 Treatment of other cardiovas- blood cell turnover, such as hemodialy- subject to acute complications of diabe-
cular risk factors should be sis, recent blood loss or transfusion, or tes, including dehydration, poor wound
individualized in older adults erythropoietin therapy, are commonly healing, and hyperglycemic hyperosmo-
seen in older adults and can falsely in-
Table 13.1—Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with
diabetes
Fasting or
Patient characteristics/ preprandial Bedtime Blood
health status Rationale Reasonable A1C goal‡ glucose glucose pressure Lipids
Healthy (few coexisting Longer remaining <7.0–7.5% (53–58 80–130 mg/dL 80–180 mg/dL <130/80 Statin, unless
chronic illnesses, intact life expectancy mmol/mol) (4.4–7.2 (4.4–10.0 mmHg contraindicated
cognitive and functional mmol/L) mmol/L) or not tolerated
status)
Complex/intermediate Intermediate <8.0% (64 mmol/mol) 90–150 mg/dL 100–180 mg/dL <130/80 Statin, unless
(multiple coexisting remaining life (5.0–8.3 (5.6–10.0 mmHg contraindicated
chronic illnesses* or two expectancy, mmol/L) mmol/L) or not tolerated
or more instrumental high treatment
This table represents a consensus framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults
with diabetes. The patient characteristic categories are general concepts. Not every patient will clearly fall into a particular category. Consider-
ation of patient and caregiver preferences is an important aspect of treatment individualization. Additionally, a patient’s health status and
preferences may change over time. ADL, activities of daily living; LTC, long-term care. ‡A lower A1C goal may be set for an 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, heart failure, depression, emphysema, falls, hypertension,
incontinence, stage 3 or worse chronic kidney disease, myocardial infarction, and stroke. “Multiple” means at least three, but many patients
may have five or more (66). **The presence of a single end-stage chronic illness, such as stage 3–4 heart failure or oxygen-dependent lung
disease, chronic kidney disease requiring dialysis, or uncontrolled metastatic cancer, may cause significant symptoms or impairment of func-
tional status and significantly reduce life expectancy. Adapted from Kirkman et al. (3).
morbidity and mortality are likely to LIFESTYLE MANAGEMENT Lifestyle management in older adults
result from a clinical focus on compre- should be tailored to frailty status. Dia-
Recommendations
hensive cardiovascular risk factor modifi- betes in the aging population is associ-
13.13 Optimal nutrition and pro-
cation. There is strong evidence from ated with reduced muscle strength, poor
tein intake is recommended
clinical trials of the value of treating hy- muscle quality, and accelerated loss of
for older adults; regular ex-
pertension in older adults (61,62), with muscle mass, which may result in sarco-
ercise, including aerobic ac-
treatment of hypertension to individual- penia and/or osteopenia (65,66). Diabetes
tivity, weight-bearing exercise,
ized target levels indicated in most. is also recognized as an independent risk
and/or resistance training,
There is less evidence for lipid-lowering factor for frailty. Frailty is characterized by
should be encouraged in all
therapy and aspirin therapy, although decline in physical performance and an
older adults who can safely
the benefits of these interventions for increased risk of poor health outcomes
engage in such activities. B
primary and secondary prevention are due to physiologic vulnerability and func-
13.14 For older adults with type 2
likely to apply to older adults whose life tional or psychosocial stressors. Inadequate
diabetes, overweight/obesity,
expectancies equal or exceed the time nutritional intake, particularly inadequate
and capacity to safely exer-
frames of the clinical trials (63). In the protein intake, can increase the risk of
cise, an intensive lifestyle in-
case of statins, the follow-up time of sarcopenia and frailty in older adults.
tervention focused on dietary
clinical trials ranged from 2 to 6 years. Management of frailty in diabetes in-
changes, physical activity, and
While the time frame of trials can be cludes optimal nutrition with adequate
modest weight loss (e.g.,
used to inform treatment decisions, a protein intake combined with an exercise
5–7%) should be considered
more specific concept is the time to program that includes aerobic, weight-
for its benefits on quality of
benefit for a therapy. For statins, a bearing, and resistance training. The ben-
life, mobility and physical func-
meta-analysis of the previously men- efits of a structured exercise program (as
tioning, and cardiometabolic
tioned trials showed that the time to in the Lifestyle Interventions and Inde-
risk factor control. A
benefit is 2.5 years (64). pendence for Elders [LIFE] study) in frail
diabetesjournals.org/care Older Adults S221
older adults include reducing sedentary the risk of hypoglycemia if it determination of whether a person is
time, preventing mobility disability, and can be achieved within the in- considered overtreated requires an elicita-
reducing frailty (67,68). The goal of these dividualized A1C target. B tion of the person’s perceptions of the
programs is not weight loss but en- 13.18 Simplification of complex treat- current medication burden and preferen-
hanced functional status. ces for treatments. For those seeking to
ment plans (especially insulin)
For nonfrail older adults with type 2 simplify their diabetes regimen, deintensi-
is recommended to reduce the
diabetes and overweight or obesity, an fication of regimens in individuals taking
risk of hypoglycemia and poly-
intensive lifestyle intervention designed noninsulin glucose-lowering medications
pharmacy and decrease the
to reduce weight is beneficial across can be achieved by either lowering the
multiple outcomes. The Look AHEAD burden of the disease if it can
be achieved within the individ- dose or discontinuing some medications,
(Action for Health in Diabetes) trial is
ualized A1C target. B as long as the individualized glycemic tar-
described in Section 8, “Obesity and
13.19 Consider costs of care and in- gets are maintained (89). When older
Weight Management for the Prevention
Titrate dose of basal insulin based on fasting If mealtime insulin ≤10 units/dose:
fingerstick glucose test results over a week Discontinue prandial insulin and add
If prandial insulin >10 units/dose:
noninsulin agent(s)
↓ dose by 50% and add noninsulin
Additional Tips Using patient and drug characteristics to guide decision-making, as depicted in
Fig. 9.3 and Table 9.2, select additional agent(s) as needed:
Do not use rapid- and short-acting insulin at bedtime
Every 2 weeks, adjust insulin dose and/or add glucose-lowering agents based on
While adjusting prandial insulin, may use simplified fingerstick glucose testing performed before lunch and before dinner
sliding scale, for example:
Goal: 90–150 mg/dL (5.0–8.3 mmo/L) before meals; may change
{Premeal glucose >250 mg/dL (13.9 mmol/L), goal based on overall health and goals of care**
give 2 units of short- or rapid-acting insulin
If 50% of premeal fingerstick values over 2 weeks are above goal, increase the
{Premeal glucose >350 mg/dL (19.4 mmol/L), dose or add another agent
give 4 units of short- or rapid-acting insulin
If >2 premeal fingerstick values/week are <90 mg/dL (5.0 mmol/L),
Stop sliding scale when not needed daily decrease the dose of medication
Figure 13.1—Algorithm to simplify insulin regimen for older adults with type 2 diabetes. eGFR, estimated glomerular filtration rate. *Basal insulins: glar-
gine U-100 and U-300, detemir, degludec, and human NPH. **See Table 13.1. ¥Prandial insulins: short-acting (regular human insulin) or rapid-acting
(lispro, aspart, and glulisine). §Premixed insulins: 70/30, 75/25, and 50/50 products. Adapted with permission from Munshi et al. (93).
vitamin B12 deficiency should be consid- Incretin-Based Therapies other populations (100). See Section 9,
ered (96). Oral dipeptidyl peptidase 4 (DPP-4) “Pharmacologic Approaches to Glycemic
inhibitors have few side effects and Treatment,” and Section 10, “Cardio-
minimal risk of hypoglycemia, but their vascular Disease and Risk Management,”
Thiazolidinediones
cost may be a barrier to some older for a more extensive discussion regard-
Thiazolidinediones, if used at all, should be
adults. DPP-4 inhibitors do not reduce ing the specific indications for this class
used very cautiously in older adults on in-
or increase major adverse cardiovascular of agents. In a systematic review and
sulin therapy as well as in those with or at
outcomes (100). Across the trials of this meta-analysis of GLP-1 receptor agonist
risk for heart failure, osteoporosis, falls or
drug class, there appears to be no inter- trials, these agents have been found to
fractures, and/or macular edema (97,98).
action by age-group (101–103). A chal- reduce major adverse cardiovascular
Lower doses of a thiazolidinedione in com-
lenge of interpreting the age-stratified events, cardiovascular deaths, stroke, and
bination therapy may mitigate these side
analyses of this drug class and other car- myocardial infarction to the same degree
effects.
diovascular outcomes trials is that while for people over and under 65 years of
most of these analyses were prespeci- age (104). While the evidence for this class
Insulin Secretagogues fied, they were not powered to detect of agents for older adults continues to
Sulfonylureas and other insulin secreta- differences. grow, there are a number of practical is-
gogues are associated with hypoglyce- GLP-1 receptor agonists have demon- sues that should be considered specifi-
mia and should be used with caution. strated cardiovascular benefits among cally for older people. These drugs are
If used, sulfonylureas with a shorter du- people with diabetes and established injectable agents (with the exception of
ration of action, such as glipizide, are atherosclerotic cardiovascular disease oral semaglutide) (105), which require
preferred. Glyburide is a longer-acting (ASCVD) and those at higher ASCVD visual, motor, and cognitive skills for ap-
sulfonylurea and should be avoided in risk, and newer trials are expanding propriate administration. Agents with a
older adults (99). our understanding of their benefits in weekly dosing schedule may reduce the
diabetesjournals.org/care Older Adults S223
Table 13.2—Considerations for treatment regimen simplification and deintensification/deprescribing in older adults with
diabetes (93,128)
When may treatment
Patient characteristics/ Reasonable A1C/ When may regimen deintensification/
health status treatment goal Rationale/considerations simplification be required? deprescribing be required?
Healthy (few coexisting <7.0–7.5% (53–58 Patients can generally If severe or recurrent If severe or recurrent
chronic illnesses, mmol/mol) perform complex tasks to hypoglycemia occurs in hypoglycemia occurs in
intact cognitive and maintain good glycemic patients on insulin patients on noninsulin
functional status) control when health is therapy (regardless of therapies with high risk
stable A1C) of hypoglycemia
During acute illness, patients If wide glucose excursions (regardless of A1C)
may be more at risk for are observed If wide glucose excursions
administration or dosing If cognitive or functional are observed
Treatment regimen simplification refers to changing strategy to decrease the complexity of a medication regimen (e.g., fewer administration
times, fewer blood glucose checks) and decreasing the need for calculations (such as sliding-scale insulin calculations or insulin-carbohydrate
ratio calculations). Deintensification/deprescribing refers to decreasing the dose or frequency of administration of a treatment or discontinu-
ing a treatment altogether. ADL, activities of daily living; LTC, long-term care.
S224 Older Adults Diabetes Care Volume 46, Supplement 1, January 2023
burden of administration. GLP-1 receptor Other Factors to Consider A1C, reducing glycemic variability, and
agonists may also be associated with The needs of older adults with diabetes reducing risk of hypoglycemia (45) (see
nausea, vomiting, and diarrhea. Given and their caregivers should be evaluated Section 7, “Diabetes Technology,” and
the gastrointestinal side effects of this to construct a tailored care plan. Im- Section 9, “Pharmacologic Approaches to
class, GLP-1 receptor agonists may not paired social functioning may reduce Glycemic Treatment”). In older people
be preferred in older adults who are these individuals’ quality of life and in- with type 1 diabetes, administration of
experiencing unexplained weight loss. crease the risk of functional dependency insulin may become more difficult as
(7). The person’s living situation must complications, cognitive impairment,
Sodium–Glucose Cotransporter 2 be considered as it may affect diabetes and functional impairment arise. This in-
Inhibitors management and support needs. Social creases the importance of caregivers in
SGLT2 inhibitors are administered orally, and instrumental support networks (e.g., the lives of these individuals. Many
which may be convenient for older adults adult children, caretakers) that provide older people with type 1 diabetes re-
instrumental or emotional support for
well as the LTC staff and caregivers Another consideration for the LTC set- and dignity are primary goals
(115). Training should include diabetes ting is that unlike in the hospital setting, for diabetes management at
detection and institutional quality as- health care professionals are not required the end of life. C
sessment. LTC facilities should develop to evaluate patients daily. According to
their own policies and procedures for federal guidelines, assessments should
prevention and management of hypogly- be done at least every 30 days for the The management of the older adult at
cemia. With the increased longevity of first 90 days after admission and then the end of life receiving palliative medi-
populations, the care of people with dia- at least once every 60 days. Although in cine or hospice care is a unique situation.
betes and its complications in LTC is an practice patients may actually be seen Overall, palliative medicine promotes
area that warrants greater study. more frequently, the concern is that comfort, symptom control and preven-
these individuals may have uncontrolled tion (pain, hypoglycemia, hyperglycemia,
Resources glucose levels or wide excursions with- and dehydration), and preservation of
out the practitioner being notified. Health
1. A stable patient: Continue with the across the disease course: diabetes & aging study. impairment and Alzheimer’s disease. Discov Med
person’s previous regimen, with a J Gen Intern Med 2012;27:1674–1681 2013;16:277–286
7. Laiteerapong N, Karter AJ, Liu JY, et al. 23. Tomlin A, Sinclair A. The influence of cognition
focus on 1) the prevention of on self-management of type 2 diabetes in older
Correlates of quality of life in older adults with
hypoglycemia and 2) the manage- diabetes: the diabetes & aging study. Diabetes people. Psychol Res Behav Manag 2016;9:7–20
ment of hyperglycemia using blood Care 2011;34:1749–1753 24. National Institute on Aging. Assessing
glucose testing, keeping levels below 8. McClintock MK, Dale W, Laumann EO, Waite Cognitive Impairment in Older Patients. Accessed
the renal threshold of glucose, and L. Empirical redefinition of comprehensive health 19 October 2022. Available from https://www.
and well-being in the older adults of the United nia.nih.gov/health/assessing-cognitive-impairment-
hyperglycemia-mediated dehydration. older-patients
States. Proc Natl Acad Sci U S A 2016;113:E3071–
There is no role for A1C monitoring. 25. Alzheimer’s Association. Cognitive Assessment.
E3080
2. A patient with organ failure: Pre- 9. Laiteerapong N, Iveniuk J, John PM, Laumann Accessed 19 October 2022. Available from https://
venting hypoglycemia is of greatest EO, Huang ES. Classification of older adults who alz.org/professionals/healthcare-professionals/
significance. Dehydration must be have diabetes by comorbid conditions, United cognitive-assessment
26. Folstein MF, Folstein SE, McHugh PR. “Mini-
prevented and treated. In people States, 2005-2006. Prev Chronic Dis 2012;9:E100
Study Group. Effects of intensive glucose older adults with diabetes. Diabetes Care 2020; older adults: the LIFE study randomized clinical trial.
lowering in type 2 diabetes. N Engl J Med 43:1724–1731 JAMA 2014;311:2387–2396
2008;358:2545–2559 53. Brown SES, Meltzer DO, Chin MH, Huang 68. Gill TM, Baker DI, Gottschalk M, Peduzzi PN,
38. Duckworth W, Abraira C, Moritz T, et al.; ES. Perceptions of quality-of-life effects of Allore H, Byers A. A program to prevent
VADT Investigators. Glucose control and vascular treatments for diabetes mellitus in vulnerable functional decline in physically frail, elderly
complications in veterans with type 2 diabetes. N and nonvulnerable older patients. J Am Geriatr persons who live at home. N Engl J Med
Engl J Med 2009;360:129–139 Soc 2008;56:1183–1190 2002;347:1068–1074
39. Toschi E, Slyne C, Sifre K, et al. The relationship 54. NGSP. Factors that Interfere with HbA1c Test 69. Curtis JM, Horton ES, Bahnson J, et al.; Look
between cgm-derived metrics, A1C, and risk of Results. Accessed 19 October 2022. Available AHEAD Research Group. Prevalence and predictors
hypoglycemia in older adults with type 1 diabetes. from http://www.ngsp.org/factors.asp of abnormal cardiovascular responses to exercise
Diabetes Care 2020;43:2349–2354 55. Huang ES, Zhang Q, Gandra N, Chin MH, testing among individuals with type 2 diabetes: the
40. Carlson AL, Kanapka LG, Miller KM, et al. Meltzer DO. The effect of comorbid illness and Look AHEAD (Action for Health in Diabetes) study.
Hypoglycemia and glycemic control in older functional status on the expected benefits of Diabetes Care 2010;33:901–907
adults with type 1 diabetes: baseline results from intensive glucose control in older patients with 70. Bray G, Gregg E, Haffner S, et al.; Look
the WISDM Study. J Diabetes Sci Technol 2021; type 2 diabetes: a decision analysis. Ann Intern Ahead Research Group. Baseline characteristics
medication non-adherence among older U.S. deficiency in the Diabetes Prevention Program expectancy of type 1 diabetes: the Pittsburgh
adults with diabetes from 2010 to 2014. J Health Outcomes Study. J Clin Endocrinol Metab 2016; Epidemiology of Diabetes Complications study
Med Econ 2018;4:7 101:1754–1761 cohort. Diabetes 2012;61:2987–2992
82. Schmittdiel JA, Steers N, Duru OK, et al. 97. Schwartz AV, Chen H, Ambrosius WT, et al. 113. Bullard KM, Cowie CC, Lessem SE, et al.
Patient-provider communication regarding drug Effects of TZD use and discontinuation on Prevalence of diagnosed diabetes in adults by
costs in Medicare Part D beneficiaries with fracture rates in ACCORD Bone Study. J Clin diabetes type—United States, 2016. MMWR
diabetes: a TRIAD Study. BMC Health Serv Res Endocrinol Metab 2015;100:4059–4066 Morb Mortal Wkly Rep 2018;67:359–361
2010;10:164 98. Billington EO, Grey A, Bolland MJ. The effect 114. Heise T, Nosek L, Rønn BB, et al. Lower
83. Patel MR, Resnicow K, Lang I, Kraus K, of thiazolidinediones on bone mineral density within-subject variability of insulin detemir in
Heisler M. Solutions to address diabetes-related and bone turnover: systematic review and meta- comparison to NPH insulin and insulin glargine
financial burden and cost-related nonadherence: analysis. Diabetologia 2015;58:2238–2246 in people with type 1 diabetes. Diabetes 2004;
results from a pilot study. Health Educ Behav 99. American Geriatrics Society 2015 Beers 53:1614–1620
2018;45:101–111 Criteria Update Expert Panel. American Geriatrics 115. Munshi MN, Florez H, Huang ES, et al.
84. Arnold SV, Lipska KJ, Wang J, Seman L, Mehta Society 2015 updated Beers criteria for potentially Management of diabetes in long-term care and
SN, Kosiborod M. Use of intensive glycemic inappropriate medication use in older adults. J Am skilled nursing facilities: a position statement of
patients with type 2 diabetes in a national guidelines for treating frail older adults with 128. Munshi MN, Slyne C, Segal AR, Saul N,
sample of nursing homes. JAMA Intern Med type 2 diabetes: from the Diabetes Care Program Lyons C, Weinger K. Liberating A1C goals in older
2018;178:713–715 of Nova Scotia (DCPNS) and the Palliative and adults may not protect against the risk of
127. Mallery LH, Ransom T, Steeves B, Cook B, Therapeutic Harmonization (PATH) program. J Am hypoglycemia. J Diabetes Complications 2017;31:
Dunbar P, Moorhouse P. Evidence-informed Med Dir Assoc 2013;14:801–808 1197–1199
hormone; consider normal; IgG tTG and monitoring acceptable initially ratio; random sample retinal photography pulses, pinprick, 10-g
antithyroglobulin and deamidated gliadin acceptable initially monofilament
antithyroid antibodies if IgA sensation tests,
peroxidase antibodies deficient vibration, and ankle
reflexes
When to start Soon after diagnosis Soon after diagnosis At diagnosis Soon after diagnosis; Puberty or >10 years Puberty or $11 years old, Puberty or $10 years
preferably after old, whichever is whichever is earlier, old, whichever is
glycemia has earlier, and diabetes and diabetes duration earlier, and diabetes
improved and duration of 5 years of 3–5 years duration of 5 years
$2 years old
Follow-up frequency Every 1–2 years if Within 2 years and Every visit If LDL #100 mg/dL, If normal, annually; if If normal, every 2 years; If normal, annually
thyroid antibodies then at 5 years after repeat at 9–11 years abnormal, repeat consider less frequently
negative; more often diagnosis; sooner if old; then, if <100 with confirmation in (every 4 years) if
if symptoms develop symptoms develop mg/dL, every 3 years two of three samples A1C <8% and eye
or presence of over 6 months professional agrees
thyroid antibodies
Target NA NA <90th percentile for LDL <100 mg/dL Albumin-to-creatinine No retinopathy No neuropathy
age, sex, and height; ratio <30 mg/g
if $13 years old,
<120/80 mmHg
Treatment Appropriate treatment After confirmation, Lifestyle modification If abnormal, optimize Optimize glycemia and Optimize glycemia; Optimize glycemia;
of underlying thyroid start gluten-free for elevated blood glycemia and medical blood pressure; ACE treatment per referral to neurology
disorder diet pressure (90th to nutrition therapy; if inhibitor* if albumin- ophthalmology
<95th percentile for after 6 months LDL to-creatinine ratio is
age, sex, and height >160 mg/dL or elevated in two of
or, if $13 years old, >130 mg/dL with three samples over
120–129/<80 mmHg); cardiovascular risk 6 months
lifestyle modification factor(s), initiate statin
and ACE inhibitor or therapy (for those aged
ARB* for hypertension >10 years)*
($95th percentile for
age, sex, and height or,
if $13 years old,
$130/80 mmHg)
ARB, angiotensin receptor blocker; NA, not applicable; tTG, tissue transglutaminase. *Due to the potential teratogenic effects, individuals of childbearing age should receive reproductive counseling, and
medication should be avoided in individuals of childbearing age who are not using reliable contraception.
Children and Adolescents
S231
Table 14.1B—Recommendations for screening and treatment of complications and related conditions in pediatric type 2 diabetes
Polycystic ovarian
syndrome (for
Nonalcoholic Obstructive sleep adolescent female
Hypertension Nephropathy Neuropathy Retinopathy fatty liver disease apnea individuals) Dyslipidemia
Corresponding 14.77–14.80 14.81–14.86 14.87 and 14.88 14.89–14.92 14.93 and 14.94 14.95 14.96–14.98 14.100–14.104
recommendations
Children and Adolescents
Method Blood pressure Albumin-to- Foot exam with foot Dilated fundoscopy AST and ALT Screening for Screening for Lipid profile
monitoring creatinine ratio; pulses, pinprick, measurement symptoms symptoms;
random sample 10-g monofilament laboratory
acceptable sensation tests, evaluation if
initially vibration, and positive
ankle reflexes symptoms
When to start At diagnosis At diagnosis At diagnosis At/soon after At diagnosis At diagnosis At diagnosis Soon after diagnosis,
diagnosis preferably after
glycemia has
improved
Follow-up frequency Every visit If normal, annually; If normal, annually If normal, annually Annually Every visit Every visit Annually
if abnormal,
repeat with
confirmation in
two of three
samples over
6 months
Target <90th percentile for <30 mg/g No neuropathy No retinopathy NA NA NA LDL <100 mg/dL,
age, sex, and height; HDL >35 mg/dL,
if $13 years old, triglycerides
<130/80 mmHg <150 mg/dL
Treatment Lifestyle modification Optimize glycemia Optimize glycemia; Optimize glycemia; Refer to gastro- If positive symptoms, If no contra- If abnormal, optimize
for elevated blood and blood referral to treatment per enterology for refer to sleep indications, oral glycemia and medical
pressure (90th to pressure; ACE neurology ophthalmology persistently specialist and contraceptive pills; nutrition therapy; if
<95th percentile for inhibitor* if elevated or polysomnogram medical nutrition after 6 months, LDL
age, sex, and height albumin-to- worsening therapy; metformin >130 mg/dL, initiate
or, if $13 years old, creatinine ratio transaminases statin therapy (for
120–129/<80 mmHg); is elevated in those aged >10
lifestyle modification two of three years)*; if triglycerides
and ACE inhibitor or samples over >400 mg/dL fasting
ARB* for hypertension 6 months or >1,000 mg/dL
($95th percentile for nonfasting, begin
age, sex, and height fibrate
or, if $13 years,
$130/80 mmHg)
ARB, angiotensin receptor blocker; NA, not applicable. *Due to the potential teratogenic effects, individuals of childbearing age should receive reproductive counseling, and medication should be
avoided in individuals of childbearing age who are not using reliable contraception.
Diabetes Care Volume 46, Supplement 1, January 2023
eating between 10 and 12 years social adjustment (peer relationships) diabetes. These psychosocial factors are
of age. Refer to a qualified men- and school performance can facilitate significantly related to self-management
tal health professional for further both well-being and academic achieve- difficulties, elevated A1C, reduced qual-
assessment and treatment if ment (52). Elevated A1C is a risk factor ity of life, and higher rates of acute and
indicated. B for underperformance at school and in- chronic diabetes complications.
creased absenteeism (53).
Shared decision-making with youth re- Glycemic Monitoring, Insulin
Rapid and dynamic cognitive, develop- garding the adoption of management Delivery, and Targets
mental, and emotional changes occur dur- plan components and self-management Recommendations
ing childhood, adolescence, and emerging behaviors can improve diabetes self- 14.18 All youth with type 1 diabetes
adulthood. Diabetes management during efficacy, participation in diabetes care, should monitor glucose levels
childhood and adolescence places sub- and metabolic outcomes (26,54). Although multiple times daily (up to
cognitive abilities vary, the ethical posi-
technology, including continu- conjunction with A1C whenever achieving a lower A1C should be bal-
ous glucose monitors, insulin possible. E anced against the risks of hypoglycemia
pumps, connected insulin pens, and the developmental burdens of in-
and automated insulin delivery tensive treatment plans in youth (107).
systems as prescribed by their Current standards for diabetes manage- Recent data with newer devices and in-
diabetes care team. E ment reflect the need to minimize hy- sulins indicate that the risk of hypogly-
14.23 A1C goals must be individual- perglycemia as safely as possible. The cemia with lower A1C is less than it was
ized and reassessed over time. Diabetes Control and Complications Trial before (108–117). Some data suggest
An A1C of <7% (53 mmol/mol) (DCCT), which did not enroll children that there could be a threshold where
is appropriate for many children <13 years of age, demonstrated that lower A1C is associated with more hypo-
and adolescents. B near normalization of blood glucose glycemia (118,119); however, the confi-
14.24 Less stringent A1C goals (such levels was more difficult to achieve in dence intervals were large, suggesting
Please refer to Section 7, “Diabetes Tech- peroxidase and antithyroglo- diabetes, or IgG tTG and dea-
nology,” for more information on the use bulin antibodies soon after midated gliadin antibodies if
of blood glucose meters, CGM, and insu- diagnosis. B IgA is deficient. B
lin pumps. More information on insulin 14.30 Measure thyroid-stimulating 14.32 Repeat screening within 2 years
injection technique can be found in Sec- hormone concentrations at di- of diabetes diagnosis and then
tion 9, “Pharmacologic Approaches to agnosis when clinically stable again after 5 years and con-
Glycemic Treatment.”
or soon after optimizing glyce- sider more frequent screening
mia. If normal, suggest recheck- in youth who have symptoms
Key Concepts in Setting Glycemic Targets
• Targets should be individualized, and
ing every 1–2 years or sooner or a first-degree relative with
if the youth has positive thyroid celiac disease. B
lower targets may be reasonable based
antibodies or develops symp- 14.33 Individuals with confirmed ce-
on a benefit–risk assessment.
toms or signs suggestive of liac disease should be placed
• Blood glucose targets should be modi-
(155). European guidelines on screening nutrition, physical activity, sleep, (<100 mg/dL [2.6 mmol/L]),
for celiac disease in children (not specific and, if appropriate, weight a lipid profile repeated every
to children with type 1 diabetes) suggest management. C 3 years is reasonable. E
that biopsy may not be necessary in 14.36 In addition to lifestyle mod-
symptomatic children with high anti- ification, ACE inhibitors or
body titers (i.e., greater than 10 times angiotensin receptor blockers Dyslipidemia Treatment
the upper limit of normal) provided that should be started for treat- Recommendations
further testing is performed (verification ment of confirmed hyperten-
of endomysial antibody positivity on a 14.40 If lipids are abnormal, initial
sion (defined as blood pressure therapy should consist of op-
separate blood sample) (156). Whether consistently $95th percentile
this approach may be appropriate for timizing glycemia and medical
for age, sex, and height or, in nutrition therapy to limit the
asymptomatic children in high-risk groups
adolescents aged $13 years, amount of calories from fat
remains an open question, though evi-
media thickness have yielded incon- Although intervention data are sparse, smoking rates are significantly higher
sistent results (162,163). the American Heart Association catego- among youth with diabetes than among
rizes children with type 1 diabetes in the youth without diabetes (182,183). In
Screening. Diabetes predisposes to the highest tier for cardiovascular risk and youth with diabetes, it is important to
development of accelerated arterioscle- recommends both lifestyle and pharma- avoid additional CVD risk factors. Smok-
rosis. Lipid evaluation for these patients cologic treatment for those with elevated ing increases the risk of the onset of al-
contributes to risk assessment and identi- LDL cholesterol levels (175,178). Initial buminuria; therefore, smoking avoidance
fies an important proportion of those with therapy should include a nutrition plan is important to prevent both microvas-
dyslipidemia. Therefore, initial screening that restricts saturated fat to 7% of total cular and macrovascular complications
should be done soon after diagnosis. If calories and dietary cholesterol to (170,184). Discouraging cigarette smok-
the initial screen is normal, subsequent 200 mg/day (170). Data from random- ing, including electronic cigarettes (185,
screening may be done at 9–11 years of ized clinical trials in children as young as 186), is an important part of routine dia-
age, which is a stable time for lipid as- betes care. In light of CDC evidence of
childbearing age who are not Retinopathy (like albuminuria) most Section 2, “Classification and Diagnosis of
using reliable contraception. B commonly occurs after the onset of pu- Diabetes.” For additional support for these
berty and after 5–10 years of diabetes recommendations, see the ADA position
duration (192). It is currently recognized statement “Evaluation and Management
Data from 7,549 participants <20 years that there is a low risk of development of of Youth-Onset Type 2 Diabetes” (3).
of age in the T1D Exchange clinic registry vision-threatening retinal lesions prior to The prevalence of type 2 diabetes in
emphasize the importance of meeting 12 years of age (193,194). A 2019 publi- youth has continued to increase over
glycemic and blood pressure goals, par- cation based on the follow-up of the the past 20 years (4). The CDC published
ticularly as diabetes duration increases, DCCT adolescent cohort supports a lower projections for type 2 diabetes prevalence
in order to reduce the risk of diabetic kid- frequency of eye examinations than pre- using the SEARCH database; assuming a
ney disease. The data also underscore viously recommended, particularly in 2.3% annual increase, the prevalence in
the importance of routine screening to adolescents with A1C closer to the target those under 20 years of age will quadru-
ple in 40 years (199,200).
14.52 If screening is normal, repeat ketosis may be present in pediatric indi- and adolescents, should be
screening at a minimum of viduals with clinical features of type 2 encouraged to participate in
3-year intervals E, or more fre- diabetes (including obesity and acantho- at least 60 min of moderate to
quently if BMI is increasing. C sis nigricans) (209). The presence of islet vigorous physical activity daily
autoantibodies has been associated (with muscle and bone strength
14.53 Fasting plasma glucose, 2-h
with faster progression to insulin defi- training at least 3 days/week) B
plasma glucose during a 75-g
ciency (209). At the onset, DKA occurs and to decrease sedentary
oral glucose tolerance test,
in 6% of youth aged 10–19 years with behavior. C
and A1C can be used to test
type 2 diabetes (215). Although uncom- 14.59 Nutrition for youth with pre-
for prediabetes or diabetes in
mon, type 2 diabetes has been ob- diabetes and type 2 diabetes,
children and adolescents. B served in prepubertal children under
14.54 Children and adolescents with like for all children and adoles-
the age of 10 years, and thus it should
overweight or obesity in whom cents, should focus on healthy
be part of the differential in children
lifestyle or metformin only who or without long-acting insulin), Glycemic targets should be individual-
achieve significant weight im- glucagon-like peptide 1 recep- ized, taking into consideration the long-
provement. E tor agonist therapy approved term health benefits of more stringent
14.64 Less stringent A1C goals (such for youth with type 2 diabetes targets and risk for adverse effects, such
as 7.5% [58 mmol/mol]) may should be considered in chil- as hypoglycemia. A lower target A1C in
be appropriate if there is an in- dren 10 years of age or older if youth with type 2 diabetes when com-
creased risk of hypoglycemia. E they have no past medical his- pared with those recommended in type 1
14.65 A1C targets for individuals on tory or family history of medul- diabetes is justified by a lower risk of
insulin should be individual- lary thyroid carcinoma or hypoglycemia and higher risk of compli-
multiple endocrine neoplasia cations (202,219–222).
ized, taking into account the
type 2. A Self-management in pediatric diabe-
relatively low rates of hypogly-
14.72 Individuals treated with metfor- tes involves both the youth and their
cemia in youth-onset type 2
parents/adult caregivers. Individuals and
New-Onset Diabetes in Youth With Overweight or Obesity With Clinical Suspicion of Type 2 Diabetes
Initiate lifestyle management and diabetes education
Metformin
Metformin • Titrate up to 2,000 mg per day Manage DKA or HHNK
• Titrate up to 2,000 mg per day as tolerated i.v. insulin until acidosis resolves, then
as tolerated subcutaneous, as for type 1 diabetes
Long-acting insulin: start at 0.5 units/kg/day until antibodies are known
and titrate every 2–3 days based on
BGM
NEGATIVE POSITIVE
Continue metformin
Consider adding glucagon-like peptide 1 receptor
agonist approved for youth with type 2 diabetes
Titrate/initiate insulin therapy; if using long-acting insulin
only and glycemic target not met with escalating
doses, then add prandial insulin; total daily insulin
dose may exceed 1 unit/kg/day
Figure 14.1—Management of new-onset diabetes in youth with overweight or obesity with clinical suspicion of type 2 diabetes. A1C 8.5% 5 69
mmol/mol. Adapted from the ADA position statement “Evaluation and Management of Youth-Onset Type 2 Diabetes” (3). BGM, blood glucose
monitoring; CGM, continuous glucose monitoring; DKA, diabetic ketoacidosis; HHNK, hyperosmolar hyperglycemic nonketotic syndrome; i.v., intra-
venous; MDI, multiple daily injections.
to safely manage the device. Initial treat- therapy in youth with type 2 diabetes; the CGM in youth with type 2 diabetes are
ment should also be with insulin when the combination did not perform better than sparse (233), CGM could be consid-
distinction between type 1 diabetes and metformin alone in achieving durable ered in individuals requiring frequent
type 2 diabetes is unclear and in patients glycemic control (227). blood glucose monitoring for diabetes
who have random blood glucose concen- A randomized clinical trial in youth management.
trations $250 mg/dL (13.9 mmol/L) and/ aged 10–17 years with type 2 diabetes
or A1C $8.5% (69 mmol/mol) (226). demonstrated the addition of subcuta- Metabolic Surgery
Metformin therapy should be added af- neous liraglutide (up to 1.8 mg daily) to Recommendations
ter resolution of ketosis/ketoacidosis. metformin (with or without long-acting 14.75 Metabolic surgery may be
When initial insulin treatment is not insulin) as safe and effective to de- considered for the treatment
required, initiation of metformin is rec- crease A1C (estimated decrease of 1.06 of adolescents with type 2
ommended. The TODAY study found that percentage points at 26 weeks and 1.30 diabetes who have severe obe-
metformin alone provided durable glyce- percentage points at 52 weeks), al- sity (BMI >35 kg/m2) and who
mic control (A1C #8% [64 mmol/mol] though it did increase the frequency of have elevated A1C and/or
for 6 months) in approximately half of gastrointestinal side effects (229). Lira- serious comorbidities despite
the subjects (227). The Restoring Insulin glutide and once-weekly exenatide ex- lifestyle and pharmacologic
Secretion (RISE) Consortium study did not tended release are approved for the intervention. A
demonstrate differences in measures of treatment of type 2 diabetes in youth 14.76 Metabolic surgery should be
glucose or b-cell function preservation be- aged 10 years or older (230–232). performed only by an experi-
tween metformin and insulin, but there Blood glucose monitoring plans enced surgeon working as part
was more weight gain with insulin (228). should be individualized, taking into of a well-organized and engaged
To date, the TODAY study is the only consideration the pharmacologic treat- multidisciplinary team, including a
trial combining lifestyle and metformin ment of the person. Although data on
S244 Children and Adolescents Diabetes Care Volume 46, Supplement 1, January 2023
or slow the progression of 14.98 Metformin, in addition to life- age who are not using reli-
retinopathy. B style modification, is likely to able contraception. B
14.91 Less frequent examination (ev- improve the menstrual cyclicity 14.104 If triglycerides are >400 mg/dL
ery 2 years) may be considered and hyperandrogenism in fe- (4.7 mmol/L) fasting or
if achieving glycemic targets male individuals with type 2 >1,000 mg/dL (11.6 mmol/L)
and a normal eye exam. C diabetes. E nonfasting, optimize glycemia
14.92 Programs that use retinal pho- and begin fibrate, with a goal
tography (with remote reading of <400 mg/dL (4.7 mmol/L)
or use of a validated assess- Cardiovascular Disease fasting to reduce risk for pan-
ment tool) to improve access creatitis. C
Recommendation
to diabetic retinopathy screen- 14.99 Intensive lifestyle interventions
ing can be appropriate screening focusing on weight loss, dysli-
These diabetes comorbidities also ap- sociocultural context and efforts to per- who have diabetes. During this period
pear to be higher than in youth with sonalize diabetes management are of of major life transitions, youth may be-
type 1 diabetes despite shorter diabetes critical importance to minimize barriers gin to move out of their parents’ homes
duration and lower A1C (252). In addition, to care, enhance participation, and max- and become increasingly responsible for
the progression of vascular abnormali- imize response to treatment. their diabetes care. Their new responsi-
ties appears to be more pronounced in Evidence about psychiatric disorders bilities include self-management of their
youth-onset type 2 diabetes than with and symptoms in youth with type 2 dia- diabetes, making medical appointments,
type 1 diabetes of similar duration, in- betes is limited (256–260), but given the and financing health care once they are
cluding ischemic heart disease and stroke sociocultural context for many youth and no longer covered by their parents’ health
(255). the medical burden and obesity associ- insurance plans (ongoing coverage until
ated with type 2 diabetes, ongoing sur- age 26 years is currently available under
Psychosocial Factors veillance of mental health/behavioral provisions of the U.S. Affordable Care
2. Chiang JL, Maahs DM, Garvey KC, et al. Type 1 International Society for Pediatric and Adolescent 31. Hood KK, Beavers DP, Yi-Frazier J, et al.
diabetes in children and adolescents: a position Diabetes (ISPAD) endorsed by JDRF and supported Psychosocial burden and glycemic control during
statement by the American Diabetes Association. by the American Diabetes Association (ADA). the first 6 years of diabetes: results from the
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DIABETES IN PREGNANCY
The prevalence of diabetes in pregnancy has been increasing in the U.S. in parallel
with the worldwide epidemic of obesity. Not only is the prevalence of type 1 diabe-
tes and type 2 diabetes increasing in individuals of reproductive age, but there is
also a dramatic increase in the reported rates of gestational diabetes mellitus
(GDM). Diabetes confers significantly greater maternal and fetal risk largely related
to the degree of hyperglycemia but also related to chronic complications and co-
morbidities of diabetes. In general, specific risks of diabetes in pregnancy include
spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia,
neonatal hypoglycemia, hyperbilirubinemia, and neonatal respiratory distress syn-
drome, among others. In addition, diabetes in pregnancy may increase the risk of
obesity, hypertension, and type 2 diabetes in offspring later in life (1,2).
Preconception Counseling
Recommendations
15.1 Starting at puberty and continuing in all people with diabetes and re- Disclosure information for each author is
available at https://doi.org/10.2337/dc23-SDIS.
productive potential, preconception counseling should be incorporated
into routine diabetes care. A Suggested citation: ElSayed NA, Aleppo G, Aroda
VR, et al., American Diabetes Association. 15.
15.2 Family planning should be discussed, and effective contraception (with Management of diabetes in pregnancy: Standards
consideration of long-acting, reversible contraception) should be pre- of Care in Diabetes—2023. Diabetes Care 2023;
scribed and used until an individual’s treatment plan and A1C are opti- 46(Suppl. 1):S254–S266
mized for pregnancy. A © 2022 by the American Diabetes Association.
15.3 Preconception counseling should address the importance of achieving Readers may use this article as long as the
glucose levels as close to normal as is safely possible, ideally A1C work is properly cited, the use is educational
<6.5% (48 mmol/mol), to reduce the risk of congenital anomalies, pre- and not for profit, and the work is not altered.
eclampsia, macrosomia, preterm birth, and other complications. A More information is available at https://www.
diabetesjournals.org/journals/pages/license.
diabetesjournals.org/care Management of Diabetes in Pregnancy S255
All individuals with diabetes and repro- to make well-informed decisions (8). Pre- point is the need to incorporate a ques-
ductive potential should be informed conception counseling resources tailored tion about plans for pregnancy into the
about the importance of achieving and for adolescents are available at no cost routine primary and gynecologic care of
maintaining as near euglycemia as safely through the American Diabetes Associa- people with diabetes. Preconception
possible prior to conception and through- tion (ADA) (15). care for people with diabetes should in-
out pregnancy. Observational studies show clude the standard screenings and care
an increased risk of diabetic embryopathy, Preconception Care recommended for any person planning
especially anencephaly, microcephaly, con- pregnancy (16). Prescription of prenatal
Recommendations
genital heart disease, renal anomalies, vitamins with at least 400 mg of folic
15.4 Individuals with preexisting
and caudal regression, directly propor- acid and 150 mg of potassium iodide
diabetes who are planning a
tional to elevations in A1C during the (18) is recommended prior to concep-
pregnancy should ideally begin
first 10 weeks of pregnancy (3). Although tion. Review and counseling on the use
receiving care in preconception
observational studies are confounded by
GLYCEMIC TARGETS IN
Table 15.1—Checklist for preconception care for people with diabetes (16,19)
PREGNANCY
Preconception education should include:
w Comprehensive nutrition assessment and recommendations for:
Recommendations
Overweight/obesity or underweight
15.7 Fasting and postprandial blood Meal planning
glucose monitoring are recom- Correction of dietary nutritional deficiencies
mended in both gestational Caffeine intake
diabetes mellitus and pre- Safe food preparation technique
w Lifestyle recommendations for:
existing diabetes in pregnancy
Regular moderate exercise
to achieve optimal glucose lev- Avoidance of hyperthermia (hot tubs)
els. Glucose targets are fasting Adequate sleep
plasma glucose <95 mg/dL w Comprehensive diabetes self-management education
w Counseling on diabetes in pregnancy per current standards, including natural history of
(5.3 mmol/L) and either 1-h post-
the A1C target in diabetes and w Genetic carrier status (based on history):
and glucose management indi- w Management plan for general health, gynecologic concerns, comorbid conditions, or
cator calculations should not complications, if present, including hypertension, nephropathy, retinopathy; Rh
be used in pregnancy as es- incompatibility; and thyroid dysfunction
timates of A1C. C DKA, diabetic ketoacidosis; DVT/PE, deep vein thrombosis/pulmonary embolism; ECG, elec-
15.13 Nutrition counseling should en- trocardiogram; NAFLD, nonalcoholic fatty liver disease; PCOS, polycystic ovary syndrome;
dorse a balance of macronutrients TSH, thyroid-stimulating hormone.
diabetesjournals.org/care Management of Diabetes in Pregnancy S257
including nutrient-dense fruits, Processed foods, fatty red meat, and Lower limits are based on the mean
vegetables, legumes, whole sweetened foods and beverages should of normal blood glucose in pregnancy
grains, and healthy fats with be limited (26). (33). Lower limits do not apply to individ-
n-3 fatty acids that include uals with type 2 diabetes treated with
nuts and seeds and fish in the Insulin Physiology nutrition alone. Hypoglycemia in preg-
eating pattern. E Given that early pregnancy is a time of nancy is as defined and treated in Rec-
enhanced insulin sensitivity and lower ommendations 6.10–6.15 (Section 6,
glucose levels, many people with type 1 “Glycemic Targets”). These values repre-
Pregnancy in people with normal glu- diabetes will have lower insulin require- sent optimal control if they can be
cose metabolism is characterized by ments and an increased risk for hypo- achieved safely. In practice, it may be
fasting levels of blood glucose that are glycemia (27). Around 16 weeks, insulin challenging for a person with type 1 dia-
lower than in the nonpregnant state resistance begins to increase, and total betes to achieve these targets without
should be achieved without hypoglyce- alerts. A prospective, observational study GDM is characterized by an increased risk
mia, which, in addition to the usual ad- including 20 pregnant people with type 1 of large-for-gestational-age birth weight
verse sequelae, may increase the risk of diabetes simultaneously monitored with and neonatal and pregnancy complica-
low birth weight (43). Given the alter- intermittently scanning CGM (isCGM) and tions and an increased risk of long-term
ation in red blood cell kinetics during real-time CGM (rtCGM) for 7 days in maternal type 2 diabetes and abnormal
pregnancy and physiological changes in early pregnancy demonstrated a higher glucose metabolism of offspring in child-
glycemic parameters, A1C levels may percentage of time below range in the hood. These associations with maternal
need to be monitored more frequently isCGM group. Asymptomatic hypoglyce- oral glucose tolerance test (OGTT) results
than usual (e.g., monthly). mia measured by isCGM should there- are continuous with no clear inflection
fore not necessarily lead to a reduction points (35,52). Offspring with exposure to
Continuous Glucose Monitoring in
of insulin dose and/or increased carbo- untreated GDM have reduced insulin sen-
hydrate intake at bedtime unless these
Pregnancy sitivity and b-cell compensation and are
episodes are confirmed by blood glucose
• Two-hour postprandial glucose <120 testing may be useful to identify those Metformin
mg/dL (6.7 mmol/L) who are severely restricting carbohy- Metformin was associated with a lower
drates to control blood glucose. Sim- risk of neonatal hypoglycemia and less
The glycemic target lower limits de- ple carbohydrates will result in higher maternal weight gain than insulin in sys-
fined above for preexisting diabetes apply postmeal excursions. tematic reviews (74,77–79). However,
for GDM treated with insulin. Depending metformin readily crosses the placenta,
on the population, studies suggest that Physical Activity resulting in umbilical cord blood levels
70–85% of people diagnosed with GDM A systematic review demonstrated im- of metformin as high or higher than si-
under Carpenter-Coustan criteria can provements in glucose control and reduc- multaneous maternal levels (80,81). In
manage GDM with lifestyle modification tions in need to start insulin or insulin the Metformin in Gestational Diabetes:
alone; it is anticipated that this propor- dose requirements with an exercise inter- The Offspring Follow-Up (MiG TOFU)
tion will be even higher if the lower Inter- vention. There was heterogeneity in the study’s analyses of 7- to 9-year-old off-
spring, the 9-year-old offspring exposed
Insulin It may be suited for pregnancy because the but can require much higher doses of in-
Insulin use should follow the guidelines predictive low-glucose threshold for sus- sulin, sometimes necessitating concen-
below. Both multiple daily insulin injec- pending insulin is in the range of premeal trated insulin formulations. Insulin is the
tions and continuous subcutaneous insulin and overnight glucose value targets in preferred treatment for type 2 diabetes
infusion are reasonable delivery strategies, pregnancy and may allow for more in pregnancy. An RCT of metformin
and neither has been shown to be supe- aggressive prandial dosing. See SENSOR- added to insulin for the treatment of
rior to the other during pregnancy (92). AUGMENTED PUMPS and AUTOMATED INSULIN DELIVERY type 2 diabetes found less maternal
SYSTEMS in Section 7, “Diabetes Technology,” weight gain and fewer cesarean births.
MANAGEMENT OF PREEXISTING for more information on these systems. There were fewer macrosomic neonates,
TYPE 1 DIABETES AND TYPE 2
but there was a doubling of small-for-
DIABETES IN PREGNANCY Type 1 Diabetes gestational-age neonates (107). As in
Insulin Use Pregnant individuals with type 1 diabe- type 1 diabetes, insulin requirements
studies are needed to assess the long- had an even better composite outcome POSTPARTUM CARE
term effects of prenatal aspirin exposure score than those without diabetes (118).
Recommendations
on offspring (116). As a result of the CHAP study, ACOG
15.23 Insulin resistance decreases
issued a Practice Advisory recommend-
dramatically immediately post-
PREGNANCY AND DRUG ing a blood pressure of 140/90 mmHg
as the threshold for initiation or titration partum, and insulin require-
CONSIDERATIONS
of medical therapy for chronic hyperten- ments need to be evaluated
Recommendations sion in pregnancy (119) rather than their and adjusted as they are often
15.21 In pregnant individuals with previously recommended threshold of roughly half the prepregnancy
diabetes and chronic hyper- 160/110 mmHg (120). requirements for the initial
tension, a blood pressure The CHAP study provides additional few days postpartum. C
threshold of 140/90 mmHg for guidance for the management of hyper- 15.24 A contraceptive plan should be
initiation or titration of ther- tension in pregnancy. Data from the discussed and implemented
tested for persistent diabetes or predia- 20% at 10 years, 30% at 20 years, 40% those with diabetes, should be supported
betes at 4–12 weeks postpartum with a at 30 years, 50% at 40 years, and 60% at in attempts to breastfeed. Breastfeeding
fasting 75-g OGTT using nonpregnancy cri- 50 years (129). In the prospective Nurses’ may also confer longer-term metabolic
teria as outlined in Section 2, “Classification Health Study II (NHS II), subsequent dia- benefits to both mother (139) and off-
and Diagnosis of Diabetes,” specifically betes risk after a history of GDM was sig- spring (140). Breastfeeding reduces the
Table 2.2. In the absence of unequivocal nificantly lower in those who followed risk of developing type 2 diabetes in
hyperglycemia, a positive screen for dia- healthy eating patterns (130). Adjusting mothers with previous GDM. It may
betes requires two abnormal values. If for BMI attenuated this association mod- improve the metabolic risk factors
both the fasting plasma glucose ($126 erately, but not completely. Interpreg- of offspring, but more studies are
mg/dL [7.0 mmol/L]) and 2-h plasma glu- nancy weight gain is associated with needed (141). However, lactation can
cose ($200 mg/dL [11.1 mmol/L]) are ab- increased risk of adverse pregnancy out- increase the risk of overnight hypo-
normal in a single screening test, then comes (131) and higher risk of GDM, glycemia, and insulin dosing may need
the diagnosis of diabetes is made. If only while in people with BMI >25 kg/m2,
a Danish population-based cohort study of 573 exposure to angiotensin-converting enzyme inhi- and adverse pregnancy outcomes. N Engl J Med
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Recommendations
16.1 Perform an A1C test on all people with diabetes or hyperglycemia (blood
glucose >140 mg/dL [7.8 mmol/L]) admitted to the hospital if not per-
formed in the prior 3 months. B
16.2 Insulin should be administered using validated written or computerized Disclosure information for each author is
protocols that allow for predefined adjustments in the insulin dosage available at https://doi.org/10.2337/dc23-SDIS.
based on glycemic fluctuations. B Suggested citation: ElSayed NA, Aleppo G,
Aroda VR, et al., American Diabetes Association.
16. Diabetes care in the hospital: Standards of Care
Considerations on Admission in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):
S267–S278
High-quality hospital care for diabetes requires standards for care delivery, which are
best implemented using structured order sets and quality improvement strategies for © 2022 by the American Diabetes Association.
process improvement. Unfortunately, “best practice” protocols, reviews, and guide- Readers may use this article as long as the
work is properly cited, the use is educational
lines (2,4) are inconsistently implemented within hospitals. To correct this, medical and not for profit, and the work is not altered.
centers striving for optimal inpatient diabetes treatment should establish protocols More information is available at https://www.
and structured order sets, which include computerized provider order entry (CPOE). diabetesjournals.org/journals/pages/license.
S268 Diabetes Care in the Hospital Diabetes Care Volume 46, Supplement 1, January 2023
Initial orders should state the type of Appropriately trained specialists or spe- Standard Definitions of Glucose
diabetes (i.e., type 1, type 2, gestational cialty teams may reduce the length of Abnormalities
diabetes mellitus, pancreatogenic diabetes) stay and improve glycemic and other clini- Hyperglycemia in hospitalized patients is de-
when it is known. Because inpatient treat- cal outcomes (21–23). In addition, the fined as blood glucose levels >140 mg/dL
ment and discharge planning are more ef- increased risk of 30-day readmission fol- (7.8 mmol/L) (33). Blood glucose levels
fective if based on preadmission glycemia, lowing hospitalization that has been at- persistently above this level warrant prompt
A1C should be measured for all people tributed to diabetes can be reduced, and interventions, such as alterations in nu-
with diabetes or hyperglycemia admit- costs saved when inpatient care is pro- trition or changes to medications that
ted to the hospital if an A1C test has not vided by a specialized diabetes manage- cause hyperglycemia. An admission A1C
been performed in the previous 3 months ment team (21,24,25). In a cross-sectional value $6.5% (48 mmol/mol) suggests that
(5–8). In addition, diabetes self-manage- study comparing usual care to specialists the onset of diabetes preceded hospitaliza-
ment knowledge and behaviors should reviewing diabetes cases and making tion (see Section 2, “Classification and
be assessed on admission, and diabetes recommendations virtually through the Diagnosis of Diabetes”) (33,34). Hypoglyce-
significantly higher mortality (27.5% vs. More frequent POC blood glucose moni- teams allow the use of CGM in selected
25%). The intensively treated group had toring ranging from every 30 min to every people with diabetes on an individual ba-
10- to 15-fold greater rates of hypoglyce- 2 h is the required standard for safe use sis, mostly in noncritical care settings, pro-
mia, which may have contributed to the of intravenous insulin. Safety standards vided both the individual and the glucose
adverse outcomes noted. The findings for blood glucose monitoring that prohibit management team are well educated in
from NICE-SUGAR are supported by sev- sharing lanceting devices, other testing the use of this technology. CGM is not cur-
eral meta-analyses and a randomized con- materials, and needles are mandatory (45). rently approved for intensive care unit use
trolled trial, some of which suggest that The vast majority of hospital glucose due to accuracy concerns such as hypovo-
tight glycemic management increases monitoring is performed with FDA-approved lemia, hypoperfusion, and use of therapies
mortality compared with more moder- prescription POC glucose monitoring sys- such as vasopressor agents.
ate glycemic targets and generally causes tems with and capillary blood taken from During the coronavirus disease 2019
higher rates of hypoglycemia (38–40). finger sticks, similar to the process per- (COVID-19) pandemic, many institutions
written or computerized protocols that safer procedure is administering pran- help minimize hyperglycemia and avoid
allow for predefined adjustments in the dial insulin immediately after eating, rebound hypoglycemia (83,84). The dose
infusion rate, accounting for glycemic with the dose adjusted to be appropriate of basal insulin is best calculated on the
fluctuations and insulin dose (64). for the amount of carbohydrates ingested basis of the insulin infusion rate during
(71). the last 6 h when stable glycemic goals
Noncritical Care Setting A randomized controlled trial has shown were achieved (85). For people being transi-
In most instances, insulin is the pre- that basal-bolus treatment improved glyce- tioned to concentrated insulin (U-200,
ferred treatment for hyperglycemia in mic outcomes and reduced hospital com- U-300, or U-500) in the inpatient setting,
hospitalized patients. However, in certain plications compared with a correction or it is important to ensure correct dosing
circumstances, it may be appropriate to supplemental insulin without basal insulin by utilizing an individual pen or cartridge
continue home therapies, including oral (formerly known as sliding scale) in general for each person and by meticulous phar-
glucose-lowering medications (64,65). If surgery for people with type 2 diabetes macy and nursing supervision of the dose
oral medications are held in the hospital (74). Prolonged use of correction or sup- administered (85,86).
16.10 Treatment regimens should the hospital (103), possibly as a result the risk for a subsequent event, partly
be reviewed and changed as of decreased insulin clearance. Studies because of impaired counterregulation
necessary to prevent further of “bundled” preventive therapies, includ- (108,109). This relationship also holds
hypoglycemia when a blood ing proactive surveillance of glycemic true for people with diabetes in the in-
glucose value of <70 mg/dL outliers and an interdisciplinary data- patient setting. For example, in a study of
(3.9 mmol/L) is documented. C driven approach to glycemic management, hospitalized individuals treated for hyper-
showed that hypoglycemic episodes in glycemia, 84% who had an episode of
the hospital could be prevented. Com- “severe hypoglycemia” (defined in the
People with or without diabetes may pared with baseline, two such studies study as <40 mg/dL [2.2 mmol/L]) had
experience hypoglycemia in the hospital found that hypoglycemic events fell by a preceding episode of hypoglycemia
setting. While hypoglycemia is associated 56–80% (99,104,105). The Joint Commis- (<70 mg/dL [3.9 mmol/L]) during the
with increased mortality (97), in many sion recommends that all hypoglycemic same admission (110). In another study
the menu at any time during the day. This STANDARDS FOR SPECIAL nutrition bag is the safest way to prevent
option improves patient satisfaction but SITUATIONS hypoglycemia if the parenteral nutrition
complicates meal-insulin coordination. Enteral/Parenteral Feedings is stopped or interrupted. Correctional
Finally, if the hospital food service sup- For individuals receiving enteral or par- insulin should be administered subcu-
ports carbohydrate counting, this option enteral feedings who require insulin, taneously to address any hyperglyce-
should be made available to people the insulin orders should include cover- mia. For full enteral/parenteral feeding
with diabetes counting carbohydrates age of basal, prandial, and correctional guidance, please refer to review articles
at home (115,116). needs (115,122,123). It is essential that detailing this topic (122,124,125).
people with type 1 diabetes continue to Because continuous enteral or paren-
SELF-MANAGEMENT IN THE receive basal insulin even if feedings are teral nutrition results in a continuous
HOSPITAL discontinued. postprandial state, efforts to bring blood
Diabetes self-management in the hospi- Most adults receiving basal insulin glucose levels to below 140 mg/dL
improved time in range (70–180 mg/dL); insulin analogs on glycemia in periop- (146). Individuals with uncomplicated
however, there was an increase in hypo- erative care. DKA may sometimes be treated with
glycemia (133). Whatever insulin orders subcutaneous insulin in the emergency
are initiated, daily adjustments based on A recent review concluded that peri- department or step-down units (147).
levels of glycemia and anticipated changes operative glycemic targets tighter than This approach may be safer and more
in type, doses, and duration of glucocorti- 80–180 mg/dL (4.4–10.0 mmol/L) did cost-effective than treatment with intra-
coids, along with POC blood glucose moni- not improve outcomes and was asso- venous insulin. If subcutaneous insulin
toring, are critical to reducing rates of ciated with more hypoglycemia (137); administration is used, it is important to
hypoglycemia and hyperglycemia. therefore, in general, stricter glycemic provide an adequate fluid replacement,
targets are not advised. Evidence from frequent POC blood glucose monitoring,
Perioperative Care a recent study indicates that compared treatment of any concurrent infections,
It is estimated that up to 20% of general with usual dosing, a reduction of insulin and appropriate follow-up to avoid re-
given the evening before surgery by
within 1 month of discharge is advised place increases the likelihood that care reduce readmission rates (151,155).
for all individuals experiencing hyper- they will attend. While there is no standard to prevent re-
glycemia in the hospital. If glycemic admissions, several successful strate-
medications are changed or glucose It is recommended that the following gies have been reported (151). These
management is not optimal at discharge, areas of knowledge be reviewed and ad- include targeting ketosis-prone people
an earlier appointment (in 1–2 weeks) is dressed before hospital discharge: with type 1 diabetes (157), insulin treat-
preferred, and frequent contact may be ment of individuals with admission A1C
needed to avoid hyperglycemia and • Identification of the health care pro- >9% (75 mmol/mol) (158), and the use
hypoglycemia. A discharge algorithm fessionals who will provide diabetes of a transitional care model (159). For
for glycemic medication adjustment based care after discharge. people with diabetic kidney disease, col-
on admission A1C, diabetes medications • Level of understanding related to the laborative patient-centered medical
before admission, and insulin usage diabetes diagnosis, glucose monitor- homes may decrease risk-adjusted re-
ing, home glucose goals, and when to
11. Garg R, Schuman B, Bader A, et al. Effect of 27. Endocrine Society. Clinical Practice Guidelines. GLUCO-CABG trial. Diabetes Care 2015;38:1665–
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Ann Surg 2018;267:858–862 28. Magee MF, Baker KM, Bardsley JK, Wesley D, hyperglycemia and continuous intravenous insulin
12. van den Boom W, Schroeder RA, Manning Smith KM. Diabetes to go-inpatient: pragmatic infusions on outcomes of cardiac surgical
MW, Setji TL, Fiestan GO, Dunson DB. Effect of lessons learned from implementation of technology- procedures: the Portland Diabetic Project. Endocr
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planning from hospital to home. Cochrane Database 2022. Available from https://psnet.ahrq.gov/ Diabetic kidney disease: a report from an ADA
Managing the daily health demands of diabetes can be challenging. People living
with diabetes should not have to face discrimination due to diabetes. By advocat-
ing for the rights of those with diabetes at all levels, the American Diabetes Associ-
ation (ADA) can help to ensure that they live a healthy and productive life. A
strategic goal of the ADA is for more children and adults with diabetes to live free
from the burden of discrimination. The ADA is also focused on making sure cost is
not a barrier to successful diabetes management.
One tactic for achieving these goals has been to implement the ADA Standards of
Care through advocacy-oriented position statements. The ADA publishes evidence-based,
peer-reviewed statements on topics such as diabetes and employment, diabetes and
driving, insulin access and affordability, and diabetes management in certain settings such
as schools, childcare programs, and detention facilities. In addition to the ADA’s clinical
documents, these advocacy statements are important tools in educating schools, employ-
ers, licensing agencies, policy makers, and others about the intersection of diabetes man-
agement and the law and for providing scientifically supported policy recommendations.
ADVOCACY STATEMENTS
The following is a partial list of advocacy statements ordered by publication date, with
the most recent statement appearing first. A comprehensive list of advocacy state- Disclosure information for each author is
ments is available at professional.diabetes.org/content/key-statements-and-reports. available at https://doi.org/10.2337/dc23-SDIS.
Suggested citation: ElSayed NA, Aleppo G,
Insulin Access and Affordability Aroda VR, et al., American Diabetes Association.
The ADA’s Insulin Access and Affordability Working Group compiled public informa- 17. Diabetes advocacy: Standards of Care in
Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):
tion and convened a series of meetings with stakeholders throughout the insulin S279–S280
supply chain to learn how each entity affects the cost of insulin for the consumer.
Their conclusions and recommendations are published in an ADA statement (1). © 2022 by the American Diabetes Association.
Readers may use this article as long as the
work is properly cited, the use is educational
Diabetes Care in the School Setting and not for profit, and the work is not altered.
A sizable portion of a child’s day is spent in school, so close communication with More information is available at https://www.
and training and cooperation of school personnel are essential to optimize diabetes diabetesjournals.org/journals/pages/license.
S280 Diabetes Advocacy Diabetes Care Volume 46, Supplement 1, January 2023
management, safety, and access to all licensing requirements applied by both diabetes for employment, including how
school-sponsored opportunities. Refer state and federal jurisdictions. For an an assessment should be performed and
to the published ADA position state- overview of existing licensing rules for what changes (accommodations) in the
ment for diabetes management infor- people with diabetes, factors that impact workplace may be needed for an individ-
mation for students with diabetes in driving for this population, and general ual with diabetes, refer to the published
elementary and secondary school set- guidelines for assessing driver fitness and ADA position statement (5).
tings (2). determining appropriate licensing restric-
tions, refer to the published ADA position References
Care of Young Children With 1. Cefalu WT, Dawes DE, Gavlak G, et al.; Insulin
statement (4).
Diabetes in the Childcare Setting Access and Affordability Working Group. Insulin
Editor’s note: Federal commercial driv- Access and Affordability Working Group: conclusions
Very young children (aged <6 years) with
ing rules for individuals with insulin- and recommendations [published correction
diabetes have legal protections and can appears in Diabetes Care 2018;41:1831]. Diabetes
treated diabetes changed on 19 November
be safely cared for by childcare professio-