THE JOURNAL OF CLINICAL AND APPLIED RESEARCH AND EDUCATION VOLUME 41 | SUPPLEMENT 1
W W W. D I A B E T E S . O R G / D I A B E T E S C A R E JANUARY 2018
PPLEMESUNT
1
AMERICAN DIABETES ASSOCIATION
STANDARDS OF
MEDICAL CARE
IN DIABETES—2018
ISSN 0149-5992
January 2018 Volume 41, Supplement 1 [T]he simple word Care may suffice to express [the journal’s] philosophical
mission. The new journal is designed to promote better patient care by
EDITOR IN CHIEF serving the expanded needs of all health professionals committed to the care
of patients with diabetes. As such, the American Diabetes Association views
Matthew C. Riddle, MD Diabetes Care as a reaffirmation of Francis Weld Peabody’s contention that
“the secret of the care of the patient is in caring for the patient.”
ASSOCIATE EDITORS
—Norbert Freinkel, Diabetes Care, January-February 1978
George Bakris, MD
Lawrence Blonde, MD, FACP EDITORIAL BOARD Maureen Monaghan, PhD, CDE
Andrew J.M. Boulton, MD Kristen J. Nadeau, MD, MS
David D’Alessio, MD Nicola Abate, MD Kwame Osei, MD
Mary de Groot, PhD Vanita R. Aroda, MD Kevin A. Peterson, MD, MPH, FRCS(Ed),
Eddie L. Greene, MD Geremia Bolli, MD
Frank B. Hu, MD, MPH, PhD John B. Buse, MD, PhD FAAFP
Steven E. Kahn, MB, ChB Robert J. Chilton, DO, FACC, FAHA Jonathan Q. Purnell, MD
Sanjay Kaul, MD, FACC, FAHA Kenneth Cusi, MD, FACP, FACE Peter Reaven, MD
Derek LeRoith, MD, PhD Paresh Dandona, MD, PhD Ravi Retnakaran, MD, MSc, FRCPC
Robert G. Moses, MD J. Hans DeVries, MD, PhD Helena Wachslicht Rodbard, MD
Stephen Rich, PhD Ele Ferrannini, MD Elizabeth Seaquist, MD
Julio Rosenstock, MD Franco Folli, MD, PhD Guntram Schernthaner, MD
William V. Tamborlane, MD Meredith A. Hawkins, MD, MS David J. Schneider, MD
Judith Wylie-Rosett, EdD, RD Richard Hellman, MD Norbert Stefan, MD
Norbert Hermanns, PhD, MSc Jan S. Ulbrecht, MB, BS
Irl B. Hirsch, MD, MACP Joseph Wolfsdorf, MD, BCh
George S. Jeha, MD Tien Yin Wong, MBBS, FRCSE, FRANZCO,
Lee M. Kaplan, MD, PhD
M. Sue Kirkman, MD MPH, PhD
Ildiko Lingvay, MD, MPH, MSCS Bernard Zinman, CM, MD, FRCPC, FACP
Harold David McIntyre, MD, FRACP
AMERICAN DIABETES ASSOCIATION OFFICERS
CHAIR OF THE BOARD PRESIDENT-ELECT, MEDICINE & SCIENCE
Karen Talmadge, PhD Louis Philipson, MD
PRESIDENT, MEDICINE & SCIENCE PRESIDENT-ELECT, HEALTH CARE &
EDUCATION
Jane Reusch, MD
Gretchen Youssef, MS, RD, CDE
PRESIDENT, HEALTH CARE &
EDUCATION SECRETARY/TREASURER-ELECT
Felicia Hill-Briggs, PhD, ABPP Brian Bertha, JD, MBA
SECRETARY/TREASURER INTERIM CHIEF EXECUTIVE OFFICER
Michael Ching, CPA Martha Parry Clark
CHAIR OF THE BOARD-ELECT CHIEF SCIENTIFIC, MEDICAL & MISSION OFFICER
David J. Herrick, MBA William T. Cefalu, MD
The mission of the American Diabetes Association
is to prevent and cure diabetes and to improve
the lives of all people affected by diabetes.
PRINT ISSN 0149-5992 Diabetes Care is a journal for the health care practitioner that is intended to
ONLINE ISSN 1935-5548 increase knowledge, stimulate research, and promote better management of people
PRINTED IN THE USA with diabetes. To achieve these goals, the journal publishes original research on
human studies in the following categories: Clinical Care/Education/Nutrition/
Psychosocial Research, Epidemiology/Health Services Research, Emerging
Technologies and Therapeutics, Pathophysiology/Complications, and Cardiovascular
and Metabolic Risk. The journal also publishes ADA statements, consensus reports,
clinically relevant review articles, letters to the editor, and health/medical news or points
of view. Topics covered are of interest to clinically oriented physicians, researchers,
epidemiologists, psychologists, diabetes educators, and other health professionals.
More information about the journal can be found online at care.diabetesjournals.org.
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January 2018 Volume 41, Supplement 1
Standards of Medical Care in Diabetes—2018
S1 Introduction S86 9. Cardiovascular Disease and Risk
S3 Professional Practice Committee Management
S4 Summary of Revisions: Standards of Medical Care in
Hypertension/Blood Pressure Control
Diabetes—2018 Lipid Management
S7 1. Improving Care and Promoting Health in Antiplatelet Agents
Coronary Heart Disease
Populations
S105 10. Microvascular Complications and Foot Care
Diabetes and Population Health
Tailoring Treatment for Social Context Diabetic Kidney Disease
Diabetic Retinopathy
S13 2. Classification and Diagnosis of Diabetes Neuropathy
Foot Care
Classification
Diagnostic Tests for Diabetes S119 11. Older Adults
Categories of Increased Risk for Diabetes (Prediabetes)
Type 1 Diabetes Neurocognitive Function
Type 2 Diabetes Hypoglycemia
Gestational Diabetes Mellitus Treatment Goals
Monogenic Diabetes Syndromes Pharmacologic Therapy
Cystic Fibrosis–Related Diabetes Treatment in Skilled Nursing Facilities
Posttransplantation Diabetes Mellitus
and Nursing Homes
S28 3. Comprehensive Medical Evaluation and End-of-Life Care
Assessment of Comorbidities
S126 12. Children and Adolescents
Patient-Centered Collaborative Care
Comprehensive Medical Evaluation Type 1 Diabetes
Assessment of Comorbidities Type 2 Diabetes
Transition From Pediatric to Adult Care
S38 4. Lifestyle Management
S137 13. Management of Diabetes in Pregnancy
Diabetes Self-Management Education and Support
Nutrition Therapy Diabetes in Pregnancy
Physical Activity Preconception Counseling
Smoking Cessation: Tobacco and e-Cigarettes Glycemic Targets in Pregnancy
Psychosocial Issues Management of Gestational Diabetes Mellitus
Management of Preexisting Type 1 Diabetes
S51 5. Prevention or Delay of Type 2 Diabetes
and Type 2 Diabetes in Pregnancy
Lifestyle Interventions Pregnancy and Drug Considerations
Pharmacologic Interventions Postpartum Care
Prevention of Cardiovascular Disease
Diabetes Self-management Education and Support S144 14. Diabetes Care in the Hospital
S55 6. Glycemic Targets Hospital Care Delivery Standards
Glycemic Targets in Hospitalized Patients
Assessment of Glycemic Control Bedside Blood Glucose Monitoring
A1C Testing Antihyperglycemic Agents in Hospitalized Patients
A1C Goals Hypoglycemia
Hypoglycemia Medical Nutrition Therapy in the Hospital
Intercurrent Illness Self-management in the Hospital
Standards for Special Situations
S65 7. Obesity Management for the Treatment of Type 2 Transition From the Acute Care Setting
Diabetes Preventing Admissions and Readmissions
Assessment S152 15. Diabetes Advocacy
Diet, Physical Activity, and Behavioral Therapy
Pharmacotherapy Advocacy Position Statements
Metabolic Surgery
S154 Professional Practice Committee, American College of
S73 8. Pharmacologic Approaches to Glycemic Treatment Cardiology—Designated Representatives, and
American Diabetes Association Staff Disclosures
Pharmacologic Therapy for Type 1 Diabetes
Surgical Treatment for Type 1 Diabetes S156 Index
Pharmacologic Therapy for Type 2 Diabetes
This issue is freely accessible online at care.diabetesjournals.org.
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Diabetes Care Volume 41, Supplement 1, January 2018 S3 PROFESSIONAL PRACTICE COMMITTEE
Professional Practice Committee:
Standards of Medical Care in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S3 | https://doi.org/10.2337/dc18-SPPC01
The Professional Practice Committee (see pp. S154–S155). The ADA funds de- CPsychol; Jane Reusch, MD; and Sharon
(PPC) of the American Diabetes Asso- velopment of the Standards of Care out of Solomon, MD.
ciation (ADA) is responsible for the its general revenues and does not use in-
“Standards of Medical Care in Diabetes” dustry support for this purpose. MEMBERS OF THE PPC
position statement, referred to as the Rita R. Kalyani, MD, MHS, FACP (Chair)
Standards of Care. The PPC is a multidis- For the current revision, PPC members Christopher P. Cannon, MD
ciplinary expert committee comprised systematically searched MEDLINE for hu- Andrea L. Cherrington, MD, MPH*
of physicians, diabetes educators, regis- man studies related to each section and Donald R. Coustan, MD
tered dietitians, and others who have published since 1 January 2017. Recom- Ian H. de Boer, MD, MS*
expertise in a range of areas, including mendations were revised based on new Hope Feldman, CRNP, FNP-BC
adult and pediatric endocrinology, epi- evidence or, in some cases, to clarify the Judith Fradkin, MD
demiology, public health, lipid research, prior recommendation or match the David Maahs, MD, PhD
hypertension, preconception planning, strength of the wording to the strength Melinda Maryniuk, MEd, RD, CDE
and pregnancy care. Appointment to of the evidence. A table linking the Medha N. Munshi, MD*
the PPC is based on excellence in clinical changes in recommendations to new ev- Joshua J. Neumiller, PharmD, CDE, FASCP
practice and research. Although the pri- idence can be reviewed at professional Guillermo E. Umpierrez, MD, CDE, FACE, FACP*
mary role of the PPC is to review and .diabetes.org/SOC. The Standards of Care *Subgroup leaders
update the Standards of Care, it may was approved by ADA’s Board of Directors,
also be involved in ADA statements, re- which includes health care professionals, AMERICAN COLLEGE OF
ports, and reviews. scientists, and lay people. CARDIOLOGY—DESIGNATED
REPRESENTATIVES (SECTION 9)
The ADA adheres to the National Feedback from the larger clinical com- Sandeep Das, MD, MPH, FACC
Academy of Medicine Standards for De- munity was valuable for the 2017 revision Mikhail Kosiborod, MD, FACC
veloping Trustworthy Clinical Practice of the Standards of Care. Readers who
Guidelines. All members of the PPC wish to comment on the 2018 Standards ADA STAFF
are required to disclose potential con- of Care are invited to do so at professional Erika Gebel Berg, PhD
flicts of interest with industry and/or .diabetes.org/SOC. (Corresponding author: [email protected])
other relevant organizations. These dis- Tamara Darsow, PhD
closures are discussed at the onset of The PPC would like to thank the follow- Matthew P. Petersen
each Standards of Care revision meet- ing individuals who provided their exper- Sacha Uelmen, RDN, CDE
ing. Members of the committee, their tise in reviewing and/or consulting with William T. Cefalu, MD
employers, and their disclosed conflicts the committee: Pamela Allweiss, MD, MPH;
of interest are listed in the “Professional David D’Alessio, MD; Thomas Gardner,
Practice Committee Disclosures” table MD, MS; William H. Herman, MD, MPH;
Felicia Hill-Briggs, PhD; Nisa Maruthur,
MD, MHS; Alicia McAuliffe-Fogarty, PhD,
© 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
Diabetes Care Volume 41, Supplement 1, January 2018 S1
Introduction: Standards of Medical INTRODUCTION
Care in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S1–S2 | https://doi.org/10.2337/dc18-SINT01
Diabetes is a complex, chronic illness re- continue to rely on them as the most au- current position. The Standards of Care
quiring continuous medical care with mul- thoritative and current guidelines for dia- receives annual review and approval by
tifactorial risk-reduction strategies beyond betes care. Readers who wish to comment the ADA Board of Directors.
glycemic control. Ongoing patient self- on the 2018 Standards of Care are invited
management education and support are to do so at professional.diabetes.org/SOC. ADA Statement
critical to preventing acute complications An ADA statement is an official ADA point
and reducing the risk of long-term compli- ADA STANDARDS, STATEMENTS, of view or belief that does not contain clin-
cations. Significant evidence exists that REPORTS, and REVIEWS ical practice recommendations and may be
supports a range of interventions to im- issued on advocacy, policy, economic, or
prove diabetes outcomes. The ADA has been actively involved in the medical issues related to diabetes. ADA
development and dissemination of diabe- statements undergo a formal review pro-
The American Diabetes Association’s tes care standards, guidelines, and related cess, including a review by the appropriate
(ADA’s) “Standards of Medical Care in documents for over 25 years. The ADA’s national committee, ADA mission staff, and
Diabetes,” referred to as the Standards clinical practice recommendations are the Board of Directors.
of Care, is intended to provide clinicians, viewed as important resources for health
patients, researchers, payers, and other care professionals who care for people Consensus Report
interested individuals with the compo- with diabetes. An expert consensus report of a particu-
nents of diabetes care, general treatment lar topic contains a comprehensive ex-
goals, and tools to evaluate the quality of Standards of Care amination and is authored by an expert
care. The Standards of Care recommen- This document is an official ADA position, panel (i.e., consensus panel) and repre-
dations are not intended to preclude clin- is authored by the ADA, and provides all sents the panel’s collective analysis, eval-
ical judgment and must be applied in the of the ADA’s current clinical practice rec- uation, and opinion. The need for an
context of excellent clinical care, with ommendations. To update the Standards expert consensus report arises when clini-
adjustments for individual preferences, of Care, the ADA’s Professional Practice cians, scientists, regulators, and/or policy
comorbidities, and other patient factors. Committee (PPC) performs an extensive makers desire guidance and/or clarity
For more detailed information about clinical diabetes literature search, supple- on a medical or scientific issue related
management of diabetes, please refer to mented with input from ADA staff and the to diabetes for which the evidence
Medical Management of Type 1 Diabetes medical community at large. The PPC up- is contradictory, emerging, or incomplete.
(1) and Medical Management of Type 2 dates the Standards of Care annually, or Expert consensus reports may also high-
Diabetes (2). more frequently online should the PPC light gaps in evidence and propose areas
determine that new evidence or regula- of future research to address these gaps.
The recommendations include screen- tory changes (e.g., drug approvals, label An expert consensus report is not an ADA
ing, diagnostic, and therapeutic actions changes) merit immediate incorporation. position and represents expert opinion
that are known or believed to favorably The Standards of Care supersedes all pre- only but is produced under the auspices
affect health outcomes of patients with di- vious ADA position statementsdand the of the Association by invited experts. An
abetes. Many of these interventions have recommendations thereindon clinical expert consensus report may be devel-
also been shown to be cost-effective (3). topics within the purview of the Stand- oped after an ADA Clinical Conference
ards of Care; ADA position statements, or Research Symposium.
The ADA strives to improve and update while still containing valuable analyses,
the Standards of Care to ensure that clini- should not be considered the ADA’s
cians, health plans, and policy makers can
“Standards of Medical Care in Diabetes” was originally approved in 1988.
© 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
S2 Introduction Diabetes Care Volume 41, Supplement 1, January 2018
Table 1—ADA evidence-grading system for “Standards of Medical Care in Diabetes” B, or C, depending on the quality of evi-
dence. Expert opinion E is a separate cat-
Level of evidence Description egory for recommendations in which
there is no evidence from clinical trials,
A Clear evidence from well-conducted, generalizable in which clinical trials may be impractical,
randomized controlled trials that are adequately or in which there is conflicting evidence.
powered, including
c Evidence from a well-conducted multicenter trial Recommendations with an A rating are
c Evidence from a meta-analysis that incorporated based on large well-designed clinical trials
quality ratings in the analysis or well-done meta-analyses. Generally,
these recommendations have the best
Compelling nonexperimental evidence, i.e., “all or none” chance of improving outcomes when ap-
rule developed by the Centre for Evidence-Based plied to the population to which they
Medicine at the University of Oxford are appropriate. Recommendations
with lower levels of evidence may be
Supportive evidence from well-conducted randomized equally important but are not as well
controlled trials that are adequately powered, including supported.
c Evidence from a well-conducted trial at one or more
institutions Of course, evidence is only one compo-
c Evidence from a meta-analysis that incorporated nent of clinical decision- making. Clini-
quality ratings in the analysis cians care for patients, not populations;
guidelines must always be interpreted
B Supportive evidence from well-conducted cohort studies with the individual patient in mind. Indi-
c Evidence from a well-conducted prospective cohort vidual circumstances, such as comorbid
study or registry and coexisting diseases, age, education,
c Evidence from a well-conducted meta-analysis of disability, and, above all, patients’ val-
cohort studies ues and preferences, must be considered
and may lead to different treatment tar-
Supportive evidence from a well-conducted case-control gets and strategies. Furthermore, con-
study ventional evidence hierarchies, such as
the one adapted by the ADA, may miss
C Supportive evidence from poorly controlled or nuances important in diabetes care. For
uncontrolled studies example, although there is excellent evi-
c Evidence from randomized clinical trials with one or dence from clinical trials supporting the
more major or three or more minor methodological importance of achieving multiple risk
flaws that could invalidate the results factor control, the optimal way to achieve
c Evidence from observational studies with high this result is less clear. It is difficult to as-
potential for bias (such as case series with comparison sess each component of such a complex
with historical controls) intervention.
c Evidence from case series or case reports
References
Conflicting evidence with the weight of evidence 1. American Diabetes Association. Medical Man-
supporting the recommendation agement of Type 1 Diabetes. 7th ed. Wang CC,
Shah AC, Eds. Alexandria, VA, American Diabetes
E Expert consensus or clinical experience Association, 2017
2. American Diabetes Association. Medical Man-
Scientific Review evolution in the evaluation of scientific evi- agement of Type 2 Diabetes. 7th ed. Burant CF,
A scientific review is a balanced review dence and in the development of evidence- Young LA, Eds. Alexandria, VA, American Diabetes
and analysis of the literature on a scien- based guidelines. In 2002, the ADA devel- Association, 2012
tific or medical topic related to diabetes. oped a classification system to grade the 3. Li R, Zhang P, Barker LE, Chowdhury FM, Zhang
A scientific review is not an ADA position quality of scientific evidence supporting X. Cost-effectiveness of interventions to prevent
and does not contain clinical practice ADA recommendations. A 2015 analysis of and control diabetes mellitus: a systematic re-
recommendations but is produced un- the evidence cited in the Standards of Care view. Diabetes Care 2010;33:1872–1894
der the auspices of the Association by found steady improvement in quality 4. Grant RW, Kirkman MS. Trends in the evi-
invited experts. The scientific review may over the previous 10 years, with the dence level for the American Diabetes Associ-
provide a scientific rationale for clini- 2014 Standards of Care for the first time ation’s “Standards of Medical Care in Diabetes”
cal practice recommendations in the having the majority of bulleted recom- from 2005 to 2014. Diabetes Care 2015;38:
Standards of Care. The category may also mendations supported by A- or B-level 6–8
include task force and expert committee evidence (4). A grading system (Table 1)
reports. developed by the ADA and modeled
after existing methods was used to clarify
GRADING OF SCIENTIFIC EVIDENCE and codify the evidence that forms the
basis for the recommendations. ADA rec-
Since the ADA first began publishing practice ommendations are assigned ratings of A,
guidelines, there has been considerable
S4 Diabetes Care Volume 41, Supplement 1, January 2018
SUMMARY OF REVISIONS Summary of Revisions: Standards of Medical Care
in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S4–S6 | https://doi.org/10.2337/dc18-SREV01
GENERAL CHANGES A new recommendation was added The immunization section was updated
about using reliable data metrics to assess for clarity to more closely align with rec-
The field of diabetes care is rapidly changing and improve the quality of diabetes care ommendations from the Centers for Dis-
as new research, technology, and treat- and reduce costs. ease Control and Prevention.
ments that can improve the health and
well-being of people with diabetes continue Additional discussion was included on Text was added about the importance
to emerge. With annual updates since 1989, the social determinants of health. of language choice in patient-centered
the American Diabetes Association’s (ADA’s) communication.
“Standards of Medical Care in Diabetes” Text was added describing the emerg-
(Standards of Care) has long been a leader ing use of telemedicine in diabetes care. Pancreatitis was added to the section
in producing guidelines that capture the on comorbidities, including a new recom-
most current state of the field. Starting in Section 2. Classification and Diagnosis mendation about the consideration of
2018, the ADA will update the Standards of of Diabetes islet autotransplantation to prevent post-
Care even more frequently online should As a result of recent evidence describing surgical diabetes in patients with medi-
the Professional Practice Committee de- potential limitations in A1C measure- cally refractory chronic pancreatitis who
termine that new evidence or regulatory ments due to hemoglobin variants, assay require total pancreatectomy.
changes merit immediate incorporation interference, and conditions associated
into the Standards of Care. In addition, with red blood cell turnover, additional A recommendation was added to
the Standards of Care will now become recommendations were added to clarify consider checking serum testosterone in
the ADA’s sole source of clinical practice the appropriate use of the A1C test gener- men with diabetes and signs and symp-
recommendations, superseding all prior ally and in the diagnosis of diabetes in toms of hypogonadism.
position and scientific statements. The these special cases.
change is intended to clarify the Associa- Section 4. Lifestyle Management
tion’s current positions by consolidating The recommendation for testing for A recommendation was modified to in-
all clinical practice recommendations into prediabetes and type 2 diabetes in children clude individual and group settings as
the Standards of Care. For further informa- and adolescents was changed, suggesting well as technology-based platforms for
tion on changes to the classification and testing for youth who are overweight or the delivery of effective diabetes self-
definitions of ADA Standards of Care, obese and have one or more additional management education and support.
statements, reports, and reviews, see risk factors (Table 2.5).
the Introduction. Additional explanation was added to
A clarification was added that, while the nutrition section to clarify the ADA’s
Although levels of evidence for several generally not recommended, commu- recommendations that there is no univer-
recommendations have been updated, nity screening may be considered in sal ideal macronutrient distribution and
these changes are not addressed below specific situations where an adequate that eating plans should be individualized.
as the clinical recommendations have re- referral system for positive tests is
mained the same. Changes in evidence level established. Text was added to address the role of
from, for example, E to C are not noted low-carbohydrate diets in people with
below. The 2018 Standards of Care con- Additional detail was added regarding diabetes.
tains, in addition to many minor changes current research on antihyperglycemic
that clarify recommendations or reflect treatment in people with posttransplan- Section 5. Prevention or Delay of
new evidence, the following more substan- tation diabetes mellitus. Type 2 Diabetes
tive revisions. The recommendation regarding the use of
Section 3. Comprehensive Medical metformin in the prevention of prediabe-
SECTION CHANGES Evaluation and Assessment of tes was reworded to better reflect the data
Comorbidities from the Diabetes Prevention Program.
Section 1. Improving Care and The table describing the components of a
Promoting Health in Populations comprehensive medical evaluation (Table Section 6. Glycemic Targets
This section was renamed to better capture its 3.1) was substantially redesigned and re- Based on new data, the recommendation
subject matter and was reorganized for clarity. organized, incorporating information about for the use of continuous glucose monitor-
the recommended frequency of the compo- ing (CGM) in adults with type 1 diabetes is
nents of care at both initial and follow-up no longer limited to those ages 25 and
visits. above but has been expanded to all adults
© 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
care.diabetesjournals.org Summary of Revisions S5
(18 and above) who are not meeting glyce- Section 9. Cardiovascular Disease that combines information on staging
mic targets. and Risk Management chronic kidney disease and the appro-
A new recommendation was added that all priate kidney-related care for each stage.
Additional text was added about a new hypertensive patients with diabetes should
intermittent or “flash” CGM device that monitor their blood pressure at home to help A new Table 10.2 was included describ-
was recently approved for adult use. identify masked or white coat hypertension, as ing the complications of chronic kidney
well as to improve medication-taking behavior. disease and related medical and labora-
Details were added about new CGM de- tory evaluations.
vices that no longer require confirmatory A new figure (Fig. 9.1) was added to
self-monitoring of blood glucose for treat- illustrate the recommended antihyper- A new section on acute kidney injury
ment decisions. tensive treatment approach for adults was included.
with diabetes and hypertension.
As in Section 2, this section now includes The effect of specific glucose-lowering
an expanded discussion of the limitations A new table (Table 9.1) was added sum- medications on the delay and progression
of A1C in certain populations based on the marizing studies of intensive versus stan- of kidney disease was discussed, with ref-
presence of hemoglobin variants, differ- dard hypertension treatment strategies. erence to recent CVOT trials that examined
ences in red blood cell turnover rates, eth- kidney effects as secondary outcomes.
nicity, and age. A recommendation was added to consider
mineralocorticoid receptor antagonist ther- A new recommendation was added on
To clarify the classification of hypogly- apy in patients with resistant hypertension. the noninferiority of the anti–vascular endo-
cemia, level 1 hypoglycemia was renamed thelial growth factor treatment ranibizumab
“hypoglycemia alert value” from “glucose The lipid management recommendations in reducing the risk of vision loss in patients
alert value.” were modified to stratify risk based on two with proliferative diabetic retinopathy
broad categories: those with documented when compared with the traditional stan-
Section 7. Obesity Management ASCVD and those without. dard treatment, panretinal laser photoco-
for the Treatment of Type 2 Diabetes agulation therapy.
To provide a second set of cost informa- Owing to studies suggesting similar ben-
tion, the table of medications for the efits in older versus middle-aged adults, recom- A new section was added describing
treatment of obesity (Table 7.2) was up- mendations were consolidated for patients the mixed evidence on the use of hyper-
dated to include National Average Drug with diabetes 40–75 years and .75 years of baric oxygen therapy in people with dia-
Acquisition Cost (NADAC) prices. age without ASCVD to use moderate-intensity betic foot ulcers.
statin.
Section 8. Pharmacologic Approaches Section 11. Older Adults
to Glycemic Treatment Table 9.2 (“Recommendations for sta- Three new recommendations were added
New recommendations for antihyperglyce- tin and combination treatment in adults to highlight the importance of individualiz-
mic therapy for adults with type 2 diabetes with diabetes”) was updated based on ing pharmacologic therapy in older adults to
have been added to reflect recent cardio- the new risk stratification approach and reduce the risk of hypoglycemia, avoid over-
vascular outcomes trial (CVOT) data, indi- consolidated age-groups. treatment, and simplify complex regimens if
cating that people with atherosclerotic possible while maintaining the A1C target.
cardiovascular disease (ASCVD) should be- To accommodate recent data on new
gin with lifestyle management and metfor- classes of lipid-lowering medications, a re- Section 12. Children and Adolescents
min and subsequently incorporate an commendation was modified to provide To make the section more comprehensive
agent proven to reduce major adverse additional guidance on adding nonstatin and to reflect emerging data on diabetes
cardiovascular events and/or cardiovascu- LDL-lowering therapies for patients with technologies, additional recommendations
lar mortality after considering drug-specific diabetes and ASCVD who have LDL choles- were added on the treatment of type 1
and patient factors. terol $70 mg/dL despite maximally toler- diabetes in children and adolescents regard-
ated statin dose. ing intensive insulin regimens, self-monitoring
The algorithm for antihyperglycemic ofbloodglucose,CGM,and automated insulin
treatment (Fig. 8.1) was updated to incor- The same recommendations were added delivery systems.
porate the new ASCVD recommendation. here as in Section 8 that people with type 2
diabetes and ASCVD should begin with life- The recommended risk-based timing of
A new table was added (Table 8.1) to style management and metformin and sub- celiac disease screenings for youth and ad-
summarize drug-specific and patient fac- sequently incorporate an agent proven to olescents with type 1 diabetes was defined.
tors of antihyperglycemic agents. Figure reduce major adverse cardiovascular events
8.1 and Table 8.1 are meant to be used and/or cardiovascular mortality after con- A recommendation regarding esti-
together to guide the choice of antihy- sidering drug-specific and patient factors. mating glomerular filtration rate was re-
perglycemic agents as part of patient– moved because of the poor performance
provider shared decision-making. The text was substantially modified to of the estimating equation in youth.
describe CVOT data on new diabetes agents
Table 8.2 was modified to focus on the and outcomes in people with type 2 diabe- The type 2 diabetes in children section
pharmacology and mechanisms of avail- tes, providing support for the new ASCVD was substantially expanded, with several
able glucose-lowering medicines in the recommendations. new recommendations, based on a re-
U.S. cent ADA review.
A new Table 9.4 was added to summa-
To provide a second set of cost infor- rize the CVOT studies. Section 13. Management of Diabetes
mation for antihyperglycemic agents, in Pregnancy
NADAC data was added to the average Section 10. Microvascular A recommendation was added to empha-
wholesale prices information in Table Complications and Foot Care size that insulin is the preferred agent for
8.3 and Table 8.4. A new table was added (Table 10.1), re-
placing previous tables 10.1 and 10.2,
S6 Summary of Revisions Diabetes Care Volume 41, Supplement 1, January 2018
the management of type 1 and type 2 di- type 1 and type 2 diabetes to take Section 14. Diabetes Care in the Hospital
abetes in pregnancy. low-dose aspirin starting at the end of Insulin degludec was added to the insulin
the first trimester to lower the risk of dosing for enteral/parenteral feedings
Based on new evidence, a recom- preeclampsia. (Table 14.1).
mendation was added for women with
Diabetes Care Volume 41, Supplement 1, January 2018 S7
1. Improving Care and Promoting American Diabetes Association
Health in Populations: Standards of
Medical Care in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S7–S12 | https://doi.org/10.2337/dc18-S001
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” 1. IMPROVING CARE AND PROMOTING HEALTH
includes ADA’s current clinical practice recommendations and is intended to provide
the components of diabetes care, general treatment goals and guidelines, and tools
to evaluate quality of care. Members of the ADA Professional Practice Committee, a
multi-disciplinary expert committee, are responsible for updating the Standards of
Care annually, or more frequently as warranted. For a detailed description of ADA
standards, statements, and reports, as well as the evidence-grading system for ADA’s
clinical practice recommendations, please refer to the Standards of Care Introduction.
Readers who wish to comment on the Standards of Care are invited to do so at
professional.diabetes.org/content/clinical-practice-recommendations.
DIABETES AND POPULATION HEALTH
Recommendations
c Ensure treatment decisions are timely, rely on evidence-based guidelines, and are
made collaboratively with patients based on individual preferences, prognoses, and
comorbidities. B
c Align approaches to diabetes management with the Chronic Care Model, em-
phasizing productive interactions between a prepared proactive care team and
an informed activated patient. A
c Care systems should facilitate team-based care, patient registries, decision sup-
port tools, and community involvement to meet patient needs. B
c Efforts to assess the quality of diabetes care and create quality improvement
strategies should incorporate reliable data metrics, to promote improved processes
of care and health outcomes, with simultaneous emphasis on costs. E
Population health is defined as “the health outcomes of a group of individuals, Suggested citation: American Diabetes Associa-
including the distribution of health outcomes within the group”; these outcomes tion. 1. Improving care and promoting health in
can be measured in terms of health outcomes (mortality, morbidity, health, and func- populations: Standards of Medical Care in
tional status), disease burden (incidence and prevalence), and behavioral and meta- Diabetesd2018. Diabetes Care 2018;41(Suppl.
bolic factors (exercise, diet, A1C, etc.) (1). Clinical practice recommendations for health 1):S7–S12
care providers are tools that can ultimately improve health across populations; how-
ever, for optimal outcomes, diabetes care must also be individualized for each patient. © 2017 by the American Diabetes Association.
Thus, efforts to improve population health will require a combination of system-level Readers may use this article as long as the work
and patient-level approaches. With such an integrated approach in mind, the American is properly cited, the use is educational and not
Diabetes Association (ADA) highlights the importance of patient-centered care, defined for profit, and the work is not altered. More infor-
as care that is respectful of and responsive to individual patient preferences, needs, and mation is available at http://www.diabetesjournals
values and that ensures that patient values guide all clinical decisions (2). Clinical .org/content/license.
S8 Improving Care and Promoting Health Diabetes Care Volume 41, Supplement 1, January 2018
practice recommendations, whether these factors into consideration and is psychosocial issues (25,26); and identify-
based on evidence or expert opinion, an effective framework for improving ing, developing, and engaging community
are intended to guide an overall ap- the quality of diabetes care (8). resources and public policies that support
proach to care. The science and art of healthy lifestyles (27). The National Diabe-
medicine come together when the clini- Six Core Elements. The CCM includes six tes Education Program maintains an on-
cian is faced with making treatment rec- core elements to optimize the care of pa- line resource (www.betterdiabetescare
ommendations for a patient who may tients with chronic disease: .nih.gov) to help health care professionals
not meet the eligibility criteria used in design and implement more effective
the studies on which guidelines are based. 1. Delivery system design (moving from a health care delivery systems for those
Recognizing that one size does not fit all, reactive to a proactive care delivery with diabetes.
the standards presented here provide system where planned visits are coordi-
guidance for when and how to adapt recom- nated through a team-based approach) The care team, which includes the pa-
mendations for an individual. tient, should prioritize timely and appro-
2. Self-management support priate intensification of lifestyle and/or
Care Delivery Systems 3. Decision support (basing care on evidence- pharmacologic therapy for patients who
Over the past 10 years, the proportion of have not achieved the recommended
patients with diabetes who achieve recom- based, effective care guidelines) metabolic targets (28–30). Strategies
mended A1C, blood pressure, and LDL cho- 4. Clinical information systems (using regis- shown to improve care team behavior
lesterol levels has increased (3). The mean and thereby catalyze reductions in A1C,
A1C nationally among people with diabe- tries that can provide patient-specific and blood pressure, and/or LDL cholesterol
tes has declined from 7.6% (60 mmol/mol) population-based support to the care include engaging in explicit and collabo-
in 1999–2002 to 7.2% (55 mmol/mol) in team) rative goal setting with patients (31,32);
2007–2010 based on the National Health 5. Community resources and policies identifying and addressing language,
and Nutrition Examination Survey (NHANES), (identifying or developing resources numeracy, or cultural barriers to care
with younger adults less likely to meet to support healthy lifestyles) (33–35); integrating evidence-based
treatment targets than older adults (3). 6. Health systems (to create a quality- guidelines and clinical information tools
This has been accompanied by improve- oriented culture) into the process of care (16,36,37); solic-
ments in cardiovascular outcomes and iting performance feedback, setting re-
has led to substantial reductions in end- Redefining the roles of the health care minders, and providing structured care
stage microvascular complications. delivery team and empowering patient (e.g., guidelines, formal case manage-
self-management are fundamental to ment, and patient education resources)
Nevertheless, 33–49% of patients still the successful implementation of the (7); and incorporating care management
do not meet targets for glycemic, blood CCM (9). Collaborative, multidisciplinary teams including nurses, dietitians, pharma-
pressure, or cholesterol control, and only teams are best suited to provide care cists, and other providers (17,38). Initiatives
14% meet targets for all three measures for people with chronic conditions such such as the Patient-Centered Medical
while also avoiding smoking (3). Evidence as diabetes and to facilitate patients’ Home show promise for improving health
suggests that progress in cardiovascular self-management (10–12). outcomes by fostering comprehensive
risk factor control (particularly tobacco primary care and offering new opportuni-
use) may be slowing (3,4). Certain seg- Strategies for System-Level Improvement ties for team-based chronic disease man-
ments of the population, such as young agement (39).
adults and patients with complex comor- Optimal diabetes management requires
bidities, financial or other social hard- an organized, systematic approach and For rural populations or those with lim-
ships, and/or limited English proficiency, the involvement of a coordinated team ited physical access to health care, teleme-
face particular challenges to goal-based of dedicated health care professionals dicine is an approach with a growing body
care (5–7). Even after adjusting for these working in an environment where patient- of evidence for its effectiveness, particu-
patient factors, the persistent variability centered high-quality care is a priority larly with regards to glycemic control as
in the quality of diabetes care across pro- (7,13,14). While many diabetes processes measured by A1C (40,41). Telemedicine
viders and practice settings indicates that of care have improved nationally in the is defined as the use of telecommunica-
substantial system-level improvements past decade, the overall quality of care for tions to facilitate remote delivery of health-
are still needed. patients with diabetes remains subopti- related services and clinical information
mal (15). Efforts to increase the quality (42). Interactive strategies that facilitate
Chronic Care Model of diabetes care include providing care communication between providers and
that is concordant with evidence-based patients, including the use of web-based
Numerous interventions to improve ad- guidelines (16); expanding the role of portal or text messaging and those that
herence to the recommended standards teams to implement more intensive dis- incorporate medication adjustment ap-
have been implemented. However, a ma- ease management strategies (7,17,18); pear more effective. There is limited data
jor barrier to optimal care is a delivery tracking medication-taking behavior at a available on the cost-effectiveness of these
system that is often fragmented, lacks systems level (19); redesigning the orga- strategies.
clinical information capabilities, dupli- nization of care process (20); implement-
cates services, and is poorly designed for ing electronic health record tools (21,22); Successful diabetes care also requires a
the coordinated delivery of chronic care. empowering and educating patients systematic approach to supporting patients’
The Chronic Care Model (CCM) takes (23,24); removing financial barriers and behavior change efforts. High-quality di-
reducing patient out-of-pocket costs abetes self-management education and
for diabetes education, eye exams, self-
monitoring of blood glucose, and necessary
medications (7); assessing and addressing
care.diabetesjournals.org Improving Care and Promoting Health S9
support (DSMES) has been shown to im- quality (48,49). Using patient registries can be drawn upon to inform systems-
prove patient self-management, satisfac- and electronic health records, health sys- level strategies in diabetes. For example,
tion, and glucose outcomes. National tems can evaluate the quality of diabetes the National Academy of Medicine has
DSMES standards call for an integrated care being delivered and perform inter- published a framework for educating
approach that includes clinical content vention cycles as part of quality improve- health care professionals on the impor-
and skills, behavioral strategies (goal set- ment strategies (50). Critical to these tance of social determinants of health. Fur-
ting, problem solving), and engagement efforts is provider adherence to clinical thermore, there are resources available for
with psychosocial concerns (26). For practice recommendations and accurate, the inclusion of standardized sociodemo-
more information on DSMES, see Section reliable data metrics that include socio- graphic variables in electronic medical re-
4 “Lifestyle Management.” demographic variables to examine health cords to facilitate the measurement of
equity within and across populations (51). health inequities as well as the impact of
In devising approaches to support dis- interventions designed to reduce those in-
ease self-management, it is notable that In addition to quality improvement equities (61–63).
in 23% of cases, uncontrolled A1C, blood efforts, other strategies that simulta-
pressure, or lipids was associated with neously improve the quality of care and Social determinants of health are not
poor medication-taking behaviors (19). could potentially reduce costs are gaining always recognized and often go undis-
At a system level, “adequate” medication momentum and include reimbursement cussed in the clinical encounter (57). A
taking is defined as 80% (calculated as the structures that, in contrast to visit-based study by Piette et al. (64) found that among
number of pills taken by the patient in a billing, reward the provision of appropriate patients with chronic illnesses, two-thirds
given time period divided by the number and high-quality care to achieve metabolic of those who reported not taking medi-
of pills prescribed by the physician in that goals (52) and incentives that accommo- cations as prescribed due to cost never
same time period) (19). If medication tak- date personalized care goals (7,53). shared this with their physician. In a
ing is 80% or above and treatment goals more recent study using data from the
are not met, then treatment intensifica- TAILORING TREATMENT FOR National Health Interview Survey (NHIS),
tion should be considered (e.g., uptitra- SOCIAL CONTEXT Patel et al. (57) found that half of adults
tion). Barriers to medication taking may with diabetes reported financial stress
include patient factors (remembering to Recommendations and one-fifth reported food insecurity
obtain or take medications, fear, depres- (FI). Creating systems-level mechanisms
sion, or health beliefs), medication factors c Providers should assess social con- to screen for social determinants of
(complexity, multiple daily dosing, cost, text, including potential food insecu- health may help overcome structural bar-
or side effects), and system factors (inad- rity, housing stability, and financial riers and communication gaps between
equate follow-up or support). Success in barriers, and apply that information patients and providers (57). In addition,
overcoming barriers to medication taking to treatment decisions. A brief, validated screening tools for some
may be achieved if the patient and pro- social determinants of health exist and
vider agree on a targeted approach for a c Refer patients to local community could facilitate discussion around factors
specific barrier (11). resources when available. B that significantly impact treatment during
the clinical encounter. Below is a discussion
The Affordable Care Act has resulted in c Provide patients with self-management of assessment and treatment consider-
increased access to care for many individ- support from lay health coaches, ations in the context of FI, homelessness,
uals with diabetes with an emphasis on navigators, or community health and limited English proficiency/low literacy.
health promotion and disease prevention workers when available. A
(43). As mandated by the Affordable Care Food Insecurity
Act, the Agency for Healthcare Research Health inequities related to diabetes and FI is the unreliable availability of nutri-
and Quality developed a National Quality its complications are well documented tious food and the inability to consistently
Strategy based on the triple aims that and are heavily influenced by social deter- obtain food without resorting to socially
include improving the health of a popula- minants of health (54–58). Social determi- unacceptable practices. Over 14% (or one
tion, overall quality and patient experi- nants of health are defined as the economic, of every seven people) of the U.S. popu-
ence of care, and per capita cost (44,45). environmental, political, and social condi- lation is food insecure. The rate is higher
As health care systems and practices tions in which people live and are responsi- in some racial/ethnic minority groups, in-
adapt to the changing landscape of health ble for a major part of health inequality cluding African American and Latino pop-
care, it will be important to integrate tra- worldwide (59). The ADA recognizes the ulations, in low-income households, and
ditional disease-specific metrics with association between social and environ- in homes headed by a single mother. The
measures of patient experience, as well mental factors and the prevention and risk for type 2 diabetes is increased twofold
as cost, in assessing the quality of diabe- treatment of diabetes and has issued a in those with FI (60). Risk for FI can be as-
tes care (46,47). Information and guid- call for research that seeks to better un- sessed with a validated two-item screen-
ance specific to quality improvement derstand how these social determinants ing tool (65) that includes the statements:
and practice transformation for diabetes influence behaviors and how the relation- 1) “Within the past 12 months we worried
care is available from the National Diabe- ships between these variables might be whether our food would run out before
tes Education Program practice transfor- modified for the prevention and manage- we got money to buy more” and 2)
mation website and the National Institute ment of diabetes (60). While a comprehen- “Within the past 12 months the food we
for Diabetes and Digestive and Kidney sive strategy to reduce diabetes-related bought just didn’t last and we didn’t have
Diseases report on diabetes care and health inequities in populations has not
been formally studied, general recommen-
dations from other chronic disease models
S10 Improving Care and Promoting Health Diabetes Care Volume 41, Supplement 1, January 2018
money to get more.” An affirmative re- be familiar with resources or have access in U.S. diabetes care, 1999-2010. N Engl J Med
sponse to either statement had a sensi- to social workers that can facilitate tem- 2013;368:1613–1624
tivity of 97% and specificity of 83%. porary housing for their patients as a way 4. Wang J, Geiss LS, Cheng YJ, et al. Long-term
to improve diabetes care. and recent progress in blood pressure levels
Treatment Considerations among U.S. adults with diagnosed diabetes,
Language Barriers 1988-2008. Diabetes Care 2011;34:1579–1581
In those with diabetes and FI, the priority Providers who care for non-English speak- 5. Kerr EA, Heisler M, Krein SL, et al. Beyond co-
is mitigating the increased risk for uncon- ers should develop or offer educational morbidity counts: how do comorbidity type and
trolled hyperglycemia and severe hypo- programs and materials in multiple lan- severity influence diabetes patients’ treatment
glycemia. Reasons for the increased risk guages with the specific goals of prevent- priorities and self-management? J Gen Intern
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rich processed foods, binge eating, finan- read or write in English. The National Stan- Language barriers, physician-patient language
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medication prescriptions, and anxiety/ propriate Services in Health and Health sured Latinos with diabetes: the Diabetes Study
depression leading to poor diabetes self- Care provide guidance on how health of Northern California (DISTANCE). J Gen Intern
care behaviors. Hypoglycemia can occur as a care providers can reduce language bar- Med 2011;26:170–176
result of inadequate or erratic carbohydrate riers by improving their cultural compe- 7. TRIAD Study Group. Health systems, patients
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assistance (68). The site offers a number 2010;33:940–947
If using a sulfonylurea in patients with of resources and materials that can be 8. Stellefson M, Dipnarine K, Stopka C. The
FI, glipizide may be considered due to its used to improve the quality of care deliv- Chronic Care Model and diabetes management
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may be costly, many pharmaceutical com- means of promoting translation of clinical 11. Katon WJ, Lin EHB, Von Korff M, et al. Collab-
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long-acting insulin analog may be prescribed (61), particularly in underserved commu- chronic care model in primary care settings: a
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30. Raebel MA, Ellis JL, Schroeder EB, et al. In- org/Home.aspx. Accessed 25 September 2017 60. Hill JO, Galloway JM, Goley A, et al. Socioeco-
tensification of antihyperglycemic therapy among 47. Burstin H, Johnson K. Getting to better care logical determinants of prediabetes and type 2
patients with incident diabetes: a Surveillance and outcomes for diabetes through measurement diabetes. Diabetes Care 2013;36:2430–2439
Prevention and Management of Diabetes Mellitus [article online], 2016. Available from http://www 61. Institute of Medicine. Capturing social and
(SUPREME-DM) study. Pharmacoepidemiol Drug .ajmc.com/journals/evidence-based-diabetes- behavioral domains and measures in electronic
Saf 2014;23:699–710 management/2016/march-2016/getting-to-better- health records: phase 2 [Internet], 2014. Wash-
31. Grant RW, Pabon-Nau L, Ross KM, Youatt EJ, care-and-outcomes-for-diabetes-through- ington, DC, The National Academies Press. Avail-
Pandiscio JC, Park ER. Diabetes oral medication measurement. Accessed 26 September 2017 able from https://www.nap.edu/catalog/18951/
initiation and intensification: patient views com- 48. National Institute of Diabetes and Digestive capturing-social-and-behavioral-domains-and-
pared with current treatment guidelines. Diabe- and Kidney Diseases. Practice transformation for measures-in-electronic-health-records. Accessed
tes Educ 2011;37:78–84 physicians & health care teams [Internet]. Avail- 26 September 2017
32. Tamhane S, Rodriguez-Gutierrez R, Hargraves I, able from https://www.niddk.nih.gov/health- 62. Chin MH, Clarke AR, Nocon RS, et al. A road-
Montori VM. Shared decision-making in diabetes information/health-communication-programs/ndep/ map and best practices for organizations to re-
care. Curr Diab Rep 2015;15:112 health-care-professionals/practice-transformation/ duce racial and ethnic disparities in health care.
33. Schillinger D, Piette J, Grumbach K, et al. Clos- Pages/resourcedetail.aspx. Accessed 26 September J Gen Intern Med 2012;27:992–1000
ing the loop: physician communication with dia- 2017 63. National Quality Forum. National voluntary
betic patients who have low health literacy. Arch 49. National Institute of Diabetes and Digestive consensus standards for ambulatory cared
Intern Med 2003;163:83–90 and Kidney Diseases. Diabetes care and quality: measuring healthcare disparities [Internet], 2008.
34. Rosal MC, Ockene IS, Restrepo A, et al. Ran- past, present, and future [Internet]. Available from Available from https://www.qualityforum.org/
domized trial of a literacy-sensitive, culturally tai- https://www.niddk.nih.gov/health-information/ Publications/2008/03/National_Voluntary_
lored diabetes self-management intervention for health-communication-programs/ndep/health-care- Consensus_Standards_for_Ambulatory_Care%E2%
low-income Latinos: Latinos en control. Diabetes professionals/practice-transformation/defining- 80%94Measuring_Healthcare_Disparities.aspx.
Care 2011;34:838–844 quality-care/diabetes-care-quality/Pages/default Accessed 21 October 2017
35. Osborn CY, Cavanaugh K, Wallston KA, et al. .aspx. Accessed 26 September 2017 64. Piette JD, Heisler M, Wagner TH. Cost-related
Health literacy explains racial disparities in diabe- 50. O’Connor PJ, Sperl-Hillen JM, Fazio CJ, medication underuse among chronically ill adults:
tes medication adherence. J Health Commun Averbeck BM, Rank BH, Margolis KL. Outpatient the treatments people forgo, how often, and who
2011;16(Suppl. 3):268–278 diabetes clinical decision support: current status and is at risk. Am J Public Health 2004;94:1782–1787
future directions. Diabet Med 2016;33:734–741
S12 Improving Care and Promoting Health Diabetes Care Volume 41, Supplement 1, January 2018
65. Hager ER, Quigg AM, Black MM, et al. Devel- prevention-chronic-care/improve/community/ conditions. Cochrane Database Syst Rev 2007;4:
opment and validity of a 2-item screen to identify index.html. Accessed 10 October 2016 CD005108
families at risk for food insecurity. Pediatrics 2010; 70. Shah M, Kaselitz E, Heisler M. The role of 74. Rosenthal EL, Rush CH, Allen CG; Project on
126:e26–e32 community health workers in diabetes: update CHW Policy & Practice. Understanding scope and
66. Seligman HK, Schillinger D. Hunger and socio- on current literature. Curr Diab Rep 2013;13: competencies: a contemporary look at the United
economic disparities in chronic disease. N Engl J 163–171 States community health worker field: progress report
Med 2010;363:6–9 71. Heisler M, Vijan S, Makki F, Piette JD. Diabe- of the community health worker (CHW) core consen-
67. Montgomery AE, Fargo JD, Kane V, Culhane tes control with reciprocal peer support versus sus (C3) project: building national consensus on CHW
DP. Development and validation of an instrument nurse care management: a randomized trial. core roles, skills, and qualities [Internet], 2016. Avail-
to assess imminent risk of homelessness among Ann Intern Med 2010;153:507–515 able from http://files.ctctcdn.com/a907c850501/
veterans. Public Health Rep 2014;129:428–436 72. Long JA, Jahnle EC, Richardson DM, 1c1289f0-88cc-49c3-a238-66def942c147pdf. Ac-
68. U.S. Department of Health and Human Ser- Loewenstein G, Volpp KG. Peer mentoring and cessed 26 September 2017
vices. Think cultural health [Internet]. Available financial incentives to improve glucose control 75. U.S. Department of Health and Human Ser-
from https://www.thinkculturalhealth.hhs.gov/. in African American veterans: a randomized trial. vices. Community health workers help patients
Accessed 26 September 2017 Ann Intern Med 2012;156:416–424 manage diabetes [Internet]. Available from
69. Agency for Healthcare Research and Quality. 73. Foster G, Taylor SJC, Eldridge SE, Ramsay J, https://www.thecommunityguide.org/content/
Clinical-community linkages [Internet]. Avail- Griffiths CJ. Self-management education pro- community-health-workers-help-patients-
able from http://www.ahrq.gov/professionals/ grammes by lay leaders for people with chronic manage-diabetes. Accessed 26 September 2017
Diabetes Care Volume 41, Supplement 1, January 2018 S13
2. Classification and Diagnosis of American Diabetes Association
Diabetes: Standards of Medical
Care in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S13–S27 | https://doi.org/10.2337/dc18-S002
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” 2. CLASSIFICATION AND DIAGNOSIS OF DIABETES
includes ADA’s current clinical practice recommendations and is intended to provide
the components of diabetes care, general treatment goals and guidelines, and tools
to evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee, are responsible for updating the Standards of
Care annually, or more frequently as warranted. For a detailed description of ADA
standards, statements, and reports, as well as the evidence-grading system for ADA’s
clinical practice recommendations, please refer to the Standards of Care Introduc-
tion. Readers who wish to comment on the Standards of Care are invited to do so
at professional.diabetes.org/SOC.
CLASSIFICATION
Diabetes can be classified into the following general categories:
1. Type 1 diabetes (due to autoimmune b-cell destruction, usually leading to absolute
insulin deficiency)
2. Type 2 diabetes (due to a progressive loss of b-cell insulin secretion frequently on
the background of insulin resistance)
3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third
trimester of pregnancy that was not clearly overt diabetes prior to gestation)
4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes
(such as neonatal diabetes and maturity-onset diabetes of the young [MODY]),
diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), and
drug- or chemical-induced diabetes (such as with glucocorticoid use, in the treat-
ment of HIV/AIDS, or after organ transplantation)
This section reviews most common forms of diabetes but is not comprehensive. For Suggested citation: American Diabetes Associa-
additional information, see the American Diabetes Association (ADA) position state- tion. 2. Classification and diagnosis of diabetes:
ment “Diagnosis and Classification of Diabetes Mellitus” (1). Standards of Medical Care in Diabetesd2018.
Diabetes Care 2018;41(Suppl. 1):S13–S27
Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinical
presentation and disease progression may vary considerably. Classification is important © 2017 by the American Diabetes Association.
for determining therapy, but some individuals cannot be clearly classified as having Readers may use this article as long as the work
type 1 or type 2 diabetes at the time of diagnosis. The traditional paradigms of type 2 is properly cited, the use is educational and not
diabetes occurring only in adults and type 1 diabetes only in children are no longer for profit, and the work is not altered. More infor-
accurate, as both diseases occur in both age-groups. Children with type 1 diabe- mation is available at http://www.diabetesjournals
tes typically present with the hallmark symptoms of polyuria/polydipsia, and approx- .org/content/license.
imately one-third present with diabetic ketoacidosis (DKA) (2). The onset of type 1
diabetes may be more variable in adults, and they may not present with the classic
symptoms seen in children. Occasionally, patients with type 2 diabetes may present
with DKA, particularly ethnic minorities (3). Although difficulties in distinguishing
S14 Classification and Diagnosis of Diabetes Diabetes Care Volume 41, Supplement 1, January 2018
diabetes type may occur in all age-groups defects related to inflammation and met- that compared with FPG and A1C cut
at onset, the true diagnosis becomes abolic stress among other contributors, points, the 2-h PG value diagnoses more
more obvious over time. including genetic factors. Future classi- people with diabetes.
fication schemes for diabetes will likely
In both type 1 and type 2 diabetes, focus on the pathophysiology of the un- A1C
various genetic and environmental fac- derlying b-cell dysfunction and the stage
tors can result in the progressive loss of of disease as indicated by glucose status Recommendations
b-cell mass and/or function that mani- (normal, impaired, or diabetes) (4).
fests clinically as hyperglycemia. Once c To avoid misdiagnosis or missed
hyperglycemia occurs, patients with all DIAGNOSTIC TESTS FOR DIABETES diagnosis, the A1C test should be
forms of diabetes are at risk for devel- performed using a method that is
oping the same chronic complications, Diabetes may be diagnosed based on certified by the NGSP and standard-
although rates of progression may differ. plasma glucose criteria, either the fasting ized to the Diabetes Control and
The identification of individualized thera- plasma glucose (FPG) or the 2-h plasma Complications Trial (DCCT) assay. B
pies for diabetes in the future will require glucose (2-h PG) value during a 75-g oral
better characterization of the many paths glucose tolerance test (OGTT), or A1C cri- c Marked discordance between mea-
to b-cell demise or dysfunction (4). teria (6) (Table 2.2). sured A1C and plasma glucose
levels should raise the possibility
Characterization of the underlying Generally, FPG, 2-h PG during 75-g of A1C assay interference due to
pathophysiology is more developed in OGTT, and A1C are equally appropriate hemoglobin variants (i.e., hemoglo-
type 1 diabetes than in type 2 diabetes. for diagnostic testing. It should be noted binopathies) and consideration of
It is now clear from studies of first-degree that the tests do not necessarily detect using an assay without interference
relatives of patients with type 1 diabetes diabetes in the same individuals. The ef- or plasma blood glucose criteria to
that the persistent presence of two or ficacy of interventions for primary pre- diagnose diabetes. B
more autoantibodies is an almost certain vention of type 2 diabetes (7,8) has
predictor of clinical hyperglycemia and primarily been demonstrated among in- c In conditions associated with in-
diabetes. The rate of progression is de- dividuals who have impaired glucose tol- creased red blood cell turnover,
pendent on the age at first detection of erance (IGT) with or without elevated such as sickle cell disease, pregnancy
antibody, number of antibodies, antibody fasting glucose, not for individuals with (second and third trimesters), hemo-
specificity, and antibody titer. Glucose isolated impaired fasting glucose (IFG) dialysis, recent blood loss or transfu-
and A1C levels rise well before the clinical or for those with prediabetes defined by sion, or erythropoietin therapy, only
onset of diabetes, making diagnosis A1C criteria. plasma blood glucose criteria should
feasible well before the onset of DKA. Three be used to diagnose diabetes. B
distinct stages of type 1 diabetes can be The same tests may be used to screen
identified (Table 2.1) and serve as a for and diagnose diabetes and to detect The A1C test should be performed using a
framework for future research and regu- individuals with prediabetes. Diabetes method that is certified by the NGSP
latory decision-making (4,5). may be identified anywhere along the (www.ngsp.org) and standardized or
spectrum of clinical scenarios: in seem- traceable to the Diabetes Control and
The paths to b-cell demise and dys- ingly low-risk individuals who happen to Complications Trial (DCCT) reference as-
function are less well defined in type 2 have glucose testing, in individuals tested say. Although point-of-care A1C assays
diabetes, but deficient b-cell insulin se- based on diabetes risk assessment, and in may be NGSP certified, proficiency testing
cretion, frequently in the setting of insulin symptomatic patients. is not mandated for performing the test,
resistance, appears to be the common de- so use of point-of-care assays for diagnos-
nominator. Characterization of subtypes Fasting and 2-Hour Plasma Glucose tic purposes is not recommended but
of this heterogeneous disorder have been The FPG and 2-h PG may be used to di- may be considered in the future if pro-
developed and validated in Scandinavian agnose diabetes (Table 2.2). The concor- ficiency testing is performed, documented,
and Northern European populations but dance between the FPG and 2-h PG tests and deemed acceptable.
have not been confirmed in other ethnic is imperfect, as is the concordance be-
and racial groups. Type 2 diabetes is pri- tween A1C and either glucose-based The A1C has several advantages com-
marily associated with insulin secretory test. Numerous studies have confirmed pared with the FPG and OGTT, including
greater convenience (fasting not required),
Table 2.1—Staging of type 1 diabetes (4,5) Stage 2 Stage 3
Stage 1 c New-onset hyperglycemia
c Symptomatic
Characteristics c Autoimmunity c Autoimmunity
Diagnostic criteria c Normoglycemia c Dysglycemia c Clinical symptoms
c Presymptomatic c Presymptomatic c Diabetes by standard criteria
c Multiple autoantibodies
c No IGT or IFG c Multiple autoantibodies
c Dysglycemia: IFG and/or IGT
c FPG 100–125 mg/dL (5.6–6.9 mmol/L)
c 2-h PG 140–199 mg/dL (7.8–11.0 mmol/L)
c A1C 5.7–6.4% (39–47 mmol/mol) or $10% increase in A1C
care.diabetesjournals.org Classification and Diagnosis of Diabetes S15
Table 2.2—Criteria for the diagnosis of diabetes Confirming the Diagnosis
FPG $126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* Unless there is a clear clinical diagnosis
(e.g., patient in a hyperglycemic crisis
OR or with classic symptoms of hyperglyce-
2-h PG $200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the mia and a random plasma glucose $200
mg/dL [11.1 mmol/L]), a second test is
WHO, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.* required for confirmation. It is recom-
mended that the same test be repeated
OR or a different test be performed without
A1C $6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is delay using a new blood sample for con-
firmation. For example, if the A1C is 7.0%
NGSP certified and standardized to the DCCT assay.* (53 mmol/mol) and a repeat result is 6.8%
OR (51 mmol/mol), the diagnosis of diabetes
is confirmed. If two different tests (such
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma as A1C and FPG) are both above the di-
glucose $200 mg/dL (11.1 mmol/L). agnostic threshold, this also confirms
the diagnosis. On the other hand, if a pa-
*In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing. tient has discordant results from two
different tests, then the test result that
greater preanalytical stability, and less red blood cell turnover, such as those is above the diagnostic cut point should
day-to-day perturbations during stress with the sickle cell trait, an A1C assay with- be repeated, with consideration of the
and illness. However, these advantages out interference from hemoglobin variants possibility of A1C assay interference. The
may be offset by the lower sensitivity of should be used. An updated list of A1C diagnosis is made on the basis of the con-
A1C at the designated cut point, greater assays with interferences is available at firmed test. For example, if a patient meets
cost, limited availability of A1C testing in www.ngsp.org/interf.asp. the diabetes criterion of the A1C (two
certain regions of the developing world, results $6.5% [48 mmol/mol]) but not
and the imperfect correlation between African Americans heterozygous for the FPG (,126 mg/dL [7.0 mmol/L]), that per-
A1C and average glucose in certain indi- common hemoglobin variant HbS may son should nevertheless be considered to
viduals. National Health and Nutrition have, for any given level of mean glycemia, have diabetes.
Examination Survey (NHANES) data indi- lower A1C by about 0.3% than those with-
cate that an A1C cut point of $6.5% out the trait (11). Another genetic variant, Since all the tests have preanalytic and
(48 mmol/mol) identifies a prevalence X-linked glucose-6-phosphate dehydro- analytic variability, it is possible that an
of undiagnosed diabetes that is one-third genase G202A, carried by 11% of African abnormal result (i.e., above the diagnostic
of that using glucose criteria (9). Americans, was associated with a decrease threshold), when repeated, will produce a
in A1C of about 0.8% in hemizygous men value below the diagnostic cut point. This
When using A1C to diagnose diabetes, and 0.7% in homozygous women com- scenario is likely for FPG and 2-h PG if the
it is important to recognize that A1C is pared with those without the variant (12). glucose samples remain at room temper-
an indirect measure of average blood ature and are not centrifuged promptly.
glucose levels and to take other factors Even in the absence of hemoglobin Because of the potential for preanalytic
into consideration that may impact he- variants, A1C levels may vary with race/ variability, it is critical that samples for
moglobin glycation independently of ethnicity independently of glycemia plasma glucose be spun and separated
glycemia including age, race/ethnicity, (13–15). For example, African Americans immediately after they are drawn. If pa-
and anemia/hemoglobinopathies. may have higher A1C levels than non- tients have test results near the margins
Hispanic whites with similar fasting and of the diagnostic threshold, the health care
Age postglucose load glucose levels (16), and professional should follow the patient
A1C levels may be higher for a given mean closely and repeat the test in 3–6 months.
The epidemiological studies that formed glucose concentration when measured
the basis for recommending A1C to diag- with continuous glucose monitoring CATEGORIES OF INCREASED RISK
nose diabetes included only adult popula- (17). Though conflicting data exists, African FOR DIABETES (PREDIABETES)
tions. Therefore, it remains unclear whether Americans may also have higher levels
A1C and the same A1C cut point should be of fructosamine and glycated albumin Recommendations
used to diagnose diabetes in children and and lower levels of 1,5-anhydroglucitol,
adolescents (see p. S20 SCREENING AND TESTING suggesting that their glycemic burden c Screening for prediabetes and risk
(particularly postprandially) may be higher for future diabetes with an informal
FOR TYPE 2 DIABETES AND PREDIABETES IN CHILDREN (18,19). The association of A1C with risk assessment of risk factors or vali-
for complications appears to be similar in dated tools should be considered
AND ADOLESCENTS for additional information) African Americans and non-Hispanic in asymptomatic adults. B
(9,10). whites (20,21).
c Testing for prediabetes and risk for
Race/Ethnicity/Hemoglobinopathies Red Blood Cell Turnover future diabetes in asymptomatic
people should be considered in
Hemoglobin variants can interfere with In conditions associated with increased adults of any age who are over-
the measurement of A1C, although most red blood cell turnover, such as sickle weight or obese (BMI $25 kg/m2
assays in use in the U.S. are unaffected by cell disease, pregnancy (second and third
the most common variants. Marked dis- trimesters), hemodialysis, recent blood
crepancies between measured A1C and loss or transfusion, or erythropoietin ther-
plasma glucose levels should prompt con- apy, only plasma blood glucose criteria
sideration that the A1C assay may not be should be used to diagnose diabetes (22).
reliable for that individual. For patients
with a hemoglobin variant but normal
S16 Classification and Diagnosis of Diabetes Diabetes Care Volume 41, Supplement 1, January 2018
or $23 kg/m2 in Asian Americans) Table 2.3—Criteria for testing for diabetes or prediabetes in asymptomatic adults
and who have one or more addi- 1. Testing should be considered in overweight or obese (BMI $25 kg/m2 or $23 kg/m2 in Asian
tional risk factors for diabetes (Table
2.3). B Americans) adults who have one or more of the following risk factors:
c For all people, testing should begin c First-degree relative with diabetes
at age 45 years. B c High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific
c If tests are normal, repeat testing car-
ried out at a minimum of 3-year in- Islander)
tervals is reasonable. C c History of CVD
c To test for prediabetes, fasting plasma c Hypertension ($140/90 mmHg or on therapy for hypertension)
glucose, 2-h plasma glucose during c HDL cholesterol level ,35 mg/dL (0.90 mmol/L) and/or a triglyceride level .250 mg/dL
75-g oral glucose tolerance test, and
A1C are equally appropriate. B (2.82 mmol/L)
c In patients with prediabetes, identify c Women with polycystic ovary syndrome
and, if appropriate, treat other car- c Physical inactivity
diovascular disease risk factors. B c Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis
c Testing for prediabetes should be
considered in children and adoles- nigricans)
cents who are overweight or obese
(BMI .85th percentile for age and 2. Patients with prediabetes (A1C $5.7% [39 mmol/mol], IGT, or IFG) should be tested yearly.
sex, weight for height .85th per-
centile, or weight .120% of ideal 3. Women who were diagnosed with GDM should have lifelong testing at least every 3 years.
for height) and who have additional
risk factors for diabetes (Table 2.5). E 4. For all other patients, testing should begin at age 45 years.
Description 5. If results are normal, testing should be repeated at a minimum of 3-year intervals, with
“Prediabetes” is the term used for individ- consideration of more frequent testing depending on initial results and risk status.
uals whose glucose levels do not meet the
criteria for diabetes but are too high to be review of 44,203 individuals from 16 co- interventions and vigilant follow-up should
considered normal (23,24). Patients with hort studies with a follow-up interval be pursued for those considered at very
prediabetes are defined by the presence averaging 5.6 years (range 2.8–12 years), high risk (e.g., those with A1C .6.0%
of IFG and/or IGT and/or A1C 5.7–6.4% those with A1C between 5.5 and 6.0% [42 mmol/mol]).
(39–47 mmol/mol) (Table 2.4). Prediabe- (between 37 and 42 mmol/mol) had a
tes should not be viewed as a clinical substantially increased risk of diabetes Table 2.4 summarizes the categories of
entity in its own right but rather as an (5-year incidence from 9 to 25%). Those prediabetes and Table 2.3 the criteria for
increased risk for diabetes and cardio- with an A1C range of 6.0–6.5% (42– prediabetes testing. The ADA diabetes
vascular disease (CVD). Criteria for testing 48 mmol/mol) had a 5-year risk of devel- risk test is an additional option for screen-
for diabetes or prediabetes in asymp- oping diabetes between 25 and 50% ing (Fig. 2.1) (diabetes.org/socrisktest).
tomatic adults is outlined in Table 2.3. and a relative risk 20 times higher com- For additional background regarding risk
Prediabetes is associated with obesity (es- pared with A1C of 5.0% (31 mmol/mol) factors and screening for prediabetes, see
pecially abdominal or visceral obesity), (26). In a community-based study of Afri- pp. S19–S20 (SCREENING AND TESTING FOR TYPE 2
dyslipidemia with high triglycerides and/or can American and non-Hispanic white
low HDL cholesterol, and hypertension. adults without diabetes, baseline A1C DIABETES AND PREDIABETES IN ASYMPTOMATIC ADULTS
was a stronger predictor of subsequent
Diagnosis diabetes and cardiovascular events and SCREENING AND TESTING FOR TYPE 2 DIABETES
IFG is defined as FPG levels between than fasting glucose (27). Other analyses AND PREDIABETES IN CHILDREN AND ADOLESCENTS).
100 and 125 mg/dL (between 5.6 and suggest that A1C of 5.7% (39 mmol/mol)
6.9 mmol/L) (24,25) and IGT as 2-h PG or higher is associated with a diabetes risk TYPE 1 DIABETES
during 75-g OGTT levels between 140 and similar to that of the high-risk participants
199 mg/dL (between 7.8 and 11.0 mmol/L) in the Diabetes Prevention Program (DPP) Recommendations
(23). It should be noted that the World (28), and A1C at baseline was a strong
Health Organization (WHO) and numerous predictor of the development of glucose- c Plasma blood glucose rather than
other diabetes organizations define the IFG defined diabetes during the DPP and its A1C should be used to diagnose the
cutoff at 110 mg/dL (6.1 mmol/L). follow-up (29). acute onset of type 1 diabetes in in-
dividuals with symptoms of hypergly-
As with the glucose measures, several Hence, it is reasonable to consider an A1C cemia. E
prospective studies that used A1C to range of 5.7–6.4% (39–47 mmol/mol) as
predict the progression to diabetes as identifying individuals with prediabe- c Screening for type 1 diabetes with a
defined by A1C criteria demonstrated a tes. Similar to those with IFG and/or panel of autoantibodies is currently
strong, continuous association between A1C IGT, individuals with A1C of 5.7–6.4% recommended only in the setting
and subsequent diabetes. In a systematic (39–47 mmol/mol) should be informed of a research trial or in first-degree
of their increased risk for diabetes and family members of a proband with
CVD and counseled about effective type 1 diabetes. B
strategies to lower their risks (see Sec-
tion 5 “Prevention or Delay of Type 2 c Persistence of two or more autoan-
Diabetes”). Similar to glucose measure- tibodies predicts clinical diabetes
ments, the continuum of risk is curvi- and may serve as an indication for
linear, so as A1C rises, the diabetes risk intervention in the setting of a clin-
rises disproportionately (26). Aggressive ical trial. B
Diagnosis
In a patient with classic symptoms,
measurement of plasma glucose is suf-
ficient to diagnose diabetes (symptoms
care.diabetesjournals.org Classification and Diagnosis of Diabetes S17
Table 2.4—Categories of increased risk for diabetes (prediabetes)* cohorts from Finland, Germany, and the
FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG) U.S. Of the 585 children who developed
more than two autoantibodies, nearly
OR 70% developed type 1 diabetes within
2-h PG during 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT) 10 years and 84% within 15 years (31).
These findings are highly significant be-
OR cause while the German group was re-
A1C 5.7–6.4% (39–47 mmol/mol) cruited from offspring of parents with
type 1 diabetes, the Finnish and American
*For all three tests, risk is continuous, extending below the lower limit of the range and becoming groups were recruited from the general
disproportionately greater at the higher end of the range. population. Remarkably, the findings
in all three groups were the same, sug-
of hyperglycemia or hyperglycemic crisis also related to environmental factors gesting that the same sequence of events
plus a random plasma glucose $200 mg/ that are still poorly defined. Although pa- led to clinical disease in both “sporadic”
dL [11.1 mmol/L]). In these cases, know- tients are not typically obese when they and familial cases of type 1 diabetes. In-
ing the plasma glucose level is critical be- present with type 1 diabetes, obesity deed, the risk of type 1 diabetes increases
cause, in addition to confirming that should not preclude the diagnosis. Pa- as the number of relevant autoantibodies
symptoms are due to diabetes, it will in- tients with type 1 diabetes are also prone detected increases (32–34).
form management decisions. Some pro- to other autoimmune disorders such as
viders may also want to know the A1C to Hashimoto thyroiditis, Graves disease, Although there is currently a lack of
determine how long a patient has had Addison disease, celiac disease, vitiligo, accepted screening programs, one should
hyperglycemia. The criteria to diagnose autoimmune hepatitis, myasthenia gravis, consider referring relatives of those with
diabetes are listed in Table 2.2. and pernicious anemia (see Section 3 type 1 diabetes for antibody testing for
“Comprehensive Medical Evaluation and risk assessment in the setting of a clinical
Immune-Mediated Diabetes Assessment of Comorbidities”). research study (www.diabetestrialnet
This form, previously called “insulin- .org). Widespread clinical testing of asymp-
dependent diabetes” or “juvenile-onset Idiopathic Type 1 Diabetes tomatic low-risk individuals is not currently
diabetes,” accounts for 5–10% of diabetes Some forms of type 1 diabetes have no recommended due to lack of approved
and is due to cellular-mediated autoimmune known etiologies. These patients have therapeutic interventions. Individuals who
destruction of the pancreatic b-cells. Auto- permanent insulinopenia and are prone test positive should be counseled about
immune markers include islet cell auto- to DKA, but have no evidence of b-cell the risk of developing diabetes, diabetes
antibodies and autoantibodies to GAD autoimmunity. Although only a minority symptoms, and DKA prevention. Numer-
(GAD65), insulin, the tyrosine phospha- of patients with type 1 diabetes fall into ous clinical studies are being conducted
tases IA-2 and IA-2b, and ZnT8. Type 1 this category, of those who do, most are to test various methods of preventing
diabetes is defined by the presence of of African or Asian ancestry. Individuals type 1 diabetes in those with evidence of
one or more of these autoimmune markers. with this form of diabetes suffer from ep- autoimmunity (www.clinicaltrials.gov).
The disease has strong HLA associations, isodic DKA and exhibit varying degrees of
with linkage to the DQA and DQB genes. insulin deficiency between episodes. This TYPE 2 DIABETES
These HLA-DR/DQ alleles can be either form of diabetes is strongly inherited and
predisposing or protective. is not HLA associated. An absolute re- Recommendations
quirement for insulin replacement therapy
The rate of b-cell destruction is quite in affected patients may be intermittent. c Screening for type 2 diabetes with
variable, being rapid in some individuals an informal assessment of risk fac-
(mainly infants and children) and slow in Testing for Type 1 Diabetes Risk tors or validated tools should be
others (mainly adults). Children and ado- The incidence and prevalence of type 1 considered in asymptomatic adults. B
lescents may present with DKA as the first diabetes is increasing (30). Patients with
manifestation of the disease. Others have type 1 diabetes often present with acute c Testing for type 2 diabetes in asymp-
modest fasting hyperglycemia that can symptoms of diabetes and markedly tomatic people should be consid-
rapidly change to severe hyperglycemia elevated blood glucose levels, and ap- ered in adults of any age who are
and/or DKA with infection or other stress. proximately one-third are diagnosed overweight or obese (BMI $25
Adults may retain sufficient b-cell function with life-threatening DKA (2). Several kg/m2 or $23 kg/m2 in Asian Amer-
to prevent DKA for many years; such in- studies indicate that measuring islet au- icans) and who have one or more
dividuals eventually become dependent toantibodies in relatives of those with additional risk factors for diabetes
on insulin for survival and are at risk for type 1 diabetes may identify individuals (Table 2.3). B
DKA. At this latter stage of the disease, who are at risk for developing type 1 di-
there is little or no insulin secretion, as abetes (5). Such testing, coupled with ed- c For all people, testing should begin
manifested by low or undetectable levels ucation about diabetes symptoms and at age 45 years. B
of plasma C-peptide. Immune-mediated di- close follow-up, may enable earlier iden-
abetes commonly occurs in childhood and tification of type 1 diabetes onset. A study c If tests are normal, repeat testing
adolescence, but it can occur at any age, reported the risk of progression to type 1 carried out at a minimum of 3-year
even in the 8th and 9th decades of life. diabetes from the time of seroconversion intervals is reasonable. C
to autoantibody positivity in three pediatric
Autoimmune destruction of b-cells has c To test for type 2 diabetes, fasting
multiple genetic predispositions and is plasma glucose, 2-h plasma glucose
during 75-g oral glucose tolerance test,
and A1C are equally appropriate. B
S18 Classification and Diagnosis of Diabetes Diabetes Care Volume 41, Supplement 1, January 2018
Figure 2.1—ADA risk test (diabetes.org/socrisktest).
care.diabetesjournals.org Classification and Diagnosis of Diabetes S19
c In patients with diabetes, identify 36). Type 2 diabetes frequently goes un- assessment tool, such as the ADA risk
and treat other cardiovascular dis- diagnosed for many years because hy- test (Fig. 2.1) (diabetes.org/socrisktest),
ease risk factors. B perglycemia develops gradually and, is recommended to guide providers on
at earlier stages, is often not severe whether performing a diagnostic test
c Testing for type 2 diabetes should enough for the patient to notice the clas- (Table 2.2) is appropriate. Prediabetes
be considered in children and ado- sic diabetes symptoms. Nevertheless, and type 2 diabetes meet criteria for con-
lescents who are overweight or even undiagnosed patients are at in- ditions in which early detection is appro-
obese (BMI .85th percentile for creased risk of developing macrovascular priate. Both conditions are common and
age and sex, weight for height and microvascular complications. impose significant clinical and public
.85th percentile, or weight .120% health burdens. There is often a long pre-
of ideal for height) and who have Whereas patients with type 2 diabetes symptomatic phase before the diagnosis
additional risk factors for diabetes may have insulin levels that appear nor- of type 2 diabetes. Simple tests to detect
(Table 2.5). E mal or elevated, the higher blood glucose preclinical disease are readily available.
levels in these patients would be expected The duration of glycemic burden is a strong
Description to result in even higher insulin values had predictor of adverse outcomes. There are
Type 2 diabetes, previously referred to their b-cell function been normal. Thus, effective interventions that prevent pro-
as “noninsulin-dependent diabetes” or insulin secretion is defective in these pa- gression from prediabetes to diabetes (see
“adult-onset diabetes,” accounts for 90– tients and insufficient to compensate for Section 5 “Prevention or Delay of Type 2
95% of all diabetes. This form encom- insulin resistance. Insulin resistance may Diabetes”) and reduce the risk of diabetes
passes individuals who have relative improve with weight reduction and/or complications (see Section 9 “Cardiovas-
(rather than absolute) insulin deficiency pharmacologic treatment of hyperglyce- cular Disease and Risk Management” and
and have peripheral insulin resistance. mia but is seldom restored to normal. Section 10 “Microvascular Complications
At least initially, and often throughout and Foot Care”).
their lifetime, these individuals may not The risk of developing type 2 diabe-
need insulin treatment to survive. tes increases with age, obesity, and lack Approximately one-quarter of people
of physical activity. It occurs more fre- with diabetes in the U.S. and nearly half
There are various causes of type 2 di- quently in women with prior GDM, in of Asian and Hispanic Americans with di-
abetes. Although the specific etiologies those with hypertension or dyslipidemia, abetes are undiagnosed (37,38). Although
are not known, autoimmune destruction and in certain racial/ethnic subgroups screening of asymptomatic individuals to
of b-cells does not occur and patients do (African American, American Indian, identify those with prediabetes or diabe-
not have any of the other known causes Hispanic/Latino, and Asian American). It tes might seem reasonable, rigorous clin-
of diabetes. Most but not all patients with is often associated with a strong genetic ical trials to prove the effectiveness of
type 2 diabetes are overweight or obese. predisposition or family history in first- such screening have not been conducted
Excess weight itself causes some degree degree relatives, more so than type 1 di- and are unlikely to occur.
of insulin resistance. Patients who are not abetes. However, the genetics of type 2
obese or overweight by traditional weight diabetes is poorly understood. In adults A large European randomized con-
criteria may have an increased percent- without traditional risk factors for type 2 trolled trial compared the impact of
age of body fat distributed predominantly diabetes and/or younger age, consider screening for diabetes and intensive
in the abdominal region. antibody testing to exclude the diagnosis multifactorial intervention with that of
of type 1 diabetes (i.e., GAD). screening and routine care (39). General
DKA seldom occurs spontaneously in practice patients between the ages of
type 2 diabetes; when seen, it usually Screening and Testing for Type 2 40 and 69 years were screened for diabe-
arises in association with the stress of an- Diabetes and Prediabetes in tes and randomly assigned by practice to
other illness such as infection or with the Asymptomatic Adults intensive treatment of multiple risk fac-
use of certain drugs (e.g., corticosteroids, Screening for prediabetes and type 2 di- tors or routine diabetes care. After 5.3
atypical antipsychotics, and sodium– abetes through an informal assessment years of follow-up, CVD risk factors were
glucose cotransporter 2 inhibitors) (35, of risk factors (Table 2.3) or with an modestly but significantly improved with
intensive treatment compared with rou-
Table 2.5—Risk-based screening for type 2 diabetes or prediabetes in asymptomatic tine care, but the incidence of first CVD
children and adolescents in a clinical setting* events or mortality was not significantly
different between the groups (39). The
Criteria excellent care provided to patients in
c Overweight (BMI .85th percentile for age and sex, weight for height .85th percentile, or the routine care group and the lack of
weight .120% of ideal for height) A an unscreened control arm limited the
authors’ ability to determine whether
Plus one or more additional risk factors based on the strength of their association with diabetes as screening and early treatment improved
indicated by evidence grades: outcomes compared with no screening
c Maternal history of diabetes or GDM during the child’s gestation A and later treatment after clinical diag-
c Family history of type 2 diabetes in first- or second-degree relative A noses. Computer simulation modeling
c Race/ethnicity (Native American, African American, Latino, Asian American, Pacific Islander) A studies suggest that major benefits are
c Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, likely to accrue from the early diagnosis
hypertension, dyslipidemia, polycystic ovary syndrome, or small-for-gestational-age birth weight) B and treatment of hyperglycemia and
*Persons aged ,18 years.
S20 Classification and Diagnosis of Diabetes Diabetes Care Volume 41, Supplement 1, January 2018
cardiovascular risk factors in type 2 reduced and individuals with false-negative limited data supporting A1C for diag-
diabetes (40); moreover, screening, be- tests will be retested before substantial time nosing type 2 diabetes in children and
ginning at age 30 or 45 years and indepen- elapses and complications develop (47). adolescents. Although A1C is not recom-
dent of risk factors, may be cost-effective mended for diagnosis of diabetes in chil-
(,$11,000 per quality-adjusted life-year Community Screening dren with cystic fibrosis or symptoms
gained) (41). suggestive of acute onset of type 1 diabe-
Ideally, testing should be carried out tes and only A1C assays without interfer-
Additional considerations regarding within a health care setting because of ence are appropriate for children with
testing for type 2 diabetes and prediabe- the need for follow-up and treatment. hemoglobinopathies, the ADA continues
tes in asymptomatic patients include the Community screening outside a health to recommend A1C for diagnosis of type 2
following. care setting is generally not recom- diabetes in this cohort (54,55).
mended because people with positive
Age tests may not seek, or have access to, GESTATIONAL DIABETES MELLITUS
appropriate follow-up testing and care.
Age is a major risk factor for diabetes. However, in specific situations where an Recommendations
Testing should begin at age 45 years for adequate referral system is established
all patients. Screening should be consid- beforehand for positive tests, community c Test for undiagnosed diabetes at
ered in overweight or obese adults of screening may be considered. Commu- the first prenatal visit in those
any age with one or more risk factors for nity testing may also be poorly targeted; with risk factors, using standard di-
diabetes. i.e., it may fail to reach the groups most at agnostic criteria. B
risk and inappropriately test those at very
BMI and Ethnicity low risk or even those who have already c Test for gestational diabetes melli-
been diagnosed (48). tus at 24–28 weeks of gestation in
In general, BMI $25 kg/m2 is a risk factor pregnant women not previously
for diabetes. However, data suggest that Screening in Dental Practices known to have diabetes. A
the BMI cut point should be lower for
the Asian American population (42,43). Because periodontal disease is associated c Test women with gestational diabe-
The BMI cut points fall consistently be- with diabetes, the utility of screening in a tes mellitus for persistent diabetes
tween 23 and 24 kg/m2 (sensitivity of dental setting and referral to primary care at 4–12 weeks postpartum, using
80%) for nearly all Asian American sub- as a means to improve the diagnosis of the oral glucose tolerance test and
groups (with levels slightly lower for Jap- prediabetes and diabetes has been ex- clinically appropriate nonpregnancy
anese Americans). This makes a rounded plored (49–51), with one study estimating diagnostic criteria. E
cut point of 23 kg/m2 practical. An argu- that 30% of patients $30 years of age
ment can be made to push the BMI cut seen in general dental practices had dys- c Women with a history of gesta-
point to lower than 23 kg/m2 in favor of glycemia (51). Further research is needed tional diabetes mellitus should
increased sensitivity; however, this would to demonstrate the feasibility, effective- have lifelong screening for the de-
lead to an unacceptably low specificity ness, and cost-effectiveness of screening velopment of diabetes or prediabe-
(13.1%). Data from the WHO also suggest in this setting. tes at least every 3 years. B
that a BMI of $23 kg/m2 should be used
to define increased risk in Asian Ameri- Screening and Testing for Type 2 c Women with a history of gesta-
cans (44). The finding that half of diabetes Diabetes and Prediabetes in Children tional diabetes mellitus found to
in Asian Americans is undiagnosed sug- and Adolescents have prediabetes should receive in-
gests that testing is not occurring at lower In the last decade, the incidence and prev- tensive lifestyle interventions or
BMI thresholds (37,38). alence of type 2 diabetes in adolescents metformin to prevent diabetes. A
has increased dramatically, especially in
Evidence also suggests that other pop- racial and ethnic minority populations Definition
ulations may benefit from lower BMI cut (30). See Table 2.5 for recommendations For many years, GDM was defined as any
points. For example, in a large multiethnic on risk-based screening for type 2 diabe- degree of glucose intolerance that was
cohort study, for an equivalent incidence tes or prediabetes in asymptomatic chil- first recognized during pregnancy (23), re-
rate of diabetes, a BMI of 30 kg/m2 in non- dren and adolescents in a clinical setting. See gardless of whether the condition may
Hispanic whites was equivalent to a BMI Section 12 “Children and Adolescents” for have predated the pregnancy or persisted
of 26 kg/m2 in African Americans (45). additional information on type 2 diabetes after the pregnancy. This definition facili-
in children and adolescents. tated a uniform strategy for detection and
Medications classification of GDM, but it was limited by
Some studies question the validity of imprecision.
Certain medications, such as glucocorti- A1C in the pediatric population, especially
coids, thiazide diuretics, and atypical an- among certain ethnicities, and suggest The ongoing epidemic of obesity and
tipsychotics (46), are known to increase OGTT or FPG as more suitable diagnos- diabetes has led to more type 2 diabetes
the risk of diabetes and should be consid- tic tests (52). However, many of these in women of childbearing age, with an in-
ered when deciding whether to screen. studies do not recognize that diabetes di- crease in the number of pregnant women
agnostic criteria are based on long-term with undiagnosed type 2 diabetes (56).
Testing Interval health outcomes, and validations are not Because of the number of pregnant
currently available in the pediatric popu- women with undiagnosed type 2 diabetes,
The appropriate interval between screen- lation (53). The ADA acknowledges the it is reasonable to test women with risk
ing tests is not known (47). The rationale factors for type 2 diabetes (Table 2.3) at
for the 3-year interval is that with this in- their initial prenatal visit, using standard
terval, the number of false-positive tests
that require confirmatory testing will be
care.diabetesjournals.org Classification and Diagnosis of Diabetes S21
diagnostic criteria (Table 2.2). Women di- One-Step Strategy Two-Step Strategy
agnosed with diabetes by standard diag-
nostic criteria in the first trimester should The IADPSG defined diagnostic cut points In 2013, the National Institutes of Health
be classified as having preexisting preges- for GDM as the average fasting, 1-h, and (NIH) convened a consensus develop-
tational diabetes (type 2 diabetes or, very 2-h PG values during a 75-g OGTT in ment conference to consider diagnostic
rarely, type 1 diabetes or monogenic dia- women at 24–28 weeks of gestation criteria for diagnosing GDM (68). The
betes). GDM is diabetes that is first diag- who participated in the HAPO study at 15-member panel had representatives
nosed in the second or third trimester of which odds for adverse outcomes reached from obstetrics/gynecology, maternal-
pregnancy that is not clearly either preex- 1.75 times the estimated odds of these fetal medicine, pediatrics, diabetes re-
isting type 1 or type 2 diabetes (see Section outcomes at the mean fasting, 1-h, and search, biostatistics, and other related
13 “Management of Diabetes in Preg- 2-h PG levels of the study population. fields. The panel recommended a two-
nancy”). The International Association of This one-step strategy was anticipated to step approach to screening that used a
the Diabetes and Pregnancy Study Groups significantly increase the incidence of 1-h 50-g glucose load test (GLT) followed
(IADPSG) GDM diagnostic criteria for the GDM (from 5–6% to 15–20%), primarily by a 3-h 100-g OGTT for those who screened
75-g OGTT as well as the GDM screening because only one abnormal value, not positive. The American College of Ob-
and diagnostic criteria used in the two- two, became sufficient to make the di- stetricians and Gynecologists (ACOG) rec-
step approach were not derived from agnosis (63). The anticipated increase in ommends any of the commonly used
data in the first half of pregnancy, so the incidence of GDM could have a sub- thresholds of 130, 135, or 140 mg/dL for
the diagnosis of GDM in early pregnancy stantial impact on costs and medical in- the 1-h 50-g GLT (69). A systematic review
by either FPG or OGTT values is not evi- frastructure needs and has the potential for the U.S. Preventive Services Task Force
dence based (57). to “medicalize” pregnancies previously compared GLT cutoffs of 130 mg/dL
categorized as normal. Nevertheless, (7.2 mmol/L) and 140 mg/dL (7.8 mmol/L)
Because GDM confers increased risk the ADA recommends these diagnostic (70). The higher cutoff yielded sensitivity
for the development of type 2 diabetes criteria with the intent of optimizing of 70–88% and specificity of 69–89%,
after delivery (58,59) and because effec- gestational outcomes because these cri- while the lower cutoff was 88–99% sensi-
tive prevention interventions are avail- teria were the only ones based on preg- tive and 66–77% specific. Data regarding
able (60,61), women diagnosed with nancy outcomes rather than end points a cutoff of 135 mg/dL are limited. As for
GDM should receive lifelong screening such as prediction of subsequent mater- other screening tests, choice of a cutoff
for prediabetes and type 2 diabetes. nal diabetes. is based upon the trade-off between sen-
sitivity and specificity. The use of A1C at
Diagnosis The expected benefits to the offspring 24–28 weeks of gestation as a screening
GDM carries risks for the mother and ne- are inferred from intervention trials that test for GDM does not function as well as
onate. Not all adverse outcomes are of focused on women with lower levels of the GLT (71).
equal clinical importance. The Hypergly- hyperglycemia than identified using older
cemia and Adverse Pregnancy Outcome GDM diagnostic criteria. Those trials Key factors cited by the NIH panel in
(HAPO) study (62), a large-scale multina- found modest benefits including reduced their decision-making process were the
tional cohort study completed by more rates of large-for-gestational-age births lack of clinical trial data demonstrating
than 23,000 pregnant women, demon- and preeclampsia (64,65). It is important the benefits of the one-step strategy
strated that risk of adverse maternal, fe- to note that 80–90% of women being and the potential negative consequences
tal, and neonatal outcomes continuously treated for mild GDM in two randomized of identifying a large group of women
increased as a function of maternal glyce- controlled trials could be managed with with GDM, including medicalization of
mia at 24–28 weeks of gestation, even lifestyle therapy alone. The OGTT glucose pregnancy with increased health care uti-
within ranges previously considered nor- cutoffs in these two trials overlapped lization and costs. Moreover, screening
mal for pregnancy. For most complications, with the thresholds recommended by with a 50-g GLT does not require fasting
there was no threshold for risk. These re- the IADPSG, and in one trial (65), the 2-h and is therefore easier to accomplish for
sults have led to careful reconsideration of PG threshold (140 mg/dL [7.8 mmol/L]) many women. Treatment ofhigher-threshold
the diagnostic criteria for GDM. GDM di- was lower than the cutoff recommended maternal hyperglycemia, as identified by the
agnosis (Table 2.6) can be accomplished by the IADPSG (153 mg/dL [8.5 mmol/L]). two-step approach, reduces rates of neona-
with either of two strategies: No randomized controlled trials of identi- tal macrosomia, large-for-gestational-age
fying and treating GDM using the IADPSG births (72), and shoulder dystocia, without
1. “One-step” 75-g OGTT or criteria versus older criteria have been increasing small-for-gestational-age births.
2. “Two-step” approach with a 50-g (non- published to date. Data are also lacking ACOG currently supports the two-step ap-
on how the treatment of lower levels of proach (69) but most recently noted that
fasting) screen followed by a 100-g hyperglycemia affects a mother’s future one elevated value, as opposed to two, may
OGTT for those who screen positive risk for the development of type 2 diabe- be used for the diagnosis of GDM. If this
tes and her offspring’s risk for obesity, approach is implemented, the incidence of
Different diagnostic criteria will identify diabetes, and other metabolic disorders. GDM by the two-step strategy will likely in-
different degrees of maternal hypergly- Additional well-designed clinical studies crease markedly. ACOG recommends either
cemia and maternal/fetal risk, leading are needed to determine the optimal in- of two sets of diagnostic thresholds for the
some experts to debate, and disagree on, tensity of monitoring and treatment of 3-h 100-g OGTT (73,74). Each is based on
optimal strategies for the diagnosis of women with GDM diagnosed by the different mathematical conversions of
GDM. one-step strategy (66,67). the original recommended thresholds,
S22 Classification and Diagnosis of Diabetes Diabetes Care Volume 41, Supplement 1, January 2018
Table 2.6—Screening for and diagnosis of GDM
One-step strategy
Perform a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and 2 h, at 24–28 weeks of gestation in women not previously
diagnosed with overt diabetes.
The OGTT should be performed in the morning after an overnight fast of at least 8 h.
The diagnosis of GDM is made when any of the following plasma glucose values are met or exceeded:
c Fasting: 92 mg/dL (5.1 mmol/L)
c 1 h: 180 mg/dL (10.0 mmol/L)
c 2 h: 153 mg/dL (8.5 mmol/L)
Two-step strategy
Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 24–28 weeks of gestation in women not previously diagnosed with
overt diabetes.
If the plasma glucose level measured 1 h after the load is $130 mg/dL, 135 mg/dL, or 140 mg/dL (7.2 mmol/L, 7.5 mmol/L, or 7.8 mmol/L), proceed to a
100-g OGTT.
Step 2: The 100-g OGTT should be performed when the patient is fasting.
The diagnosis of GDM is made if at least two* of the following four plasma glucose levels (measured fasting and 1 h, 2 h, 3 h during OGTT) are met or
exceeded:
Carpenter-Coustan (73) or NDDG (74)
c Fasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L)
c1h 180 mg/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L)
c2h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L)
c3h 140 mg/dL (7.8 mmol/L) 145 mg/dL (8.0 mmol/L)
NDDG, National Diabetes Data Group. *ACOG recently noted that alternatively one elevated value can be used for diagnosis.
which used whole blood and nonenzymatic outcomes with one-step versus two-step approach further evaluation, treat-
methods for glucose determination. A re- approaches have been inconsistent to date ment, and genetic counseling. E
cent secondary analysis of data from a ran- (78,79). In addition, pregnancies compli-
domized clinical trial of identification and cated by GDM per the IADPSG criteria, but Monogenic defects that cause b-cell dys-
treatment of mild GDM (75) demon- not recognized as such, have comparable function, such as neonatal diabetes and
strated that treatment was similarly ben- outcomes to pregnancies diagnosed as MODY, represent a small fraction of pa-
eficial in patients meeting only the lower GDM by the more stringent two-step crite- tients with diabetes (,5%). Table 2.7
thresholds (73) and in those meeting only ria (80,81). There remains strong consen- describes the most common causes of
the higher thresholds (74). If the two-step sus that establishing a uniform approach monogenic diabetes. For a comprehen-
approach is used, it would appear advan- to diagnosing GDM will benefit patients, sive list of causes, see Genetic Diagnosis
tageous to use the lower diagnostic thresh- caregivers, and policy makers. Longer- of Endocrine Disorders (82).
olds as shown in step 2 in Table 2.6. term outcome studies are currently under
way. Neonatal Diabetes
Future Considerations Diabetes occurring under 6 months of age
MONOGENIC DIABETES is termed “neonatal” or “congenital” di-
The conflicting recommendations from SYNDROMES abetes, and about 80–85% of cases can be
expert groups underscore the fact that found to have an underlying monogenic
there are data to support each strategy. Recommendations cause (83). Neonatal diabetes occurs much
A cost-benefit estimation comparing the less often after 6 months of age, whereas
two strategies concluded that the one- c All children diagnosed with diabe- autoimmune type 1 diabetes rarely occurs
step approach is cost-effective only if tes in the first 6 months of life before 6 months of age. Neonatal diabetes
patients with GDM receive postdelivery should have immediate genetic can either be transient or permanent. Tran-
counseling and care to prevent type 2 di- testing for neonatal diabetes. A sient diabetes is most often due to over-
abetes (76). The decision of which strategy expression of genes on chromosome 6q24,
to implement must therefore be made c Children and adults, diagnosed in is recurrent in about half of cases, and may
based on the relative values placed on fac- early adulthood, who have diabetes be treatable with medications other than
tors that have yet to be measured (e.g., not characteristic of type 1 or type 2 insulin. Permanent neonatal diabetes is
willingness to change practice based on diabetes that occurs in successive most commonly due to autosomal domi-
correlation studies rather than intervention generations (suggestive of an auto- nant mutations in the genes encoding the
trial results, available infrastructure, and somal dominant pattern of inheri- Kir6.2 subunit (KCNJ11) and SUR1 subunit
importance of cost considerations). tance) should have genetic testing (ABCC8) of the b-cell KATP channel. Correct
for maturity-onset diabetes of the diagnosis has critical implications because
As the IADPSG criteria (“one-step strat- young. A most patients with KATP-related neonatal
egy”) have been adopted internationally, diabetes will exhibit improved glycemic
further evidence has emerged to support c In both instances, consultation control when treated with high-dose oral
improved pregnancy outcomes with cost with a center specializing in diabe-
savings (77) and may be the preferred ap- tes genetics is recommended to
proach. Data comparing population-wide understand the significance of
these mutations and how best to
care.diabetesjournals.org Classification and Diagnosis of Diabetes S23
Table 2.7—Most common causes of monogenic diabetes (82)
Gene Inheritance Clinical features
MODY GCK AD GCK-MODY: stable, nonprogressive elevated fasting blood
Neonatal diabetes glucose; typically does not require treatment;
HNF1A AD microvascular complications are rare; small rise in 2-h PG
level on OGTT (,54 mg/dL [3 mmol/L])
HNF4A AD
HNF1A-MODY: progressive insulin secretory defect with
HNF1B AD presentation in adolescence or early adulthood; lowered
renal threshold for glucosuria; large rise in 2-h PG level on
KCNJ11 AD OGTT (.90 mg/dL [5 mmol/L]); sensitive to sulfonylureas
INS AD
AD HNF4A-MODY: progressive insulin secretory defect with
ABCC8 AD for paternal duplications presentation in adolescence or early adulthood; may have
6q24 (PLAGL1, HYMA1) large birth weight and transient neonatal hypoglycemia;
AD sensitive to sulfonylureas
GATA6 AR
EIF2AK3 X-linked HNF1B-MODY: developmental renal disease (typically
FOXP3 cystic); genitourinary abnormalities; atrophy of the
pancreas; hyperuricemia; gout
Permanent or transient: IUGR; possible developmental delay
and seizures; responsive to sulfonylureas
Permanent: IUGR; insulin requiring
Transient or permanent: IUGR; rarely developmental delay;
responsive to sulfonylureas
Transient: IUGR; macroglossia; umbilical hernia;
mechanisms include UPD6, paternal duplication or
maternal methylation defect; may be treatable with
medications other than insulin
Permanent: pancreatic hypoplasia; cardiac malformations;
pancreatic exocrine insufficiency; insulin requiring
Permanent: Wolcott-Rallison syndrome: epiphyseal
dysplasia; pancreatic exocrine insufficiency; insulin
requiring
Permanent: immunodysregulation, polyendocrinopathy,
enteropathy X-linked (IPEX) syndrome: autoimmune
diabetes; autoimmune thyroid disease; exfoliative
dermatitis; insulin requiring
AD, autosomal dominant; AR, autosomal recessive; IUGR, intrauterine growth restriction.
sulfonylureas instead of insulin. Insulin gene (MODY2), HNF1A-MODY (MODY3), and therapy for GCK-MODY; sulfonylureas as
(INS) mutations are the second most com- HNF4A-MODY (MODY1). first-line therapy for HNF1A-MODY and
mon cause of permanent neonatal dia- HNF4A-MODY). Additionally, diagnosis
betes, and, while treatment presently is Clinically, patients with GCK-MODY ex- can lead to identification of other affected
intensive insulin management, there are hibit mild, stable, fasting hyperglycemia
important genetic considerations, as most and do not require antihyperglycemic family members.
of the mutations that cause diabetes are therapy except sometimes during preg- A diagnosis of MODY should be consid-
dominantly inherited. nancy. Patients with HNF1A- or HNF4A-
MODY usually respond well to low doses ered in individuals who have atypical di-
Maturity-Onset Diabetes of the Young of sulfonylureas, which are considered abetes and multiple family members with
MODY is frequently characterized by on- first-line therapy. Mutations or deletions in diabetes not characteristic of type 1 or
set of hyperglycemia at an early age (clas- HNF1B are associated with renal cysts and type 2 diabetes, although admittedly “atyp-
sically before age 25 years, although uterine malformations (renal cysts and di- ical diabetes” is becoming increasingly
diagnosis may occur at older ages). abetes [RCAD] syndrome). Other extremely difficult to precisely define in the absence
MODY is characterized by impaired insu- rare forms of MODY have been reported to of a definitive set of tests for either type
lin secretion with minimal or no defects in involve other transcription factor genes in- of diabetes. In most cases, the presence of
insulin action (in the absence of coexis- cluding PDX1 (IPF1) and NEUROD1. autoantibodies for type 1 diabetes pre-
tent obesity). It is inherited in an autoso- cludes further testing for monogenic dia-
mal dominant pattern with abnormalities Diagnosis betes, but the presence of autoantibodies
in at least 13 genes on different chromo- A diagnosis of one of the three most com- in patients with monogenic diabetes has
somes identified to date. The most com- mon forms of MODY including GCK- been reported (84). Individuals in whom
monly reported forms are GCK-MODY MODY, HNF1A-MODY, and HNF4A-MODY monogenic diabetes is suspected should
allows for more cost-effective therapy (no be referred to a specialist for further eval-
uation if available, and consultation is
S24 Classification and Diagnosis of Diabetes Diabetes Care Volume 41, Supplement 1, January 2018
available from several centers. Readily c Patients with cystic fibrosis–related Insulin remains the most widely used
available commercial genetic testing fol- diabetes should be treated with in- therapy for CFRD (94).
lowing the criteria listed below now sulin to attain individualized glyce-
enables a cost-effective (85), often cost- mic goals. A Additional resources for the clinical
saving, genetic diagnosis that is increas- management of CFRD can be found in
ingly supported by health insurance. A c Beginning 5 years after the diagnosis the position statement “Clinical Care
biomarker screening pathway such as the of cystic fibrosis–related diabetes, Guidelines for Cystic Fibrosis–Related Di-
combination of urinary C-peptide/creatinine annual monitoring for complications abetes: A Position Statement of the
ratio and antibody screening may aid in of diabetes is recommended. E American Diabetes Association and a Clin-
determining who should get genetic ical Practice Guideline of the Cystic Fibro-
testing for MODY (86). It is critical to cor- Cystic fibrosis–related diabetes (CFRD) is sis Foundation, Endorsed by the Pediatric
rectly diagnose one of the monogenic the most common comorbidity in people Endocrine Society” (95) and in the Interna-
forms of diabetes because these pa- with cystic fibrosis, occurring in about tional Society for Pediatric and Adoles-
tients may be incorrectly diagnosed 20% of adolescents and 40–50% of adults. cent Diabetes’s 2014 clinical practice
with type 1 or type 2 diabetes, leading to Diabetes in this population, compared consensus guidelines (96).
suboptimal, even potentially harmful, treat- with individuals with type 1 or type 2 di-
ment regimens and delays in diagnosing abetes, is associated with worse nutri- POSTTRANSPLANTATION
other family members (87). The correct di- tional status, more severe inflammatory DIABETES MELLITUS
agnosis is especially critical for those with lung disease, and greater mortality. Insu-
GCK-MODY mutations where multiple lin insufficiency is the primary defect in Recommendations
studies have shown that no complications CFRD. Genetically determined b-cell func-
ensue in the absence of glucose-lowering tion and insulin resistance associated with c Patients should be screened after
therapy (88). Genetic counseling is rec- infection and inflammation may also con- organ transplantation for hypergly-
ommended to ensure that affected individ- tribute to the development of CFRD. cemia, with a formal diagnosis of
uals understand the patterns of inheritance Milder abnormalities of glucose tolerance posttransplantation diabetes melli-
and the importance of a correct diagnosis. are even more common and occur at ear- tus being best made once a patient
lier ages than CFRD. Whether individuals is stable on an immunosuppressive
The diagnosis of monogenic diabetes with IGT should be treated with insulin regimen and in the absence of an
should be considered in children and replacement has not currently been de- acute infection. E
adults diagnosed with diabetes in early termined. Although screening for diabe-
adulthood with the following findings: tes before the age of 10 years can identify c The oral glucose tolerance test is
risk for progression to CFRD in those with the preferred test to make a diag-
○ Diabetes diagnosed within the first abnormal glucose tolerance, no benefit nosis of posttransplantation diabe-
6 months of life (with occasional cases has been established with respect to tes mellitus. B
presenting later, mostly INS and ABCC8 weight, height, BMI, or lung function.
mutations) (83,89) Continuous glucose monitoring or HOMA c Immunosuppressive regimens shown
of b-cell function (90) may be more sen- to provide the best outcomes for pa-
○ Diabetes without typical features of sitive than OGTT to detect risk for pro- tient and graft survival should be
type 1 or type 2 diabetes (negative di- gression to CFRD; however, evidence used, irrespective of posttransplanta-
abetes-associated autoantibodies, linking these results to long-term out- tion diabetes mellitus risk. E
nonobese, lacking other metabolic fea- comes is lacking, and these tests are not
tures, especially with strong family recommended for screening (91). Several terms are used in the literature to
history of diabetes) describe the presence of diabetes follow-
CFRD mortality has significantly de- ing organ transplantation. “New-onset di-
○ Stable, mild fasting hyperglycemia creased over time, and the gap in mortal- abetes after transplantation” (NODAT) is
(100–150 mg/dL [5.5–8.5 mmol/L]), ity between cystic fibrosis patients with one such designation that describes indi-
stable A1C between 5.6 and 7.6% (be- and without diabetes has considerably viduals who develop new-onset diabetes
tween 38 and 60 mmol/mol), espe- narrowed (92). There are limited clinical following transplant. NODAT excludes pa-
cially if nonobese trial data on therapy for CFRD. The largest tients with pretransplant diabetes that
study compared three regimens: premeal was undiagnosed as well as posttrans-
CYSTIC FIBROSIS–RELATED insulin aspart, repaglinide, or oral placebo plant hyperglycemia that resolves by the
DIABETES in cystic fibrosis patients with diabetes or time of discharge (97). Another term,
abnormal glucose tolerance. Participants “posttransplantation diabetes mellitus”
Recommendations all had weight loss in the year preced- (PTDM) (97,98), describes the presence
ing treatment; however, in the insulin- of diabetes in the posttransplant setting
c Annual screening for cystic fibrosis– treated group, this pattern was reversed, irrespective of the timing of diabetes onset.
related diabetes with oral glucose and patients gained 0.39 (6 0.21) BMI
tolerance test should begin by age units (P 5 0.02). The repaglinide-treated Hyperglycemia is very common during
10 years in all patients with cystic fi- group had initial weight gain, but this was the early posttransplant period, with
brosis not previously diagnosed with not sustained by 6 months. The placebo ;90% of kidney allograft recipients ex-
cystic fibrosis–related diabetes. B group continued to lose weight (93). hibiting hyperglycemia in the first few
weeks following transplant (97–100).
c A1C is not recommended as a In most cases, such stress- or steroid-
screening test for cystic fibrosis– induced hyperglycemia resolves by the
related diabetes. B time of discharge (100,101). Although
care.diabetesjournals.org Classification and Diagnosis of Diabetes S25
the use of immunosuppressive therapies metformin was safe to use in renal trans- transethnic genome-wide meta-analysis. PLoS
is a major contributor to the development plant recipients (108), but its safety has Med 2017;14:e1002383
of PTDM, the risks of transplant rejection not been determined in other types of 13. Ziemer DC, Kolm P, Weintraub WS, et al.
outweigh the risks of PTDM and the role organ transplant. Thiazolidinediones Glucose-independent, black-white differences in
of the diabetes care provider is to treat have been used successfully in patients hemoglobin A1c levels: a cross-sectional analysis
hyperglycemia appropriately regard- with liver and kidney transplants, but of 2 studies. Ann Intern Med 2010;152:770–777
less of the type of immunosuppression side effects include fluid retention, heart 14. Kumar PR, Bhansali A, Ravikiran M, et al. Util-
(97). Risk factors for PTDM include both failure, and osteopenia (109,110). Dipep- ity of glycated hemoglobin in diagnosing type 2
general diabetes risks (such as age, fam- tidyl peptidase 4 inhibitors do not interact diabetes mellitus: a community-based study.
ily history of diabetes, etc.) as well as with immunosuppressant drugs and have J Clin Endocrinol Metab 2010;95:2832–2835
transplant-specific factors, such as use demonstrated safety in small clinical trials 15. Herman WH. Are there clinical implications of
of immunosuppressant agents (102). racial differences in HbA1c? Yes, to not consider
Whereas posttransplantation hyperglyce- (111,112). Well-designed intervention tri- can do great harm! Diabetes Care 2016;39:1458–
mia is an important risk factor for subse- als examining the efficacy and safety of 1461
quent PTDM, a formal diagnosis of PTDM these and other antihyperglycemic agents 16. Herman WH, Ma Y, Uwaifo G, et al.; Diabetes
is optimally made once the patient is sta- in patients with PTDM are needed. Prevention Program Research Group. Differences
ble on maintenance immunosuppression in A1C by race and ethnicity among patients with
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tients with hyperglycemia and PTDM af- tiation of diabetes by pathophysiology, natural his- BHR, et al. Racial and ethnic differences in mean
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Groups criteria. Obstet Gynecol 2014;124: 94. Onady GM, Stolfi A. Insulin and oral agents Pract 2008;14:979–984
571–578 for managing cystic fibrosis-related diabetes. Co- 109. Budde K, Neumayer H-H, Fritsche L,
81. Mayo K, Melamed N, Vandenberghe H, chrane Database Syst Rev 2016;4:CD004730 Sulowicz W, Stompoˆr T, Eckland D. The pharma-
Berger H. The impact of adoption of the Interna- 95. Moran A, Brunzell C, Cohen RC, et al.; CFRD cokinetics of pioglitazone in patients with im-
tional Association of Diabetes in Pregnancy Study Guidelines Committee. Clinical care guidelines for paired renal function. Br J Clin Pharmacol 2003;
Group criteria for the screening and diagnosis of cystic fibrosis-related diabetes: a position state- 55:368–374
gestational diabetes. Am J Obstet Gynecol 2015; ment of the American Diabetes Association and a 110. Luther P, Baldwin D Jr. Pioglitazone in the
212:224.e1–224.e9 clinical practice guideline of the Cystic Fibrosis management of diabetes mellitus after transplan-
82. Carmody D, Støy J, Greeley SA, Bell GI, Foundation, endorsed by the Pediatric Endocrine tation. Am J Transplant 2004;4:2135–2138
Philipson LH. A clinical guide to monogenic diabe- Society. Diabetes Care 2010;33:2697–2708 111. Strøm Halden TA, A˚ sberg A, Vik K, Hartmann
tes. In Genetic Diagnosis of Endocrine Disorders. 96. Moran A, Pillay K, Becker DJ, Acerini CL; In- A, Jenssen T. Short-term efficacy and safety of
2nd ed. Weiss RE, Refetoff S, Eds. Philadelphia, PA, ternational Society for Pediatric and Adolescent sitagliptin treatment in long-term stable renal re-
Elsevier, 2016 Diabetes. ISPAD Clinical Practice Consensus cipients with new-onset diabetes after transplan-
83. De Franco E, Flanagan SE, Houghton JAL, et al. Guidelines 2014. Management of cystic fibrosis- tation. Nephrol Dial Transplant 2014;29:926–933
The effect of early, comprehensive genomic test- related diabetes in children and adolescents. Pe- 112. Lane JT, Odegaard DE, Haire CE, Collier DS,
ing on clinical care in neonatal diabetes: an inter- diatr Diabetes 2014;15(Suppl. 20):65–76 Wrenshall LE, Stevens RB. Sitagliptin therapy in
national cohort study. Lancet 2015;386:957–963 97. Sharif A, Hecking M, de Vries APJ, et al. Pro- kidney transplant recipients with new-onset dia-
84. Urbanova´ J, Rypa´cˇkova´ B, Procha´zkova´ Z, ceedings from an international consensus meet- betes after transplantation. Transplantation 2011;
et al. Positivity for islet cell autoantibodies in pa- ing on posttransplantation diabetes mellitus: 92:e56–e57
tients with monogenic diabetes is associated with
S28 Diabetes Care Volume 41, Supplement 1, January 2018
3. Comprehensive Medical American Diabetes Association
Evaluation and Assessment
of Comorbidities: Standards of
Medical Care in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S28–S37 | https://doi.org/10.2337/dc18-S003
3. MEDICAL EVALUATION AND COMORBIDITIES The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
includes ADA’s current clinical practice recommendations and is intended to provide
the components of diabetes care, general treatment goals and guidelines, and tools
to evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee, are responsible for updating the Standards of
Care annually, or more frequently as warranted. For a detailed description of ADA
standards, statements, and reports, as well as the evidence-grading system for ADA’s
clinical practice recommendations, please refer to the Standards of Care In-
troduction. Readers who wish to comment on the Standards of Care are invited to
do so at professional.diabetes.org/SOC.
PATIENT-CENTERED COLLABORATIVE CARE
Recommendation
c A patient-centered communication style that uses person-centered and
strength-based language, active listening, elicits patient preferences and beliefs,
and assesses literacy, numeracy, and potential barriers to care should be used to
optimize patient health outcomes and health-related quality of life. B
A successful medical evaluation depends on beneficial interactions between the pa- Suggested citation: American Diabetes Association.
tient and the care team. The Chronic Care Model (1–3) (see Section 1 “Improving Care 3. Comprehensive medical evaluation and assess-
and Promoting Health in Populations”) is a patient-centered approach to care that ment of comorbidities: Standards of Medical Care in
requires a close working relationship between the patient and clinicians involved in treat- Diabetesd2018. Diabetes Care 2018;41(Suppl. 1):
ment planning. People with diabetes should receive health care from an interdisciplinary S28–S37
team that may include physicians, nurse practitioners, physician assistants, nurses, dietitians,
© 2017 by the American Diabetes Association.
exercise specialists, pharmacists, dentists, podiatrists, and mental health professionals. Readers may use this article as long as the work
Individuals with diabetes must assume an active role in their care. The patient, family is properly cited, the use is educational and not
or support persons, physician, and health care team should together formulate the for profit, and the work is not altered. More infor-
management plan, which includes lifestyle management (see Section 4 “Lifestyle mation is available at http://www.diabetesjournals
Management”). .org/content/license.
Treatment goals and plans should be created with the patients based on their indi-
vidual preferences, values, and goals. The management plan should take into account
the patient’s age, cognitive abilities, school/work schedule and conditions, health
beliefs, support systems, eating patterns, physical activity, social situation, finan-
cial concerns, cultural factors, literacy and numeracy (mathematical literacy),
diabetes complications and duration of disease, comorbidities, health priorities,
other medical conditions, preferences for care, and life expectancy. Various
care.diabetesjournals.org Comprehensive Medical Evaluation and Assessment of Comorbidities S29
strategies and techniques should be used ○ Begin patient engagement in the Additional referrals should be arranged as nec-
to support patients’ self-management formulation of a care management essary (Table 3.2). Clinicians should ensure
efforts, including providing education on plan. B that individuals with diabetes are appropri-
problem-solving skills for all aspects of ately screened for complications and comor-
diabetes management. ○ Develop a plan for continuing care. B bidities. Discussing and implementing an
c A follow-up visit should include approach to glycemic control with the patient
Provider communications with patients/ is a part, not the sole goal, of care.
families should acknowledge that multiple most components of the initial com-
factors impact glycemic management, but prehensive medical evaluation in- Immunization
also emphasize that collaboratively de- cluding: interval medical history;
veloped treatment plans and a healthy assessment of medication-taking be- Recommendations
lifestyle can significantly improve dis- havior and intolerance/side effects;
ease outcomes and well-being (4–7). physical examination; laboratory c Provide routinely recommended
Thus, the goal of provider-patient com- evaluation as appropriate to assess vaccinations for children and adults
munication is to establish a collaborative attainment of A1C and metabolic tar- with diabetes by age. C
relationship and to assess and address gets; and assessment of risk for com-
self-management barriers without blaming plications, diabetes self-management c Annual vaccination against influenza
patients for “noncompliance” or “nonad- behaviors, nutrition, psychosocial is recommended for all people $6
herence” when the outcomes of self- health, and the need for referrals, months of age, including those with
management are not optimal (8). The immunizations, or other routine diabetes. C
familiar terms “noncompliance” and “non- health maintenance screening. B
adherence” denote a passive, obedient c Vaccination against pneumococcal
role for a person with diabetes in “follow- The comprehensive medical evaluation disease, including pneumococcal
ing doctor’s orders” that is at odds with includes the initial and follow-up evalua- pneumonia, with 13-valent pneumo-
the active role people with diabetes take tions, assessment of complications, psy- coccal conjugate vaccine (PCV13) is
in directing the day-to-day decision- chosocial assessment, management of recommended for children before
making, planning, monitoring, evaluation, comorbid conditions, and engagement age 2 years. People with diabetes
and problem-solving involved in diabetes of the patient throughout the process. ages 2 through 64 years should also
self-management. Using a nonjudgmen- While a comprehensive list is provided receive 23-valent pneumococcal
tal approach that normalizes periodic lapses in Table 3.1, in clinical practice, the pro- polysaccharide vaccine (PPSV23). At
in self-management may help minimize pa- vider may need to prioritize the compo- age $65 years, regardless of vacci-
tients’ resistance to reporting problems nents of the medical evaluation given the nation history, additional PPSV23
with self-management. Empathizing and available resources and time. The goal is to vaccination is necessary. C
using active listening techniques, such as provide the health care team information
open-ended questions, reflective state- to optimally support a patient. In addition c Administer 3-dose series of hepatitis
ments, and summarizing what the patient to the medical history, physical examina- B vaccine to unvaccinated adults with
said, can help facilitate communication. tion, and laboratory tests, providers should diabetes ages 19 through 59 years. C
Patients’ perceptions about their own abil- assess diabetes self-management behav-
ity, or self-efficacy, to self-manage dia- iors, nutrition, and psychosocial health c Consider administering 3-dose se-
betes are one important psychosocial (see Section 4 “Lifestyle Management”) ries of hepatitis B vaccine to unvac-
factor related to improved diabetes self- and give guidance on routine immuniza- cinated adults with diabetes ages
management and treatment outcomes in tions. The assessment of sleep pattern and $60 years. C
diabetes (9–13) and should be a target of duration should be considered; a recent
ongoing assessment, patient education, meta-analysis found that poor sleep quality, Children and adults with diabetes should
and treatment planning. short sleep, and long sleep were associated receive vaccinations according to age-
with higher A1C in people with type 2 di- specific recommendations (15,16). The
COMPREHENSIVE MEDICAL abetes (14). Interval follow-up visits should child and adolescent vaccination schedule
EVALUATION occur at least every 3–6 months, individual- is available at www.cdc.gov/vaccines/
ized to the patient, and then annually. schedules/hcp/imz/child-adolescent.
Recommendations html, and the adult vaccination schedule
Lifestyle management and psychosocial is available at www.cdc.gov/vaccines/
c A complete medical evaluation care are the cornerstones of diabetes man- schedules/hcp/imz/adult.html. These im-
should be performed at the initial agement. Patients should be referred for munization schedules include vaccination
visit to: diabetes self-management education and schedules specifically for children, adoles-
support (DSMES), medical nutrition therapy cents, and adults with diabetes.
○ Confirm the diagnosis and classify (MNT), and psychosocial/emotional health
diabetes. B concerns if indicated. Patients should receive People with diabetes are at higher risk
recommended preventive care services (e.g., for hepatitis B infection and are more likely
○ Evaluate for diabetes complications immunizations, cancer screening, etc.); to develop complications from influenza
and potential comorbid conditions. E smoking cessation counseling; and ophthal- and pneumococcal disease. The Centers
mological, dental, and podiatric referrals. for Disease Control and Prevention (CDC)
○ Review previous treatment and risk Advisory Committee on Immunization Prac-
factor control in patients with es- tices (ACIP) recommends influenza, pneumo-
tablished diabetes. E coccal, and hepatitis B vaccinations specifically
for people with diabetes. Vaccination against
tetanus-diphtheria-pertussis, measles-mumps-
S30 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 41, Supplement 1, January 2018
Continued on p. S31
care.diabetesjournals.org Comprehensive Medical Evaluation and Assessment of Comorbidities S31
S32 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 41, Supplement 1, January 2018
Table 3.2—Referrals for initial care need to be aware of common comorbidities to remediate deficits. Treatment
management that affect people with diabetes and may should be tailored to avoid signifi-
c Eye care professional for annual dilated complicate management (19–23). Diabetes cant hypoglycemia. B
comorbidities are conditions that affect
eye exam people with diabetes more often than age- Diabetes is associated with a significantly
c Family planning for women of matched people without diabetes. The list increased risk and rate of cognitive decline
below includes many of the common comor- and an increased risk of dementia (30,31).
reproductive age bidities observed in patients with diabetes A recent meta-analysis of prospective ob-
c Registered dietitian for MNT but is not necessarily inclusive of all the con- servational studies in people with diabe-
c DSMES ditions that have been reported. tes showed 73% increased risk of all types
c Dentist for comprehensive dental and of dementia, 56% increased risk of Alz-
Autoimmune Diseases heimer dementia, and 127% increased
periodontal examination risk of vascular dementia compared with
c Mental health professional, if indicated Recommendation individuals without diabetes (32). The re-
verse is also true: people with Alzheimer
rubella, human papillomavirus, and shin- c Consider screening patients with dementia are more likely to develop di-
gles are also important for adults with diabe- type 1 diabetes for autoimmune abetes than people without Alzheimer
tes, as they are for the general population. thyroid disease and celiac disease dementia. In a 15-year prospective study
soon after diagnosis. B of community-dwelling people .60 years
Influenza of age, the presence of diabetes at base-
People with type 1 diabetes are at in- line significantly increased the age- and
Influenza is a common, preventable infec- creased risk for other autoimmune dis- sex-adjusted incidence of all-cause de-
tious disease associated with high mortality eases including thyroid disease, primary mentia, Alzheimer disease, and vascular
and morbidity in vulnerable populations in- adrenal insufficiency, celiac disease, auto- dementia compared with rates in those
cluding the young and the elderly and people immune gastritis, autoimmune hepatitis, with normal glucose tolerance (33).
with chronic diseases. Influenza vaccination dermatomyositis, and myasthenia gravis
in people with diabetes has been found to (24–26). Type 1 diabetes may also occur Hyperglycemia
significantly reduce influenza and diabetes- with other autoimmune diseases in the
related hospital admissions (17). context of specific genetic disorders or pol- In those with type 2 diabetes, the degree
yglandular autoimmune syndromes (27). and duration of hyperglycemia are re-
Pneumococcal Pneumonia In autoimmune diseases, the immune sys- lated to dementia. More rapid cognitive
tem fails to maintain self-tolerance to spe- decline is associated with both increased
Like influenza, pneumococcal pneumonia cific peptides within target organs. It is likely A1C and longer duration of diabetes (34).
is a common, preventable disease. People that many factors trigger autoimmune dis- The Action to Control Cardiovascular Risk
with diabetes may be at increased risk for ease; however, common triggering factors in Diabetes (ACCORD) study found that
the bacteremic form of pneumococcal infec- are known for only some autoimmune con- each 1% higher A1C level was associated
tion and have been reported to have a high ditions (i.e., gliadin peptides in celiac disease) with lower cognitive function in individu-
risk of nosocomial bacteremia, with a mortal- (see Section 12 “Children and Adolescents”). als with type 2 diabetes (35). However,
ity rate as high as 50% (18). The American the ACCORD study found no difference
Diabetes Association (ADA) endorses recom- Cancer in cognitive outcomes in participants ran-
mendations from the CDC ACIP that adults Diabetes is associated with increased risk of domly assigned to intensive and standard
age $65 years, who are at higher risk for cancers of the liver, pancreas, endometrium, glycemic control, supporting the recom-
pneumococcal disease, receive an additional colon/rectum, breast, and bladder (28). The mendation that intensive glucose control
23-valent pneumococcal polysaccharide association may result from shared risk fac- should not be advised for the improve-
vaccine (PPSV23), regardless of prior pneumo- tors between type 2 diabetes and cancer ment of cognitive function in individuals
coccal vaccination history. See detailed rec- (older age, obesity, and physical inactivity) with type 2 diabetes (36).
ommendations at www.cdc.gov/vaccines/ but may also be due to diabetes-related
hcp/acip-recs/vacc-specific/pneumo.html. factors (29), such as underlying disease Hypoglycemia
physiology or diabetes treatments, al-
Hepatitis B though evidence for these links is scarce. In type 2 diabetes, severe hypoglycemia is
Patients with diabetes should be encour- associated with reduced cognitive func-
Compared with the general population, aged to undergo recommended age- and tion, and those with poor cognitive func-
people with type 1 or type 2 diabetes sex-appropriate cancer screenings and to tion have more severe hypoglycemia. In a
have higher rates of hepatitis B. This may reduce their modifiable cancer risk factors long-term study of older patients with
be due to contact with infected blood or (obesity, physical inactivity, and smoking). type 2 diabetes, individuals with one or
through improper equipment use (glucose more recorded episode of severe hypo-
monitoring devices or infected needles). Be- Cognitive Impairment/Dementia glycemia had a stepwise increase in risk
cause of the higher likelihood of transmis- of dementia (37). Likewise, the ACCORD
sion, hepatitis B vaccine is recommended for Recommendation trial found that as cognitive function de-
adults with diabetes age ,60 years. For creased, the risk of severe hypoglycemia
adults age $60 years, hepatitis B vaccine c In people with a history of cognitive increased (38). Tailoring glycemic therapy
may be administered at the discretion of the impairment/dementia, intensive
treating clinician based on the patient’s like- glucose control cannot be expected
lihood of acquiring hepatitis B infection.
ASSESSMENT OF COMORBIDITIES
Besides assessing diabetes-related com-
plications, clinicians and their patients
care.diabetesjournals.org Comprehensive Medical Evaluation and Assessment of Comorbidities S33
may help to prevent hypoglycemia in in- Conversely, prediabetes and/or diabetes Hearing Impairment
dividuals with cognitive dysfunction. has been found to develop in approxi- Hearing impairment, both in high-
mately one-third of patients after an epi- frequency and low/mid-frequency ranges,
Nutrition sode of acute pancreatitis (47), thus the is more common in people with diabetes
relationship is likely bidirectional. Postpan- than in those without, perhaps due to
In one study, adherence to the Mediter- creatitis diabetes may include either new- neuropathy and/or vascular disease. In a
ranean diet correlated with improved onset disease or previously unrecognized National Health and Nutrition Examination
cognitive function (39). However, a recent diabetes (48). Studies of patients treated Survey (NHANES) analysis, hearing impair-
Cochrane review found insufficient ev- with incretin-based therapies for diabetes ment was about twice as prevalent in peo-
idence to recommend any dietary change have also reported that pancreatitis may ple with diabetes compared with those
for the prevention or treatment of cogni- occur more frequently with these medica- without, after adjusting for age and other
tive dysfunction (40). tions, but results have been mixed (49,50). risk factors for hearing impairment (61).
Statins Islet autotransplantation should be con- HIV
sidered for patients requiring total pancre-
A systematic review has reported that atectomy for medically refractory chronic Recommendation
data do not support an adverse effect pancreatitis to prevent postsurgical diabe-
of statins on cognition (41). The U.S. tes. Approximately one-third of patients c Patients with HIV should be screened
Food and Drug Administration (FDA) post- undergoing total pancreatectomy with is- for diabetes and prediabetes with
marketing surveillance databases have let autotransplantation are insulin free one a fasting glucose level every 6–12
also revealed a low reporting rate for cog- year postoperatively, and observational months before starting antiretrovi-
nitive-related adverse events, including studies from different centers have dem- ral therapy and 3 months after
cognitive dysfunction or dementia, with onstrated islet graft function up to a de- starting or changing antiretroviral
statin therapy, similar to rates seen with cade after the surgery in some patients therapy. If initial screening results
other commonly prescribed cardiovascular (51–55). Both patient and disease factors are normal, checking fasting glu-
medications (41). Therefore, fear of cog- should be carefully considered when de- cose every year is advised. E
nitive decline should not be a barrier to ciding the indications and timing of this
statin use in individuals with diabetes surgery. Surgeries should be performed in Diabetes risk is increased with certain
and a high risk for cardiovascular disease. skilled facilities that have demonstrated protease inhibitors (PIs) and nucleoside
expertise in islet autotransplantation. reverse transcriptase inhibitors (NRTIs).
Fatty Liver Disease New-onset diabetes is estimated to oc-
Diabetes is associated with the develop- Fractures cur in more than 5% of patients infected
ment of nonalcoholic chronic liver disease Age-specific hip fracture risk is signifi- with HIV on PIs, whereas more than 15%
and with hepatocellular carcinoma (42). cantly increased in people with both may have prediabetes (62). PIs are asso-
Elevations of hepatic transaminase con- type 1 (relative risk 6.3) and type 2 (relative ciated with insulin resistance and may
centrations are associated with higher risk 1.7) diabetes in both sexes (56). Type 1 also lead to apoptosis of pancreatic b-cells.
BMI, waist circumference, and triglycer- diabetes is associated with osteoporosis, NRTIs also affect fat distribution (both lip-
ide levels and lower HDL cholesterol lev- but in type 2 diabetes, an increased risk of ohypertrophy and lipoatrophy), which is
els. Interventions that improve metabolic hip fracture is seen despite higher bone associated with insulin resistance.
abnormalities in patients with diabetes mineral density (BMD) (57). In three large
(weight loss, glycemic control, and treat- observational studies of older adults, Individuals with HIV are at higher risk
ment with specific drugs for hyperglyce- femoral neck BMD T score and the World for developing prediabetes and diabe-
mia or dyslipidemia) are also beneficial Health Organization Fracture Risk Assess- tes on antiretroviral (ARV) therapies,
for fatty liver disease (43,44). ment Tool (FRAX) score were associated so a screening protocol is recommended
with hip and nonspine fractures. Fracture (63). The A1C test underestimates glyce-
Pancreatitis risk was higher in participants with dia- mia in people with HIV and is not recom-
betes compared with those without dia- mended for diagnosis and may present
Recommendation betes for a given T score and age or for a challenges for monitoring (64). In those
given FRAX score (58). Providers should with prediabetes, weight loss through
c Islet autotransplantation should be assess fracture history and risk factors in healthy nutrition and physical activity
considered for patients requiring older patients with diabetes and recom- may reduce the progression toward dia-
total pancreatectomy for medically mend measurement of BMD if appro- betes. Among patients with HIV and
refractory chronic pancreatitis to priate for the patient’s age and sex. diabetes, preventive health care using
prevent postsurgical diabetes. C Fracture prevention strategies for people an approach similar to that used in pa-
with diabetes are the same as for the tients without HIV is critical to reduce
Diabetes is linked to diseases of the exo- general population and include vitamin D the risks of microvascular and macrovas-
crine pancreas such as pancreatitis, which supplementation. For patients with type cular complications.
may disrupt the global architecture or 2 diabetes with fracture risk factors,
physiology of the pancreas, often result- thiazolidinediones (59) and sodium– For patients with HIV and ARV-associated
ing in both exocrine and endocrine glucose cotransporter 2 inhibitors (60) hyperglycemia, it may be appropriate to
dysfunction. Up to half of patients with di- should be used with caution. consider discontinuing the problematic
abetes may have impaired exocrine pan- ARV agents if safe and effective alternatives
creas function (45). People with diabetes are available (65). Before making ARV sub-
are at an approximately twofold higher stitutions, carefully consider the possible
risk of developing acute pancreatitis (46).
S34 Comprehensive Medical Evaluation and Assessment of Comorbidities Diabetes Care Volume 41, Supplement 1, January 2018
effect on HIV virological control and the diabetes than in those without (74,75). The Behavioral Risk Factor Surveillance
potential adverse effects of new ARV Current evidence suggests that periodon- System (BRFSS) estimated the lifetime
agents. In some cases, antihyperglycemic tal disease adversely affects diabetes out- prevalence of generalized anxiety disorder
agents may still be necessary. comes, although evidence for treatment to be 19.5% in people with either type 1 or
benefits remains controversial (23). type 2 diabetes (79). Common diabetes-
Low Testosterone in Men specific concerns include fears related to
Psychosocial/Emotional Disorders hypoglycemia (80,81), not meeting blood
Recommendation Prevalence of clinically significant psycho- glucose targets (78), and insulin injections
pathology diagnoses are considerably or infusion (82). Onset of complications
c In men with diabetes who have more common in people with diabetes presents another critical point when
symptoms or signs of hypogonadism than in those without the disease (76). anxiety can occur (83). People with dia-
such as decreased sexual desire Symptoms, both clinical and subclinical, betes who exhibit excessive diabetes self-
(libido) or activity, or erectile dys- that interfere with the person’s ability management behaviors well beyond what
function, consider screening with a to carry out daily diabetes self-manage- is prescribed or needed to achieve glycemic
morning serum testosterone level. B ment tasks must be addressed. Providers targets may be experiencing symptoms of
should consider an assessment of symp- obsessive-compulsive disorder (84).
Mean levels of testosterone are lower in toms of depression, anxiety, and disor-
men with diabetes compared with age- dered eating, and of cognitive capacities General anxiety is a predictor of injection-
matched men without diabetes, but obesity using patient-appropriate standardized/ related anxiety and associated with
is a major confounder (66,67). Treatment validated tools at the initial visit, at peri- fear of hypoglycemia (81,85). Fear of hy-
in asymptomatic men is controversial. odic intervals, and when there is a change poglycemia and hypoglycemia unaware-
Testosterone replacement in men with in disease, treatment, or life circum- ness often co-occur, and interventions
symptomatic hypogonadism may have ben- stance. Including caregivers and family aimed at treating one often benefit both
efits including improved sexual function, members in this assessment is recom- (86). Fear of hypoglycemia may explain
well being, muscle mass and strength, and mended. Diabetes distress is addressed avoidance of behaviors associated with
bone density. (68). In men with diabetes in Section 4 “Lifestyle Management,” as lowering glucose such as increasing in-
who have symptoms or signs of low testos- this state is very common and distinct sulin doses or frequency of monitoring.
terone (hypogonadism), a morning total from the psychological disorders dis- If fear of hypoglycemia is identified and
testosterone should be measured using an cussed below (77). a person does not have symptoms of
accurate and reliable assay. Free or bioavail- hypoglycemia, a structured program,
able testosterone levels should also be mea- Anxiety Disorders blood glucose awareness training, deliv-
sured in men with diabetes who have total ered in routine clinical practice, can im-
testosterone levels close to the lower limit, Recommendations prove A1C, reduce the rate of severe
given expected decreases in sex hormone– hypoglycemia, and restore hypoglycemia
binding globulin with diabetes. Further c Consider screening for anxiety in awareness (87,88).
testing (such as luteinizing hormone and people exhibiting anxiety or worries
follicle-stimulating hormone levels) may regarding diabetes complications, Depression
be needed to distinguish between pri- insulin injections or infusion, taking
mary and secondary hypogonadism. medications, and/or hypoglycemia Recommendations
that interfere with self-management
Obstructive Sleep Apnea behaviors and those who express c Providers should consider annual
Age-adjusted rates of obstructive sleep fear, dread, or irrational thoughts screening of all patients with diabetes,
apnea, a risk factor for cardiovascular and/or show anxiety symptoms especially those with a self-reported
disease, are significantly higher (4- to such as avoidance behaviors, exces- history of depression, for depressive
10-fold) with obesity, especially with cen- sive repetitive behaviors, or social symptoms with age-appropriate de-
tral obesity (69). The prevalence of ob- withdrawal. Refer for treatment if pression screening measures, recog-
structive sleep apnea in the population anxiety is present. B nizing that further evaluation will be
with type 2 diabetes may be as high as necessary for individuals who have a
23%, and the prevalence of any sleep dis- c People with hypoglycemia unaware- positive screen. B
ordered breathing may be as high as 58% ness, which can co-occur with fear of
(70,71). In obese participants enrolled in hypoglycemia, should be treated us- c Beginning at diagnosis of complica-
the Action for Health in Diabetes (Look ing blood glucose awareness training tions or when there are significant
AHEAD) trial, it exceeded 80% (72). Sleep (or other evidence-based interven- changes in medical status, consider
apnea treatment (lifestyle modification, tion) to help reestablish awareness assessment for depression. B
continuous positive airway pressure, of hypoglycemia and reduce fear of
oral appliances, and surgery) significantly hypoglycemia. A c Referrals for treatment of depres-
improves quality of life and blood pressure sion should be made to mental
control. The evidence for a treatment ef- Anxiety symptoms and diagnosable disor- health providers with experience us-
fect on glycemic control is mixed (73). ders (e.g., generalized anxiety disorder, ing cognitive behavioral therapy,
body dysmorphic disorder, obsessive- interpersonal therapy, or other evi-
Periodontal Disease compulsive disorder, specific phobias, dence-based treatment approaches
Periodontal disease is more severe, and and posttraumatic stress disorder) are in conjunction with collaborative
may be more prevalent, in patients with common in people with diabetes (78). care with the patient’s diabetes
treatment team. A
care.diabetesjournals.org Comprehensive Medical Evaluation and Assessment of Comorbidities S35
History of depression, current depression, (98,99); in people with type 2 diabetes, those taking second-generation (atypical)
and antidepressant medication use are bingeing (excessive food intake with an
risk factors for the development of type accompanying sense of loss of control) antipsychotics such as olanzapine require
2 diabetes, especially if the individual is most commonly reported. For people
has other risk factors such as obesity with type 2 diabetes treated with insulin, greater monitoring because of an increase
and family history of type 2 diabetes intentional omission is also frequently re-
(89–91). Elevated depressive symptoms ported (100). People with diabetes and in risk of type 2 diabetes associated with
and depressive disorders affect one in diagnosable eating disorders have high
four patients with type 1 or type 2 diabe- rates of comorbid psychiatric disorders this medication (106).
tes (92). Thus, routine screening for de- (101). People with type 1 diabetes and
pressive symptoms is indicated in this eating disorders have high rates of diabe- References
high-risk population including people tes distress and fear of hypoglycemia
with type 1 or type 2 diabetes, gestational (102). 1. Stellefson M, Dipnarine K, Stopka C. The
diabetes mellitus, and postpartum diabe- Chronic Care Model and diabetes management
tes. Regardless of diabetes type, women When evaluating symptoms of disor- in US primary care settings: a systematic review.
have significantly higher rates of depres- dered or disrupted eating in people with Prev Chronic Dis 2013;10:E26
sion than men (93). diabetes, etiology and motivation for the 2. Coleman K, Austin BT, Brach C, Wagner EH.
behavior should be considered (97,103). Evidence on the Chronic Care Model in the new
Routine monitoring with patient- Adjunctive medication such as glucagon- millennium. Health Aff (Millwood) 2009;28:75–85
appropriate validated measures can help like peptide 1 receptor agonists (104) may 3. Gabbay RA, Bailit MH, Mauger DT, Wagner EH,
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Diabetes Care Volume 41, Supplement 1, January 2018 S51
5. Prevention or Delay of Type 2 American Diabetes Association
Diabetes: Standards of Medical
Care in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S51–S54 | https://doi.org/10.2337/dc18-S005
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” 5. PREVENTION OR DELAY OF TYPE 2 DIABETES
includes ADA’s current clinical practice recommendations and is intended to provide
the components of diabetes care, general treatment goals and guidelines, and tools
to evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee, are responsible for updating the Standards of
Care annually, or more frequently as warranted. For a detailed description of ADA
standards, statements, and reports, as well as the evidence-grading system for ADA’s
clinical practice recommendations, please refer to the Standards of Care Introduction.
Readers who wish to comment on the Standards of Care are invited to do so at
professional.diabetes.org/SOC.
For guidelines related to screening for increased risk for type 2 diabetes (prediabetes),
please refer to Section 2 “Classification and Diagnosis of Diabetes.”
Recommendations
c At least annual monitoring for the development of diabetes in those with pre-
diabetes is suggested. E
c Patients with prediabetes should be referred to an intensive behavioral lifestyle
intervention program modeled on the Diabetes Prevention Program to achieve
and maintain 7% loss of initial body weight and increase moderate-intensity
physical activity (such as brisk walking) to at least 150 min/week. A
c Technology-assisted tools including Internet-based social networks, distance
learning, and mobile applications that incorporate bidirectional communi-
cation may be useful elements of effective lifestyle modification to prevent
diabetes. B
c Given the cost-effectiveness of diabetes prevention, such intervention programs
should be covered by third-party payers. B
Screening for prediabetes and type 2 diabetes risk through an informal assess- Suggested citation: American Diabetes Association.
ment of risk factors (Table 2.3) or with an assessment tool, such as the American 5. Prevention or delay of type 2 diabetes: Standards
Diabetes Association risk test (Fig. 2.1), is recommended to guide providers on of Medical Care in Diabetesd2018. Diabetes Care
whether performing a diagnostic test for prediabetes (Table 2.4) and previ- 2018;41(Suppl. 1):S51–S54
ously undiagnosed type 2 diabetes (Table 2.2) is appropriate (see Section
2 “Classification and Diagnosis of Diabetes”). Those determined to be at high risk © 2017 by the American Diabetes Association.
for type 2 diabetes, including people with A1C 5.7–6.4% (39–47 mmol/mol), im- Readers may use this article as long as the work
paired glucose tolerance, or impaired fasting glucose, are ideal candidates for is properly cited, the use is educational and not
for profit, and the work is not altered. More infor-
diabetes prevention efforts. Using A1C to screen for prediabetes may be problem- mation is available at http://www.diabetesjournals
.org/content/license.
atic in the presence of certain hemoglobinopathies or conditions that affect red
blood cell turnover. See Section 2 “Classification and Diagnosis of Diabetes” and
S52 Prevention or Delay of Type 2 Diabetes Diabetes Care Volume 41, Supplement 1, January 2018
Section 6 “Glycemic Targets” for addi- encouraged to distribute their activity showed beneficial effects in those with pre-
tional details on the appropriate use of throughout the week with a minimum fre- diabetes (1), moderate-intensity physical
the A1C test. quency of three times per week with at least activity has been shown to improve insu-
10 min per session. A maximum of 75 min of lin sensitivity and reduce abdominal fat in
At least annual monitoring for the de- strength training could be applied toward the children and young adults (18,19). On the
velopment of diabetes in those with pre- total 150 min/week physical activity goal (6). basis of these findings, providers are en-
diabetes is suggested. couraged to promote a DPP-style pro-
To implement the weight loss and gram, including its focus on physical
LIFESTYLE INTERVENTIONS physical activity goals, the DPP used an in- activity, to all individuals who have been
dividual model of treatment rather than a identified to be at an increased risk of
The Diabetes Prevention Program group-based approach. This choice was type 2 diabetes. In addition to aerobic
The strongest evidence for diabetes preven- based on a desire to intervene before par- activity, an exercise regimen designed to
tion comes from the Diabetes Prevention ticipants had the possibility of developing prevent diabetes may include resistance
Program (DPP) (1). The DPP demonstrated diabetes or losing interest in the program. training (6,20). Breaking up prolonged
that an intensive lifestyle intervention The individual approach also allowed for sedentary time may also be encouraged,
could reduce the incidence of type 2 di- tailoring of interventions to reflect the di- as it is associated with moderately lower
abetes by 58% over 3 years. Follow-up of versity of the population (6). postprandial glucose levels (21,22). The
three large studies of lifestyle interven- preventative effects of exercise appear
tion for diabetes prevention has shown The DPP intervention was administered to extend to the prevention of gestational
sustained reduction in the rate of conver- as a structured core curriculum followed diabetes mellitus (GDM) (23).
sion to type 2 diabetes: 43% reduction at by a more flexible maintenance program
20 years in the Da Qing study (2), 43% of individual sessions, group classes, moti- Technology Assistance to Deliver
reduction at 7 years in the Finnish Diabetes vational campaigns, and restart opportuni- Lifestyle Interventions
Prevention Study (DPS) (3), and 34% reduc- ties. The 16-session core curriculum was Information technology platforms may
tion at 10 years (4) and 27% reduction at completed within the first 24 weeks of effectively deliver the core components of
15 years (5) in the U.S. Diabetes Preven- the program and included sections on low- the DPP (24–26), lowering weight, reduc-
tion Program Outcomes Study (DPPOS). ering calories, increasing physical activity, ing risk for diabetes and cardiovascular
self-monitoring, maintaining healthy life- disease, and achieving cost savings
The two major goals of the DPP inten- style behaviors, and psychological, social, (27,28). Recent studies support content
sive, behavioral, lifestyle intervention and motivational challenges. For further de- delivery through virtual small groups
were to achieve and maintain a minimum tails on the core curriculum sessions, refer (29), Internet-driven social networks
of 7% weight loss and 150 min of physical to ref. 6. (30,31), cell phones, and other mobile de-
activity per week similar in intensity to vices. Mobile applications for weight loss
brisk walking. The DPP lifestyle interven- Nutrition and diabetes prevention have been vali-
tion was a goal-based intervention: all Reducing caloric intake is of paramount im- dated for their ability to reduce A1C in
participants were given the same weight portance for those at high risk for develop- the setting of prediabetes (31). The Cen-
loss and physical activity goals, but indi- ing type 2 diabetes, though recent evidence ters for Disease Control and Prevention
vidualization was permitted in the specific suggests that the quality of fats consumed (CDC) Diabetes Prevention Recognition
methods used to achieve the goals (6). in the diet is more important than the total Program (DPRP) (http://www.cdc.gov/
quantity of dietary fat (7–9). For example, diabetes/prevention/recognition/index
The 7% weight loss goal was selected be- the Mediterranean diet, which is relative- .htm) has begun to certify electronic and
cause it was feasible to achieve and maintain ly high in monounsaturated fats, may mobile health-based modalities as effec-
and likely to lessen the risk of developing help to prevent type 2 diabetes (10–12). tive vehicles for DPP-based interventions
diabetes. Participants were encouraged to that may be considered alongside more
achieve the 7% weight loss during the first Whereas overall healthy low-calorie traditional face-to-face and coach-driven
6 months of the intervention. The recom- eating patterns should be encouraged, programs. A recent study showed that an
mended pace of weight loss was 1–2 there is also some evidence that particu- all-mobile approach to administering DPP
lb/week. Calorie goals were calculated by lar dietary components impact diabetes content can be effective as a prevention
estimating the daily calories needed to risk. Higher intakes of nuts (13), berries tool, at least over the short term, in over-
maintain the participant’s initial weight (14), yogurt (15), coffee, and tea (16) are as- weight and obese individuals at high risk
and subtracting 500–1,000 calories/day sociated with reduced diabetes risk. Con- for diabetes (32).
(depending on initial body weight). The versely, red meats and sugar-sweetened
initial focus was on reducing total dietary beverages are associated with an in- Cost-effectiveness
fat. After several weeks, the concept of creased risk of type 2 diabetes (8). A cost-effectiveness model suggested
calorie balance and the need to restrict that the lifestyle intervention used in
calories as well as fat was introduced (6). As is the case for those with diabetes, the DPP was cost-effective (33). Actual
individualized medical nutrition therapy cost data from the DPP and DPPOS con-
The goal for physical activity was selected (see Section 4 “Lifestyle Management” firmed this (34). Group delivery of DPP
to approximate at least 700 kcal/week for more detailed information) is effective content in community or primary care
expenditure from physical activity. For in lowering A1C in individuals diagnosed settings has the potential to reduce over-
ease of translation, this goal was described with prediabetes (17). all program costs while still producing
as at least 150 min of moderate-intensity
physical activity per week similar in inten- Physical Activity
sity to brisk walking. Participants were Just as 150 min/week of moderate-intensity
physical activity, such as brisk walking,
care.diabetesjournals.org Prevention or Delay of Type 2 Diabetes S53
weight loss and diabetes risk reduction Metformin was overall less effective to people with prediabetes. Currently,
(35–37). The use of community health than lifestyle modification in the DPP there are significant barriers to the pro-
workers to support DPP efforts has been and DPPOS, though group differences de- vision of education and support to those
shown to be effective with cost savings clined over time (5) and metformin may with prediabetes. However, the strate-
(38) (see Section 1 “Improving Care and be cost-saving over a 10-year period (34). gies for supporting successful behavior
Promoting Health in Populations” for more It was as effective as lifestyle modification change and the healthy behaviors recom-
information). The CDC helps to coordi- in participants with BMI $35 kg/m2 but mended for people with prediabetes are
nate the National Diabetes Prevention not significantly better than placebo in comparable to those for diabetes. Al-
Program (National DPP), a resource de- those over 60 years of age (1). In the though reimbursement remains a barrier,
signed to bring evidence-based lifestyle DPP, for women with history of GDM, studies show that providers of diabetes
change programs for preventing type 2 metformin and intensive lifestyle mod- self-management education and support
diabetes to communities (http://www ification led to an equivalent 50% reduc- are particularly well equipped to assist
.cdc.gov/diabetes/prevention/index.htm). tion in diabetes risk (46), and both people with prediabetes in developing
Early results from the CDC’s National DPP interventions remained highly effective and maintaining behaviors that can pre-
during the first 4 years of implementation during a 10-year follow-up period (47). vent or delay the development of diabe-
are promising (39). On 7 July 2016, the Metformin should be recommended as tes (17,50).
Centers for Medicare and Medicaid Ser- an option for high-risk individuals (e.g.,
vices (CMS) proposed expanded Medi- those with a history of GDM or those References
care reimbursement coverage for DPP with BMI $35). Consider monitoring 1. Knowler WC, Barrett-Connor E, Fowler SE,
programs in an effort to expand preventive B12 levels in those taking metformin et al.; Diabetes Prevention Program Research
services using a cost-effective model with chronically to check for possible defi- Group. Reduction in the incidence of type 2 di-
proposed implementation in 2018 (https:// ciency (see Section 8 “Pharmacologic abetes with lifestyle intervention or metformin.
innovation.cms.gov/initiatives/medicare- Approaches to Glycemic Treatment” for N Engl J Med 2002;346:393–403
diabetes-prevention-program/). more details). 2. Li G, Zhang P, Wang J, et al. The long-term
effect of lifestyle interventions to prevent diabe-
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CARDIOVASCULAR DISEASE Study: a 20-year follow-up study. Lancet 2008;
Recommendations 371:1783–1789
Recommendation 3. Lindstro¨m J, Ilanne-Parikka P, Peltonen M,
c Metformin therapy for prevention et al.; Finnish Diabetes Prevention Study Group.
of type 2 diabetes should be consid- c Screening for and treatment of Sustained reduction in the incidence of type 2 di-
ered in those with prediabetes, espe- modifiable risk factors for cardio- abetes by lifestyle intervention: follow-up of the
cially for those with BMI $35 kg/m2, vascular disease is suggested for Finnish Diabetes Prevention Study. Lancet 2006;
those aged ,60 years, and women those with prediabetes. B 368:1673–1679
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mellitus. A People with prediabetes often have other Diabetes Prevention Program Research Group.
cardiovascular risk factors, including hyper- 10-year follow-up of diabetes incidence and
c Long-term use of metformin may be tension and dyslipidemia, and are at in- weight loss in the Diabetes Prevention Program
associated with biochemical vitamin creased risk for cardiovascular disease Outcomes Study. Lancet 2009;374:1677–1686
B12 deficiency, and periodic mea- (48). Although treatment goals for people 5. Nathan DM, Barrett-Connor E, Crandall JP,
surement of vitamin B12 levels should with prediabetes are the same as for the et al. Long-term effects of lifestyle intervention
be considered in metformin-treated general population (49), increased vigi- or metformin on diabetes development and mi-
patients, especially in those with ane- lance is warranted to identify and treat crovascular complications: the DPP Outcomes
mia or peripheral neuropathy. B these and other cardiovascular risk fac- Study. Lancet Diabetes Endocrinol 2015;3:866–
tors (e.g., smoking). 875
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min, a-glucosidase inhibitors, orlistat, DIABETES SELF-MANAGEMENT Group. The Diabetes Prevention Program (DPP):
glucagon-like peptide 1 (GLP-1) receptor EDUCATION AND SUPPORT description of lifestyle intervention. Diabetes Care
agonists, and thiazolidinediones have 2002;25:2165–2171
each been shown to decrease incident di- Recommendation 7. Jacobs S, Harmon BE, Boushey CJ, et al. A priori-
abetes to various degrees in those with defined diet quality indexes and risk of type 2 di-
prediabetes in research studies (1,40–45), c Diabetes self-management educa- abetes: the Multiethnic Cohort. Diabetologia
though none are approved by the U.S. tion and support programs may be 2015;58:98–112
Food and Drug Administration specifically appropriate venues for people with 8. Ley SH, Hamdy O, Mohan V, Hu FB. Prevention
for diabetes prevention. One has to bal- prediabetes to receive education and management of type 2 diabetes: dietary com-
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as pharmacologic therapy for diabetes dietary indices both strongly predict risk of
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the Mediterranean diet on type 2 diabetes and 26. Oldenburg B, Taylor CB, O’Neil A, Cocker F, 39. Ely EK, Gruss SM, Luman ET, et al. A national
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17. Parker AR, Byham-Gray L, Denmark R, Winkle 31. Sepah SC, Jiang L, Peters AL. Long-term out- tes in patients with impaired glucose tolerance or
PJ. The effect of medical nutrition therapy by a comes of a Web-based diabetes prevention pro- impaired fasting glucose: a randomised controlled
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Diabetes Care Volume 41, Supplement 1, January 2018 S55
6. Glycemic Targets: Standards of American Diabetes Association
Medical Care in Diabetesd2018
Diabetes Care 2018;41(Suppl. 1):S55–S64 | https://doi.org/10.2337/dc18-S006
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” 6. GLYCEMIC TARGETS
includes ADA’s current clinical practice recommendations and is intended to provide
the components of diabetes care, general treatment goals and guidelines, and tools to
evaluate quality of care. Members of the ADA Professional Practice Committee, a
multidisciplinary expert committee, are responsible for updating the Standards of
Care annually, or more frequently as warranted. For a detailed description of ADA
standards, statements, and reports, as well as the evidence-grading system for ADA’s
clinical practice recommendations, please refer to the Standards of Care Introduction.
Readers who wish to comment on the Standards of Care are invited to do so at
professional.diabetes.org/SOC.
ASSESSMENT OF GLYCEMIC CONTROL
Patient self-monitoring of blood glucose (SMBG) and A1C are available to health
care providers and patients to assess the effectiveness and safety of a manage-
ment plan on glycemic control. Continuous glucose monitoring (CGM) also has
an important role in assessing the effectiveness and safety of treatment in sub-
groups of patients with type 1 diabetes and in selected patients with type 2 di-
abetes. Data indicate similar A1C and safety with the use of CGM compared with
SMBG (1).
Recommendations Suggested citation: American Diabetes Associa-
tion. 6. Glycemic targets: Standards of Medical
c Most patients using intensive insulin regimens (multiple-dose insulin or in- Care in Diabetesd2018. Diabetes Care 2018;
sulin pump therapy) should perform self-monitoring of blood glucose (SMBG) 41(Suppl. 1):S55–S64
prior to meals and snacks, at bedtime, occasionally postprandially, prior to
exercise, when they suspect low blood glucose, after treating low blood © 2017 by the American Diabetes Association.
glucose until they are normoglycemic, and prior to critical tasks such as Readers may use this article as long as the work
driving. B is properly cited, the use is educational and not
for profit, and the work is not altered. More infor-
c When prescribed as part of a broad educational program, SMBG may help to mation is available at http://www.diabetesjournals
guide treatment decisions and/or self-management for patients taking less fre- .org/content/license.
quent insulin injections B or noninsulin therapies. E
c When prescribing SMBG, ensure that patients receive ongoing instruction and
regular evaluation of SMBG technique, SMBG results, and their ability to use
SMBG data to adjust therapy. E
c When used properly, continuous glucose monitoring (CGM) in conjunction with
intensive insulin regimens is a useful tool to lower A1C in adults with type 1
diabetes who are not meeting glycemic targets. A
c CGM may be a useful tool in those with hypoglycemia unawareness and/or
frequent hypoglycemic episodes. C
c Given the variable adherence to CGM, assess individual readiness for continuing
CGM use prior to prescribing. E
S56 Glycemic Targets Diabetes Care Volume 41, Supplement 1, January 2018
c When prescribing CGM, robust di- should be advised against purchasing or most CGM devices include alarms for hypo-
abetes education, training, and sup- reselling preowned or secondhand test and hyperglycemic excursions. The inter-
port are required for optimal CGM strips, as these may give incorrect results. mittent or “flash” CGM device, very re-
implementation and ongoing use. E Only unopened vials of glucose test strips cently approved for adult use only (18),
should be used to ensure SMBG accuracy. differs from previous CGM devices. Spe-
c People who have been successfully cifically, it does not have alarms, does not
using CGM should have continued For Patients on Intensive Insulin Regimens require calibration with SMBG, and does
access after they turn 65 years of not communicate continuously (only on
age. E Most patients using intensive insulin demand). It is reported to have a lower
regimens (multiple-dose insulin or insulin cost than traditional systems. A study in
Self-monitoring of Blood Glucose pump therapy) should perform SMBG adults with well-controlled type 1 diabe-
Major clinical trials of insulin-treated pa- prior to meals and snacks, at bedtime, oc- tes found that flash CGM users spent less
tients have included SMBG as part of casionally postprandially, prior to exercise, time in hypoglycemia than those using
multifactorial interventions to demon- when they suspect low blood glucose, af- SMBG (19). However, due to significant
strate the benefit of intensive glycemic ter treating low blood glucose until they differences between flash CGM and other
control on diabetes complications. SMBG are normoglycemic, and prior to critical CGM devices, more discussion is needed
is thus an integral component of effective tasks such as driving. For many patients, on outcomes and regarding specific rec-
therapy (2). SMBG allows patients to eval- this will require testing 6–10 (or more) ommendations.
uate their individual response to therapy times daily, although individual needs
and assess whether glycemic targets are may vary. A database study of almost For most CGM systems, confirmatory
being achieved. Integrating SMBG results 27,000 children and adolescents with SMBG is required to make treatment de-
into diabetes management can be a type 1 diabetes showed that, after adjust- cisions, though a randomized controlled
useful tool for guiding medical nutrition ment for multiple confounders, increased trial of 226 adults suggested that an en-
therapy and physical activity, preventing daily frequency of SMBG was significantly hanced CGM device could be used safely
hypoglycemia, and adjusting medications associated with lower A1C (–0.2% per ad- and effectively without regular confirma-
(particularly prandial insulin doses). Among ditional test per day) and with fewer tory SMBG in patients with well-controlled
patients with type 1 diabetes, there is a acute complications (8). type 1 diabetes at low risk of severe hy-
correlation between greater SMBG fre- poglycemia (1). Two CGM devices are now
quency and lower A1C (3). The patient’s For Patients Using Basal Insulin and/or Oral approved by the U.S. Food and Drug Ad-
specific needs and goals should dictate Agents ministration (FDA) for making treatment
SMBG frequency and timing. decisions without SMBG confirmation
The evidence is insufficient regarding (18,20), including the flash CGM device.
Optimization when to prescribe SMBG and how often
testing is needed for patients who do not use Although performed with older gener-
SMBG accuracy is dependent on the instru- intensive insulin regimens, such as those ation CGM devices, a 26-week random-
ment and user, so it is important to evalu- with type 2 diabetes using oral agents ized trial of 322 patients with type 1
ate each patient’s monitoring technique, and/or basal insulin. For patients using diabetes showed that adults aged $25 years
both initially and at regular intervals basal insulin, assessing fasting glucose using intensive insulin therapy and CGM
thereafter. Optimal use of SMBG requires with SMBG to inform dose adjustments experienced a 0.5% reduction in A1C
proper review and interpretation of the to achieve blood glucose targets results (from ;7.6% to 7.1% [;60 mmol/mol
data, by both the patient and the pro- in lower A1Cs (9,10). to 54 mmol/mol]) compared with those
vider. Among patients who check their using intensive insulin therapy with SMBG
blood glucose at least once daily, many For individuals with type 2 diabetes on (21). The greatest predictor of A1C lower-
report taking no action when results are less intensive insulin therapy, more fre- ing for all age-groups was frequency of
high or low. In a yearlong study of insulin- quent SMBG (e.g., fasting, before/after sensor use, which was highest in those
naive patients with suboptimal initial meals) may be helpful, as increased fre- aged $25 years and lower in younger
glycemic control, a group trained in struc- quency is associated with meeting A1C age-groups. Two clinical trials in adults
tured SMBG (a paper tool was used at targets (11). with type 1 diabetes not meeting A1C
least quarterly to collect and interpret targets and using multiple daily injections
7-point SMBG profiles taken on 3 consec- Several randomized trials have called also found that the use of CGM compared
utive days) reduced their A1C by 0.3 per- into question the clinical utility and cost- with usual care resulted in lower A1C levels
centage points more than the control effectiveness of routine SMBG in noninsu- than SMBG over 24–26 weeks (22,23).
group (4). Patients should be taught lin-treated patients (12–15). Meta-analyses Other small, short-term studies have
how to use SMBG data to adjust food in- have suggested that SMBG can reduce A1C demonstrated similar A1C reductions us-
take, exercise, or pharmacologic therapy by 0.25–0.3% at 6 months (16,17), but the ing CGM compared with SMBG in adults
to achieve specific goals. The ongoing effect was attenuated at 12 months in with A1C levels $7% (53 mmol/mol)
need for and frequency of SMBG should one analysis (16). A key consideration is (24,25).
be reevaluated at each routine visit to that performing SMBG alone does not
avoid overuse (5–7). SMBG is especially lower blood glucose levels. To be useful, A registry study of 17,317 participants
important for insulin-treated patients to the information must be integrated into confirmed that more frequent CGM use is
monitor for and prevent asymptomatic clinical and self-management plans. associated with lower A1C (26), whereas
hypoglycemia and hyperglycemia. Patients another study showed that children
Continuous Glucose Monitoring with .70% sensor use (i.e., $5 days per
CGM measures interstitial glucose (which
correlates well with plasma glucose), and
care.diabetesjournals.org Glycemic Targets S57
week) missed fewer school days (27). A1C TESTING when the A1C result does not correlate
Small randomized controlled trials in with the patient’s SMBG levels. Options
adults and children with baseline A1C Recommendations for monitoring include more frequent and/
,7.0–7.5% (53–58 mmol/mol) have con- or different timing of SMBG or CGM use.
firmed favorable outcomes including a c Perform the A1C test at least two Other measures of average glycemia such
reduced frequency of hypoglycemia (de- times a year in patients who are as fructosamine and 1,5-anhydroglucitol
fined as a blood glucose level ,70 mg/dL meeting treatment goals (and who are available, but their translation into
[3.9 mmol/L]) and maintaining A1C ,7% have stable glycemic control). E average glucose levels and their prog-
(53 mmol/mol) during the study period in nostic significance are not as clear as
groups using CGM, suggesting that CGM c Perform the A1C test quarterly in for A1C. Though some variability exists
may provide further benefit for individu- patients whose therapy has changed among different individuals, generally
als with type 1 diabetes who already have or who are not meeting glycemic the association between mean glucose
good glycemic control (28–30). goals. E and A1C within an individual correlates
over time (42).
A meta-analysis suggests that com- c Point-of-care testing for A1C provides
pared with SMBG, CGM is associated the opportunity for more timely A1C does not provide a measure of
with short-term A1C lowering of ;0.26% treatment changes. E glycemic variability or hypoglycemia. For
in insulin-treated patients (31). The long- patients prone to glycemic variability,
term effectiveness of CGM needs to be A1C reflects average glycemia over especially patients with type 1 diabetes
determined. This technology may be par- approximately 3 months and has strong or type 2 diabetes with severe insulin de-
ticularly useful in insulin-treated patients predictive value for diabetes complica- ficiency, glycemic control is best evalu-
with hypoglycemia unawareness and/or tions (39,40). Thus, A1C testing should ated by the combination of results from
frequent hypoglycemic episodes, although be performed routinely in all patients A1C and SMBG or CGM. A1C may also
studies have not shown consistent reduc- with diabetesdat initial assessment and confirm the accuracy of the patient’s me-
tions in severe hypoglycemia (31–33). A as part of continuing care. Measurement ter (or the patient’s reported SMBG re-
CGM device equipped with an automatic approximately every 3 months deter- sults) and the adequacy of the SMBG
low glucose suspend feature has been mines whether patients’ glycemic targets testing schedule.
approved by the FDA. The Automation have been reached and maintained. The
to Simulate Pancreatic Insulin Response frequency of A1C testing should depend A1C and Mean Glucose
(ASPIRE) trial of 247 patients with type 1 on the clinical situation, the treatment Table 6.1 shows the correlation between
diabetes and documented nocturnal hypo- regimen, and the clinician’s judgment. A1C levels and mean glucose levels based
glycemia showed that sensor-augmented The use of point-of-care A1C testing may on two studies: the international A1C-
insulin pump therapy with a low glucose provide an opportunity for more timely Derived Average Glucose (ADAG) study,
suspend function significantly reduced treatment changes during encounters be- which assessed the correlation between
nocturnal hypoglycemia over 3 months tween patients and providers. Patients A1C and frequent SMBG and CGM in
without increasing A1C levels (34). with type 2 diabetes with stable glycemia 507 adults (83% non-Hispanic whites)
These devices may offer the opportunity well within target may do well with A1C with type 1, type 2, and no diabetes (43),
to reduce hypoglycemia for those with testing only twice per year. Unstable or and an empirical study of the average
a history of nocturnal hypoglycemia. intensively managed patients (e.g., preg- blood glucose levels at premeal, post-
The FDA has also approved the first nant women with type 1 diabetes) may meal, and bedtime associated with spec-
hybrid closed-loop system. The safety of require testing more frequently than every ified A1C levels using data from the
hybrid closed-loop systems has been sup- 3 months (41). ADAG trial (37). The American Diabetes
ported in the literature (35) and may have Association (ADA) and the American As-
advantages over sensor-augmented A1C Limitations sociation for Clinical Chemistry have de-
pump therapy in specific populations, The A1C test is an indirect measure of termined that the correlation (r 5 0.92) in
such as pregnant women with type 1 average glycemia and, as such, is subject the ADAG trial is strong enough to justify
diabetes (36). to limitations. As with any laboratory test, reporting both the A1C result and the es-
there is variability in the measurement of timated average glucose (eAG) result
Due to variable adherence, optimal A1C. Although such variability is less on an when a clinician orders the A1C test. Clini-
CGM use requires an assessment of indi- intraindividual basis than that of blood cians should note that the mean plasma
vidual readiness for the technology as glucose measurements, clinicians should glucose numbers in the table are based on
well as initial and ongoing education exercise judgment when using A1C as the ;2,700 readings per A1C in the ADAG
and support (26,37). Additionally, pro- sole basis for assessing glycemic control, trial. In a recent report, mean glucose
viders need to provide robust diabetes particularly if the result is close to the measured with CGM versus central labo-
education, training, and support for opti- threshold that might prompt a change in ratory–measured A1C in 387 participants
mal CGM implementation and ongoing medication therapy. Conditions that affect in three randomized trials demonstrated
use. As people with type 1 or type 2 red blood cell turnover (hemolytic and that A1C may underestimate or overesti-
diabetes are living longer, healthier lives, other anemias, recent blood transfusion, mate mean glucose. Thus, as suggested, a
individuals who have been successfully use of drugs that stimulate erythropo- patient’s CGM profile has considerable
using CGM should have continued access esis, end-stage kidney disease, and potential for optimizing his or her glyce-
to these devices after they turn 65 years pregnancy) may result in discrepancies mic management (42).
of age (38). between the A1C result and the pa-
tient’s true mean glycemia. Hemoglobin
variants must be considered, particularly
S58 Glycemic Targets Diabetes Care Volume 41, Supplement 1, January 2018
Mean bedtime glucose mmol/L 7.5 (7.3–7.8) Data in parentheses represent 95% CI, unless otherwise noted. A calculator for converting A1C results into eAG, in either mg/dL or mmol/L, is available at http://professional.diabetes.org/eAG. *These estimates are A1C Differences in Ethnic Populations
8.5 (8.0–8.9) based on ADAG data of ;2,700 glucose measurements over 3 months per A1C measurement in 507 adults with type 1, type 2, and no diabetes. The correlation between A1C and average glucose was 0.92 (43). and Children
9.8 (9.2–10.4) In the ADAG study, there were no signif-
9.7 (9.0–10.4) icant differences among racial and ethnic
12.3 (10.9–13.8) groups in the regression lines between
A1C and mean glucose, although the
mg/dL 136 (131–141) study was underpowered to detect a
153 (145–161) difference and there was a trend toward
177 (166–188) a difference between the African/African
175 (163–188) American and non-Hispanic white co-
222 (197–248) horts, with higher A1C values observed
in Africans/African Americans compared
Mean postmeal glucose mmol/L 8.0 (7.7–8.2) with non-Hispanic whites for a given
9.1 (8.8–9.4) mean glucose. Other studies have also
9.8 (9.4–10.2) demonstrated higher A1C levels in African
10.5 (10.0–10.9) Americans than in whites at a given mean
11.4 (10.8–12.0) glucose concentration (44,45). Moreover,
African Americans heterozygous for the
mg/dL 144 (139–148) common hemoglobin variant HbS may
164 (159–169) have, for any level of mean glycemia,
176 (170–183) lower A1C by about 0.3 percentage points
189 (180–197) than those without the trait (46). Another
206 (195–217) genetic variant, X-linked glucose-6-phosphate
dehydrogenase G202A, carried by 11% of
Mean premeal glucose mmol/L 6.5 (6.4–6.7) African Americans, was associated with a
7.7 (7.4–8.0) decrease in A1C of about 0.8% in hemi-
8.4 (8.2–8.7) zygous men and 0.7% in homozygous
8.6 (8.2–8.9) women compared to those without the
9.9 (9.3–10.6) trait (47).
mg/dL 118 (115–121) A small study comparing A1C to CGM
139 (134–144) data in children with type 1 diabetes
152 (147–157) found a highly statistically significant cor-
155 (148–161) relation between A1C and mean blood glu-
179 (167–191) cose, although the correlation (r 5 0.7) was
significantly lower than in the ADAG trial
Mean fasting glucose mmol/L 6.8 (6.5–7.0) (48). Whether there are clinically mean-
7.9 (7.5–8.3) ingful differences in how A1C relates to
8.4 (7.9–9.0) average glucose in children or in different
9.3 (8.7–9.8) ethnicities is an area for further study
9.9 (9.1–10.7) (44,49,50). Until further evidence is avail-
able, it seems prudent to establish A1C
Table 6.1—Mean glucose levels for specified A1C levels (37,43) mg/dL 122 (117–127) goals in these populations with consider-
142 (135–150) ation of both individualized SMBG and
152 (143–162) A1C results.
167 (157–177)
178 (164–192) A1C GOALS
Mean plasma glucose* mmol/L 7.0 (5.5–8.5) For glycemic goals in children, please refer to
8.6 (6.8–10.3) Section 12 “Children and Adolescents.”
10.2 (8.1–12.1) For glycemic goals in pregnant women,
11.8 (9.4–13.9) please refer to Section 13 “Management
13.4 (10.7–15.7) of Diabetes in Pregnancy.”
14.9 (12.0–17.5)
16.5 (13.3–19.3) Recommendations
mg/dL 126 (100–152) c A reasonable A1C goal for many
154 (123–185) nonpregnant adults is ,7% (53
183 (147–217) mmol/mol). A
212 (170–249)
240 (193–282) c Providers might reasonably suggest
269 (217–314) more stringent A1C goals (such
298 (240–347) as ,6.5% [48 mmol/mol]) for se-
lected individual patients if this
A1C % (mmol/mol) 6 (42)
5.5–6.49 (37–47)
6.5–6.99 (47–53)
7 (53)
7.0–7.49 (53–58)
7.5–7.99 (58–64)
8 (64)
8.0–8.5 (64–69)
9 (75)
10 (86)
11 (97)
12 (108)
care.diabetesjournals.org Glycemic Targets S59
can be achieved without significant curvilinear relationship between A1C and death compared with those previously ran-
hypoglycemia or other adverse ef- microvascular complications. Such anal- domized to the standard arm (62). The
fects of treatment (i.e., polyphar- yses suggest that, on a population level, benefit of intensive glycemic control in
macy). Appropriate patients might the greatest number of complications will this cohort with type 1 diabetes has
include those with short duration of be averted by taking patients from very been shown to persist for several decades
diabetes, type 2 diabetes treated poor control to fair/good control. These (63) and to be associated with a modest
with lifestyle or metformin only, analyses also suggest that further lower- reduction in all-cause mortality (64).
long life expectancy, or no signifi- ing of A1C from 7% to 6% [53 mmol/mol
cant cardiovascular disease. C to 42 mmol/mol] is associated with fur- Cardiovascular Disease and Type 2 Diabetes
c Less stringent A1C goals (such ther reduction in the risk of microvascular
as ,8% [64 mmol/mol]) may be ap- complications, although the absolute risk In type 2 diabetes, there is evidence that
propriate for patients with a history reductions become much smaller. Given more intensive treatment of glycemia in
of severe hypoglycemia, limited life the substantially increased risk of hypo- newly diagnosed patients may reduce
expectancy, advanced microvascu- glycemia in type 1 diabetes trials and long-term CVD rates. During the UKPDS,
lar or macrovascular complications, with polypharmacy in type 2 diabetes, there was a 16% reduction in CVD events
extensive comorbid conditions, or the risks of lower glycemic targets out- (combined fatal or nonfatal MI and sud-
long-standing diabetes in whom weigh the potential benefits on microvas- den death) in the intensive glycemic con-
the goal is difficult to achieve de- cular complications. trol arm that did not reach statistical
spite diabetes self-management significance (P 5 0.052), and there was
education, appropriate glucose ACCORD, ADVANCE, and VADT no suggestion of benefit on other CVD
monitoring, and effective doses of outcomes (e.g., stroke). However, after
multiple glucose-lowering agents Three landmark trials (Action to Control 10 years of observational follow-up, those
including insulin. B Cardiovascular Risk in Diabetes [ACCORD], originally randomized to intensive glyce-
Action in Diabetes and Vascular Disease: mic control had significant long-term re-
A1C and Microvascular Complications Preterax and Diamicron MR Controlled ductions in MI (15% with sulfonylurea or
Hyperglycemia defines diabetes, and gly- Evaluation [ADVANCE], and Veterans Af- insulin as initial pharmacotherapy, 33%
cemic control is fundamental to diabetes fairs Diabetes Trial [VADT]) showed that with metformin as initial pharmacother-
management. The Diabetes Control and lower A1C levels were associated with re- apy) and in all-cause mortality (13% and
Complications Trial (DCCT) (2), a prospec- duced onset or progression of some micro- 27%, respectively) (56).
tive randomized controlled trial of inten- vascular complications (58–60).
sive versus standard glycemic control in ACCORD, ADVANCE, and VADT sug-
patients with type 1 diabetes, showed de- The concerning mortality findings in gested no significant reduction in CVD
finitively that better glycemic control is the ACCORD trial (61), discussed below, outcomes with intensive glycemic control
associated with significantly decreased and the relatively intense efforts required in participants followed for 3.5–5.6 years
rates of development and progression of to achieve near-euglycemia should also who had more advanced type 2 diabetes
microvascular (retinopathy [51], neurop- be considered when setting glycemic tar- than UKPDS participants. All three trials
athy, and diabetic kidney disease) compli- gets. However, on the basis of physician were conducted in relatively older partic-
cations. Follow-up of the DCCT cohorts in judgment and patient preferences, select ipants with longer known duration of di-
the Epidemiology of Diabetes Interven- patients, especially those with little co- abetes (mean duration 8–11 years) and
tions and Complications (EDIC) study morbidity and long life expectancy, may either CVD or multiple cardiovascular risk
(52) demonstrated persistence of these benefit from adopting more intensive gly- factors. The target A1C among intensive
microvascular benefits despite the fact cemic targets (e.g., A1C target ,6.5% control subjects was ,6% (42 mmol/mol)
that the glycemic separation between [48 mmol/mol]) as long as significant hy- in ACCORD, ,6.5% (48 mmol/mol) in
the treatment groups diminished and dis- poglycemia does not become a barrier. ADVANCE, and a 1.5% reduction in A1C
appeared during follow-up. compared with control subjects in VADT,
A1C and Cardiovascular Disease with achieved A1C of 6.4% vs. 7.5%
The Kumamoto Study (53) and UK Pro- Outcomes (46 mmol/mol vs. 58 mmol/mol) in ACCORD,
spective Diabetes Study (UKPDS) (54,55) 6.5% vs. 7.3% (48 mmol/mol vs. 56
confirmed that intensive glycemic control Cardiovascular Disease and Type 1 Diabetes mmol/mol) in ADVANCE, and 6.9% vs.
significantly decreased rates of microvas- 8.4% (52 mmol/mol vs. 68 mmol/mol) in
cular complications in patients with type 2 Cardiovascular disease (CVD) is a more VADT. Details of these studies are re-
diabetes. Long-term follow-up of the common cause of death than microvascular viewed extensively in “Intensive Glycemic
UKPDS cohorts showed enduring effects complications in populations with diabetes. Control and the Prevention of Cardiovas-
of early glycemic control on most micro- There is evidence for a cardiovascular ben- cular Events: Implications of the ACCORD,
vascular complications (56). efit of intensive glycemic control after long- ADVANCE, and VA Diabetes Trials” (65).
term follow-up of cohorts treated early in
Therefore, achieving A1C targets the course of type 1 diabetes. In the DCCT, The glycemic control comparison in
of ,7% (53 mmol/mol) has been shown there was a trend toward lower risk of CVD ACCORD was halted early due to an in-
to reduce microvascular complications of events with intensive control. In the 9-year creased mortality rate in the intensive
diabetes. Epidemiological analyses of the post-DCCT follow-up of the EDIC cohort, compared with the standard treatment
DCCT (2) and UKPDS (57) demonstrate a participants previously randomized to the arm (1.41% vs. 1.14% per year; hazard ra-
intensive arm had a significant 57% reduc- tio 1.22 [95% CI 1.01–1.46]), with a similar
tion in the risk of nonfatal myocardial in- increase in cardiovascular deaths. Analysis
farction (MI), stroke, or cardiovascular
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