Diabetes Care Volume 46, Supplement 1, January 2023 S41

25 June 2023. Sections 2 and 3 have been updated based on U.S. Food and Drug Administration approval of a new drug to delay the incidence of
type 1 diabetes. The changes are described in detail in: Addendum. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—
2023. Diabetes Care 2023;46(Suppl. 1):S19–S40 (https://doi.org/10.2337/dc23-ad08) and Addendum. 3. Prevention or Delay of Type 2 Diabetes and
Associated Comorbidities: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S41–S48 (https://doi.org/10.2337/dc23-ad08a).

3. Prevention or Delay of Nuha A. ElSayed, Grazia Aleppo,

Vanita R. Aroda, Raveendhara R. Bannuru,
Diabetes and Associated Florence M. Brown, Dennis Bruemmer,
Billy S. Collins, Jason L. Gaglia,
Comorbidities: Standards of Marisa E. Hilliard, Diana Isaacs,
Eric L. Johnson, Scott Kahan,
Care in Diabetes—2023 Kamlesh Khunti, Jose Leon, Sarah K. Lyons,
Mary Lou Perry, Priya Prahalad,
Diabetes Care 2023;46(Suppl. 1):S41–S48 | https://doi.org/10.2337/dc23-S003 Richard E. Pratley, Jane Jeffrie Seley,

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Robert C. Stanton, and Robert A. Gabbay,
on behalf of the American Diabetes

3. PREVENTION OR DELAY OF TYPE 2 DIABETES

Association

The American Diabetes Association (ADA) “Standards of Care in Diabetes” in-

cludes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guide-
lines, and tools to evaluate quality of care. Members of the ADA Professional
Practice Committee, a multidisciplinary expert committee, are responsible for up-
dating the Standards of Care annually, or more frequently as warranted. For a de-
tailed description of ADA standards, statements, and reports, as well as the
evidence-grading system for ADA’s clinical practice recommendations and a full
list of Professional Practice Committee members, please refer to Introduction
and Methodology. Readers who wish to comment on the Standards of Care are
invited to do so at professional.diabetes.org/SOC.

For guidelines related to screening for increased risk for type 1 and type 2 diabetes
(prediabetes), please refer to Section 2, “Classification and Diagnosis of Diabetes.”
For guidelines related to screening, diagnosis, and management of type 2 diabetes
in youth, please refer to Section 14, “Children and Adolescents.”

Recommendation
3.1 Monitor for the development of type 2 diabetes in those with prediabetes
at least annually; modify based on individual risk/benefit assessment. E

Screening for prediabetes and type 2 diabetes risk through an informal assessment
of risk factors (Table 2.3) or with an assessment tool, such as the American Diabetes
Association risk test (Fig. 2.1), is recommended to guide health care professionals on
Disclosure information for each author is
whether performing a diagnostic test for prediabetes (Table 2.5) and previously un- available at https://doi.org/10.2337/dc23-SDIS.
diagnosed type 2 diabetes (Table 2.2) is appropriate (see Section 2, “Classification
Suggested citation: ElSayed NA, Aleppo G,
and Diagnosis of Diabetes”). Testing high-risk adults for prediabetes is warranted be- Aroda VR, et al., American Diabetes Association.
cause the laboratory assessment is safe and reasonable in cost, substantial time ex- 3. Prevention or delay of diabetes and asso-
ists before the development of type 2 diabetes and its complications during which ciated comorbidities: Standards of Care in
one can intervene, and there is an effective means of preventing or delaying type 2 Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):
S41–S48
diabetes in those determined to have prediabetes with an A1C 5.7–6.4% (39–
47 mmol/mol), impaired glucose tolerance, or impaired fasting glucose. The utility of © 2022 by the American Diabetes Association.
A1C screening for prediabetes and diabetes may be limited in the presence of hemoglo- Readers may use this article as long as the
work is properly cited, the use is educational
binopathies and conditions that affect red blood cell turnover. See Section 2, and not for profit, and the work is not altered.
“Classification and Diagnosis of Diabetes,” and Section 6, “Glycemic Targets,” for More information is available at https://www.
additional details on the appropriate use and limitations of A1C testing. diabetesjournals.org/journals/pages/license.
S42 Prevention or Delay of Type 2 Diabetes and Associated Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023

LIFESTYLE BEHAVIOR CHANGE type 2 diabetes: 39% reduction at 30 To implement the weight loss and
FOR DIABETES PREVENTION years in the Da Qing study (5), 43% re- physical activity goals, the DPP used an
duction at 7 years in the Finnish DPS (2), individual model of treatment rather than
Recommendations
and 34% reduction at 10 years (6) and a group-based approach. This choice was
3.2 Refer adults with overweight/
27% reduction at 15 years (7) in the U.S. based on a desire to intervene before
obesity at high risk of type 2 di-
Diabetes Prevention Program Outcomes participants had the possibility of devel-
abetes, as typified by the Diabetes
Study (DPPOS). oping diabetes or losing interest in the
Prevention Program (DPP), to an The two major goals of the DPP inten- program. The individual approach also al-
intensive lifestyle behavior change sive lifestyle intervention were to achieve lowed for the tailoring of interventions to
program to achieve and maintain and maintain a minimum of 7% weight reflect the diversity of the population (8).
a weight reduction of at least 7% loss and 150 min moderate-intensity phys- The DPP intervention was adminis-
of initial body weight through ical activity per week, such as brisk walk- tered as a structured core curriculum fol-
healthy reduced-calorie diet and ing. The DPP lifestyle intervention was a lowed by a flexible maintenance program
$150 min/week of moderate-

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goal-based intervention. All participants of individual counseling, group sessions,
intensity physical activity. A were given the same weight loss and motivational campaigns, and restart op-
3.3 A variety of eating patterns can physical activity goals, but individualization portunities. The 16-session core curriculum
be considered to prevent dia- was permitted in the specific methods was completed within the first 24 weeks
betes in individuals with predi- used to achieve the goals (8). Although of the program. It included sessions on
abetes. B weight loss was the most important fac- lowering calories, increasing physical ac-
3.4 Given the cost-effectiveness of tor in reducing the risk of incident diabe- tivity, self-monitoring, maintaining healthy
lifestyle behavior modification tes, it was also found that achieving the lifestyle behaviors, and guidance on
programs for diabetes preven- target behavioral goal of at least 150 min managing psychological, social, and moti-
tion, such diabetes prevention of physical activity per week, even without vational challenges. Further details are
programs should be offered to achieving the weight loss goal, reduced the available regarding the core curriculum
adults at high risk of type 2 di- incidence of type 2 diabetes by 44% (9). sessions (8).
abetes. A Diabetes prevention The 7% weight loss goal was selected
programs should be covered by because it was feasible to achieve and
Nutrition
third-party payers, and incon- maintain and likely to lessen the risk of
Nutrition counseling for weight loss in the
sistencies in access should be developing diabetes. Participants were
DPP lifestyle intervention arm included a
addressed. encouraged to achieve the $7% weight
reduction of total dietary fat and calories
3.5 Based on individual preference, loss during the first 6 months of the in-
(1,8,9). However, evidence suggests that
certified technology-assisted di- tervention. Further analysis suggests max-
there is not an ideal percentage of calo-
abetes prevention programs imal prevention of diabetes with at least
ries from carbohydrate, protein, and fat
may be effective in preventing 7–10% weight loss (9). The recommended
for all people to prevent diabetes; there-
type 2 diabetes and should be pace of weight loss was 1–2 lb/week. Cal-
fore, macronutrient distribution should be
considered. B orie goals were calculated by estimating
the daily calories needed to maintain the based on an individualized assessment of
participant’s initial weight and subtracting current eating patterns, preferences, and
The Diabetes Prevention Program 500–1,000 calories/day (depending on ini- metabolic goals (10). Based on other inter-
Several major randomized controlled tri- tial body weight). The initial focus of the vention trials, a variety of eating patterns
als, including the Diabetes Prevention dietary intervention was on reducing total characterized by the totality of food and
Program (DPP) trial (1), the Finnish Dia- fat rather than calories. After several beverages habitually consumed (10,11)
betes Prevention Study (DPS) (2), and weeks, the concept of calorie balance may also be appropriate for individuals
the Da Qing Diabetes Prevention Study and the need to restrict calories and fat with prediabetes (10), including Mediter-
(Da Qing study) (3), demonstrate that was introduced (8). ranean-style and low-carbohydrate eating
lifestyle/behavioral intervention with an The goal for physical activity was se- plans (12–15). Observational studies have
individualized reduced-calorie meal plan lected to approximate at least 700 kcal/ also shown that vegetarian, plant-based
is highly effective in preventing or delay- week expenditure from physical activity. (may include some animal products), and
ing type 2 diabetes and improving other For ease of translation, this goal was Dietary Approaches to Stop Hypertension
cardiometabolic markers (such as blood described as at least 150 min of moderate- (DASH) eating patterns are associated
pressure, lipids, and inflammation) (4). intensity physical activity per week, similar with a lower risk of developing type 2 di-
The strongest evidence for diabetes pre- in intensity to brisk walking. Partici- abetes (16–19). Evidence suggests that
vention in the U.S. comes from the DPP pants were encouraged to distribute the overall quality of food consumed (as
trial (1). The DPP demonstrated that in- their activity throughout the week with measured by the Healthy Eating Index,
tensive lifestyle intervention could re- a minimum frequency of three times Alternative Healthy Eating Index, and
duce the risk of incident type 2 diabetes per week and at least 10 min per ses- DASH score), with an emphasis on whole
by 58% over 3 years. Follow-up of three sion. A maximum of 75 min of strength grains, legumes, nuts, fruits, and vegeta-
large studies of lifestyle intervention for training could be applied toward the bles and minimal refined and processed
diabetes prevention showed sustained total 150 min/week physical activity foods, is also associated with a lower
reduction in the risk of progression to goal (8). risk of type 2 diabetes (18,20–22). As is
diabetesjournals.org/care Prevention or Delay of Type 2 Diabetes and Associated Comorbidities S43

the case for those with diabetes, individ- locations of CDC-recognized diabetes pre- by third-party payers remains problem-
ualized medical nutrition therapy (see vention lifestyle change programs (cdc. atic. Counseling by a registered dietitian
Section 5, “Facilitating Positive Health gov/diabetes/prevention/find-a-program. nutritionist (RDN) has been shown to
Behaviors and Well-being to Improve html). To be eligible for this program, in- help individuals with prediabetes im-
Health Outcomes,” for more detailed in- dividuals must have a BMI in the over- prove eating habits, increase physical
formation) is effective in lowering A1C weight range and be at risk for diabetes activity, and achieve 7–10% weight loss
in individuals diagnosed with prediabe- based on laboratory testing, a previous (10,46–48). Individualized medical nutri-
tes (23). diagnosis of GDM, or a positive risk test tion therapy (see Section 5, “Facilitating
(cdc.gov/prediabetes/takethetest/). Dur- Positive Health Behaviors and Well-being
Physical Activity ing the first 4 years of implementation of to Improve Health Outcomes,” for more
Just as 150 min/week of moderate- the CDC’s National DPP, 35.5% achieved detailed information) is also effective in
intensity physical activity, such as brisk the 5% weight loss goal (41). The CDC improving glycemia in individuals diag-
walking, showed beneficial effects in has also developed the Diabetes Pre- nosed with prediabetes (23,46). Further-

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those with prediabetes (1), moderate- vention Impact Tool Kit (nccd.cdc.gov/ more, trials involving medical nutrition
intensity physical activity has been shown toolkit/diabetesimpact) to help organi- therapy for adults with prediabetes found
to improve insulin sensitivity and reduce zations assess the economics of provid- significant reductions in weight, waist
abdominal fat in children and young ing or covering the National DPP lifestyle circumference, and glycemia. Individu-
adults (24,25). Based on these findings, change program (42). In an effort to ex- als with prediabetes can benefit from
health care professionals are encouraged pand preventive services using a cost- referral to an RDN for individualized
to promote a DPP-style program, includ- effective model, the Centers for Medicare medical nutrition therapy upon diagnosis
ing a focus on physical activity, to all indi- & Medicaid Services expanded Medicare and at regular intervals throughout their
viduals who have been identified to be reimbursement coverage for the National treatment plan (47,49). Other health care
at an increased risk of type 2 diabetes. In DPP lifestyle intervention to organiza- professionals, such as pharmacists and
addition to aerobic activity, a physical ac- tions recognized by the CDC that be- diabetes care and education specialists,
tivity plan designed to prevent diabetes come Medicare suppliers for this service may be considered for diabetes preven-
may include resistance training (8,26,27). (innovation.cms.gov/innovation-models/ tion efforts (50,51).
Breaking up prolonged sedentary time medicare-diabetes-prevention-program). Technology-assisted programs may ef-
may also be encouraged, as it is associ- The locations of Medicare DPPs are fectively deliver the DPP program (52–57).
ated with moderately lower postprandial available online at innovation.cms.gov/ Such technology-assisted programs may
glucose levels (28,29). The preventive ef- innovation-models/medicare-diabetes- deliver content through smartphones,
fects of physical activity appear to extend prevention-program/mdpp-map. To qual- web-based applications, and telehealth
to the prevention of gestational diabetes ify for Medicare coverage, individuals and may be an acceptable and efficacious
mellitus (GDM) (30). must have BMI >25 kg/m2 (or BMI option to bridge barriers, particularly for
>23 kg/m2 if self-identified as Asian) low-income individuals and people resid-
and laboratory testing consistent with pre- ing in rural locations; however, not all pro-
Delivery and Dissemination of
Lifestyle Behavior Change for diabetes in the last year. Medicaid cover- grams are effective in helping people
Diabetes Prevention age of the DPP lifestyle intervention is also reach targets for diabetes prevention
Because the intensive lifestyle interven- expanding on a state-by-state basis. (52,58–60). The CDC Diabetes Preven-
tion in the DPP was effective in prevent- While CDC-recognized behavioral coun- tion Recognition Program (DPRP) (cdc.
ing type 2 diabetes among those at high seling programs, including Medicare DPP gov/diabetes/prevention/requirements-
risk for the disease and lifestyle behavior services, have met minimum quality recognition.htm) certifies technology-
change programs for diabetes prevention standards and are reimbursed by many assisted modalities as effective vehicles
were shown to be cost-effective, broader payers, lower retention rates have been for DPP-based programs; such programs
efforts to disseminate scalable lifestyle reported for younger adults and racial/ must use an approved curriculum, include
behavior change programs for diabetes ethnic minority populations (43). There- interaction with a coach, and attain the
prevention with coverage by third-party DPP outcomes of participation, physical
fore, other programs and modalities of
payers ensued (31–35). Group delivery of activity reporting, and weight loss. There-
behavioral counseling for diabetes pre-
DPP content in community or primary fore, health care professionals should con-
vention may also be appropriate and ef-
sider referring adults with prediabetes
care settings has demonstrated the po- ficacious based on individual preferences
to certified technology-assisted DPP pro-
tential to reduce overall program costs and availability. The use of community
grams based on their preferences.
while still producing weight loss and dia- health workers to support DPP efforts
betes risk reduction (36–40). has been shown to be effective and
The Centers for Disease Control and cost-effective (44,45) (see Section 1, PHARMACOLOGIC INTERVENTIONS
Prevention (CDC) developed the National “Improving Care and Promoting Health Recommendations
Diabetes Prevention Program (National in Populations,” for more information). 3.6 Metformin therapy for the pre-
DPP), a resource designed to bring such The use of community health workers vention of type 2 diabetes should
evidence-based lifestyle change programs may facilitate the adoption of behavior be considered in adults at high
for preventing type 2 diabetes to com- changes for diabetes prevention while risk of type 2 diabetes, as typi-
munities (cdc.gov/diabetes/prevention/ bridging barriers related to social deter- fied by the Diabetes Prevention
index.htm). This online resource includes minants of health. However, coverage
S44 Prevention or Delay of Type 2 Diabetes and Associated Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023

Program, especially those aged 25– potential benefit in specific populations increases with time (88), with a significantly
59 years with BMI $35 kg/m2, (77–80). Further research is needed to higher risk for vitamin B12 deficiency (<150
higher fasting plasma glucose define characteristics and clinical indica- pmol/L) noted at 4.3 years in the HOME (Hy-
(e.g., $110 mg/dL), and higher tors where vitamin D supplementation perinsulinaemia: the Outcome of its Meta-
may be of benefit (61). bolic Effects) study (88) and significantly
A1C (e.g., $6.0%), and in individ-
No pharmacologic agent has been ap- greater risk of low B12 levels (#203 pg/mL)
uals with prior gestational diabe-
proved by the U.S. Food and Drug Ad- at 5 years in the DPP (87). It has been sug-
tes mellitus. A
ministration for a specific indication of gested that a person who has been on met-
3.7 Long-term use of metformin
type 2 diabetes prevention. The risk ver- formin for more than 4 years or is at risk for
may be associated with bio-
sus benefit of each medication in sup- vitamin B12 deficiency should be monitored
chemical vitamin B12 deficiency;
port of person-centered goals must be for vitamin B12 deficiency annually (89).
consider periodic measurement weighed in addition to cost, side effects,
of vitamin B12 levels in metfor- and efficacy considerations. Metformin PREVENTION OF VASCULAR

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min-treated individuals, espe- has the longest history of safety data as DISEASE AND MORTALITY
cially in those with anemia or a pharmacologic therapy for diabetes
peripheral neuropathy. B prevention (81). Recommendations
Metformin was overall less effective 3.8 Prediabetes is associated with
than lifestyle modification in the DPP, heightened cardiovascular risk;
Because weight loss through behavior therefore, screening for and
changes in diet and physical activity alone though group differences declined over
time in the DPPOS (7), and metformin treatment of modifiable risk fac-
can be difficult to maintain long term (6), tors for cardiovascular disease
may be cost-saving over a 10-year pe-
people at high risk of diabetes may bene- are suggested. B
riod (33). In the DPP, metformin was as
fit from support and additional pharma- 3.9 Statin therapy may increase the
effective as lifestyle modification in par-
cotherapeutic options, if needed. Various risk of type 2 diabetes in peo-
ticipants with BMI $35 kg/m2 and in
pharmacologic agents used to treat dia- ple at high risk of developing
younger participants aged 25–44 years
betes have been evaluated for diabetes type 2 diabetes. In such individ-
(1). In individuals with a history of GDM
prevention. Metformin, a-glucosidase in- uals, glucose status should be
in the DPP, metformin and intensive life-
hibitors, glucagon-like peptide 1 receptor monitored regularly and diabe-
style modification led to an equivalent
agonists (liraglutide, semaglutide), thia- tes prevention approaches rein-
50% reduction in diabetes risk (82).
zolidinediones, testosterone (61), and in- forced. It is not recommended
Both interventions remained highly effec-
sulin have been shown to lower the that statins be discontinued. B
tive during a 10-year follow-up period
incidence of diabetes in specific popula- 3.10 In people with a history of
(83). By the time of the 15-year follow-
tions (62–67), whereas diabetes preven- stroke and evidence of insulin
up (DPPOS), exploratory analyses demon-
tion was not seen with nateglinide (68). resistance and prediabetes, pio-
strated that participants with a higher glitazone may be considered to
In the DPP, weight loss was an impor- baseline fasting glucose ($110 mg/dL
tant factor in reducing the risk of progres- lower the risk of stroke or myo-
vs. 95–109 mg/dL), those with a higher cardial infarction. However, this
sion, with every kilogram of weight loss A1C (6.0–6.4% vs. <6.0%), and individuals
conferring a 16% reduction in risk of pro- benefit needs to be balanced
with a history of GDM (vs. individuals with- with the increased risk of weight
gression over 3.2 years (9). In postpartum out a history of GDM) experienced higher gain, edema, and fracture. A
individuals with GDM, the risk of type 2 dia- risk reductions with metformin, identifying Lower doses may mitigate the
betes increased by 18% for every 1 unit subgroups of participants that benefitted risk of adverse effects. C
BMI above the preconception baseline the most from metformin (84). In the In-
(69). Several medications evaluated for dian Diabetes Prevention Program (IDPP-1),
weight loss (e.g., orlistat, phentermine top- metformin and lifestyle intervention re- People with prediabetes often have
iramate, liraglutide, semaglutide, and tirze- duced diabetes risk similarly at 30 months; other cardiovascular risk factors, includ-
patide) have been shown to decrease the of note, the lifestyle intervention in IDPP-1 ing hypertension and dyslipidemia (90),
incidence of diabetes to various degrees in was less intensive than that in the DPP and are at increased risk for cardiovas-
those with prediabetes (67,70–72). (85). Based on findings from the DPP, met- cular disease (91,92). If indicated, evalu-
Studies of other pharmacologic agents formin should be recommended as an op- ation for tobacco use and referral for
have shown some efficacy in diabetes tion for high-risk individuals (e.g., those tobacco cessation should be part of rou-
prevention with valsartan but no effi- with a history of GDM or those with BMI tine care for those at risk for diabetes.
cacy in preventing diabetes with ramipril $35 kg/m2). Consider periodic monitoring Of note, the years immediately follow-
or anti-inflammatory drugs (73–76). Al- of vitamin B12 levels in those taking met- ing smoking cessation may represent
though the Vitamin D and Type 2 Dia- formin chronically to check for possible a time of increased risk for diabetes
betes (D2d) prospective randomized deficiency (86,87) (see Section 9, “Pharma- (93–95), a time when individuals should
controlled trial showed no significant cologic Approaches to Glycemic Treatment,” be monitored for diabetes development
benefit of vitamin D versus placebo on for more details).While there is not a univer- and receive concurrent evidence-based
the progression to type 2 diabetes in sally accepted recommended periodicity of lifestyle behavior change for diabetes
individuals at high risk (77), post hoc monitoring, it is notable that the lowering prevention described in this section. See
analyses and meta-analyses suggest a effect of metformin on vitamin B12 Section 5, “Facilitating Positive Health
diabetesjournals.org/care Prevention or Delay of Type 2 Diabetes and Associated Comorbidities S45

Behaviors and Well-being to Improve though risks of weight gain, edema, and glucose 110–125 mg/dL, 2-h postchallenge
Health Outcomes,” for more detailed in- fracture were higher in the pioglitazone glucose 173–199 mg/dL, and A1C $6.0%),
formation. The lifestyle interventions for treatment group (107–109). Lower doses and individuals with a history of gestational
weight loss in study populations at risk may mitigate the adverse effects, though diabetes (1,82,83). In contrast, in the com-
for type 2 diabetes have shown a reduc- further study is needed to confirm the munity-based Atherosclerosis Risk in Com-
tion in cardiovascular risk factors and benefit at lower doses (110). munities (ARIC) study, observational follow-
the need for medications used to treat up of older adults (mean age 75 years)
these cardiovascular risk factors (96,97). PERSON-CENTERED CARE GOALS with laboratory evidence of prediabetes
In longer-term follow-up, lifestyle inter- (based on A1C 5.7–6.4% and/or fasting
ventions for diabetes prevention also Recommendations glucose 100–125 mg/dL), but not meeting
prevented the development of micro- 3.11 In adults with overweight/ specific BMI criteria, found much lower
vascular complications among women obesity at high risk of type 2 progression to diabetes over 6 years: 9%
enrolled in the DPPOS and in the study diabetes, care goals should in- of those with A1C-defined prediabetes,

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population enrolled in the China Da Qing clude weight loss or preven- 8% with impaired fasting glucose (112).
Diabetes Prevention Outcome Study (7,98). tion of weight gain, minimizing Thus, it is important to individualize
The lifestyle intervention in the latter the progression of hypergly- the risk/benefit of intervention and con-
study was also efficacious in preventing cemia, and attention to cardio- sider person-centered goals. Risk models
cardiovascular disease and mortality at vascular risk and associated have explored risk-based benefit, gener-
23 and 30 years of follow-up (3,5). Treat- comorbidities. B ally finding higher benefit of the inter-
ment goals and therapies for hyperten- 3.12 Pharmacotherapy (e.g., for weight vention in those at highest risk (9).
sion and dyslipidemia in the primary management, minimizing the Diabetes prevention and observational
prevention of cardiovascular disease for progression of hyperglycemia, studies highlight key principles that may
people with prediabetes should be based cardiovascular risk reduction) guide person-centered goals. In the DPP,
on their level of cardiovascular risk. In- may be considered to support which enrolled a high-risk population
creased vigilance is warranted to identify person-centered care goals. B meeting criteria for overweight/obesity,
and treat these and other cardiovascular 3.13 More intensive preventive ap- weight loss was an important mediator
diseases risk factors (99). Statins have proaches should be considered of diabetes prevention or delay, with
been associated with a modestly in- in individuals who are at partic- greater metabolic benefit generally seen
creased risk of diabetes (100–104). In ularly high risk of progression with greater weight loss (9,113). In the
the DPP, statin use was associated with to diabetes, including individuals DPP/DPPOS, progression to diabetes,
greater diabetes risk irrespective of the with BMI $35 kg/m2, those at duration of diabetes, and mean level of
treatment group (pooled hazard ratio higher glucose levels (e.g., fasting glycemia were important determinants
[95% CI] for incident diabetes 1.36 plasma glucose 110–125 mg/dL, of the development of microvascular
[1.17–1.58]) (102). In studies of primary 2-h postchallenge glucose 173– complications (7). Furthermore, the ability
prevention of cardiovascular disease, 199 mg/dL, A1C $6.0%), and to achieve normal glucose regulation, even
cardiovascular and mortality benefits individuals with a history of ges- once, during the DPP was associated with a
of statin therapy exceed the risk of di- tational diabetes mellitus. A lower risk of diabetes and lower risk of mi-
abetes (105,106), suggesting a favor- crovascular complications (114). Observa-
able benefit-to-harm balance with statin tional follow-up of the Da Qing study
therapy. Hence, discontinuation of sta- Individualized risk/benefit should be con- also showed that regression from impaired
tins is not recommended in this popula- sidered in screening, intervention, and glucose tolerance to normal glucose toler-
tion due to concerns of diabetes risk. monitoring to prevent or delay type 2 ance or remaining with impaired glucose
Cardiovascular outcome trials in people diabetes and associated comorbidities. tolerance rather than progressing to type 2
without diabetes also inform risk reduc- Multiple factors, including age, BMI, and diabetes at the end of the 6-year interven-
tion potential in people without diabetes other comorbidities, may influence the tion trial resulted in significantly lower risk
at increased cardiometabolic risk (see risk of progression to diabetes and life- of cardiovascular disease and microvascu-
Section 10, “Cardiovascular Disease and time risk of complications (111,112). In lar disease over 30 years (115). Prediabetes
Risk Management,” for more details). The the DPP, which enrolled high-risk individ- is associated with increased cardiovascular
IRIS (Insulin Resistance Intervention after uals with impaired glucose tolerance, ele- disease and mortality (92), emphasizing
Stroke) trial was a dedicated study of vated fasting glucose, and elevated BMI, the importance of attending to cardiovas-
people with a recent (<6 months) stroke the crude incidence of diabetes within cular risk in this population.
or transient ischemic attack, without dia- the placebo arm was 11.0 cases per Pharmacotherapy for weight manage-
betes but with insulin resistance, as de- 100 person-years, with a cumulative ment (see Section 8, “Obesity and Weight
fined by a HOMA of insulin resistance 3-year incidence of diabetes of 28.9% (1). Management for the Prevention and
index of $3.0, evaluating pioglitazone Characteristics of individuals in the DPP/ Treatment of Type 2 Diabetes,” for more
(target dose of 45 mg daily) compared DPPOS who were at particularly high risk details), minimizing the progression of hy-
with placebo. At 4.8 years, the risk of of progression to diabetes (crude inci- perglycemia (see Section 9, “Pharmacologic
stroke or myocardial infarction, as well as dence of diabetes 14–22 cases/100 person- Approaches to Glycemic Treatment,” for
the risk of diabetes, was lower within the years) included BMI $35 kg/m2, those at more details), and cardiovascular risk re-
pioglitazone group than with placebo, higher glucose levels (e.g., fasting plasma duction (see Section 10, “Cardiovascular
S46 Prevention or Delay of Type 2 Diabetes and Associated Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023

Disease and Risk Management,” for more 2. Lindstr€ om J, Ilanne-Parikka P, Peltonen M, diabetes risk: a prospective study. Nutr Diabetes
details) are important tools that can be con- et al.; Finnish Diabetes Prevention Study Group. 2018;8:12
Sustained reduction in the incidence of type 2 17. Lee Y, Park K. Adherence to a vegetarian diet
sidered to support individualized person-- diabetes by lifestyle intervention: follow-up of and diabetes risk: a systematic review and meta-
centered goals, with more intensive the Finnish Diabetes Prevention Study. Lancet analysis of observational studies. Nutrients 2017;
preventive approaches considered in indi- 2006;368:1673–1679 9:E603
viduals at high risk of progression. 3. Li G, Zhang P, Wang J, et al. Cardiovascular 18. Qian F, Liu G, Hu FB, Bhupathiraju SN, Sun Q.
mortality, all-cause mortality, and diabetes incidence Association between plant-based dietary patterns
after lifestyle intervention for people with impaired and risk of type 2 diabetes: a systematic review
PHARMACOLOGIC INTERVENTIONS glucose tolerance in the Da Qing Diabetes Pre- and meta-analysis. JAMA Intern Med 2019;179:
FOR TYPE 1 DIABETES vention Study: a 23-year follow-up study. Lancet 1335–1344
Diabetes Endocrinol 2014;2:474–480 19. Esposito K, Chiodini P, Maiorino MI,
Recommendation 4. Nathan DM, Bennett PH, Crandall JP, et al.; Bellastella G, Panagiotakos D, Giugliano D. Which
3.14 Teplizumab-mzwv infusion to DPP Research Group. Does diabetes prevention diet for prevention of type 2 diabetes? A meta-
delay the onset of symptom- translate into reduced long-term vascular analysis of prospective studies. Endocrine 2014;
47:107–116

Downloaded from http://diabetesjournals.org/care/article-pdf/46/Supplement_1/S41/726457/dc23s003.pdf by guest on 24 April 2024

atic type 1 diabetes should be complications of diabetes? Diabetologia 2019;62:
1319–1328 20. Ley SH, Hamdy O, Mohan V, Hu FB.
considered in selected individu- 5. Gong Q, Zhang P, Wang J, et al.; Da Qing Prevention and management of type 2 diabetes:
als aged $8 years with stage 2 Diabetes Prevention Study Group. Morbidity and dietary components and nutritional strategies.
type 1 diabetes. Management mortality after lifestyle intervention for people Lancet 2014;383:1999–2007
with impaired glucose tolerance: 30-year results of 21. Jacobs S, Harmon BE, Boushey CJ, et al. A
should be in a specialized set- priori-defined diet quality indexes and risk of
the Da Qing Diabetes Prevention Outcome Study.
ting with appropriately trained type 2 diabetes: the Multiethnic Cohort. Dia-
Lancet Diabetes Endocrinol 2019;7:452–461
personnel. B 6. Knowler WC, Fowler SE, Hamman RF, et al.; betologia 2015;58:98–112
Diabetes Prevention Program Research Group. 22. Chiuve SE, Fung TT, Rimm EB, et al. Alternative
10-year follow-up of diabetes incidence and dietary indices both strongly predict risk of chronic
Teplizumab was approved to delay the weight loss in the Diabetes Prevention Program disease. J Nutr 2012;142:1009–1018
onset of stage 3 type 1 diabetes in adults 23. Parker AR, Byham-Gray L, Denmark R,
Outcomes Study. Lancet 2009;374:1677–1686
Winkle PJ. The effect of medical nutrition therapy
and pediatric patients 8 years of age and 7. Diabetes Prevention Program Research Group;
by a registered dietitian nutritionist in patients
older with stage 2 type 1 diabetes based Nathan DM, Barrett-Connor E, Crandall JP, et al.
with prediabetes participating in a randomized
Long-term effects of lifestyle intervention or
in part upon the efficacy results of a sin- metformin on diabetes development and micro-
controlled clinical research trial. J Acad Nutr Diet
gle study in relatives at risk for type 1 di- 2014;114:1739–1748
vascular complications: the DPP Outcomes Study.
24. Fedewa MV, Gist NH, Evans EM, Dishman
abetes (116). In this study, 44 individuals Lancet Diabetes Endocrinol 2015;3:866–875
RK. Exercise and insulin resistance in youth: a
were randomized to a 14-day course of 8. Diabetes Prevention Program (DPP) Research
meta-analysis. Pediatrics 2014;133:e163–e174
teplizumab and 32 to placebo. Based on Group. The Diabetes Prevention Program (DPP):
25. Davis CL, Pollock NK, Waller JL, et al. Exercise
description of lifestyle intervention. Diabetes
a Cox proportional hazards model, strati- dose and diabetes risk in overweight and obese
Care 2002;25:2165–2171
fied by age and oral glucose tolerance 9. Hamman RF, Wing RR, Edelstein SL, et al. Effect
children: a randomized controlled trial. JAMA
2012;308:1103–1112
test status at randomization, median of weight loss with lifestyle intervention on risk of 26. Sigal RJ, Alberga AS, Goldfield GS, et al.
time to stage 3 type 1 diabetes diagnosis diabetes. Diabetes Care 2006;29:2102–2107 Effects of aerobic training, resistance training, or
was 50 months in the teplizumab group 10. Evert AB, Dennison M, Gardner CD, et al. both on percentage body fat and cardiometabolic
Nutrition therapy for adults with diabetes or risk markers in obese adolescents: the Healthy
and 25 months in the placebo group, for
prediabetes: a consensus report. Diabetes Care Eating Aerobic and Resistance Training in Youth
a difference of 25 months at a median 2019;42:731–754 randomized clinical trial. JAMA Pediatr 2014;168:
follow-up time of 51 months. In prespeci- 11. Department of Health and Human Services 1006–1014
fied analyses, the presence of HLA-DR4 and Department of Agriculture. Dietary Guidelines 27. Dai X, Zhai L, Chen Q, et al. Two-year-
and absence of HLA-DR3 were associated for Americans 2015–2020, Eighth Edition. Accessed supervised resistance training prevented diabetes
12 October 2022. Available from https://www. incidence in people with prediabetes: a ran-
with more robust responses to teplizumab
health.gov/dietaryguidelines/2015/guidelines domised control trial. Diabetes Metab Res Rev
(hazard ratio 0.20 [95% CI 0.09–0.45] and 12. Salas-Salvad o J, Guasch-Ferre M, Lee C-H, 2019;35:e3143
0.18 [95% CI 0.07–0.45], respectively. The Estruch R, Clish CB, Ros E. Protective effects of 28. Thorp AA, Kingwell BA, Sethi P, Hammond L,
most common adverse reactions were lym- the Mediterranean diet on type 2 diabetes and Owen N, Dunstan DW. Alternating bouts of sitting
phopenia (73%) followed by rash (36%). metabolic syndrome. J Nutr 2016;146:920S–927S and standing attenuate postprandial glucose res-
13. Bloomfield HE, Koeller E, Greer N, MacDonald ponses. Med Sci Sports Exerc 2014;46:2053–2061
Numerous clinical studies are being con-
R, Kane R, Wilt TJ. Effects on health outcomes of a 29. Healy GN, Dunstan DW, Salmon J, et al. Breaks
ducted to test methods of preventing or Mediterranean diet with no restriction on fat in sedentary time: beneficial associations with
delaying the onset of stage 3 type 1 diabe- intake: a systematic review and meta-analysis. Ann metabolic risk. Diabetes Care 2008;31:661–666
tes in those with evidence of autoimmu- Intern Med 2016;165:491–500 30. Russo LM, Nobles C, Ertel KA, Chasan-Taber
nity without symptoms, or delaying loss of 14. Estruch R, Ros E, Salas-Salvad o J, et al.; L, Whitcomb BW. Physical activity interventions in
insulin secretory capacity after onset of PREDIMED Study Investigators. Primary pre-vention pregnancy and risk of gestational diabetes
of cardiovascular disease with a Medi-terranean mellitus: a systematic review and meta-analysis.
stage 3, some with promising results (see diet supplemented with extra-virgin olive oil or Obstet Gynecol 2015;125:576–582
ClinicalTrials.gov and trialnet.org). nuts. N Engl J Med 2018;378:e34 31. Herman WH, Hoerger TJ, Brandle M, et al.;
15. Stentz FB, Brewer A, Wan J, et al. Remission Diabetes Prevention Program Research Group.
References of pre-diabetes to normal glucose tolerance in The cost-effectiveness of lifestyle modification or
1. Knowler WC, Barrett-Connor E, Fowler SE, obese adults with high protein versus high metformin in preventing type 2 diabetes in adults
et al.; Diabetes Prevention Program Research carbohydrate diet: randomized control trial. BMJ with impaired glucose tolerance. Ann Intern Med
Group. Reduction in the incidence of type 2 Open Diabetes Res Care 2016;4:e000258 2005;142:323–332
diabetes with lifestyle intervention or metformin. 16. Chiu THT, Pan W-H, Lin M-N, Lin C-L. 32. Chen F, Su W, Becker SH, et al. Clinical and
N Engl J Med 2002;346:393–403 Vegetarian diet, change in dietary patterns, and economic impact of a digital, remotely-delivered
diabetesjournals.org/care Prevention or Delay of Type 2 Diabetes and Associated Comorbidities S47

intensive behavioral counseling program on 46. Raynor HA, Davidson PG, Burns H, et al. for weight loss in patients with prediabetes:
Medicare beneficiaries at risk for diabetes and Medical nutrition therapy and weight loss pragmatic trial. JMIR Diabetes 2019;4:e12985
cardiovascular disease. PLoS One 2016;11: questions for the Evidence Analysis Library 61. Wittert G, Bracken K, Robledo KP, et al.
e0163627 prevention of type 2 diabetes project: systematic Testosterone treatment to prevent or revert
33. Diabetes Prevention Program Research reviews. J Acad Nutr Diet 2017;117:1578–1611 type 2 diabetes in men enrolled in a lifestyle
Group. The 10-year cost-effectiveness of lifestyle 47. Sun Y, You W, Almeida F, Estabrooks P, Davy programme (T4DM): a randomised, double-
intervention or metformin for diabetes pre- B. The effectiveness and cost of lifestyle blind, placebo-controlled, 2-year, phase 3b trial.
vention: an intent-to-treat analysis of the DPP/ interventions including nutrition education for Lancet Diabetes Endocrinol 2021;9:32–45
DPPOS. Diabetes Care 2012;35:723–730 diabetes prevention: a systematic review and 62. Gerstein HC, Bosch J, Dagenais GR, et al.;
34. Alva ML, Hoerger TJ, Jeyaraman R, Amico P, meta-analysis. J Acad Nutr Diet 2017;117: ORIGIN Trial Investigators. Basal insulin and cardio-
Rojas-Smith L. Impact of the YMCA of the USA 404–421.e36 vascular and other outcomes in dysglycemia. N
Diabetes Prevention Program on Medicare 48. Briggs Early K, Stanley K. Position of the Engl J Med 2012;367:319–328
spending and utilization. Health Aff (Millwood) Academy of Nutrition and Dietetics: the role of 63. DeFronzo RA, Tripathy D, Schwenke DC,
2017;36:417–424 medical nutrition therapy and registered dietitian et al.; ACT NOW Study. Pioglitazone for diabetes
35. Zhou X, Siegel KR, Ng BP, et al. Cost- nutritionists in the prevention and treatment of prevention in impaired glucose tolerance. N Engl
effectiveness of diabetes prevention inter- prediabetes and type 2 diabetes. J Acad Nutr Diet J Med 2011;364:1104–1115

Downloaded from http://diabetesjournals.org/care/article-pdf/46/Supplement_1/S41/726457/dc23s003.pdf by guest on 24 April 2024

ventions targeting high-risk individuals and whole 2018;118:343–353 64. Gerstein HC, Yusuf S, Bosch J, et al.; DREAM
populations: a systematic review. Diabetes Care 49. Powers MA, Bardsley JK, Cypress M, et al. (Diabetes REduction Assessment with ramipril and
2020;43:1593–1616 Diabetes self-management education and support rosiglitazone Medication) Trial Investigators. Effect
36. Ackermann RT, Finch EA, Brizendine E, Zhou in adults with type 2 diabetes: a consensus report of rosiglitazone on the frequency of diabetes in
H, Marrero DG. Translating the Diabetes Pre- of the American Diabetes Association, the patients with impaired glucose tolerance or
vention Program into the community. The DEPLOY Association of Diabetes Care & Education impaired fasting glucose: a randomised controlled
Pilot Study. Am J Prev Med 2008;35:357–363 Specialists, the Academy of Nutrition and Dietetics, trial. Lancet 2006;368:1096–1105
37. Balk EM, Earley A, Raman G, Avendano EA, the American Academy of Family Physicians, the 65. le Roux CW, Astrup A, Fujioka K, et al.; SCALE
Pittas AG, Remington PL. Combined diet and American Academy of PAs, the American Obesity Prediabetes NN8022-1839 Study Group.
physical activity promotion programs to prevent Association of Nurse Practitioners, and the 3 years of liraglutide versus placebo for type 2
type 2 diabetes among persons at increased risk: American Pharmacists Association. Diabetes Care diabetes risk reduction and weight management
a systematic review for the Community Pre- 2020;43:1636–1649 in individuals with prediabetes: a randomised,
ventive Services Task Force. Ann Intern Med 50. Hudspeth BD. Power of prevention: the double-blind trial. Lancet 2017;389:1399–1409
pharmacist’s role in prediabetes management. 66. Chiasson JL, Josse RG, Gomis R, Hanefeld M,
2015;163:437–451
38. Li R, Qu S, Zhang P, et al. Economic Diabetes Spectr 2018;31:320–323 Karasik A; STOP-NIDDM Trail Research Group.
51. Butcher MK, Vanderwood KK, Hall TO, Acarbose for prevention of type 2 diabetes
evaluation of combined diet and physical activity
Gohdes D, Helgerson SD, Harwell TS. Capacity of mellitus: the STOP-NIDDM randomised trial.
promotion programs to prevent type 2 diabetes
diabetes education programs to provide both Lancet 2002;359:2072–2077
among persons at increased risk: a systematic
diabetes self-management education and to 67. Wilding JPH, Batterham RL, Calanna S, et al.;
review for the Community Preventive Services
implement diabetes prevention services. J Public STEP 1 Study Group. Once-weekly semaglutide in
Task Force. Ann Intern Med 2015;163:452–460
Health Manag Pract 2011;17:242–247 adults with overweight or obesity. N Engl J Med
39. Gilmer T, O’Connor PJ, Schiff JS, et al. Cost-
52. Grock S, Ku J-H, Kim J, Moin T. A review of 2021;384:989–1002
effectiveness of a community-based Diabetes
technology-assisted interventions for diabetes 68. Holman RR, Haffner SM, McMurray JJ, et al.;
Prevention Program with participation incentives
prevention. Curr Diab Rep 2017;17:107 NAVIGATOR Study Group. Effect of nateglinide
for Medicaid beneficiaries. Health Serv Res 2018;
53. Sepah SC, Jiang L, Peters AL. Translating the on the incidence of diabetes and cardiovascular
53:4704–4724
Diabetes Prevention Program into an online events. N Engl J Med 2010;362:1463–1476
40. Ackermann RT, Kang R, Cooper AJ, et al. Effect
social network: validation against CDC standards. 69. Dennison RA, Chen ES, Green ME, et al. The
on health care expenditures during nationwide absolute and relative risk of type 2 diabetes after
Diabetes Educ 2014;40:435–443
implementation of the Diabetes Prevention 54. Bian RR, Piatt GA, Sen A, et al. The effect of gestational diabetes: a systematic review and
Program as a health insurance benefit. Diabetes technology-mediated diabetes prevention inter- meta-analysis of 129 studies. Diabetes Res Clin
Care 2019;42:1776–1783 ventions on weight: a meta-analysis. J Med Pract 2021;171:108625
41. Ely EK, Gruss SM, Luman ET, et al. A national Internet Res 2017;19:e76 70. Torgerson JS, Hauptman J, Boldrin MN,
effort to prevent type 2 diabetes: participant-level 55. Sepah SC, Jiang L, Peters AL. Long-term Sj€
ostr€ om L. XENical in the prevention of diabetes
evaluation of CDC’s National Diabetes Prevention outcomes of a web-based diabetes prevention in obese subjects (XENDOS) study: a randomized
Program. Diabetes Care 2017;40:1331–1341 program: 2-year results of a single-arm longi- study of orlistat as an adjunct to lifestyle changes
42. Lanza A, Soler R, Smith B, Hoerger T, tudinal study. J Med Internet Res 2015;17:e92 for the prevention of type 2 diabetes in obese
Neuwahl S, Zhang P. The Diabetes Prevention 56. Moin T, Damschroder LJ, AuYoung M, et al. patients. Diabetes Care 2004;27:155–161
Impact Tool Kit: an online tool kit to assess the Results from a trial of an online Diabetes 71. Garvey WT, Ryan DH, Henry R, et al.
cost-effectiveness of preventing type 2 diabetes. Prevention Program intervention. Am J Prev Med Prevention of type 2 diabetes in subjects with
J Public Health Manag Pract 2019;25:E1–E5 2018;55:583–591 prediabetes and metabolic syndrome treated
43. Cannon MJ, Masalovich S, Ng BP, et al. 57. Michaelides A, Major J, Pienkosz E Jr, Wood M, with phentermine and topiramate extended
Retention among participants in the National Kim Y, Toro-Ramos T. Usefulness of a novel mobile release. Diabetes Care 2014;37:912–921
Diabetes Prevention Program lifestyle change Diabetes Prevention Program delivery platform 72. Jastreboff AM, Aronne LJ, Ahmad NN, et al.;
program, 2012–2017. Diabetes Care 2020;43: with human coaching: 65-week observational SURMOUNT-1 Investigators. Tirzepatide once
2042–2049 follow-up. JMIR Mhealth Uhealth 2018;6:e93 weekly for the treatment of obesity. N Engl J Med
44. The Community Guide. Diabetes Prevention: 58. Kim SE, Castro Sweet CM, Cho E, Tsai J, 2022;387:205–216
Interventions Engaging Community Health Cousineau MR. Evaluation of a digital diabetes 73. McMurray JJ, Holman RR, Haffner SM, et al.;
Workers, 2016. Accessed 12 October 2022. prevention program adapted for low-income NAVIGATOR Study Group. Effect of valsartan on
Available from https://www.thecommunityguide. patients, 2016-2018. Prev Chronic Dis 2019;16: the incidence of diabetes and cardiovascular
org/findings/diabetes-prevention-interventions- E155 events. N Engl J Med 2010;362:1477–1490
engaging-community-health-workers 59. Vadheim LM, Patch K, Brokaw SM, et al. 74. Bosch J, Yusuf S, Gerstein HC, et al.; DREAM
45. Jacob V, Chattopadhyay SK, Hopkins DP, Telehealth delivery of the Diabetes Prevention Trial Investigators. Effect of ramipril on the
et al. Economics of community health workers Program to rural communities. Transl Behav Med incidence of diabetes. N Engl J Med 2006;355:
for chronic disease: findings from Community 2017;7:286–291 1551–1562
Guide systematic reviews. Am J Prev Med 2019; 60. Fischer HH, Durfee MJ, Raghunath SG, Ritchie 75. Everett BM, Donath MY, Pradhan AD, Thuren
56:e95–e106 ND. Short message service text message support T, Pais P, Nicolau JC, et al. Anti-inflammatory
S48 Prevention or Delay of Type 2 Diabetes and Associated Comorbidities Diabetes Care Volume 46, Supplement 1, January 2023

therapy with canakinumab for the prevention 88. de Jager J, Kooy A, Lehert P, et al. Long term 102. Crandall JP, Mather K, Rajpathak SN, et al.
and management of diabetes. J Am Coll Cardiol treatment with metformin in patients with type 2 Statin use and risk of developing diabetes: results
2018;71:2392–2401. diabetes and risk of vitamin B-12 deficiency: from the Diabetes Prevention Program. BMJ
76. Ray KK, Colhoun HM, Szarek M, et al.; randomised placebo controlled trial. BMJ 2010; Open Diabetes Res Care 2017;5:e000438
ODYSSEY OUTCOMES Committees and Investi- 340:c2181 103. Preiss D, Seshasai SRK, Welsh P, et al. Risk
gators. Effects of alirocumab on cardiovascular 89. Kidney Disease: Improving Global Outcomes of incident diabetes with intensive-dose com-
and metabolic outcomes after acute coronary (KDIGO) Diabetes Work Group. KDIGO 2020 clinical pared with moderate-dose statin therapy: a
syndrome in patients with or without diabetes: a practice guideline for diabetes management in meta-analysis. JAMA 2011;305:2556–2564
prespecified analysis of the ODYSSEY OUTCOMES chronic kidney disease. Kidney Int 2020;98(4S): 104. Mansi IA, Chansard M, Lingvay I, Zhang S,
randomised controlled trial. Lancet Diabetes S1–S115 Halm EA, Alvarez CA. Association of statin
Endocrinol 2019;7:618–628 90. Ali MK, Bullard KM, Saydah S, Imperatore G, therapy initiation with diabetes progression: a
77. Pittas AG, Dawson-Hughes B, Sheehan P, et al.; Gregg EW. Cardiovascular and renal burdens of retrospective matched-cohort study. JAMA Intern
D2d Research Group. Vitamin D supplementation prediabetes in the USA: analysis of data from Med 2021;181:1562–1574
and prevention of type 2 diabetes. N Engl J Med serial cross-sectional surveys, 1988-2014. Lancet 105. Ridker PM, Pradhan A, MacFadyen JG,
2019;381:520–530 Diabetes Endocrinol 2018;6:392–403 Libby P, Glynn RJ. Cardiovascular benefits and
78. Dawson-Hughes B, Staten MA, Knowler WC, 91. Pan Y, Chen W, Wang Y. Prediabetes and diabetes risks of statin therapy in primary

Downloaded from http://diabetesjournals.org/care/article-pdf/46/Supplement_1/S41/726457/dc23s003.pdf by guest on 24 April 2024

et al.; D2d Research Group. Intratrial exposure to outcome of ischemic stroke or transient ischemic prevention: an analysis from the JUPITER trial.
vitamin D and new-onset diabetes among adults attack: a systematic review and meta-analysis. J Lancet 2012;380:565–571
with prediabetes: a secondary analysis from the Stroke Cerebrovasc Dis 2019;28:683–692 106. Cai T, Abel L, Langford O, et al. Associations
vitamin D and type 2 diabetes (D2d) study. 92. Huang Y, Cai X, Mai W, Li M, Hu Y. between statins and adverse events in primary
Diabetes Care 2020;43:2916–2922 Association between prediabetes and risk of prevention of cardiovascular disease: systematic
79. Zhang Y, Tan H, Tang J, et al. Effects of cardiovascular disease and all cause mortality: review with pairwise, network, and dose-
vitamin D supplementation on prevention of systematic review and meta-analysis. BMJ 2016; response meta-analyses. BMJ 2021;374:n1537
type 2 diabetes in patients with prediabetes: a 355:i5953 107. Kernan WN, Viscoli CM, Furie KL, et al.; IRIS
systematic review and meta-analysis. Diabetes 93. Yeh HC, Duncan BB, Schmidt MI, Wang NY, Trial Investigators. Pioglitazone after ischemic
Care 2020;43:1650–1658 Brancati FL. Smoking, smoking cessation, and risk stroke or transient ischemic attack. N Engl J Med
80. Barbarawi M, Zayed Y, Barbarawi O, Bala A, for type 2 diabetes mellitus: a cohort study. Ann 2016;374:1321–1331
Alabdouh A, Gakhal I, et al. Effect of vitamin D sup- Intern Med 2010;152:10–17 108. Inzucchi SE, Viscoli CM, Young LH, et al.; IRIS
plementation on the incidence of diabetes mellitus. 94. Oba S, Noda M, Waki K, et al.; Japan Public Trial Investigators. Pioglitazone prevents diabetes in
J Clin Endocrinol Metab 2020;105:dgaa335. Health Center-Based Prospective Study Group. patients with insulin resistance and cerebrovascular
81. Diabetes Prevention Program Research Smoking cessation increases short-term risk of disease. Diabetes Care 2016;39:1684–1692
Group. Long-term safety, tolerability, and weight type 2 diabetes irrespective of weight gain: the 109. Spence JD, Viscoli CM, Inzucchi SE, et al.; IRIS
loss associated with metformin in the Diabetes Japan Public Health Center-Based Prospective Investigators. Pioglitazone therapy in patients with
Prevention Program Outcomes Study. Diabetes Study. PLoS One 2012;7:e17061 stroke and prediabetes: a post hoc analysis of the
Care 2012;35:731–737 95. Hu Y, Zong G, Liu G, Wang M, Rosner B, Pan IRIS randomized clinical trial. JAMA Neurol
82. Ratner RE, Christophi CA, Metzger BE, et al.; A, et al. Smoking cessation, weight change, type 2 2019;76:526–535
Diabetes Prevention Program Research Group. diabetes, and mortality. N Engl J Med 2018;379: 110. Spence JD, Viscoli C, Kernan WN, et al.
Prevention of diabetes in women with a history 623–632 Efficacy of lower doses of pioglitazone after
of gestational diabetes: effects of metformin and 96. Orchard TJ, Temprosa M, Barrett-Connor E, stroke or transient ischaemic attack in patients
lifestyle interventions. J Clin Endocrinol Metab et al.; Diabetes Prevention Program Outcomes with insulin resistance. Diabetes Obes Metab
2008;93:4774–4779 Study Research Group. Long-term effects of the 2022;24:1150–1158
83. Aroda VR, Christophi CA, Edelstein SL, et al.; Diabetes Prevention Program interventions on 111. Nadeau KJ, Anderson BJ, Berg EG, et al.
Diabetes Prevention Program Research Group. cardiovascular risk factors: a report from the DPP Youth-onset type 2 diabetes consensus report:
The effect of lifestyle intervention and metformin Outcomes Study. Diabet Med 2013;30:46–55 current status, challenges, and priorities. Diabetes
on preventing or delaying diabetes among 97. Salas-Salvad o J, Dıaz-L
opez A, Ruiz-Canela Care 2016;39:1635–1642
women with and without gestational diabetes: M, et al.; PREDIMED-Plus investigators. Effect of 112. Rooney MR, Rawlings AM, Pankow JS, et al.
the Diabetes Prevention Program outcomes a lifestyle intervention program with energy- Risk of progression to diabetes among older
study 10-year follow-up. J Clin Endocrinol Metab restricted mediterranean diet and exercise on adults with prediabetes. JAMA Intern Med 2021;
2015;100:1646–1653 weight loss and cardiovascular risk factors: one- 181:511–519
84. Diabetes Prevention Program Research year results of the PREDIMED-Plus Trial. Diabetes 113. Lachin JM, Christophi CA, Edelstein SL,
Group. Long-term effects of metformin on diabetes Care 2019;42:777–788 et al.; DPP Research Group. Factors associated
prevention: identification of subgroups that 98. Gong Q, Gregg EW, Wang J, et al. Long-term with diabetes onset during metformin versus
benefited most in the Diabetes Prevention Pro- effects of a randomised trial of a 6-year lifestyle placebo therapy in the diabetes prevention
gram and Diabetes Prevention Program Outcomes intervention in impaired glucose tolerance on program. Diabetes 2007;56:1153–1159
Study. Diabetes Care 2019;42:601–608 diabetes-related microvascular complications: 114. Perreault L, Pan Q, Schroeder EB, et al.;
85. Ramachandran A, Snehalatha C, Mary S, the China Da Qing Diabetes Prevention Outcome Diabetes Prevention Program Research Group.
Mukesh B, Bhaskar AD; Indian Diabetes Prevention Study. Diabetologia 2011;54:300–307 Regression from prediabetes to normal glucose
Programme (IDPP). The Indian Diabetes Prevention 99. Arnett DK, Blumenthal RS, Albert MA, et al. regulation and prevalence of microvascular disease
Programme shows that lifestyle modification and 2019 ACC/AHA guideline on the primary in the Diabetes Prevention Program Outcomes
metformin prevent type 2 diabetes in Asian Indian prevention of cardiovascular disease: a report of Study (DPPOS). Diabetes Care 2019;42:1809–1815
subjects with impaired glucose tolerance (IDPP-1). the American College of Cardiology/American 115. Chen Y, Zhang P, Wang J, et al. Associations
Diabetologia 2006;49:289–297 Heart Association Task Force on Clinical Practice of progression to diabetes and regression to
86. Griffin SJ, Bethel MA, Holman RR, et al. Guidelines. Circulation 2019;140:e596–e646 normal glucose tolerance with development of
Metformin in non-diabetic hyperglycaemia: the 100. Thakker D, Nair S, Pagada A, Jamdade V, cardiovascular and microvascular disease among
GLINT feasibility RCT. Health Technol Assess Malik A. Statin use and the risk of developing people with impaired glucose tolerance: a
2018;22:1–64 diabetes: a network meta-analysis. Pharmaco- secondary analysis of the 30 year Da Qing
87. Aroda VR, Edelstein SL, Goldberg RB, et al.; epidemiol Drug Saf 2016;25:1131–1149 Diabetes Prevention Outcome Study. Diabetologia
Diabetes Prevention Program Research Group. 101. Macedo AF, Douglas I, Smeeth L, Forbes H, 2021;64:1279–1287
Long-term metformin use and vitamin B12 Ebrahim S. Statins and the risk of type 2 diabetes 116. Herold KC, Bundy BN, Long SA, et al.; Type 1
deficiency in the Diabetes Prevention Program mellitus: cohort study using the UK Clinical Practice Diabetes TrialNet Study Group. An anti-CD3
Outcomes Study. J Clin Endocrinol Metab 2016; Research Datalink. BMC Cardiovasc Disord 2014; antibody, teplizumab, in relatives at risk for type 1
101:1754–1761 14:85 diabetes. N Engl J Med 2019;381:603–613