Primary prevention
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Diabetes Mellitus Type 2Published by: Domus Medica | SSMGLast published: 2017Diabète sucré de type 2Published by: SSMG | Domus MedicaLast published: 2017Individualized risk-to-benefit ratio should be considered in screening, intervention, and monitoring to lower the risk of type 2 diabetes and associated comorbidities.[2] Multiple factors, including age, body mass index (BMI), and other comorbidities, may influence the risk of progression to diabetes and lifetime risk of complications. Prediabetes is associated with increased cardiovascular (CV) disease and mortality, which emphasizes the importance of attending to CV risk in this population.[2]
Screening for prediabetes
Risk factor assessment informs whether screening for prediabetes and type 2 diabetes should be performed. See Screening.
Testing high-risk adults for prediabetes is warranted because the laboratory assessment is safe and reasonable in cost, substantial time exists before the development of type 2 diabetes and its complications during which one can intervene, and there are effective approaches delaying type 2 diabetes in those with prediabetes with a hemoglobin A1c (HbA1c) of 5.7% to 6.4% (39-47 mmol/mol), impaired glucose tolerance (IGT), or impaired fasting glucose (IFG).[2]
Lifestyle changes
Lifestyle factors (obesity, physical inactivity, stress, smoking, and suboptimal sleep) are major drivers of the current diabetes epidemic. Although pharmacologic approaches can help to reverse prediabetes, lifestyle modification provides the strongest evidence of effectiveness and should remain the recommended approach.[77] Lifestyle interventions have been shown to be especially effective in older adults, while metformin has proved less effective as primary prevention in this population.[35] Evidence shows that a combination of low-risk lifestyle behaviors, including maintaining a healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption, is associated with a lower risk of incident type 2 diabetes.[78]
With aggressive prevention of obesity in all age groups, type 2 diabetes is potentially preventable.[79][80] Several clinical trials have shown that weight loss is associated with delayed or decreased onset of diabetes in high-risk adults.[48][49][50][51]
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The strongest evidence for diabetes prevention in the US comes from the Diabetes Prevention Program (DPP) trial, which demonstrated that intensive lifestyle intervention via a structured program, with the goals of at least 7% weight loss (and maintenance of this loss throughout the trial) and at least 150 minutes of moderate-intensity physical activity per week, could reduce the risk of incident type 2 diabetes by 58% over 3 years.[49] Although weight loss was the most important factor, achieving the behavioral goal of at least 150 minutes of physical activity per week, even without achieving the weight loss goal, reduced the incidence of type 2 diabetes by 44%.[49] The delivery of such programs in a digital format has demonstrated clinical effectiveness and has significant potential for widespread dissemination.[81] The American Diabetes Association (ADA) recommends referring adults with overweight or obesity at high risk of type 2 diabetes to an intensive lifestyle behavior change program to achieve and maintain a weight reduction of at least 7% of initial body weight through a healthy reduced-calorie diet and ≥150 minutes/week of moderate-intensity physical activity.[2] In addition to aerobic activity, a physical activity plan designed to prevent diabetes should include resistance training. Breaking up prolonged sedentary time should also be encouraged, as it is associated with moderately lower postprandial glucose levels.[2]
In the US, the Centers for Disease Control and Prevention (CDC) has developed the National Diabetes Prevention Program (National DPP), a resource designed to bring evidence-based lifestyle change programs for preventing type 2 diabetes to communities.[82] One key feature of the National DPP is the lifestyle change program, which focuses on nutritional and physical activity modification for individuals with prediabetes and those who are at risk for type 2 diabetes. The year-long program follows a research-based curriculum that starts with weekly group meetings for the first 6 months, followed by routine upkeep sessions to keep participants on track. To be eligible for this program, individuals must meet all four of the following criteria:[82]
Be ages 18 years or older
Have a BMI ≥25 kg/m² (or BMI ≥23 kg/m² if self-identified as Asian)
Not be previously diagnosed with type 1 or type 2 diabetes
Not be pregnant.
They must also meet one of the following requirements:
Have had a blood test result in the prediabetes range within the past year. This includes any of these tests and results:
HbA1c: 5.7% to 6.4% (39-46 mmol/mol)
Fasting plasma glucose: 100-125 mg/dL (5.6-6.9 mmol/L)
2-hour plasma glucose (after a 75 g glucose load): 140-199 mg/dL (7.8-11.0 mmol/L).
Have been previously diagnosed with gestational diabetes
Have received a high-risk result (score of 5 or higher) on the Prediabetes Risk Test. CDC: Prediabetes Risk Test Opens in new window
A variety of eating patterns can be considered to prevent type 2 diabetes in individuals with prediabetes. The ADA recommends that macronutrient distribution should be tailored to individual eating habits, preferences, and metabolic goals.[2] A dietary pattern emphasizing whole grains, legumes, nuts, fruits, and vegetables, while minimizing refined and processed foods, is linked to a reduced risk of type 2 diabetes.[2] One large meta-analysis found that the consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations.[83] Higher consumption of sugar-sweetened beverages has also been linked to an increased risk of developing type 2 diabetes; sugary drink consumption should therefore be minimized.[84] Counseling by a registered dietitian nutritionist has been shown to help individuals with prediabetes to improve eating habits.[2]
A 2022 consensus report by the ADA and European Association for the Study of Diabetes highlighted sleep as a central component in the management of prediabetes, placing it, for the first time, on the same level as other lifestyle behaviors (e.g., physical activity and nutrition).[85] The American Heart Association has also published a statement emphasizing that multidimensional sleep health, beyond just duration, significantly impacts cardiometabolic risk factors relevant to type 2 diabetes, including glucose regulation, obesity, and hypertension.[69] Sleep can be characterized using three key constructs: quantity, quality, and timing (i.e., chronotype). There is now established evidence for a U-shaped association between sleep duration and type 2 diabetes incidence, with the nadir typically occurring at 7 hours per day, with short (typically defined as <6 hours) and long (typically defined as >9 hours) sleep duration having up to a 50% increase in the risk of type 2 diabetes, including progression from prediabetes.[2] Sleep quality is defined as an individual's self-satisfaction with all aspects of the sleep experience.[70] In one meta-analysis, poor sleep quality was associated with a 40% to 84% increased risk of developing type 2 diabetes.[71] Chronotype preference has been linked with many chronic diseases, including type 2 diabetes.[2] One study found that those with a preference for evenings (i.e., going to bed late and getting up late) had a 2.5-fold higher odds ratio for type 2 diabetes than those with a preference for mornings (i.e., going to bed early and getting up early), independent of sleep duration and sleep sufficiency.[72] Although the ADA does not offer specific sleep recommendations for prediabetes, the strong correlation between inadequate sleep and increased diabetes risk implies that individuals at high risk of type 2 diabetes would benefit from education on sleep hygiene and strategies for improving sleep quality.
According to the World Health Organization (WHO), smoking cessation reduces the long-term risk of developing type 2 diabetes, despite potential short-term weight gain. Health benefits increase with longer duration of quitting.[63] The WHO recommends population-level and pharmacologic interventions to ensure access to comprehensive cessation support.[63] See Smoking cessation.
Pharmacologic preventive treatment
Because weight loss through behavior changes in diet and physical activity can be difficult to maintain long term, people at high risk of type 2 diabetes may benefit from additional support and pharmacotherapeutic options. The ADA advises that, while no pharmacologic treatment has been approved by the Food and Drug Administration (FDA) for the prevention of type 2 diabetes, pharmacotherapy (e.g., for weight management, minimizing the progression of hyperglycemia, and CV risk reduction) may be considered.[2] The risk versus benefit of each drug in support of person-centered goals should be weighed in addition to the cost and burden of administration.[2] Several pharmacologic agents, including metformin, orlistat, glucagon-like peptide-1 (GLP-1) receptor agonists, alpha-glucosidase inhibitors, thiazolidinediones, and insulin, have been shown to reduce progression from prediabetes to diabetes in specific populations.[2][86][87][88][89][90]
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In one study, dapagliflozin (a sodium-glucose cotransporter-2 [SGLT2] inhibitor) reduced the incidence of new-onset type 2 diabetes in patients with chronic kidney disease or heart failure (with HbA1c <6.5% [<48 mmol/mol] and no history of diabetes) compared with placebo, although no improvement in glycemic control was observed.[91]
Metformin is the preferred preventive treatment for most patients who require additional support in the form of pharmacotherapy (although GLP-1 receptor agonists may be favored in patients with overweight/obesity).[92][93][94][95][96] The ADA recommends that metformin should be considered in adults at high risk of type 2 diabetes, especially those ages 25-59 years with BMI ≥35 kg/m², higher fasting plasma glucose (e.g., ≥110 mg/dL [≥6 mmol/L]), and higher HbA1c (e.g., ≥6.0% [≥42 mmol/mol]), and in individuals with prior gestational diabetes mellitus.[2] Due to the established association between long-term metformin therapy and vitamin B12 deficiency, clinicians should consider periodic monitoring of B12 levels in patients receiving prolonged treatment, higher dosages, and those with predisposing factors such as a vegan dietary pattern or a history of gastric/small bowel surgery.[2] The ADA specifically recommends that patients on metformin who have been taking the drug for more than 4 years or who have additional risk factors for vitamin B12 deficiency should be monitored for vitamin B12 deficiency annually.[2] Serum vitamin B12 levels should also be tested if deficiency is suspected, such as in people with anemia or peripheral neuropathy.[2]
More aggressive multi-agent pharmacologic approaches remain controversial.[97] The ADA advises that more intensive preventive approaches (e.g., treatment targeting 10% to 15% weight loss or combination therapies) should be considered in individuals who are at particularly high risk of progression to diabetes, including individuals with BMI ≥35 kg/m², those with higher glucose levels (e.g., fasting plasma glucose 110-125 mg/dL [6.1-6.9 mmol/L], 2-hour post-challenge glucose 173-199 mg/dL [9.6-11.0 mmol/L], HbA1c ≥6.0% [≥42 mmol/mol]), and individuals with a history of gestational diabetes mellitus.[2]
CV risk reduction
Prediabetes is associated with heightened CV risk; therefore, screening for and treating modifiable risk factors for CV disease is also very important.[98][99][100] One study investigating the effect of blood pressure (BP) lowering on the risk of new-onset type 2 diabetes found that reducing systolic BP by 5 mmHg decreased the risk of type 2 diabetes by 11%.[101] However, different antihypertensive drugs had varying effects: ACE inhibitors and angiotensin-II receptor antagonists lowered the risk of new-onset diabetes compared to placebo, while beta-blockers and thiazide diuretics actually increased the risk. Calcium-channel blockers showed no significant effect.[101] Another study found that valsartan plus lifestyle modification produced a reduction in the incidence of diabetes but did not reduce the rate of CV events.[102]
While statins are associated with a slightly increased risk of new-onset type 2 diabetes, particularly in individuals with preexisting risk factors, this risk is generally considered to be outweighed by the significant benefits of statins in reducing the incidence of major adverse CV events.[103][104] When starting statin therapy in individuals with preexisting risk factors for type 2 diabetes, glucose status should be monitored regularly and diabetes prevention approaches reinforced, but statin discontinuation is not recommended.[2]
The table that follows summarizes recommendations on the primary prevention of type 2 diabetes mellitus in adults, from the ADA Standards of Care.[2]
Note that an individual patient may fall into more than one group and so interventions might be additive; please review all population and subpopulation groups to assess all that apply.
Care goals in adults at high risk of type 2 diabetes not summarized in the table include attention to cardiovascular risk; see ADA guidance for more information.[2]
Adult with overweight or obesity; at high risk of type 2 diabetes
Overweight and obesity is defined as a BMI ≥25 kg/m² (or BMI ≥23 kg/m² if self-identified as Asian). People are considered to be at high risk of type 2 diabetes if they have one or more of the following: a blood test result in the prediabetes range within the past year (HbA1c: 5.7% to 6.4% [39-46 mmol/mol]; fasting plasma glucose: 100-125 mg/dL [5.6 to 6.9 mmol/L]; 2-hour plasma glucose [after a 75 g glucose load]: 140-199 mg/dL [7.8 to 11.0 mmol/L]); a previous diagnosis of gestational diabetes; a high-risk result (score of 5 or higher) on the Prediabetes Risk Test.
All
Intervention
Refer to a lifestyle behavior change program
Refer people with overweight and obesity who are at high risk of type 2 diabetes to an intensive lifestyle behavior change program. Diabetes prevention programs encompass both nutrition and physical activity components; patients are encouraged to undertake a healthy reduced-calorie diet and to engage in a structured program of physical activity.
Based on individual preference, it is recommended that certified technology-assisted diabetes prevention programs are considered.
The CDC recommends a number of evidence-based lifestyle change programs across the US: CDC: national diabetes prevention program Opens in new window
Note that intensive behavioral change programs are not suitable in pregnancy.
Nutritional component:
Overall, the aim is to reduce total dietary fat and calories. Emphasize the consumption of whole grains, legumes, nuts, fruits and vegetables, with minimization of refined and processed foods.
An individualized approach to macronutrient distribution is recommended based on an individualized assessment of current eating patterns, preference and metabolic goals.
For those with prediabetes, prescribe an eating pattern known to be effective in preventing type 2 diabetes, such as:
Mediterranean-style eating plan
Intermittent fasting
A low-carbohydrate eating plan
Physical activity component:
In addition to aerobic activity, it is recommended that a physical activity plan designed to prevent diabetes also includes resistance training.
Encourage people to break up prolonged sedentary time, as it is associated with moderately lower postprandial glucose levels.
Lifestyle change and/or metformin (see next row) are preferred for most patients to minimize progression of hyperglycemia, but it may be reasonable to consider additional pharmacologic options on a case by case basis to support person-centered care goals.
Goal
Achieve and maintain at least 7% weight loss; achieve at least 150 minutes of moderate-intensity physical activity per week; minimization of hyperglycemic progression
In people with prediabetes, monitor for the development of type 2 diabetes at least annually; modify frequency of testing based on individual risk assessment.
Nutritional and weight loss goals:
Calorie goals may be calculated by estimating the daily calories needed to maintain the patient’s initial weight and subtracting 500-1000 calories/day (depending on initial body weight).
A reasonable recommended pace of weight loss is typically around 1-2 lb/week.
Physical activity goals:
Participants are typically encouraged to distribute their activity throughout the week with a minimum frequency of three times per week and at least 10 minutes per session.
A maximum of 75 minutes of strength training could be applied toward the total 150 minutes/week physical activity goal.
With additional pharmacologic support needed to minimize progression of hyperglycemia
Intervention
Consider metformin
Weight loss through behavior changes in diet and physical activity can be difficult to maintain long-term; some people at high risk of type 2 diabetes may benefit from pharmacologic support.
Consider metformin for all adults at risk of type 2 diabetes who require additional pharmacologic support to minimize progression of hyperglycemia, and especially for people:
Ages 25-59 years with a BMI ≥35 kg/m².
With higher fasting plasma glucose (e.g., ≥110 mg/dL [≥6 mmol/L]), and higher HbA1C (e.g., ≥6.0% [≥42 mmol/mol]).
With prior gestational diabetes mellitus.
Note that metformin has not been approved for the prevention of type 2 diabetes; consider the risk versus benefit of metformin in support of person-centered care goals with respect to this treatment decision if metformin is being considered.
Long-term use of metformin may be associated with vitamin B12 deficiency; consider periodic assessment of vitamin B12 level in metformin-treated individuals, especially in those with anemia or peripheral neuropathy.
Lifestyle change (see previous row) and/or metformin are preferred for most patients to minimize progression of hyperglycemia, but it may be reasonable to consider additional pharmacologic options on a case by case basis to support person-centered care goals.
Goal
Minimization of hyperglycemic progression
In people with prediabetes, monitor for the development of type 2 diabetes at least annually; modify frequency of testing based on individual risk assessment.
With additional pharmacologic support needed for weight loss
Intervention
Consider pharmacotherapy for weight loss
Pharmacotherapy for weight management may be considered to support person-centered care goals.
More intensive preventive approaches may be considered in people at high risk of progression to type 2 diabetes, for example those with:
BMI ≥35 kg/m².
Higher glucose levels (e.g., fasting plasma glucose 110-125 mg/dL [6.1 to 6.9 mmol/L], 2-hour post challenge glucose 173-199 mg/dL [9.6 to 11.0 mmol/L], and A1C ≥6.0% [≥42 mmol/mol]).
A history of gestational diabetes mellitus.
See Obesity in adults.
Goal
Weight loss and weight maintenance; minimization of progression of hyperglycemia
With poor sleep quality
Intervention
Consider individualized management to improve sleep quality
Consider whether it is appropriate to offer evidence-based management to improve sleep quantity and quality.
The optimization of sleep quality is increasingly recognized as a central component in the management of prediabetes; poor sleep quality has been associated with a substantially increased risk of developing type 2 diabetes.
See Insomnia.
Goal
Improved sleep quality and minimization of hyperglycemic progression
On statin therapy
Intervention
Enhanced surveillance and prevention strategy
For people at high risk of developing type 2 diabetes, statin therapy may increase this risk.
Ensure that diabetes prevention approaches are reinforced in this group (and that glucose status is monitored regularly).
It is not recommended that statins are avoided or discontinued in this group.
Goal
Reduced risk of progression to type 2 diabetes
Secondary prevention
Type 2 diabetes is associated with increased risk of both microvascular (i.e., retinopathy, neuropathy, and nephropathy) and macrovascular (i.e., ischemic heart disease, cerebrovascular disease, and peripheral vascular disease) complications, which can impose substantial socioeconomic burden and affect quality of life.[174] Patients should undergo regular screening for these complications and their associated risk factors (e.g., dilated eye exams, comprehensive foot exams, blood pressure checks, assessment of body mass index [BMI], and monitoring of hemoglobin A1c, lipid profile, renal function, urinary albumin-to-creatinine ratio). Long duration of diabetes, suboptimal glycemic control, increased glycemic variability, male sex, underlying comorbidities, and preexisting complications such as albuminuria or subclinical atherosclerosis are all associated with increased risk of microvascular and macrovascular complications.[174] The UK Prospective Diabetes Study (UKPDS) and subsequent studies have shown that achieving intensive glycemic control, especially early in the course of the disease, could have a clinically significant impact in reducing the risk of future complications.[19][491][492] Benefits of glucose-lowering therapies persisted for years after the conclusion of the initial trial period in UKPDS - despite loss of earlier glycemic between-group differences - an occurrence termed the legacy effect.[492] By contrast, intensification of glucose-lowering therapy at a later stage in people with a long duration of type 2 diabetes may not be beneficial and, in fact, may result in worse outcomes.[174]
Because of the multifactorial nature of type 2 diabetes, other modifiable risk factors, like hypertension and dyslipidemia, should also be addressed to reduce the risk of long-term complications. The Steno-2 study showed that multifactorial risk reduction targeting glycemic, blood pressure, and lipid control in those with preexisting microalbuminuria reduced both microvascular and macrovascular complications.[27]
Although the risk of macrovascular complications can be reduced by over 50% using effective multifactorial interventions, a US national survey found more than half of outpatients over age 50 years with diabetes and hypertension did not receive an antiplatelet agent, statin therapy, or ACE inhibitor/angiotensin-II receptor antagonist.[27][493] Increasing evidence indicates that sodium-glucose cotransporter-2 (SGLT2) inhibitor (or dual SGLT1/SGLT2 inhibitor) and glucagon-like peptide-1 (GLP-1) receptor agonist therapy can play a significant role in reducing future risk in individuals with comorbid atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease (CKD), and use of one these agents should be strongly considered if not contraindicated in the secondary prevention of macrovascular complications.[2][85][110] See Diabetic cardiovascular disease.
Other preventive measures include:[2][494][495][496]
Annual influenza immunizations
Vaccination against pneumococcal disease; there are two types of vaccines available in the US, the pneumococcal conjugate vaccines (PCV13, PCV15, PCV20, and PCV21) and the pneumococcal polysaccharide vaccine (PPSV23), with distinct schedules for children and adults
Vaccination against COVID-19
Single-dose vaccination against respiratory syncytial virus (RSV) for adults ages ≥75 years and for adults ages 60-74 years with diabetes complicated by CKD, neuropathy, retinopathy, or other end-organ damage, or requiring treatment with insulin or an SGLT2 inhibitor
Hepatitis B vaccination for unvaccinated adults with diabetes ages 19-59 years; considered for unvaccinated adults with diabetes ages 60 years and older
Regular dental care (patients should undergo a dental exam at least annually)
Tailored diabetes education
Use of customized footwear in patients with known neuropathy or foot deformity; and prompt and aggressive management of lower extremity infections
Regular assessment for symptoms of depression and other mental health comorbidities to facilitate timely recognition and treatment
Screening for heart failure with B-type natriuretic peptide (BNP) or N-terminal prohormone B-type natriuretic peptide (NT-proBNP) on at least a yearly basis
Screening for clinically significant liver fibrosis secondary to metabolic dysfunction-associated steatotic liver disease (MASLD; previously known as nonalcoholic fatty liver disease)
Assessment and management of fracture risk as part of routine care; dual-energy x-ray absorptiometry (DEXA) scan is recommended in all older adults (age ≥65 years) and in younger individuals (age >50 years) with bone or diabetes-related risk factors (such as insulin use or diabetes duration >10 years), with reassessment every 2-3 years
In men, screening for sexual dysfunction, particularly erectile dysfunction; if symptoms and/or signs of hypogonadism are detected (e.g., low libido, erectile dysfunction, and depression), check a morning serum total testosterone level
In women, screening for female sexual dysfunction, particularly in those with depression, anxiety, or recurrent urinary tract infections; and screening for genitourinary syndrome of menopause in postmenopausal women
Referral for family planning for individuals of childbearing potential
Low-dose aspirin in pregnant women (started at 12-16 weeks of gestation) to reduce the risk and severity of preeclampsia.
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