Prediabetes is a condition characterized by glucose or A1c levels that do not meet the criteria for diabetes while still having abnormal carbohydrate metabolism that results in elevated glucose levels.1 The diagnostic criteria for prediabetes defined by the American Diabetes Association (ADA) are outlined below.
Table 1: Criteria for defining prediabetes and diabetes in nonpregnant individuals.
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Prediabetes
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Diabetes
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Fasting Plasma Glucose (FPG)
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100-125 mg/dL
5.6-6.9 mmol/L
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≥126
≥7.0 mmol/L
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2-hour plasma glucose during 75-g Oral Glucose Tolerance Test (OGTT)
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140-199 mg/dL
7.8-11.0 mmol/L
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≥200
≥11.1 mmol/L
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A1c (%)
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5.7-6.4%
39-47 mmol/mol
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≥6.5%
≥48 mmol/mol
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As prediabetes is an intermediate state between normoglycemia and diabetes, it is a significant risk factor for the development of diabetes. One 2010 analysis of 16 cohort studies (n=44,203) with an average of 5.6 years of follow-up found that the incidence of diabetes was associated with higher A1c levels.2 The five-year incidence rate of diabetes among those with A1c levels ranging from 5.0-5.5 was <5-9%, rising to 9-25% for A1c levels from 5.5-6.0, and 25-50% for A1c levels from 6.0-6.5. Similarly, a 2007 meta-analysis by the Agency for Healthcare Research and Quality estimated that 5-10% of patients with prediabetes will develop diabetes.3
Screening
According to the Centers for Disease Control and Prevention’s (CDC) National Diabetes Statistics Report, 97.6 million adults 18 years or older had prediabetes in 2021, or about 38.0% of the adult population.4 Only 19.0% of adults with prediabetes knew they had the condition. Prediabetes does not have clear symptoms, which has informed the ADA’s screening recommendations of testing both asymptomatic adults with risk factors as well as otherwise healthy asymptomatic adults.
Specifically, the ADA recommends testing adults who are overweight or who have obesity who also have at least one of the following risk factors:1
- First-degree relative with diabetes
- High-risk race, ethnicity, or ancestry such as African American, Latino, Native American, or Asian American
- History of cardiovascular disease
- Hypertension or on therapy for hypertension
- HDL cholesterol level <35 mg/dL (<0.9 mmol/L) and/or triglyceride level >250 mg/dL (>2.8 mmol/L)
- Polycystic ovary syndrome
- Physical inactivity
- Other clinical conditions associated with insulin resistance
The ADA also recommends that asymptomatic and otherwise healthy adults be screened for prediabetes at minimum every 3 years starting at age 35 with consideration for more frequent testing depending on test results and risk factors.1 For those who have had gestational diabetes, they recommend testing every 1-3 years. For those with prediabetes, they recommend retesting annually. They further recommend closely monitoring individuals in other high-risk groups such as those with HIV, exposure to high-risk medicines, evidence of periodontal disease, and history of pancreatitis.
Prevention
For those with prediabetes, the development of type 2 diabetes can be delayed or even prevented through lifestyle modification and/or medication interventions, although lifestyle changes have been shown to be more effective at reducing risk. A study published in 2002 by the Diabetes Prevention Program (DPP) examined the effect of lifestyle interventions and metformin on the development of type 2 diabetes in 3,234 high-risk participants without diabetes.5 Over a mean follow-up of 2.8 years, the findings indicated that while both methods were effective options for reducing the incidence of diabetes in high-risk individuals, lifestyle modification was more effective. The lifestyle intervention involved losing and maintaining weight loss of at least 7% of initial body weight by eating a healthy, low-calorie, low-fat diet and engaging in moderate physical activity for at least 150 minutes each week. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in placebo, metformin, and lifestyle groups, respectively. This represented a 58% decrease in incidence for the lifestyle intervention and 31% for metformin compared to placebo.
The Da Qing Diabetes Prevention Study, a randomized controlled trial of 577 adults with impaired glucose tolerance, similarly found that diet and exercise were effective at reducing the long-term risk of type 2 diabetes.6 Participants enrolled in 1986 were randomized to either the control group or receiving a 6-year diet and exercise-based intervention. Participants were then followed up with 23 years after baseline. Among those in the control group, the incidence of diabetes was 122.9 per 1,000 person-years compared to 73.2 per 1,000 person-years for those in the intervention arm (Hazard Ratio [HR] 0.55, 95% Confidence Interval [CI] [0.40-0.76], p=0.001).
The Finnish Diabetes Prevention Study published in 2006 (n=522) had similar findings.7 The intervention involved weight loss, reduction of total and saturated fat intake, increased dietary fiber intake, and increased physical activity. Over seven years of follow-up, the incidence of diabetes was 4.3 per 100 person-years in the intervention group compared to 7.4 per 100 person-years in the control group (p=0.0001), reflecting a 43% relative risk reduction.
Lifestyle modification is effective in the prevention of type 2 diabetes, but it can be hard to maintain long-term.8 For individuals for whom lifestyle medication is not viable, medication intervention is an effective alternative. Pharmacologic therapy is mainly used in patients who are high-risk, such as those who have obesity, a history of gestational diabetes, or a higher fasting plasma glucose. The main medication used for diabetes prevention is metformin.8 Metformin has been shown to be safe and well tolerated, with no significant adverse effects.9
References
- 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care. Jan 1 2025;48(Supplement_1):S27-s49. doi:10.2337/dc25-S002
- Zhang X, Gregg EW, Williamson DF, et al. A1C Level and Future Risk of Diabetes: A Systematic Review. Diabetes Care. 2010;33(7):1665-1673. doi:10.2337/dc09-1939
- Gerstein HC, Santaguida P, Raina P, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract. Dec 2007;78(3):305-12. doi:10.1016/j.diabres.2007.05.004
- National Diabetes Statistics Report. Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services. Accessed 18 November 2024, https://www.cdc.gov/diabetes/php/data-research/index.html
- Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. Feb 7 2002;346(6):393-403. doi:10.1056/NEJMoa012512
- Li G, Zhang P, Wang J, et al. Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study. Lancet Diabetes Endocrinol. Jun 2014;2(6):474-80. doi:10.1016/s2213-8587(14)70057-9
- Lindström J, Ilanne-Parikka P, Peltonen M, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet (London, England). Nov 11 2006;368(9548):1673-9. doi:10.1016/s0140-6736(06)69701-8
- 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care. Jan 1 2025;48(1 Suppl 1):S50-s58. doi:10.2337/dc25-S003
- Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. Apr 2012;35(4):731-7. doi:10.2337/dc11-1299
