What hemoglobin A1c level defines prediabetes?

Hemoglobin A1c Level Defining Prediabetes

An A1c of 5.7–6.4% (39–47 mmol/mol) defines prediabetes according to the American Diabetes Association. 1

Diagnostic Criteria

The American Diabetes Association Standards of Care consistently define prediabetes using three possible criteria, any one of which qualifies for the diagnosis 1:

• A1c: 5.7–6.4% (39–47 mmol/mol) 1
• Fasting plasma glucose: 100–125 mg/dL (5.6–6.9 mmol/L) - termed impaired fasting glucose (IFG) 1
• 2-hour plasma glucose during 75-g OGTT: 140–199 mg/dL (7.8–11.0 mmol/L) - termed impaired glucose tolerance (IGT) 1

Evidence Supporting the A1c Threshold

The 5.7% lower threshold was selected based on robust prospective data demonstrating diabetes risk comparable to high-risk participants in the Diabetes Prevention Program 1:

• A systematic review of 44,203 individuals from 16 cohort studies (mean follow-up 5.6 years) showed those with A1c between 5.5–6.0% had substantially increased diabetes risk with 5-year incidence of 9–25% 1
• Those with A1c 6.0–6.5% had 5-year diabetes risk of 25–50% and a relative risk 20 times higher compared to A1c of 5.0% 1
• A1c was a stronger predictor of subsequent diabetes and cardiovascular events than fasting glucose in community-based studies of African American and non-Hispanic White adults 1

Important Clinical Considerations

Risk Stratification Within the Prediabetes Range

Risk is continuous and disproportionately greater at the higher end of the A1c range 1:

• Individuals with A1c above 6.0% should be considered at very high risk and warrant the most intensive interventions and particularly vigilant follow-up 1
• The curvilinear relationship means diabetes risk rises exponentially as A1c increases within the prediabetic range 1

Testing Methodology Caveats

A1c testing for prediabetes diagnosis should be performed by a clinical laboratory, not point-of-care testing, due to lack of standardization 1:

• A1c may be problematic in the presence of certain hemoglobinopathies or conditions affecting red blood cell turnover 1
• Anemia and some medications can interfere with A1c measurements 1
• For oral glucose tolerance testing, adequate carbohydrate intake (at least 150 g/day) should be assured for 3 days prior to testing 1

Screening Recommendations

Testing should begin at age 35 years for all adults, with earlier screening for those with risk factors 1:

• Adults with overweight/obesity (BMI ≥25 kg/m² or ≥23 kg/m² in Asian ancestry) plus one or more risk factors should be screened 1
• People with prediabetes should be tested yearly 1
• If results are normal, repeat testing at minimum 3-year intervals 1

Clinical Outcomes and Intervention Thresholds

Prediabetes defined by A1c 5.7–6.4% is associated with increased mortality and cardiovascular events (excess absolute risk of 7.36 per 10,000 person-years for mortality and 8.75 per 10,000 person-years for cardiovascular disease during 6.6 years) 2:

• Intensive lifestyle modification decreased diabetes incidence by 6.2 cases per 100 person-years during 3 years 2
• Metformin decreased diabetes risk by 3.2 cases per 100 person-years during 3 years, most effective for women with prior gestational diabetes and individuals younger than 60 years with BMI ≥35, fasting plasma glucose ≥110 mg/dL, or A1c ≥6.0% 2

International Variation

The World Health Organization and numerous other diabetes organizations define the impaired fasting glucose lower limit at 110 mg/dL (6.1 mmol/L) rather than 100 mg/dL, which may result in different populations being identified as having prediabetes 1