Diagnostic Criteria for Prediabetes
Prediabetes is diagnosed when any one of three tests meets specific thresholds: A1C 5.7–6.4%, fasting plasma glucose 100–125 mg/dL, or 2-hour glucose during a 75-gram oral glucose tolerance test 140–199 mg/dL. 1
Three Equally Valid Diagnostic Tests
Any single abnormal test result is sufficient to diagnose prediabetes—you do not need multiple tests or confirmation unless results are borderline: 1
- A1C 5.7–6.4% (39–47 mmol/mol), measured in an NGSP-certified laboratory standardized to the DCCT assay 1
- Fasting plasma glucose 100–125 mg/dL (5.6–6.9 mmol/L), termed Impaired Fasting Glucose (IFG), after at least 8 hours of no caloric intake 1
- 2-hour plasma glucose 140–199 mg/dL (7.8–11.0 mmol/L), termed Impaired Glucose Tolerance (IGT), during a 75-gram oral glucose tolerance test 1
Important caveat: The World Health Organization uses a higher threshold of 110 mg/dL (6.1 mmol/L) for IFG rather than 100 mg/dL, reflecting ongoing international debate about optimal cutpoints. 1
Test Selection and Practical Considerations
A1C offers the most practical screening approach because it requires no fasting and has superior preanalytical stability compared to glucose measurements, which degrade rapidly if samples are not processed immediately or kept on ice. 1
Fasting glucose has significant limitations:
- Day-to-day variability of 12–15%, meaning the same person could measure 99 mg/dL one day and 110 mg/dL the next without any true metabolic change 2, 3
- Requires strict 8-hour fast, which patients may misreport 1
- Affected by recent physical activity, illness, or acute stress 1
The oral glucose tolerance test is most sensitive but cumbersome and less reproducible, making it impractical for routine screening despite detecting more cases than fasting glucose or A1C alone. 3, 4
Critical Pre-Test Requirements for OGTT
If performing an OGTT, patients must consume at least 150 grams of carbohydrates daily for the 3 days preceding the test—fasting and carbohydrate restriction will falsely elevate glucose levels. 1
When A1C Cannot Be Used
Use only plasma glucose criteria (fasting glucose or OGTT) in these conditions where A1C is unreliable: 1
- Pregnancy (second and third trimesters and postpartum period)
- Hemoglobin variants (sickle cell disease, sickle cell trait)
- Glucose-6-phosphate dehydrogenase deficiency
- Hemodialysis
- Recent blood loss or transfusion
- Erythropoietin therapy
- Any condition with altered red blood cell turnover
The X-linked glucose-6-phosphate dehydrogenase G202A variant, carried by 11% of African Americans, decreases A1C by approximately 0.8% in homozygous men and 0.7% in homozygous women compared to those without the variant. 1
Understanding the Tests Identify Different Populations
These three tests have imperfect concordance—they identify overlapping but distinct groups of at-risk individuals. 2, 3 In one cohort of young African Americans with prediabetes, fasting glucose alone detected only 27% of cases, while a complete OGTT detected 87%. 4 The 2-hour OGTT diagnoses more people with prediabetes than fasting glucose or A1C cutoffs. 3
The clinical implication: A person with A1C 5.5% and fasting glucose 98 mg/dL may still have IGT on OGTT, representing genuine metabolic dysfunction that the other tests miss. 4
Who Should Be Screened
Screen all adults starting at age 45 years, or earlier if overweight/obese (BMI ≥25 kg/m² or ≥23 kg/m² in Asian Americans) with any of these risk factors: 1
- First-degree relative with diabetes 1
- High-risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander) 1
- History of cardiovascular disease 1
- Hypertension (≥140/90 mmHg or on antihypertensive therapy) 1
- HDL cholesterol <35 mg/dL and/or triglycerides >250 mg/dL 1
- Polycystic ovary syndrome 1
- Physical inactivity 1
- Conditions associated with insulin resistance (severe obesity, acanthosis nigricans) 1
- Women with prior gestational diabetes 1
Follow-Up Testing Intervals
Once prediabetes is identified, retest annually. 1 The progression rate is approximately 10% per year from prediabetes to diabetes, with risk increasing disproportionately at the higher end of the prediabetes range. 5
If screening is normal, repeat at minimum every 3 years, with consideration for more frequent testing based on initial results and evolving risk factors. 1
Clinical Significance and Next Steps
Prediabetes is not merely a laboratory finding—it represents a high-risk state for progression to diabetes and cardiovascular disease, with excess absolute risk of 7.36 per 10,000 person-years for mortality and 8.75 per 10,000 person-years for cardiovascular events during 6.6 years of follow-up. 5
When prediabetes is diagnosed, identify and treat other cardiovascular risk factors including hypertension, dyslipidemia, and obesity. 1 Intensive lifestyle modification (calorie restriction, ≥150 minutes/week physical activity, self-monitoring, motivational support) decreases diabetes incidence by 6.2 cases per 100 person-years over 3 years. 5
Critical evidence gap: Most intervention trials demonstrating benefit enrolled individuals with IGT (abnormal OGTT), not isolated IFG or A1C-defined prediabetes, so the effectiveness of interventions in these latter groups remains less certain. 2, 6