Prediabetes definitions vary between major international organizations, creating uncertainty regarding clinical risk assessment. A recent prospective cohort analysis and Mendelian randomization study presented at EuroPCR 2026 evaluated how these differing diagnostic criteria impact the stratification of cardiovascular disease risk.
The analysis included 452,302 adults without baseline cardiovascular disease (CVD). Prediabetes was categorized using ADA criteria, defined as fasting glucose 5.6-6.9 mmol/L or hemoglobin A1c (HbA1c) 5.7%-6.4%, and WHO/IEC criteria, defined as fasting glucose 6.1-6.9 mmol/L or HbA1c 6.0%-6.4%. Cox proportional hazards models assessed associations with incident CVD, coronary heart disease (CHD), myocardial infarction (MI), stroke, and hypertension.
Findings
- ADA-defined prediabetes was associated with increased CVD risk (HR 1.12, 95% CI 1.05-1.20).
- WHO/IEC-defined prediabetes showed a stronger association with higher CVD risk (HR 1.31, 95% CI 1.22-1.41).
- HbA1c-based prediabetes definitions contributed more strongly to cardiovascular risk associations than fasting glucose-based definitions under both criteria.
- Mendelian randomization analyses supported a relationship between genetically predicted dysglycemia and CVD (OR 1.18, 95% CI 1.10-1.27).
The findings suggest that prediabetes definitions are not interchangeable for cardiovascular risk stratification. Stricter WHO/IEC criteria identified a smaller subgroup with higher CVD risk, while genetic analyses supported an association between dysglycemia and adverse cardiovascular outcomes.
