Prediabetes represents an intermediate metabolic state preceding diabetes and has been implicated in early cardiovascular alterations driven by dysglycemia. A large cohort analysis published in Cardiovascular Diabetology evaluated cardiovascular risk associated with prediabetes using definitions from the American Diabetes Association (ADA) and the World Health Organization/International Expert Committee (WHO/IEC), and further assessed potential causal relationships between prediabetes and cardiovascular outcomes.
After excluding individuals with baseline cardiovascular disease, 278,697 participants with complete glycemic and clinical data were categorized as normoglycemia, prediabetes, or type 2 diabetes mellitus. Prediabetes was defined according to ADA criteria (fasting plasma glucose 5.6-6.9 mmol/L and/or glycated hemoglobin A1c 5.7-6.4%) and WHO/IEC criteria (fasting plasma glucose 6.1-6.9 mmol/L and/or HbA1c 6.0-6.4%). Multivariable-adjusted models evaluated associations with incident cardiovascular disease (CVD), mortality, and cardiac remodeling assessed by cardiac magnetic resonance (CMR), and Mendelian randomization (MR) analyses were conducted to explore causal relationships.
During 13.5 years of follow-up, prediabetes defined by either diagnostic framework corresponded to increased CVD risk (ADA: HR 1.14; 95% CI 1.12-1.16; WHO/IEC: HR 1.23; 95% CI 1.19-1.27), with stronger mortality associations observed among individuals meeting WHO/IEC criteria. MR analyses supported associations between prediabetes and CVD (OR 1.01; 95% CI 1.01-1.02), coronary heart disease (OR 1.09; 95% CI 1.02-1.17), myocardial infarction (OR 1.12; 95% CI 1.06-1.19), stroke (OR 1.06; 95% CI 1.02-1.10), and primary hypertension (OR 1.01; 95% CI 1.01-1.02). In an exploratory CMR substudy involving 2,512 participants, findings suggested early concentric left ventricular remodeling, particularly among individuals classified using WHO/IEC criteria.
These observations indicate that ADA and WHO/IEC definitions may differ in their prognostic utility for cardiovascular risk stratification in prediabetes.
