Abstract Body (Do not enter title and authors here): Background
Prediabetes, an intermediate metabolic state preceding diabetes, independently accelerates cardiovascular pathology through dysglycemia-driven mechanisms. This study evaluates its heterogeneous risk stratification by diagnostic criteria (ADA vs. WHO/IEC) and causal cardiovascular consequences.
Methods
In 278,697 UK Biobank participants without baseline cardiovascular disease, prediabetes was classified by ADA (fasting glucose 5.6–6.9 mmol/L/HbA1c 5.7–6.4%) and WHO/IEC (fasting glucose 6.1–6.9 mmol/L/HbA1c 6.0–6.4%) criteria. Associations with incident CVD, mortality, and cardiac remodeling (via cardiac magnetic resonance, CMR) were assessed. Mendelian randomization (MR) tested causality of prediabetes on outcomes.
Results
Over 13.5 years, prediabetes—irrespective of criteria—elevated CVD risk (ADA: HR=1.14, 95%CI:1.12–1.16; WHO/IEC: HR=1.23, 1.19–1.27), with stronger mortality associations in WHO/IEC-defined individuals. MR analyses confirmed that prediabetes was causally associated with increased 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) risks. CMR revealed early concentric left ventricular remodeling in prediabetes (mass-to-volume ratio: β=1.95%), accentuated in stricter diagnostic groups. Risks persisted across genetic susceptibility strata, underscoring dysglycemia’s universal impact.
Conclusion
Early identification of prediabetes—a critical metabolic threshold—is vital to intercept disease progression before irreversible complications develop.