Associations between prediabetes, type 2 diabetes, and incident arrhythmias: a population-based cohort study and Mendelian randomization analysis.
BACKGROUND Type 2 diabetes (T2D) is a known risk factor for arrhythmias, yet evidence for prediabetes is limited, and the two main diagnostic criteria (ADA, prioritizing sensitivity; WHO/IEC, prioritizing specificity) have not been directly compared across arrhythmia subtypes. METHODS In this prospective cohort study of 383,995 UK Biobank participants, glycemic status was defined by ADA and WHO/IEC criteria. Outcomes included atrial fibrillation, supraventricular tachycardia, bradyarrhythmia, and ventricular arrhythmia. Cox models were adjusted for clinical, lifestyle, and genetic confounders. Mendelian randomization (MR) was performed to infer causality. RESULTS Over a median 13.0 years, prediabetes and T2D were each associated with increased risks of all arrhythmias. Under ADA criteria, prediabetes hazard ratios ranged from 1.12 to 1.15; risks were higher for T2D and for progression from prediabetes to T2D. ECG changes included shortened RR and prolonged QTc intervals.MR analyses provided genetic evidence supporting a potential causal role of dysglycemia in arrhythmogenesis. CONCLUSIONS These findings highlight the differential prognostic utility of ADA and WHO/IEC criteria for arrhythmia risk stratification: the ADA criteria offer broader sensitivity for early detection, whereas the stricter WHO/IEC criteria identify a higher-risk subgroup warranting more intensive management.