Prediabetes and the risk of atrial fibrillation: systematic review, meta-analysis, and dose–response meta-analysis

BACKGROUND: Diabetes mellitus is an established risk factor for atrial fibrillation (AF), but the relationship between prediabetes and incident AF remains incompletely characterized. We conducted a systematic review and dose-response meta-analysis to evaluate the association between prediabetes and AF risk in adults and to quantify the risk gradient across the glycemic spectrum. METHODS: We systematically searched PubMed/MEDLINE, Embase, Scopus, and Web of Science for observational studies published between January 2010 and December 2025. Eligible studies compared incident or prevalent AF outcomes between adults with prediabetes and normoglycemic controls. Two independent reviewers performed study selection, data extraction, and risk of bias assessment using the ROBINS-E and QUAPAS tool. Random-effects meta-analyses pooled hazard ratios (HRs) with 95% confidence intervals (CIs), with subgroup analyses stratified by prediabetes definition and geographic region. Dose-response analyses examined the relationship across glycemic categories. RESULTS: From 1,776 identified records, 15 cohort studies encompassing approximately 26.4 million participants met inclusion criteria. Prediabetes was associated with a 15% increased risk of AF compared to normoglycemia (pooled HR 1.15, 95% CI 1.04-1.27, I2=99.3%). The association was significant in East Asian (HR 1.22, 95% CI 1.05-1.42) but not European populations (HR 1.08, 95% CI 0.97-1.20), and was consistent across prediabetes definitions, sexes, age groups, and publication era. FPG dose-response analysis demonstrated approximately 0.4% increase in AF risk per mg/dL. Egger's test was non-significant (p=0.454), though trim-and-fill analysis adjusted the estimate upward to HR 1.36 (95% CI 1.20-1.53). CONCLUSIONS: Prediabetes is associated with a modest but statistically significant increase in AF risk, with evidence of a dose-dependent relationship across the glycemic spectrum. These findings suggest that dysglycemia may contribute to AF pathogenesis before the clinical threshold for diabetes is reached. Further research is needed to determine whether glycemic interventions in prediabetes can reduce AF incidence and to elucidate the mechanistic pathways linking intermediate hyperglycemia to atrial arrhythmogenesis.