Insulin resistance and atrial fibrillation: from disease onset to post-ablation outcomes: a systematic review and meta-analysis

Objective: To systematically evaluate the impact of insulin resistance (IR) on the risk of new-onset atrial fibrillation (AF) and post-ablation recurrence, and to elucidate underlying mechanisms and translational implications for early identification and precision management of high-risk populations. Methods: A comprehensive meta-analysis was conducted by integrating 30 high-quality cohort studies from multiple countries, incorporating IR markers such as TyG index and HOMA-IR. Random-effects models were used to estimate the association between IR and both AF incidence and ablation recurrence. Subgroup analyses, sensitivity analyses, meta-regression, and GRADE quality assessment were performed to explore heterogeneity and robustness. Mechanistic pathways were systematically summarized. This study was registered in PROSPERO (CRD420251142441). Results: Pooled results demonstrated that IR significantly increased the risk of new-onset AF (HR = 1.34, 95%CI: 1.24-1.46) and post-ablation recurrence (HR = 1.57, 95%CI: 1.39-1.78), with consistent effects across subgroups by country, IR index, study type, and follow-up. Mechanistic evidence revealed that IR promotes AF development and recurrence via enhanced inflammation, oxidative stress, atrial structural remodeling, and electrical abnormalities. IR-related indices showed higher clinical utility for risk stratification in Chinese and Asian populations. Meta-regression and sensitivity analyses confirmed the robustness of these findings. The quality of evidence was rated as moderate. Conclusion: Insulin resistance is an independent risk factor for both new-onset and recurrent AF. IR-related indices have translational value for early risk identification and personalized management. Incorporating IR assessment into AF management and prevention strategies-integrating metabolic and electrophysiological perspectives-may optimize long-term outcomes and provide a foundation for precision medicine and tailored follow-up in AF care. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251142441, PROSPERO CRD420251142441.