| Title: | Insulin sensitivity, genetic predisposition, and risk of atrial fibrillation: a prospective cohort study |
| Journal: | Heart Rhythm |
| Published: | 10 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41077371/ |
| DOI: | https://doi.org/10.1016/j.hrthm.2025.10.015 |
Publication 19214
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Abstract
BACKGROUND: The estimated glucose disposal rate (eGDR) is a validated clinical metric of insulin sensitivity that may predict cardiovascular health; however, the combined and interaction relationship between eGDR and genetic predisposition in determining atrial fibrillation (AF) risk remains unclear.</p>
OBJECTIVE: This study aimed to investigate the longitudinal relationship between eGDR and incident AF risk and assess the combined and interaction effect of eGDR and genetic predisposition on AF development.</p>
METHODS: In the UK Biobank, eGDR was calculated using waist circumference, hypertension status, and glycated hemoglobin levels. Genetic predisposition was assessed via a polygenic risk score (PRS) for AF. Associations were examined using Kaplan-Meier curves, restricted cubic spline models, and Cox regression.</p>
RESULTS: Among 431,572 participants with a median follow-up of 13.53 years, 29,464 AF cases were identified. Higher eGDR quartiles demonstrated significantly lower AF incidence (log-rank P < .001), with L-shaped nonlinear association (P nonlinear < .001). Each unit increase in eGDR was associated with a 9% reduction in AF risk (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.91-0.92; P < .001), with stepwise risk reduction across quartiles (Q4 vs Q1: HR 0.67; 95% CI 0.63-0.70; P < 0.001). Participants with low PRS and high eGDR exhibited 74% lower AF risk (HR 0.26; 95% CI 0.23-0.28; P < .001) than those with high PRS and low eGDR, indicating improved insulin sensitivity confers protection across all genetic risk categories.</p>
CONCLUSION: eGDR demonstrates dose-dependent protective effects against AF across all genetic risk categories, highlighting insulin resistance as a potential intervention target for AF prevention.</p>
8 Authors
- Yutong Wang
- Yanwen Chen
- Xinyang Song
- Tao Xu
- Chenxi Xia
- Junsong Gong
- Sixian Weng
- Fang Wang
1 Application
| Application ID | Title |
|---|---|
| 144894 | Cardiovascular metabolic characteristics of regular exercisers and the effect of exercise on Atrial Fibrillation!A cohort study |
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