Mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease: a prospective cohort study.

Objective: This study explored the mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD).

Methods: In this prospective community cohort study, 82 975 participants were enrolled, with the primary outcome being the incidence of new-onset ASCVD. Using the Cox proportional hazards model, the hazard ratio (HR) and 95% confidence interval (CI) for ASCVD occurrence were computed between NAFLD and non-NAFLD groups. The correlation between NAFLD and diabetes was assessed using a binary logistic regression model, and that between NAFLD, diabetes and ASCVD using a mediation model.

Results: During follow-up, 9471 ASCVD cases were observed. Compared with individuals without NAFLD, those with NAFLD showed an increased ASCVD risk (HR: 1.424; 95% CI: 1.363-1.488; P < 0.001). Stratifying NAFLD based on metabolic subphenotypes revealed a higher ASCVD risk in the NAFLD combined with diabetes subgroup than in the non-NAFLD subgroup (HR: 1.960; 95% CI: 1.817-2.115; P < 0.001). NAFLD was positively associated with baseline diabetes (odds ratio: 2.983; 95% CI: 2.813-3.163; P < 0.001). Furthermore, NAFLD severity was positively correlated with diabetes risk. Mediation analysis indicated that diabetes partially mediated the effect of NAFLD on ASCVD incidence, accounting for 20.33% of the total effect.

Conclusion: NAFLD is an independent predictor of increased ASCVD risk, which may be slightly mediated by diabetes in patients with NAFLD. Evaluating NAFLD and diabetes may be crucial in the early screening and prevention of ASCVD.