Coffee Consumption and Risk of Diabetic Angiopathy: Mediating Role of Gut Microbiota Revealed by Mendelian...

Diabetic angiopathy (DA) is a severe complication of diabetes mellitus, contributing significantly to morbidity and mortality. Although traditional mechanisms emphasize hyperglycemia-induced oxidative stress and inflammation, emerging evidence highlights the role of gut microbiota in diabetes and its complications. Coffee consumption, rich in bioactive compounds, has been linked to metabolic health, but its relationship with DA remains unclear due to confounding factors. This study employed Mendelian randomization (MR) to investigate the causal effects of coffee consumption on DA and the mediating role of gut microbiota. Using genetic variants as instrumental variables, we analyzed summary data from large genome-wide association studies on coffee consumption, gut microbiota, and DA. Results indicated a causal association between higher coffee consumption and increased DA risk, with specific gut microbial Lawsonibacter sp002161175 partially mediating this relationship. Multivariable MR (MVMR) and Bayesian weighted MR (BWMR) supported the robustness of these findings. This study provides genetic evidence for a causal link between coffee intake and DA and suggests a potential mediating role of gut microbiota, offering insights for preventive strategies against diabetic vascular complications.