Abstract
PURPOSE: To elucidate the relationship between diabetic retinopathy (DR) and frailty and investigate genetic correlations and causality. METHODS: We analyzed data from the US National Health and Nutrition Examination Survey, which included 1003 individuals with diabetes. DR was evaluated via nonmydriatic retinal imaging, and frailty was measured using a 49-item frailty index. The association between DR and frailty was assessed using survey-weighted logistics regression adjusted for multiple covariates, including age, sex, race, education level, family income-to-poverty ratio, marital status, and Healthy Eating Index. Genetic correlations and causal relationships were investigated through linkage disequilibrium score regression and bidirectional Mendelian randomization. RESULTS: DR was significantly associated with higher odds of frailty after full adjustment (odd ratio [OR] = 4.25; 95% confidence interval [CI], 1.08-16.67; P = 0.040). The association was robust and did not significantly differ across age (P interaction = 0.080), sex (P interaction = 0.216), or race (P interaction = 0.749) groups. DR exhibited a moderate but significant genetic correlation with frailty (rg = 0.27, standard error = 0.04; P = 2.43 × 10-10). Genetically inferred DR was significantly associated with a greater frailty index (β = 0.03; 95% CI, 0.01-0.05; P < 0.001), whereas frailty was not associated with DR risk (OR = 1.20; 95% CI, 0.80-1.81; P = 0.376). CONCLUSIONS: Our findings suggest that DR is associated with an increased risk of frailty, indicating that DR not only impairs vision but also accelerates physical decline. TRANSLATIONAL RELEVANCE: This study highlights the critical need for integrated care approaches that incorporate frailty screening and proactive management in individuals with DR to prevent further health deterioration and improve both quality of life and long-term outcomes.