Abstract
This study aimed to investigate the relationship between age at diabetes diagnosis (ADD) and the development and progression of diabetic retinopathy (DR). This study combined analysis of the National Health and Nutrition Examination Survey (NHANES) data with Mendelian randomization (MR). We employed regression models, propensity score matching, generalized additive model smoothing splines (GAM), random forest algorithms, and other analytical techniques. Cross-sectional analysis of NHANES data (n = 877) showed that the DR group had a significantly younger ADD compared to the DR-free group (P < 0.001). Regression analysis revealed a significant inverse association between ADD and DR prevalence (OR = 0.96, P < 0.001). MR analysis further supported this inverse relationship (OR = 0.42, P = 0.003). Two non-linear analytical approaches identified peak DR occurrence probability at ages 24.45 (GAM) and 24.2 (Shapley additive explanations dependence plots). Additionally, younger ADD was associated with increased DR severity across all categories (P < 0.05). In conclusion, older ADD was associated with a protective effect against the development and progression of DR, as supported by both analysis of NHANES data and MR. These findings underscore the importance of increased vigilance and more frequent screening for DR in patients diagnosed with diabetes at a young age.