Causal relationship between glycemic traits and inflammatory eye diseases and their complications, and myopia: a Mendelian randomization analysis

Current evidence on glycemic traits' causal links to inflammatory eye diseases, complications, and myopia remains limited and inconsistent, particularly regarding glucose regulation. This study evaluates specific indicators to address these knowledge gaps. A two-sample Mendelian randomization framework from a genome-wide association study was used. Causal estimates were obtained using inverse variance weighting (IVW), MR-Egger, weighted median, simple model and weighted model methods. Cochran Q test, MR-Egger regression, MR-PRESSO and leave-one-out analysis were used to assess heterogeneity and pleiotropy. Higher proinsulin levels correlated with glaucoma and POAG risks (OR = 1.263, 95%CI = 1.020-1.563, P = 0.032; OR = 1.409, 95%CI = 1.075-1.846, P = 0.01). Higher BMI and fasting insulin were cataract risk factors (OR = 1.261, 95%CI = 1.135-1.401, P < 0.001; OR = 1.645, 95%CI = 1.100-2.460, P = 0.015); BMI is a risk factor for keratitis (OR = 1.463, 95%CI = 1.071-1.997, P = 0.017). Adiponectin protected against chronic conjunctivitis (OR = 0.464, 95%CI = 0.265-0.811, P = 0.007), HbA1c against retinal vein occlusion (OR = 0.266, 95%CI = 0.105-0.675, P = 0.005). High adiponectin reduced myopia (OR = 0.99, 95% CI = 0.984-0.997, P = 0.003), while high HbA1c increased it (OR = 1.018, 95% CI = 1.008-1.027, P < 0.001). Glycemic profiles increase the risk for inflammatory eye diseases and complications including keratitis, glaucoma, and cataracts but protect against chronic conjunctivitis and retinal vein occlusion. Low adiponectin and high HbA1c raise myopia risk. Targeting modifiable factors (physical activity/sugar intake) suggests novel myopia prevention strategies.