Non-linear association between serum lipid levels and diabetic retinopathy in a nationally representative Korean population

• U-shaped associations were observed between total, LDL, and non-HDL cholesterol and diabetic retinopathy. • Elevated risk was evident at very low lipid levels with additional uncertainty at higher levels. • Balanced lipid levels may be more protective than aggressive lowering alone in diabetes care. • Large, representative data highlights the role of lipid metabolism in retinal microvascular health. To investigate the associations between serum lipid levels and diabetic retinopathy (DR) in Korean adults with diabetes. Cross-sectional analysis of a nationally representative survey. We analyzed 1,378 adults with diabetes from the Korea National Health and Nutrition Examination Survey (2008–2011). DR was ascertained from fundus photographs and medical history. Lipids (total cholesterol, HDL, LDL, triglycerides, non-HDL) were modeled by quintiles and with restricted cubic splines. Multivariable logistic regression adjusted for age, sex, systolic blood pressure, hemoglobin A1c, and statin use. Sensitivity analyses used multiple imputation. DR was present in 301/1,378 participants (21.8%). Adjusted models showed no linear trends for cholesterol measures. In quintile analyses, total cholesterol exhibited higher odds of DR at both extremes versus the middle quintile (Q3): Q1 OR 1.63 (95% CI, 1.04–2.57); Q4 OR 1.64 (1.06–2.57); Q5 OR 1.59 (1.03–2.49); P for U-shape = 0.008 (Q2 OR 1.42 [0.90–2.23]). LDL and non-HDL also demonstrated U-shaped patterns (P for U-shape = 0.029 and 0.038). Spline models supported U-shaped association for total cholesterol (P = 0.031), LDL (P = 0.039), and non-HDL (P = 0.014). No consistent nonlinear associations were observed for HDL or triglycerides. Multiple-imputation results were concordant, reinforcing the U-shape for total cholesterol. Total cholesterol, LDL, and non-HDL showed U-shaped nonlinear associations with DR, indicating elevated risk at both low and high concentrations. Maintaining lipids within an intermediate range may support retinal vascular health and refine metabolic risk stratification in diabetes.