Serum Nɛ-Carboxymethyllysine as a Biomarker of Severity of Diabetic Retinopathy: A Cross-Sectional Study

Abstract

Background: Chronic hyperglycaemia accelerates the non-enzymatic glycation of proteins, generating advanced glycation end-products (AGEs) such as Nε-carboxymethyllysine (CML), which have been implicated in the microvascular pathology of diabetic retinopathy (DR). Aim: To evaluate and compare serum CML levels across the spectrum of severity of DR and to correlate CML with glycaemic and clinical parameters. Methods: This cross-sectional comparative study was conducted at a tertiary care hospital in Northern India. Two hundred age- and sex-matched subjects were divided into four equal groups (n = 50 each): proliferative DR (PDR), non-proliferative DR (NPDR), diabetes mellitus without DR, and healthy controls. Serum CML was estimated by enzyme-linked immunosorbent assay and compared using one-way ANOVA with post-hoc pairwise testing; associations with clinical and biochemical parameters were assessed using Spearman's correlation. Results: Serum CML rose progressively across the study groups (Control 433.31 ± 73.04, DM without DR 640.81 ± 78.48, NPDR 765.39 ± 69.49, PDR 861.72 ± 75.98 ng/mL; F = 309.617, p < 0.001), with every pairwise comparison reaching significance (p < 0.001). CML correlated strongly with HbA1c (r = 0.608–0.771) and fasting blood sugar (r = 0.538–0.636) across diabetic subgroups, and with diabetes duration in PDR (r = 0.359, p = 0.010). Conclusion: Serum CML increases in a stepwise fashion with worsening severity of DR and correlates strongly with glycaemic burden, supporting its candidacy as a biochemical adjunct for risk-stratifying diabetic patients for retinopathy.