Clinical Serum Lipidomic Profiling Reveals Potential Lipid Biomarkers for Early Diabetic Retinopathy

Abstract

Diabetic Retinopathy (DR) is a major micro vascular complication of Diabetes Mellitus and a leading cause of preventable vision loss. Recent evidence suggests that disturbances in lipid metabolism occur before visible retinal damage develops. Lipidomic analysis enables comprehensive profiling of circulating lipid molecules and may assist in identifying novel indicators for early DR detection.

Objective: To analyze serum lipid variations associated with early diabetic retinopathy and explore their potential role as biomarkers for its early diagnosis.

Methods: A cross-sectional study was carried out on 60 type 2 diabetes mellitus (T2DM) patients—30 with early non-proliferative diabetic retinopathy (NPDR) and 30 without any retinal abnormalities. Serum lipidomics was performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Statistical and multivariate analyses were applied to identify significantly altered lipid species between the two groups.

Results: Distinct lipidomic alterations were identified in patients with early DR. Levels of lysophospha- tidyl cholines (LPCs), sphingomyelins (SMs), and ceramides (Cers) were significantly higher, while phosphatidylcholines (PCs) and certain triglycerides were reduced. Lipid species such as LPC (17:0), Cer(d17:1/24:0), and SM(d17:1/15:0) showed strong correlations with HbA1c and DR severity (p < 0.01). Combined ROC analysis of Cer(d17:1/24:0) and LPC(17:0) produced an AUC of 0.88, indicating excellent diagnostic accuracy.

Conclusion: Serum lipidomic analysis highlights early metabolic disruptions in DR. Elevated ceramide and lysophosphatidylcholine species may serve as promising biomarkers for the early identification of retinal microvascular injury. Incorporating lipidomic markers into diabetic screening could enhance early detection and risk assessment strategies.