Alterations in the serum lipid profile predict incident diabetes in obese individuals

Aim: This study used lipidomic analysis to investigate how lipids and related metabolites are associated with insulin sensitivity and type 2 diabetes mellitus (T2DM) in the context of obesity. Methods: A descriptive cross-sectional study recruited 73 obese participants, dividing them into three diagnostic categories: (1) obesity with metabolic health (n = 24, OB group), (2) obesity with impaired glucose tolerance (n = 24, IGT group), and (3) obesity-related diabetes (n = 25, OD group). In addition, lean, metabolically healthy individuals were included as normal controls (n = 23, NC group). Blood samples were collected and analyzed for untargeted lipidomics. Results: The OB, IGT and OD groups showed a notable rise in homeostasis model assessment (HOMA) of insulin resistance compared to the NC group (all P < 0.05). The OD group exhibited higher levels of fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol than the other three groups, with a significant decrease in steady state beta cell function (HOMA-β%). Saturated fatty acids were found at higher levels in the diacylglycerol (DG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and triacylglycerol (TG) classes in both IGT and OD groups. Significant increases in disrupted TG remodeling were observed from IGT to diabetes. Receiver operating characteristic analysis indicated that the lipid species LPC (16:0), ceramide (t33:7), and lysophosphatidylethanolamine (O-19:0) have strong diagnostic capabilities for T2DM. Conclusion: This lipidomic analysis in a Chinese cohort reveals distinct serum lipid alterations associated with insulin resistance and T2DM in obesity. Several lipid species, particularly LPC, DG, PC and TG, emerged as promising biomarkers for early detection of OD.