Lipidomics Analysis of Impaired Glucose Tolerance and Type 2 Diabetes Mellitus in Overweight or Obese Elderly Adults

Abstract Background Aging, obesity, and type 2 diabetes mellitus (T2DM) form a metabolic disease continuum that has a continuously increasing prevalence. Lipidomics explains the complex interactions between lipid metabolism and metabolic diseases. We aimed to systematically investigate the plasma lipidome changes induced by impaired glucose tolerance (IGT) and T2DM in overweight/obese elderly individuals and to identify potential biomarkers to differentiate between the IGT, T2DM, and control groups. Methods In this cross-sectional study, plasma samples from 148 overweight/obese elderly individuals, including 52 patients with IGT, 47 patients with T2DM, and 49 euglycemic controls, were analyzed using a high-coverage non-targeted absolute quantitative lipidomics approach. Results We quantified 1,840 lipids from thirty-eight classes and seven lipid categories. Among overweight/obese elderly individuals, the lipidomic profiles of IGT and T2DM patients were significantly different from those of controls, while they were similar in the IGT and T2DM groups. The concentrations of diglycerides, triglycerides, phosphatidylcholines, and ceramides were altered in the IGT and T2DM groups. IGT and T2DM induced the accumulation of triglycerides with longer chain lengths and phosphatidylcholines with longer even-chains and regulated the saturation of triglyceride- and phosphatidylcholine-associated fatty acids. Finally, 17 lipids that could be used to differentiate between the IGT, T2DM, and control groups were successfully identified. Conclusion Lipidomics revealed apparent lipidome-wide changes in overweight/obese elderly patients with IGT and T2DM. This study’s results help to explain the complex dysfunctional lipid metabolism in aging, obesity, and diabetes.