Lipidomics based on UHPLC/Q-TOF-MS to characterize lipid metabolic profiling in patients with newly diagnosed type 2 diabetes mellitus with dyslipidemia

Abstract

Dyslipidemia often accompanies type 2 diabetes mellitus (T2DM). Elevated blood glucose in patients commonly leads to high levels of lipids. Lipid molecules can play a crucial role in early detection, treatment, and prognosis of T2DM with dyslipidemia. Previous lipid studies on T2DM mainly focused on Western diabetic populations with elevated blood glucose. In this research, we investigate both high blood sugar and high lipid levels to better understand changes in plasma lipid metabolism in newly diagnosed Chinese T2DM patients with dyslipidemia (NDDD). We used a plasma lipid analysis method based on ultra-high performance liquid chromatography coupled with mass spectrometry technology (UHPLC-MS) and statistical analysis to characterize lipid profiles and identify potential biomarkers in NDDD patients compared to healthy control (HC) subjects. Additionally, we examined the differences in lipid profiles between hyperlipidemia (HL) patients and HC subjects. We found significant changes in 15 and 23 lipid molecules, including lysophosphatidylcholine (LysoPC), phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and ceramide (Cer), in the NDDD and HL groups compared to the HC group. These altered lipid molecules are associated with five metabolic pathways, with sphingolipid metabolism and glycerophospholipid metabolism being the most relevant to glucose and lipid metabolism changes. These lipid biomarkers are strongly correlated with traditional markers of glucose and lipid metabolism. Notably, Cer(d18:1/24:0), SM(d18:1/24:0), SM(d18:1/16:1), SM(d18:1/24:1), and SM(d18:2/24:1) were identified as essential potential biomarkers closely linked to clinical parameters through synthetic analysis of receiver operating characteristic curves, random forest analysis, and Pearson matrix correlation. These lipid biomarkers can enhance the risk prediction for the development of T2DM in individuals with dyslipidemia but no clinical signs of high blood sugar. Furthermore, they offer insights into the pathological mechanisms of T2DM with dyslipidemia.