Plasma Lipids Associated with Endothelial Dysfunction in Patients with Type 2 Diabetes: A Cross-Sectional Study Using Lipidomic Analysis

Abstract

Patients with diabetes often develop abnormalities in lipid metabolism that can promote diabetic complications. Lipidomic studies have demonstrated that certain plasma lipid species are associated with the development of cardiovascular diseases. However, the plasma lipids associated with endothelial dysfunction remain unclear. To identify the lipids associated with flow-mediated vasodilation (FMD), an indicator of endothelial function, in patients with diabetes, we performed a cross-sectional analysis as a subanalysis of a previous lipidomic study. In total, 200 patients with type 2 diabetes were included in the analysis. A total of 55.0% were men, and the mean age (±standard deviation) was 61.1 ± 11.3 years. Their HbA1c and FMD values were 9.04 ± 1.79% (75.3 ± 19.5 mmol/mol) and 5.77 ± 2.55%, respectively. Supercritical fluid chromatography/mass spectrometry-based semi-targeted lipidomic analysis identified 349 lipids belonging to 16 lipid classes. We selected 13 distinctive lipids potentially associated with FMD, according to a sparse-group least absolute shrinkage and selection operator regularized regression model. Of these, seven phospholipids, including three phosphatidylethanolamine (PE) plasmalogens and three phosphatidylinositols (PIs), showed a positive association with FMD after adjusting for atherosclerotic risk factors. These findings may contribute to improving the assessment and management of endothelial dysfunction in patients with diabetes.