Shigero Hosoe

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.

Abnormalities in plasma lipoproteins observed in patients with diabetes promote atherosclerosis. However, the association between various lipid species and classes and atherosclerosis remains unclear. Here, we aimed to identify the plasma lipid characteristics associated with atherosclerosis progression in patients with diabetes. We performed semi-targeted lipidomic analysis of fasting plasma samples using supercritical fluid chromatography coupled with mass spectrometry in two independent patient groups with type 2 diabetes (n = 223 and 31) and evaluated cross-sectional associations between plasma lipids and carotid intima-media thickness (CIMT). Ten plasma lipid species, including eight diacylglycerols (DGs), and total DG levels were significantly associated with CIMT in both groups. Patients of the former group were partly observed for 5 years, and we investigated associations between DGs and CIMT progression in these patients (n = 101). As a result, 22 DGs among the 26 identified DGs and total DG (β = 0.398, p < 0.001) were significantly associated with the annual change in CIMT. Furthermore, plasma DG levels improved the predictive ability for CIMT progression, with an adjusted R-squared increase of 0.105 [95% confidence interval: 0.010, 0.232] in the models. Plasma DGs are associated with CIMT progression in patients with type 2 diabetes. Measurement of total plasma DG levels may be beneficial in assessing the risk of atherosclerosis progression.