Abstract
Background
Type 2 diabetes mellitus (T2DM) involves alterations in lipid metabolism beyond conventional cholesterol profiles. We examined whether specific plasma lipidomic signatures are related to pericoronary adipose tissue (PCAT) inflammation and coronary artery disease (CAD) burden.
Methods
This cross-sectional analysis included 176 T2DM participants from the GADA study. PCAT inflammation was measured by the fat attenuation index (FAI), CAD burden by Gensini/SYNTAX scores and plasma lipid species by targeted LC-MS. Multivariable regression were used to identify lipid species associated with FAI and CAD burden. For lipid species linked to both, mediation analyses were performed.
Results
We quantified 660 lipid molecular species across 20 classes. Five species were associated with FAI: sphingomyelin (SM) (34:4), phosphatidylcholines (PC) (16:0/20:4), Lysophosphatidylethanolamine (LPE) (18:1), LPE (20:4), and LPE (18:2). The three LPE species remained independently associated with both Gensini and SYNTAX scores after adjustment for clinical risk factors, conventional lipid measures, triglycerides, and hsCRP. Mediation analyses indicated that FAI accounted for part of the associations between these LPE species and CAD burden.
Conclusions
In T2DM patients, circulating LPE (18:1), LPE (20:4), and LPE (18:2) were associated with both PCAT inflammation and CAD burden. These findings point to altered LPE metabolism as a lipid-inflammatory signature linked to residual atherosclerotic burden beyond conventional lipid and glycemic measures.