Circulating lysophosphatidylethanolamine species are associated with pericoronary adipose tissue inflammation and coronary atherosclerotic burden in type 2 diabetes.
Dai D, Chen S, et al. • Diabetes & vascular disease research • 2026
Circulating LPE (18:1), LPE (20:4), and LPE (18:2) were associated with both pericoronary adipose tissue inflammation and coronary atherosclerotic burden in T2DM patients, pointing to altered LPE metabolism as a lipid-inflammatory signature linked to residual atherosclerotic burden beyond conventional lipid and glycemic measures.
Key Findings
Methods
A targeted lipidomic analysis quantified 660 lipid molecular species across 20 classes in plasma from T2DM participants.
176 T2DM participants were included from the GADA study in this cross-sectional analysis.
Plasma lipid species were measured by targeted LC-MS (liquid chromatography-mass spectrometry).
20 lipid classes were represented among the 660 quantified molecular species.
PCAT inflammation was measured by the fat attenuation index (FAI) derived from coronary CT imaging.
CAD burden was assessed using Gensini and SYNTAX scores.
Results
Five lipid species were independently associated with pericoronary adipose tissue (PCAT) inflammation as measured by fat attenuation index (FAI).
The five species associated with FAI were: SM (34:4), PC (16:0/20:4), LPE (18:1), LPE (20:4), and LPE (18:2).
Associations were identified using multivariable regression analyses.
Three of the five species belonged to the lysophosphatidylethanolamine (LPE) class.
Sphingomyelin (SM) (34:4) and phosphatidylcholine (PC) (16:0/20:4) were also among the FAI-associated species.
Results
Three LPE species — LPE (18:1), LPE (20:4), and LPE (18:2) — remained independently associated with both Gensini and SYNTAX scores after multivariable adjustment.
Associations with CAD burden persisted after adjustment for clinical risk factors, conventional lipid measures, triglycerides, and hsCRP.
Both Gensini score (a measure of coronary lesion severity) and SYNTAX score (a measure of coronary complexity) were independently predicted by these LPE species.
The three LPE species were among the five initially associated with FAI, indicating overlap between PCAT inflammation-associated and CAD burden-associated lipids.
SM (34:4) and PC (16:0/20:4) were associated with FAI but were not reported as independently associated with both CAD burden scores.
Results
Mediation analyses indicated that PCAT inflammation (FAI) accounted for part of the associations between LPE species and coronary atherosclerotic burden.
Mediation analyses were performed for lipid species linked to both FAI and CAD burden scores.
FAI served as a partial mediator in the relationship between circulating LPE species and CAD burden.
This suggests a pathway whereby LPE species may promote coronary atherosclerosis partly through pericoronary adipose tissue inflammation.
The mediation was described as partial, implying additional direct or alternative pathways also exist.
Conclusions
Altered LPE metabolism represents a lipid-inflammatory signature linked to residual atherosclerotic burden beyond conventional lipid and glycemic measures in T2DM.
The associations of LPE species with CAD burden were independent of conventional lipid measures (including triglycerides) and hsCRP.
The findings suggest LPE species capture atherosclerotic risk not reflected by standard clinical lipid panels.
The authors describe this as 'residual atherosclerotic burden beyond conventional lipid and glycemic measures.'
T2DM involves alterations in lipid metabolism beyond conventional cholesterol profiles, motivating the lipidomic approach.
What This Means
This research suggests that specific fat molecules in the blood called lysophosphatidylethanolamines (LPEs) are linked to both inflammation in the fat tissue surrounding the heart's arteries and the overall severity of coronary artery disease in people with type 2 diabetes. The study analyzed blood samples from 176 people with type 2 diabetes, measuring 660 different lipid (fat) molecules and comparing them to CT scan measurements of heart artery disease and surrounding fat tissue inflammation. Three specific LPE molecules — LPE (18:1), LPE (20:4), and LPE (18:2) — stood out as being independently associated with worse coronary artery disease, even after accounting for standard cholesterol levels, blood sugar control, and inflammation markers that doctors typically measure.
The study also found that inflammation in the fat tissue directly surrounding the coronary arteries (called pericoronary adipose tissue) partially explained the link between these LPE molecules and coronary artery disease severity. This suggests a possible biological chain: elevated LPE levels may contribute to local fat tissue inflammation around the arteries, which in turn promotes the buildup of plaque in those arteries. Importantly, these associations existed beyond what standard clinical tests can detect, pointing to a 'residual risk' that routine cholesterol or blood sugar measurements miss.
This research suggests that measuring LPE species in the blood could potentially help identify type 2 diabetes patients at higher risk for coronary artery disease who might be missed by conventional testing. It also points to LPE metabolism as a possible biological pathway connecting abnormal fat processing in diabetes to heart disease, which could eventually inform new therapeutic targets. However, as a cross-sectional study, it cannot prove causation, and further research would be needed to determine whether LPE levels can guide clinical decisions.
Dai D, Chen S, Li Q, Chu C, Li F, Maimaiti Y, et al.. (2026). Circulating lysophosphatidylethanolamine species are associated with pericoronary adipose tissue inflammation and coronary atherosclerotic burden in type 2 diabetes.. Diabetes & vascular disease research. https://doi.org/10.1177/14791641261484961