Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes

Background Disruption of lipid metabolism contributes to increased cardiovascular risk in diabetes. Methods We evaluated the associations between serum lipidomic profile and subclinical carotid atherosclerosis (SCA) in type 1 (T1D) and type 2 (T2D) diabetes, and in subjects without diabetes (controls) in a cross-sectional study. All subjects underwent a lipidomic analysis using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry, carotid ultrasound (mode B) to assess SCA, and clinical assessment. Multiple linear regression models were used to assess the association between features and the presence and burden of SCA in subjects with T1D, T2D, and controls separately. Additionally, multiple linear regression models with interaction terms were employed to determine features significantly associated with SCA within risk groups, including smoking habit, hypertension, dyslipidaemia, antiplatelet use and sex. Depending on the population under study, different confounding factors were considered and adjusted for, including sample origin, sex, age, hypertension, dyslipidaemia, body mass index, waist circumference, glycated haemoglobin, glucose levels, smoking habit, diabetes duration, antiplatelet use, and alanine aminotransferase levels. Results A total of 513 subjects (151 T1D, 155 T2D, and 207 non-diabetic control) were included, in whom the percentage with SCA was 48.3%, 49.7%, and 46.9%, respectively. A total of 27 unique lipid species were associated with SCA in subjects with T2D, in former/current smokers with T2D, and in individuals with T2D without dyslipidaemia. Phosphatidylcholines and diacylglycerols were the main SCA-associated lipidic classes. Ten different species of phosphatidylcholines were up-regulated, while 4 phosphatidylcholines containing polyunsaturated fatty acids were down-regulated. One diacylglycerol was down-regulated, while the other 3 were positively associated with SCA in individuals with T2D without dyslipidaemia. We discovered several features significantly associated with SCA in individuals with T1D, but only one sterol could be partially annotated. Conclusions We revealed a significant disruption of lipid metabolism associated with SCA in subjects with T2D, and a larger SCA-associated disruption in former/current smokers with T2D and individuals with T2D who do not undergo lipid-lowering treatment.