Plasma 16:0 Ceramide As a Marker of Cardiovascular Risk Estimated by Carotid Intima-Media Thickness in People with Type 2 Diabetes

Aim: New tools are required to better assess cardiovascular risk in individuals with type 2 diabetes mellitus (T2DM). Plasma ceramides emerge as promising candidates, given their substantial influence on the pathogenesis of both T2DM and atherosclerosis. The current study aimed to investigate whether plasma ceramides in patients with T2DM are a predictive factor for carotid intima-media thickness (CIMT), a well -established noninvasive marker for atherosclerosis that predicts adverse cardiovascular outcomes. Methods: A lipidomic analysis was carried out on the circulating ceramides of a large cohort consisting of 246 patients with T2DM who underwent a high -resolution real-time B ultrasonography to measure CIMT. Results: Both plasma 16:0 ceramide and the 16:0/24:0 ceramide ratio were positively associated with CIMT, even after adjustment for traditional cardiovascular risk factors [standardized beta +/- standard error: 0.168 +/- 0.072 ( P = 0.020) and 0.180 +/- 0.068 ( P = 0.009), respectively]. Similar independent associations were found with respect to the prediction of CIMT >= 0.80 mm [ beta = 8.07 +/- 3.90 ( P = 0.038) and 16.5 +/- 7.0 ( P = 0.019), respectively]. The goodness -of -fit for multivariate models in predicting CIMT was 5.7 and 7.6 times higher when plasma 16:0 ceramide or the 16:0/24:0 ceramide ratio were included in combination with traditional cardiovascular risk factors ( P = 0.020 and 0.015, respectively). This reached a 3.1 and 10.0 -fold increase regarding the ability to predict CIMT >= 0.80 mm ( P = 0.039 and 0.008, respectively). Conclusions: Our findings suggest that 16:0 ceramide and the 16:0/24:0 ceramide ratio may serve as plasma biomarkers to improve cardiovascular risk assessment in individuals with T2DM.