Abstract 15800: Identification of Atypical Sphingoid Bases as Biomarkers of Cardiometabolic Diseases
Sphingolipids are emerging as novel players in the pathogenesis of atherosclerosis and diabetes mellitus type 2 (T2DM). The de-novo biosynthesis of typical sphingolipids is initiated by the condensation of palmitoyl-CoA and serine through serine palmitoyltransferase (SPT). Apart from these canonical substrates the enzyme is also metabolizing other acyl-CoAs as well as alanine and glycine and thereby forms a great variety of atypical sphingoid backbones. They differ from normal sphingoids either by the length or saturation of acyl-chains or by the absence of the free hydroxyl-group in deoxysphingolipids which is normally provided by serine for the formation of complex glyco- and phosphosphingolipids. In a previous cross-sectional study we found significant and independent associations of both 1-deoxysphingosine (1-deoxySO) and acyl sphingoids with the metabolic syndrome and T2DM. In a prospective cohort study of 349 patients who underwent coronary angiography and were followed up for 8 years, we investigated their association with the incidence of cardiovascular events and newly diagnosed T2DM. One atypical acyl sphingoid showed a significant positive association with cardiovascular events (HR = 1.31, CI 95% [1.1-1.56]) even after the adjustment for known risk factors including age, sex, smoking, lipids, HbA1c, eGFR, CRP and coronary artery stenosis. In addition 1-deoxySO was identified as an independent predictor for the manifestation of T2DM (HR = 2.05, CI 95% [1.15-3.64]). Univariate logistic regression models for 1-deoxySO, HbA1c and the presence of a metabolic syndrome showed similar areas under the curves (AUC) for each variables (AUC = 0.68, 0.64 and 0.64 respectively) and the combination all three markers improved the AUC significantly (AUC = 0.77, p < 0.01). In conclusion we demonstrated that atypical sphingoid bases are significant prognostic biomarkers markers for cardiometabolic diseases.
- © 2013 by American Heart Association, Inc.