Prediction of incident diabetes mellitus or coronary artery disease by atypical sphingoid bases
A Othman, Christoph H. Säly, Heinz Drexel, Arnold von Eckardstein, Thorsten Hornemann · Diabetologie und Stoffwechsel · 2014
Sphingolipid de-novo biosynthesis is initiated by the condensation of palmitoyl-CoA and serine by the serine palmitoyltransferase (SPT). Besides these canonical substrates, SPT can also metabolize other acyl-CoAs and other amino acids, thereby generating atypical sphingoid bases. We here investigated the predictive potential of these atypical sphingoid bases for the incidence of coronary artery disease (CAD) events and type 2 diabetes mellitus (T2DM). 349 Subjects enrolled in this study were followed up for 8 years. The plasma sphingoid base profile was analyzed using LC/MS. Confirming our previous results, we found plasma levels of 1-deoxysphingolipids (1-deoxySLs, which are formed by the use of alanine instead of serine by SPT) significantly elevated in patients with the metabolic syndrome (MetS) and T2DM. In the prospective analysis, baseline 1-deoxySLs were identified as independent predictors for the development of T2DM after adjustment for HbA1c and the presence of MetS. This may reflect the toxicity of 1-deoxySLs towards beta cells which we also showed previously. In addition baseline C20 sphingoid base backbones were associated with the incidence of cardiovascular events even after the adjustment for traditional risk factors including the degree of coronary artery stenosis at baseline. Interestingly, cross sectional plasma C20-based sphingolipids were not significantly different between CAD patients and controls. Other sphingoid bases including the canonical C18-sphingoids showed no independent association with the presence or incidence of CAD. In summary, we show that atypical sphingoid bases are promising and potentially causal biomarkers of T2DM and CAD.