Plasma sphingolipid profiling reveals novel distinct biomarkers for predicting cardiovascular disease and type 2 diabetes mellitus

Objectives: Cardio-metabolic diseases remain to be a major cause of mortality and morbidity, despite the progress in risk prediction and stratification. In addition to known risk factors, sphingolipids are emerging as novel players in the pathogenesis of atherosclerosis and metabolic diseases. Sphingolipid de-novo biosynthesis is typically initiated by the condensation of palmitoyl-CoA and serine, a reaction catalyzed by the serine palmitoyltransferase (SPT). Apart from these canonical substrates, SPT can metabolize other acyl-CoAs and also alanine and glycine as alternative substrates. This forms a great variety of atypical SPT products. In our previous work, a set of these atypical metabolites emerged in several cross sectional studies as promising novel biomarkers for cardiometabolic diseases.