Development of an integrated biomarker for prediabetes and T2DM in Chinese individuals through serum lipidomic analyses

Abstract By fully elucidating the pathophysiological basis for prediabetes and T2DM in affected individuals, it may be possible to intervene at an earlier time point such that disease progression can be arrested. Dyslipidemia is a hallmark of T2DM, and as such, analyses of lipid metabolic profiles in affected patients have the potential to permit the development of an integrated lipid metabolite-based biomarker model that can facilitate early patient diagnosis and treatment. Herein, untargeted and targeted lipidomics approaches were used to analyze serum samples from newly diagnosed 93 Chinese participants in discovery cohort and 440 in validation cohort via UHPLC-MS and UHPLC-MS/MS. Establish a new biomarker model through appropriate ROC analyses. The integrated biomarker model developed herein exhibited superior diagnostic performance when used to detect prediabetes and T2DM patients within this cohort. The results of western blot analysis of frozen adipose tissue from 3- and 12-week GK rats also confirmed that acid sphingomyelinase is responsible for significant disruptions in ceramide and sphingomyelin homeostasis in prediabetes and T2DM patients. Network analyses of the biomarkers associated with this biosignature suggested that the most profoundly affected lipid metabolism pathways in the context of diabetes include de novo ceramide synthesis, sphingomyelin metabolism, and additional pathways associated with phosphatidylcholine synthesis. Together, these results offer new biological insights regarding the role of serum lipids in the context of insidious T2DM development, and may offer new avenues for future diagnostic and/or therapeutic research.