Metabolomics study of serum from patients with type 2 diabetes: Peripheral neuropathy could be associated with sphingosine and phospholipid molecules

Abnormal lipid metabolism is one of the risk factors for type 2 diabetes mellitus peripheral neuropathy (DPN). This study aimed to determine the differences in lipid metabolism in patients with type 2 diabetes and DPN and the possible pathogenesis caused by this difference. The participants comprised type 2 diabetes mellitus patients with DPN (N = 60) and healthy controls (N = 20). Blood samples were drawn from the participants in the morning in the fasting state, and then changes in serum lipids were explored using targeted metabolomics on the liquid chromatography-electrospray ionization-tandem mass spectrometry platform. Among the 1768 differentially abundant lipid metabolites, the results of orthogonal partial least squares-discriminant analysis combined with random forest analysis showed that the levels of sphingosine (SPH) (d18:0), carnitine 22:1, lysophosphatidylethanolamine (LPE) (18:0/0:0), LPC (16:0/0:0), lysophosphatidylcholine (LPC) (18:1/0:0), LPC (0:0/18:0) and LPE (0:0/18:1) were significantly different between the two groups. Spearman correlation analysis showed that SPH (d18:0), carnitine 22:1, LPE (18:0/0:0), and LPC (0:0/18:0) levels correlated highly with the patients' electromyography results. Kyoto Encyclopedia of Genes and Genomes pathway annotation and enrichment analysis of 538 differentially abundant lipid metabolites revealed that type 2 diabetes mellitus DPN was related to glycerophospholipid metabolism and glycerol metabolism. Our results further identified the dangerous lipid metabolites associated with DPN and abnormal lipid metabolism. The influence of lipid metabolites such as SPH and phospholipid molecules on DPN development in patients with type 2 diabetes mellitus were suggested and the possible pathogenic pathways were clarified, providing new insights into the clinical risk of DPN in patients with type 2 diabetes mellitus.