Analysis of serum metabolomics among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls

Abstract

Type 2 diabetes mellitus (T₂DM) has a rising prevalence and diabetic nephropathy (DN) is a major complication of T₂DM. Metabolomics could provide novel insights into the pathogenesis, so we aimed to explore serum metabolomic profiles from DN to T₂DM. Serum samples were collected from 14 biopsy-proven DNs, 14 age/gender-matched T₂DMs without renal diseases (DM), 14 age/gender-matched healthy controls (CTRL) and household contacts of DM group (HH). Serum metabolomics was analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC/MS) assays. There were a total of 1470 metabolites identified from all serum samples. 45 metabolites with significantly different intensity were found between DN and DM, e.g., biliverdin and taurine were reduced while L-arginine was increased in DN comparing to DM. DN could be distinguished from age/gender matched DM patients by L-arginine (AUC = 0.824) or taurine levels (AUC = 0.789). The metabolic pathways affected by metabolite distinctions between DN and DM also existed, among which taurine and hypotaurine metabolism exhibited the highest pathway impact. L-Methionine, deethylatrazine, L-tryptophan and fumaric acid were reduced in DM comparing with those of CTRL, but had no different intensity in DM and HH groups. The changes were demonstrated in the metabolomic profiles of biopsy-proven DN compared to DM. Biopsy-proven DN patients could be distinguished from age/gender matched DM by L-arginine or taurine levels in serum metabolomic profiles. Taurine and hypotaurine metabolism pathway had the highest impact in pathway set enrichment analysis, which potentially affected the pathogenesis of DN from T₂DM.