Ultra‐high performance liquid chromatography coupled to tandem mass spectrometry‐based metabolomics study of diabetic distal symmetric polyneuropathy

AIMS/INTRODUCTION: Distal symmetric polyneuropathy (DSPN) is a common complication of type 2 diabetes mellitus, but the underlining mechanisms have not yet been elucidated. The current study was designed to screen the feature metabolites classified as potential biomarkers, and to provide deeper insights into the underlying distinctive metabolic changes during disease progression. MATERIALS AND METHODS: Plasma metabolite profiles were obtained by the ultra‐high liquid chromatography coupled to tandem mass spectrometry method from healthy control participants, patients with type 2 diabetes mellitus and patients with DSPN. Potential biomarkers were selected through comprehensive analysis of statistically significant differences between groups. RESULTS: Overall, 938 metabolites were identified. Among them, 12 metabolites (dimethylarginine, N6‐acetyllysine, N‐acetylhistidine, N,N,N‐trimethyl‐alanylproline betaine, cysteine, 7‐methylguanine, N6‐carbamoylthreonyladenosine, pseudouridine, 5‐methylthioadenosine, N2,N2‐dimethylguanosine, aconitate and C‐glycosyl tryptophan) were identified as the specific biomarkers. The content of 12 metabolites were significantly higher in the DSPN group compared with the other two groups. Additionally, they showed good performance to discriminate the DSPN state. Correlation analyses showed that the levels of 12 metabolites might be more closely related to the glucose metabolic changes, followed by the levels of lipid metabolism. CONCLUSIONS: The finding of the 12 signature metabolites might provide a novel perspective for the pathogenesis of DSPN. Future studies are required to test this observation further.