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

Abstract

Aims/IntroductionDistal 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 MethodsPlasma 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.ResultsOverall, 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.ConclusionsThe 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.

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“…Electrospray ionization was performed in the negative ionization mode for the compounds fructose-1,6bisphosphate, phosphoenolpyruvate (PEP), 2/3-phosphoglycerate, lactate, and pyruvate as described in the literature [24]. The analytes N2, N2-dimethylguanosine, and N6carbamoylthreonyladenosine were measured in the positive ionization mode as previously described [25]. Mass spectrometric quantitation of the compounds was carried out in the multiple reaction monitoring (MRM) mode.…”

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“…These biomarkers have the potential to complement the existing diagnostic methods and enhance early detection. Plasma metabolite profiles showed that the plasma levels of 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 significantly higher in the type 2 diabetes mellitus with DPN group than in the control and type 2 diabetes mellitus without DPN groups 15 . Receiver operating characteristic curve analyses showed that all 12 metabolites had an area under the curve >0.75, and 5‐methylthioadenosine, N6‐acetyllysine and aconitate had the strongest discriminatory power of >0.84.…”