Abstract

A non-targeted metabolomics method was employed to study metabolic characteristics in subjects with different glucose tolerance. Plasma samples of 120 participants with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and type 2 diabetes (T2D) were collected. Gas chromatography/mass spectrometry (GC/MS) was used to profile and compare the plasma metabolome among the three groups. Through the use of multivariate statistical analysis, we found distinct metabolome change from NGT to IGR and to T2D. ANOVA found that the IGR and T2D groups had perturbations of monosaccharide and lipid metabolism, disorders of glucogenic amino acids, and branched-chain amino acid catabolism. Furthermore, we also found that the levels of 2-hydroxybutyrate and 2-ketoisocaproate were progressively increased with glucose tolerance severity. The results from this study help us better understand the relationship between plasma metabolism and glucose tolerance states and also suggest that 2-hydroxybutyrate and 2-ketoisocaproate may be closely associated with the development of T2D.

Highlights

  • Diabetes is one of the most common metabolic disorders worldwide, seriously impacting human health, labor force, and economic status

  • In order to investigate the complex perturbations of the metabolism related to the glucose tolerance states, we carried out a Gas chromatography/mass spectrometry (GC/MS)-based non-targeted metabolomics study to investigate plasma samples from normal glucose tolerance (NGT), Impaired glucose regulation (IGR), and type 2 diabetes (T2D) subjects

  • Our results showed a distinct metabonome change from NGT to IGR and to T2D

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Summary

Introduction

Diabetes is one of the most common metabolic disorders worldwide, seriously impacting human health, labor force, and economic status. Impaired glucose regulation (IGR), known as pre-diabetes, is an abnormal intermediate state that exists between normal glucose tolerance (NGT) and T2D. According to the International Diabetes Federation and the American Diabetes Association, patients with T2D almost always undergo the period of IGR. Metabolomics, profiling the global state of metabolites in biological fluids and tissues, is emerging as a field with tremendous promise in extending Bomics^ from the gene to the small molecule [1]. Metabolomics has begun to play a more important role in discovering and identifying potential biomarkers discriminating normal from abnormal states. Recognition of the differential metabolites can provide insight into the underlying molecular mechanism and is helpful in clinical diagnosis

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