Metabonomic study of biochemical changes in urinary of type 2 diabetes mellitus patients after the treatment of sulfonylurea antidiabetic drugs based on ultra‐performance liquid chromatography/mass spectrometry

Abstract

A metabonomic study on biochemical changes in the urine of type 2 diabetes mellitus (T2DM) patients after the treatment of sulfonylurea (SU) antidiabetic drugs was performed. An ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) method was used to generate metabolic fingerprints for the metabonomic analysis of urinary samples obtained from 20 T2DM patients without any drug treatment and 20 T2DM patients treated with SU antidiabetic drugs and 20 normal glucose tolerance subjects. The resulting data were subjected to chemometric analysis (principal component analysis and partial least squares discriminant analysis) to investigate the effect of SU antidiabetic drugs on urinary metabolite profiles of T2DM patients. Biomarkers such as xanthine, phenylalanine, tryptophan, hippurate, phenylacetylglutamine, carnitine C8:1, carnitine C10:3, uric acid and citrate were found to be responsible for the separation of T2DM and SU-treated groups, which indicates a potential effect of SU on energy metabolism, Tricarboxylic acid (TCA) cycle, gut microflora metabolism and oxidative stress. The study may be helpful to the understanding of the action of mechanism of SU antidiabetic drugs.

Metabolomic insights into the intricate gut microbial–host interaction in the development of obesity and type 2 diabetes

“…The role of the microbial community hosted by diabese subjects in altering choline metabolism was also tested by assessing the effects of antidiabetic medication ( Huo et al, 2009 ). As shown in Table 1 , Huo et al (2015) observed increased serum levels of TMAO in overweight diabetic subjects receiving metformin treatment versus untreated diabese controls, which may indicate an intestinal bacterial regulation function of metformin. It has already been suggested that antidiabetic treatments have a beneficial effect on gut microbiota metabolism ( Huo et al, 2015 ), although the exact mechanisms are still unclear ( Moreno-Navarrete et al, 2012 ).…”

“…As shown in Table 1 , Huo et al (2015) observed increased serum levels of TMAO in overweight diabetic subjects receiving metformin treatment versus untreated diabese controls, which may indicate an intestinal bacterial regulation function of metformin. It has already been suggested that antidiabetic treatments have a beneficial effect on gut microbiota metabolism ( Huo et al, 2015 ), although the exact mechanisms are still unclear ( Moreno-Navarrete et al, 2012 ). The authors suggested a link between the deregulation of choline metabolism in T2D and a rupture of the intestinal barrier by oxidative stress ( Wei et al, 2008 ).…”

“…Urine ( Salek et al, 2007 ; Calvani et al, 2010 ; Zhao et al, 2010 ; Huo et al, 2015 ), fasting serum ( Huo et al, 2009 ; Zhang et al, 2009 ; Suhre et al, 2010 ) and plasma ( Zhao et al, 2010 ; Campbell et al, 2014 ) were the biological samples used in these studies. A data-driven untargeted approach was chosen in the majority of the studies ( Salek et al, 2007 ; Huo et al, 2009 ; Zhang et al, 2009 ; Calvani et al, 2010 ; Zhao et al, 2010 ; Campbell et al, 2014 ) while two of them provided quantitative information about known targeted metabolites ( Suhre et al, 2010 ; Huo et al, 2015 ). The metabolic changes observed in these studies and the related interpretations are summarized in Table 2 .…”

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry

“…Recently, Huo et al reported the effect of SUs, including glimepiride, on metabolomic changes. [15] They used urine samples collected from normal group, non-treated patients with T2DM and SU-treated patients with T2DM. The samples were analyzed using the ultra-performance liquid chromatography/mass spectrometry method.…”

“…[13,14] Recently, the effect of SUs on biochemical changes in patients with T2DM was investigated through the metabolomic approach. [15] However, the effects of glimepiride on endogenous metabolomic alterations in healthy subjects remain poorly understood.…”