Accelerated oligosaccharide absorption and altered serum metabolites during oral glucose tolerance test in young Japanese with impaired glucose tolerance

Abstract

Aims/IntroductionImpaired glucose tolerance (IGT) is a subtype of prediabetes, a condition having high risk for development to diabetes mellitus, but its pathophysiology is not fully understood. In the present study, we examined metabolic changes in IGT by using two types (D‐glucose [Glc] and partial hydrolysate of starch [PHS]) of oral glucose tolerance tests (OGTTs), with emphasis on serum incretins and metabolites.Materials and MethodsWe carried out the two types of OGTT (Glc/OGTT and PHS/OGTT) in 99 young Japanese individuals who had tested either positive (GU +; n = 48) or negative (GU −; n = 51) for glycosuria. After OGTT, they were sub‐grouped into five categories: normal glucose tolerance (NGT) in the GU − group (GU −/NGT; n = 49), NGT in the GU + group (GU +/NGT; n = 28), IGT (n = 12), diabetes mellitus (n = 1) and renal glycosuria (n = 9). Serum incretin and metabolites of GU −/NGT and IGT were then measured.ResultsWhen the serum insulin level at each time‐point during PHS/OGTT was expressed as its ratio relative to Glc/OGTT, it was increased time‐dependently in GU −/NGT, but not in IGT. Such an increase in the ratio was also detected of serum incretin levels in GU −/NGT, but not in IGT, suggesting a lack of deceleration of oligosaccharide absorption in IGT. Metabolome analysis showed a difference in the serum levels of two metabolites of unknown function in mammals, methylcysteine and sedoheptulose 1,7‐bisphosphate, between GU −/NGT and IGT.ConclusionsComparison of PHS/OGTT and Glc/OGTT showed that oligosaccharide absorption was accelerated in IGT. Methylcysteine and sedoheptulose 1,7‐bisphosphate could be novel markers for dysregulated glucose metabolism.

Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial

“…This suggests remarkable consistency in the pattern of changes in metabolites post-OGTT among various populations. This also confirms findings from previous studies that suggest post-prandial metabolites may differ from those at fasting [12][13][14][15][16]19,20]. The candidate metabolites that did not display significant changes during the OGTT in individual association analyses and were not heavily weighted in the PCA in this population may likely be metabolites that differ by sex, pregnancy status, race, or disease status.…”

“…Our findings, at around 36 weeks gestation, replicated relative decreases in acyl carnitines, amino acids, and fatty acids, observed in these studies, but we did not replicate the relative increases in bile acid metabolites observed in one study [19]. About 82% of the selected candidate metabolites that displayed significant changes during an OGTT in at least two previous studies [12][13][14][15][16][17][18][19][20][21][22] were associated with significant changes during OGTT at either early or mid-pregnancy in this study. This suggests remarkable consistency in the pattern of changes in metabolites post-OGTT among various populations.…”

“…This is the first study, to date, examining whether changes in metabolites post-OGTT may be different during early versus mid-pregnancy. Several studies have examined metabolomic responses to an OGTT in the general population [12][13][14][15][16][17][18], and three studies have examined the response during mid-pregnancy in Peruvian [19] and European women [20]. Our findings, at around 36 weeks gestation, replicated relative decreases in acyl carnitines, amino acids, and fatty acids, observed in these studies, but we did not replicate the relative increases in bile acid metabolites observed in one study [19].…”

Exploration of predictive metabolic factors for gestational diabetes mellitus in Japanese women using metabolomic analysis

“…Recently, the pentose phosphate pathway has been reportedly associated with adiposity, a higher glycemic phenotype and diabetes complications. In studies involving a cohort of university students, it was shown using glucose tolerance tests that alterations in the pentose phosphate pathway were associated with glucose metabolism. The pentose phosphate pathway is associated with purine metabolism, which is reportedly associated with GDM.…”

“…Metabolomic analysis was carried out as previously described. Serum and urine levels of 42 and 263 metabolites, respectively, found to be detectable under our storage conditions (−20°C) were pre‐treated and analyzed using hydrophilic interaction chromatography tandem mass spectrometry methods as previously reported.…”