Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
Nutrients. 2021 Apr 27;13(5):1474. doi: 10.3390/nu13051474.
Little is known about changes in plasma metabolome profiles during the oral glucose tolerance test (OGTT) in Chinese. We aimed to characterize plasma metabolomic profiles at 0 and 2 h of OGTT and their changes in individuals of different glycemic statuses. A total of 544 metabolites were detected at 0 and 2 h of OGTT by a nontarget strategy in subjects with normal glucose ( = 234), prediabetes ( = 281), and newly diagnosed type 2 diabetes (T2D) ( = 66). Regression model, mixed model, and partial least squares discrimination analysis were applied. Compared with subjects of normal glucose, T2D cases had significantly higher levels of glycerone at 0 h and 22 metabolites at 2 h of OGTT (false discovery rate (FDR) < 0.05, variable importance in projection (VIP) > 1). Seven of the twenty-two metabolites were also significantly higher in T2D than in prediabetes subjects at 2 h of OGTT (FDR < 0.05, VIP > 1). Two hours after glucose challenge, concentrations of 35 metabolites (normal: 18; prediabetes: 23; T2D: 13) significantly increased (FDR < 0.05, VIP > 1, fold change (FC) > 1.2), whereas those of 45 metabolites (normal: 36; prediabetes: 29; T2D: 18) significantly decreased (FDR < 0.05, VIP > 1, FC < 0.8). Distinct responses between cases and noncases were detected in metabolites including 4-imidazolone-5-acetate and 4-methylene-L-glutamine. More varieties of distinct metabolites across glycemic statuses were observed at 2 h of OGTT compared with fasting state. Whether the different patterns and responsiveness of certain metabolites in T2D reflect a poor resilience of specific metabolic pathways in regaining glucose homeostasis merits further study.
在中国人群中，关于口服葡萄糖耐量试验（OGTT）期间血浆代谢组谱变化知之甚少。我们旨在描绘不同血糖状态个体 OGTT 时 0 小时和 2 小时的血浆代谢组谱及其变化。通过非靶向策略在糖耐量正常（ = 234）、糖尿病前期（ = 281）和新诊断的 2 型糖尿病（T2D）患者（ = 66）的 OGTT 0 小时和 2 小时检测到 544 种代谢物。应用回归模型、混合模型和偏最小二乘判别分析。与糖耐量正常的个体相比，T2D 病例在 0 小时时甘油一酯水平显著升高，在 OGTT 2 小时时有 22 种代谢物水平显著升高（错误发现率（FDR）<0.05，变量重要性投影（VIP）>1）。在 OGTT 2 小时时，这 22 种代谢物中有 7 种在 T2D 中也显著高于糖尿病前期患者（FDR<0.05，VIP>1）。葡萄糖负荷后 2 小时，35 种代谢物（正常：18；糖尿病前期：23；T2D：13）的浓度显著增加（FDR<0.05，VIP>1，倍数变化（FC）>1.2），而 45 种代谢物（正常：36；糖尿病前期：29；T2D：18）的浓度显著降低（FDR<0.05，VIP>1，FC<0.8）。在代谢物中检测到病例和非病例之间的不同反应，包括 4-咪唑啉-5-乙酰胺和 4-亚甲基-L-谷氨酰胺。与空腹状态相比，OGTT 时 2 小时观察到更多不同血糖状态的不同代谢物种类。在 T2D 中，某些代谢物的不同模式和反应性是否反映了恢复葡萄糖稳态的特定代谢途径的弹性较差，值得进一步研究。
