Tryptophan and purine metabolites are consistently upregulated in the urinary metabolome of patients diagnosed with gestational diabetes mellitus throughout pregnancy: A longitudinal metabolomics study of Chinese pregnant women part 2
Tryptophan and purine metabolites are consistently upregulated in the urinary metabolome of patients diagnosed with gestational diabetes mellitus throughout pregnancy: A longitudinal metabolomics study of Chinese pregnant women part 2
复制标题
DOI：
10.1016/j.cca.2017.02.018
复制
发表时间：
2017-05-01
影响因子：
5
通讯作者：
Zhang, Hua
中科院分区：
文献类型：
--
作者：
Law, Kai P.;Han, Ting-Li;Zhang, Hua
背景资料：妊娠期糖尿病（GDM）是一种葡萄糖耐受不良的病理状态，与不良妊娠结局相关，并增加了母亲日后患2型糖尿病的风险。GDM发展的潜在机制尚未完全了解。我们使用来自正常妊娠和合并GDM的妊娠纵向队列的参与者，通过对孕妇尿液的全面代谢分析来检查GDM的病理生理学。方法：基于超高效液相色谱/混合四极杆飞行时间质谱，进行非靶向代谢组学研究，以探索妊娠期糖尿病病例和健康对照在妊娠过程中尿液代谢组的差异。采用多水平统计方法，以解决复杂的代谢组学数据从纵向cohol.Results：结果表明，色氨酸和嘌呤代谢与GDM。在胎盘激素或胎儿胎盘单位可能产生任何生理效应之前，GDM受试者中的Dahan-犬尿氨酸通路被激活。次黄嘌呤、黄嘌呤、黄嘌呤核苷和1-甲基次黄嘌呤在GDM受试者的尿液代谢组中均升高。嘌呤核苷的catastrophin最终导致尿酸的生产，这与GDM从controls.Conclusions的主题区别：结果支持的概念，GDM可能是一个易感条件，或前驱糖尿病状态，这是表现在怀孕期间。这挑战了传统的观点，认为胎盘激素是GDM胰岛素抵抗的主要原因。(C)2017爱思唯尔B. V.保留所有权利。
Background: Gestational diabetes mellitus (GDM) is a pathological state of glucose intolerance associated with adverse pregnancy outcomes and an increased risk of developing maternal type 2 diabetes later in life. The mechanisms underlying GDM development are not fully understood. We examined the pathophysiology of GDM through comprehensive metabolic profiling of maternal urine, using participants from a longitudinal cohort of normal pregnancies and pregnancies complicated by GDM.Methods: Based on ultra-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, an untargeted metabolomics study was performed to explore the differences in the urinary metabolome of GDM cases and healthy controls over the course of pregnancy. Multilevel statistical approaches were employed to address the complex metabolomic data obtained from a longitudinal cohort.Results: The results indicated that tryptophan and purine metabolism was associated with GDM. The tryptophan-kynurenine pathway was activated in the GDM subjects before placental hormones or the fetoplacental unit could have produced any physiological effect. Hypoxanthine, xanthine, xanthosine, and 1-methylhypoxanthine were all elevated in the urine metabolome of subjects with GDM. Catabolism of purine nucleosides leads ultimately to the production of uric acid, which discriminated the subjects with GDM from controls.Conclusions: The results support the notion that GDM may be a predisposed condition, or prediabetic state, which is manifested during pregnancy. This challenges the conventional view of the pathogenesis of GDM, which assumes placental hormones are the major causes of insulin resistance in GDM. (C) 2017 Elsevier B.V. All rights reserved.