title: 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.
abstract: 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.
authors.affiliation: Mass Spectrometry Centre, China-Canada-New Zealand Joint Laboratory of Maternal and Foetal Medicine, Chongqing Medical University, Chongqing, China. Electronic address: kai.law1@virginmedia.com.
authors.forename: Kai P
authors.initials: KP
authors.lastname: Law
authors.affiliation: Mass Spectrometry Centre, China-Canada-New Zealand Joint Laboratory of Maternal and Foetal Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Ting-Li
authors.initials: TL
authors.lastname: Han
authors.affiliation: Mass Spectrometry Centre, China-Canada-New Zealand Joint Laboratory of Maternal and Foetal Medicine, Chongqing Medical University, Chongqing, China; Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Mao
authors.affiliation: Mass Spectrometry Centre, China-Canada-New Zealand Joint Laboratory of Maternal and Foetal Medicine, Chongqing Medical University, Chongqing, China; Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: zh2844@gmail.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D002681:China; D015331:Cohort Studies; D016640:Diabetes, Gestational / Q000378:metabolism* / Q000652:urine*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D055432:Metabolomics; D015999:Multivariate Analysis; D011247:Pregnancy; D011687:Purines / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D011687:Purines; D014364:Tryptophan
keywords: Gestational diabetes; Longitudinal study; Metabolomics; Multilevel analysis; Purine metabolism; Tryptophan metabolism; Urine