Although metabolomics may shed light on the pathophysiology of glucose metabolism in pregnancy, systematic studies on their roles in the development of gestational diabetes (GDM) are sparse. We aimed to prospectively investigated metabolomics (both targeted and non-targeted) and GDM risk in a matched case-control study of 107 GDM and 214 non-GDM women in a multi-racial cohort. GDM diagnosis was based on Carpenter and Coustan Criteria. Twenty-two amino acids were quantified using plasma collected at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39. In addition, 331 primary metabolites were quantified by GC-TOF-MS as a part of our non-targeted approach. Adjusted odds ratios (aORs) of GDM related to metabolites (in quartiles (Q)) were estimated using conditional logistic regression after adjusting for major GDM risk factors including BMI. The present report focuses on findings using blood samples in early pregnancy 10-14GW. Alanine in GW 10-14were higher in GDM women than controls (mean: 30.5 vs. 27.6 umol/dl) and were positively related to GDM risk; aORs across increasing Qs were 1.00, 1.69, 2.86, 3.05, (P for trend =0.020). By contrast, asparigine and glycine were significantly lower in GDM women, and were inversely related to GDM risk; aORs across increasing Qs were 1.00, 0.92, 0.74, and 0.48 (P for trend = 0.045) for asparagine and 1.00, 0.42, 0.36, and 0.24 (P <0.001) for glycine. In addition, among primary metabolites from the non-targeted approach, isocitric acid levels were positively related to GDM risk; aORs across increasing Qs were 1.00, 1.30, 1.04, 2.32 (P for trend = 0.002). Furthermore, two unknown metabolites were strongly and inversely associated with GDM risk (aORs were 1.00, 0.52, 0.18, 0.11, and 1.00, 0.33, 0.12, 0.respectively; both P < 10-4).

Conclusion: Our study revealed several novel metabolites that may be implicated in the early pathogenesis of GDM, which might provide new etiological insight into the development of GDM.


C. Zhang: None. Y. Feng: None. O. Fiehn: None. M.Y. Tsai: None. Y. Zhu: None. P. Albert: None. L. Liang: None.

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