Large-Scale Longitudinal Metabolomics Study Reveals Different Trimester-Specific Alterations of Metabolites in Relation to Gestational Diabetes Mellitus

Despite the increasing research attention paid to gestational diabetes mellitus (GDM) due to its high prevalence, limited knowledge is available about its pathogenesis. In this study, 428 serum samples were collected from 107 pregnant women suffering from GDM and 107 matched healthy controls. The nontargeted metabolomics data of maternal serum samples from the first (T1, n = 214) and second trimesters (T2, n = 214) were acquired by using ultrahigh performance liquid chromatography coupled with Orbitrap mass spectrometry (MS). A total of 93 differential metabolites were identified on the basis of the accurate mass and MS/MS fragmentation. After false discovery rate correction, the levels of 31 metabolites in GDM group were significantly altered in the first trimester. The differential metabolites were mainly attributed to purine metabolism, fatty acid β-oxidation, urea cycle, and tricarboxylic acid cycle pathways. The fold changes across pregnancy (T2/T1) of six amino acids (serine, proline, leucine/isoleucine, glutamic acid, tyrosine, and ornithine), a lysophosphatidylcholine (LysoPC(20:4)), and uric acid in GDM group were significantly different from those in the control groups, suggesting that these 8 metabolites might have contributed to the occurrence and progression of GDM. The findings revealed that the amino acid metabolism, lipid metabolism, and other pathways might be disturbed prior to GDM onset and during the period from the first to the second trimester of pregnancy.