Trimester-specific urinary metabolome alterations associated with gestational diabetes mellitus: A study in different pregnancy stages

Abstract Gestational diabetes mellitus (GDM), a frequently-occurring disease during pregnancy, may cause some adverse healthy outcome of both mother and offspring. However, the knowledge about metabolite alterations during the pathogenesis and development process is limited. Here, a large longitudinal non-targeted metabolomics study of 195 pregnant women (64 women with subsequently developed GDM and 131 healthy controls) was conducted. Each participant provided urine samples at three timepoints during early, middle and late pregnancy, respectively. The metabolic profiles of 585 urine samples (195 × 3) were measured by using ultra-high performance liquid chromatography coupled with Orbitrap high-resolution mass spectrometry. Among the 56 identified metabolites, the levels of eight metabolites increased and three ones decreased in the first trimester, the concentration of one metabolite increased and those of 20 decreased in the second trimester, as well as the levels of five metabolites increased and two decreased in the third trimester. After false discovery rate correction, the levels of valine and 5-acetamidovalerate in GDM group significantly increased in the first trimester, the levels of 1-methylguanine and 1,3-dihydro-(2H)-indol-2-one significantly decreased in the second trimester and three metabolites (threonine, OH-octanedioyl-carnitine and pimelylcarnitine) increased and N-acetyltryptophan decreased in the third trimester, respectively. Six metabolites, such as pantothenic acid and threonine, had significant interaction effects between gestational stage (different trimester) and group (GDM or control). The differential metabolites were involved in “tryptophan metabolism”, “purine metabolism”, “valine, leucine and isoleucine degradation” and other pathways. The findings may provide insights into further pathogenesis study of GDM.