Untargeted metabolomics profiling of gestational diabetes mellitus: insights into early diagnosis and metabolic pathway alterations.

Introduction: Gestational Diabetes Mellitus (GDM) is a metabolic disorder marked by Q10 hyperglycemia that can negatively affect both mothers and newborns. The increasing prevalence of GDM and the limitations associated with the standard diagnostic test highlight the urgent need for early screening strategies that promote timely interventions. Methods: This study aims to investigate the metabolic profile associated with GDM through an untargeted metabolomic analysis using mass spectrometry (MS)- based omics. Serum samples were collected from 40 pregnant women at weeks 24-28 of gestation based on the 2-h 75-g oral glucose tolerance test (OGTT); 50% were diagnosed with GDM (n = 20), and the remaining were considered a control group. Results and discussion: The results showed distinct metabolic differences between women with GDM and those without, with 222 significantly dysregulated metabolites, 120 up- and 102 downregulated in GDM compared to the control group. Key metabolic pathways, such as tryptophan, inositol phosphate, phenylalanine, and histidine metabolism, were notably dysregulated in GDM. The study also found that specific metabolites, like N-Acetylproline and Serylmethionine, with area under the curve (AUC) of 0.978 and 0.968, respectively, showed high accuracy in distinguishing between GDM and non-GDM women. This study would enhance our understanding of metabolic alterations in GDM and could contribute to early prediction and management strategies.