Metabolomic profiling reveals early biomarkers of gestational diabetes mellitus and associated hepatic steatosis

Abstract

Background: This study aims to identify early metabolomic biomarkers of gestational diabetes mellitus (GDM) and evaluate their association with hepatic steatosis. Methods: We compared maternal serum metabolomic profiles between women who developed GDM (n = 118) and matched controls (n = 118) during the first (10–14 gestational weeks) and second (24–28 gestational weeks) trimesters using ultra-performance liquid chromatography coupled with mass spectrometry. Mediation analysis was performed to evaluate the mediating role of metabolic dysfunction-associated steatotic liver disease (MASLD) in the relationship between metabolites and subsequent development of GDM. A refined prediction model was developed to predict GDM using established clinical factors and selected metabolites. Results: Significant alterations in circulating metabolites, including amino acids, bile acids, and phospholipids, were observed in the GDM group compared to controls during early pregnancy. Mediation analysis revealed that several metabolites, including glycocholic acid (proportion mediated (PM) = 31.9%), butanoyl carnitine (PM = 25.7%), and uric acid (PM = 22.4%), had significant indirect effects on GDM incidence mediated by hepatic steatosis. The refined prediction model composed of clinical factors and selected metabolites in the first trimester demonstrated higher performance in predicting GDM development than the established prediction model composed solely of clinical factors (AUC, 0.85 vs. 0.63, p < 0.001). Conclusions: Women who developed GDM exhibited altered metabolomic profiles from early pregnancy, which showed a significant correlation with GDM, with MASLD as a mediator. Selected metabolomic biomarkers may serve as predictive markers and potential targets for early risk assessment and intervention in GDM.