Distinct Serum Metabolic Profiles in Early Pregnancy Characterise Gestational Diabetes Mellitus Incidence in High-Risk Women

Abstract

ObjectivesThis study aimed to investigate and characterise the metabolic profiles of gestational diabetes mellitus (GDM) in white European (WE) and British Pakistani (BP) women with and without GDM. Methods146 serum metabolites quantified by nuclear magnetic resonance, from 2668 WEs and 2671 BP pregnant women ≤28 weeks’ gestation from the Born in Bradford cohort were analysed. Partial least squares discriminatory analyses (PLSDA) and sparse PLSDA (sPLSDA) were used to investigate the ethnic-specific metabolite signatures of future incidence of GDM. Metabolite features driven by pre-pregnancy weight status and known GDM risk factors (age, parity, multiple pregnancies and smoking status) were also explored. ResultsModels explained 60% of variance between future GDM cases/non-cases in WE mothers but only 35% in BPs, after adjusting for BMI, age, parity, smoking, and non-singleton pregnancies. Across both ethnic groups, 8 metabolites associated with future GDM status. When ethnic groups were investigated independently, 7 additional metabolites associated with future GDM in WEs were identified, while no additional associations were observed in BPs. Further stratification by BMI (healthy vs overweight/obese) uncovered a metabolic profile (characterised by fatty acids and glycolytic metabolites) unique to normal-weight BP women who later developed GDM. No difference was observed between the metabolic profiles of overweight/obese women, irrespective of ethnicity. ConclusionsIn early pregnancy, the metabolomes of future GDM cases and non-cases are distinct and differ by ethnicity. While the metabolic profiles of overweight women are largely similar in WE and BPs, a unique metabolic profile was observed in healthy weight BP women who went on to develop GDM and offers insight into the early metabolomic perturbations that precede GDM development in this high-risk (but healthy) population. Further exploration regarding the interaction between genetics and lifestyle on modifying metabolic profiles associated with GDM risk will help inform ethnically appropriate nutrition strategies. Funding SourcesHF is supported by a doctoral scholarship from the University of Leeds.