Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low and High-Risk Women Living in the UK

Abstract

Background: Gestational Diabetes Mellitus (GDM) is the most common pregnancy complication to occur worldwide, however prevalence varies substantially between ethnicities with South Asians experiencing up to 3-times the risk of the disease compared to white Europeans (WEs). Factors driving this discrepancy in prevalence and the pathogenesis of GDM are unclear, although the metabolome is of great importance due to the metabolic dysregulation characterised GDM. Objective: To characterise and distinguish the metabolic profiles of GDM in two distinct ethnic populations at < 28 weeks gestation. Design: 146 fasting serum metabolite values, quantified by nuclear magnetic resonance, from 2668 pregnant WE and 2671 pregnant Pakistani (PK) women from the Born in Bradford (BIB) cohort, were analysed using partial least squares discriminatory analyses (PLSDA). The presence of a linear relationships between metabolite values and post-oral glucose tolerance test measures of dysglycemia (fasting glucose and 2- hour post glucose) were also examined. Results: Seven metabolites were associated with GDM status in both ethnicities, while 6 additional metabolites associated with GDM only in WE women. Unique metabolic profiles were observed in healthy weight women who later developed GDM, with distinct metabolite patterns identified by ethnicity and BMI status. Of the 146 metabolite values analysed in relation to dysglycemia, quantities of lactate, histidine, apolipoprotein A1, HDL cholesterol, HDL2 cholesterol, and DHA, as well as the diameter of very low density lipoprotein particles (nm) were associated with dysglycemia in WE women; while in PK women albumin alone associated with dysglycemia. Conclusion: This is the first study to show that the metabolic risk profile for GDM differs between ethnicities and highlights a need for ethnically appropriate GDM prevention strategies.