Serum bile acid measurements in women of European and South Asian ethnicity with or without gestational diabetes mellitus: A cohort study

Author:

Schoonejans Josca M.12ORCID,Fan Hei Man1ORCID,Mitchell Alice L.12ORCID,Lövgren‐Sandblom Anita3,Sukumar Nithya45ORCID,Periyathambi Nishanthi45ORCID,Weldeselassie Yonas45ORCID,Seed Paul T.1ORCID,Molinaro Antonio6ORCID,Marschall Hanns‐Ulrich6ORCID,Saravanan Ponnusamy45ORCID,Williamson Catherine12ORCID

Affiliation:

1. Department of Women and Children's Health School of Life Course Sciences, King's College London London UK

2. Department of Metabolism, Digestion & Reproduction, Institute of Reproductive and Developmental Biology Imperial College London London UK

3. Department of Laboratory Medicine Karolinska Institutet Stockholm Sweden

4. Department of Diabetes, Endocrinology and Metabolism George Eliot Hospital Nuneaton UK

5. Populations, Evidence and Technologies, Division of Health Sciences Warwick Medical School, University of Warwick Coventry UK

6. Department of Molecular and Clinical Medicine, Wallenberg Laboratory University of Gothenburg Gothenburg Sweden

Abstract

AbstractObjectiveInvestigation of serum bile acid profiles in pregnancies complicated by gestational diabetes mellitus (GDM) in a multi‐ethnic cohort of women who are lean or obese.DesignProspective cohort study.SettingUK multicentre study.PopulationFasting serum from participants of European or South Asian self‐reported ethnicity from the PRiDE study, between 23 and 31 weeks of gestation.MethodsBile acids were measured using ultra‐performance liquid chromatography‐tandem mass spectrometry. Log‐transformed data were analysed using linear regression in STATA/IC 15.0.Main outcome measuresTotal bile acids (TBAs), C4, fasting glucose and insulin.ResultsThe TBAs were 1.327‐fold (1.105–1.594) increased with GDM in European women (P = 0.003). Women with GDM had 1.162‐fold (1.002–1.347) increased levels of the BA synthesis marker C4 (P = 0.047). In South Asian women, obesity (but not GDM) increased TBAs 1.522‐fold (1.193–1.942, P = 0.001). Obesity was associated with 1.420‐fold (1.185–1.702) increased primary/secondary BA ratio (P < 0.001) related to 1.355‐fold (1.140–1.611) increased primary BA concentrations (P = 0.001). TBAs were positively correlated with fasting glucose (P = 0.039) in all women, and with insulin (P = 0.001) and the Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR) (P = 0.001) in women with GDM.ConclusionsSerum BA homeostasis in late gestation depends on body mass index and GDM in ethnicity‐specific ways. This suggests ethnicity‐specific aetiologies may contribute to metabolic risk in European and South Asian women, with the relationship between BAs and insulin resistance of greater importance in European women. Further studies into ethnicity‐specific precision medicine for GDM are required.

Funder

Fetal Medicine Foundation

National Institute for Health Research

Medical Research Council

Publisher

Wiley

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