Paul T Seed

Objective Investigation 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. Design Prospective cohort study. Setting UK multicentre study. Population Fasting serum from participants of European or South Asian self‐reported ethnicity from the PRiDE study, between 23 and 31 weeks of gestation. Methods Bile 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 measures Total bile acids (TBAs), C4, fasting glucose and insulin. Results The 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. Conclusions Serum 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.