SFEBES2022 Poster Presentations Metabolism, Obesity and Diabetes (96 abstracts)
1Kings College London, London, United Kingdom; 2Karolinska Institutet, Stockholm, Sweden; 3University of Warwick, Coventry, United Kingdom; 4George Eliot Hospital, Nuneaton, United Kingdom; 5University of Gothenburg, Gothenburg, Sweden
Introduction: Bile acid (BA)-feeding and genetic manipulation of BA receptors affect glucose tolerance in rodent pregnancy. In non-pregnant individuals, serum BA profiles depend on BMI and ethnicity. The interaction between serum BAs, ethnicity, and BMI in gestational diabetes mellitus (GDM) remains poorly understood.
Methods: Fasted serum samples were collected between 23-31 weeks gestation. Experimental groups: lean or obese women of European (EU) or South Asian ancestry (SA), with or without GDM. Ethnicity-specific BMI thresholds: Obese >30 and >27 kg/m2; Lean <25 and <23 kg/m2 in European and SA women, respectively. Numbers per group: EU-Lean-Con (n=63), EU-Lean-GDM (n=27), EU-Ob-Con (n=74), EU-Ob-GDM (n=73), SA-Lean-Con (n=62), SA-Lean-GDM (n=10), SA-Ob-Con (n=75), SA-Ob-GDM (n=40). Serum BAs were measured with UPLC-MS/MS. Data were analysed using Mann-Whitney U tests/linear regression.
Results: Total serum BA were elevated in EU-Ob-GDM women compared to EU-Ob-Con (2.1 [1.4 3.8] vs. 1.3 [1.0 2.2] µmol/l, p=0.0001), but no GDM effect was seen in other groups. SA-Ob-Con women had elevated serum BA compared to SA-Lean-Con women (2.4 [1.2 4.7] vs. 1.6 [1.0 2.9] µmol/l, p=0.0243) as well as compared to EU-Ob-Con women (P=0.0006). Comparable results were obtained for primary, secondary, conjugated, unconjugated and 12α-hydroxylated BAs. There was no GDM effect on the relative contribution of primary, conjugated or 12α-hydroxylated BAs. Primary BAs correlated positively to fasting glucose (r2=0.12, p<0.0001) and negatively to the quantitative insulin-sensitivity check index (r2=0.11, p=0.0032) in GDM but not in control women. In SA (but not EU) women, C4 (7α-hydroxy-4-cholesten-3-one, BA synthesis measure) concentrations positively correlated to primary BA (r2=0.09, p<0.0001).
Discussion/Conclusion: The correlation of BA concentrations to measures of glucose homeostasis and BA synthesis depend on GDM status, BMI, and ethnicity. These data stress the importance of studying women of different BMI and ethnicity separately to understand individualised risk factors for GDM.