Dataset Information

Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis.

ABSTRACT:

Background and aims

Bile acids are known to contribute to hepatic glucose and lipid metabolism regulation. Although glucose homeostasis sustains well-characterized modifications during uncomplicated pregnancies, changes in bile acids concentrations and relative proportions throughout pregnancy remain unknown. Furthermore, literature shows strong associations between bile acids profiles and glucose homeostasis under normal metabolic conditions. We seek, first, to characterize bile acids' metabolic changes across trimesters and, second, to evaluate associations between changes in bile acids and glucose homeostasis indexes in the first and second trimesters.

Methods

A total of 78 women were recruited and followed at each trimester of pregnancy. Fasting serum samples were collected once per trimester in which quantitative measurement of 30 different bile acids' molecules were performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Glucose homeostasis indexes were measured in the first and second trimesters, after a 12-hour fast and following a 75?g oral glucose tolerance test.

Results

Total bile acids increased from the first trimester to late pregnancy, along with the cholic acid: chenodeoxycholic acid and conjugated: unconjugated bile acids ratios. Changes in bile acids were positively associated with elevated peripheral and hepatic insulin resistance indexes, as well as with trimestral changes in these indexes.

Conclusion

Our findings suggest that modifications occurring in bile acids' profiles during normal pregnancy are associated with changes in glucose homeostasis. Further research is needed to examine the nature of those associations and the possible outcome of bile acids changes on pathological glucose homeostasis alterations during pregnancy.

SUBMITTER: Gagnon M

PROVIDER: S-EPMC7875570 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis.

Gagnon Marianne M Trottier Jocelyn J Weisnagel S John SJ Gagnon Claudia C Carreau Anne-Marie AM Barbier Olivier O Morisset Anne-Sophie AS

Health science reports 20210210 1

<h4>Background and aims</h4>Bile acids are known to contribute to hepatic glucose and lipid metabolism regulation. Although glucose homeostasis sustains well-characterized modifications during uncomplicated pregnancies, changes in bile acids concentrations and relative proportions throughout pregnancy remain unknown. Furthermore, literature shows strong associations between bile acids profiles and glucose homeostasis under normal metabolic conditions. We seek, first, to characterize bile acids' ...[more]

PMID: 33614980

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Project description:Background and objective: The maternal glucose-insulin axis is central for metabolic adaptations required for a healthy pregnancy. Metabolic changes in obese mothers in early pregnancy have been scantly described. Here we characterized the glucose-insulin axis in the first trimester of human pregnancy and assessed the effect of maternal obesity and fat mass. Methods: In this cross-sectional study, maternal blood samples (N = 323) were collected during voluntary pregnancy termination (gestational age 4+0-11+6 weeks) after overnight fasting. Smokers (N = 198) were identified by self-report and serum cotinine levels (ELISA). Maternal BMI (kg/m2) and serum leptin (ELISA) were used as proxy measures of obesity and maternal fat mass, respectively. BMI was categorized into under-/normal weight (BMI < 25.0 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI ≥ 30.0 kg/m2), and leptin in tertiles (1st tertile: leptin < 6.80 ng/ml, 2nd tertile: leptin 6.80-12.89 ng/ml, 3rd tertile: leptin > 12.89 ng/ml). ISHOMA insulin sensitivity index was calculated from glucose and C-peptide (ELISA) serum concentrations. Analyses of covariance including multiple confounders were performed to test for differences in glucose, C-peptide and ISHOMA between gestational age periods, BMI and leptin groups. C-peptide and ISHOMA were log-transformed before analyses. Results: At weeks 7-9, fasting glucose and C-peptide levels were lower (P < 0.01 and P < 0.001, respectively) and insulin sensitivity higher (P < 0.001) than at weeks 4-6. Glucose levels were not significantly different between BMI or leptin categories. In contrast, C-peptide increased by 19% (P < 0.01) between the normal weight and the overweight group and by 39% (P < 0.001) between the overweight and obese group. In the leptin groups, C-peptide increased by 25% (P < 0.001) between the 1st and 2nd leptin tertile and by 15% (P < 0.05) between the 2nd and 3rd leptin tertile. ISHOMA decreased with higher BMI and fat mass. ISHOMA decreased by 18% (P < 0.01) between the normal weight and the overweight group and by 30% (P < 0.01) between the overweight and the obese group. In the leptin groups, ISHOMA decreased by 22% (P < 0.001) between the 1st and 2nd leptin tertile and by 14% (P < 0.05) between the 2nd and 3rd leptin tertile. Conclusions: At the group level, fasting glucose, C-peptide and insulin sensitivity dynamically change in the first trimester of human pregnancy. Maternal obesity is associated with higher C-peptide and lower insulin sensitivity at all periods in the first trimester of human pregnancy, while glucose is unaltered. These findings have implications for the timing of early gestational diabetes mellitus risk screening.

Project description:BackgroundThe bile acid (BA) pathway plays a role in regulation of food intake and glucose metabolism, based mainly on findings in animal models. Our aim was to determine whether the BA pathway is altered and correctable in human obesity and diabetes.MethodsWe conducted 3 investigations: 1) BA receptor pathways were studied in NCI-H716 enteroendocrine cell (EEC) line, whole human colonic mucosal tissue and in human colonic EEC isolated by Fluorescence-activated Cell Sorting (ex vivo) from endoscopically-obtained biopsies colon mucosa; 2) We characterized the BA pathway in 307 participants by measuring during fasting and postprandial levels of FGF19, 7αC4 and serum BA; 3) In a placebo-controlled, double-blind, randomised, 28-day trial, we studied the effect of ileo-colonic delivery of conjugated BAs (IC-CBAS) on glucose metabolism, incretins, and lipids, in participants with obesity and diabetes.FindingsHuman colonic GLP-1-producing EECs express TGR5, and upon treatment with bile acids in vitro, human EEC differentially expressed GLP-1 at the protein and mRNA level. In Ussing Chamber, GLP-1 release was stimulated by Taurocholic acid in either the apical or basolateral compartment. FGF19 was decreased in obesity and diabetes compared to controls. When compared to placebo, IC-CBAS significantly decreased postprandial glucose, fructosamine, fasting insulin, fasting LDL, and postprandial FGF19 and increased postprandial GLP-1 and C-peptide. Increase in faecal BA was associated with weight loss and with decreased fructosamine.InterpretationsIn humans, BA signalling machinery is expressed in colonic EECs, deficient in obesity and diabetes, and when stimulated with IC-CBAS, improved glucose homeostasis. ClinicalTrials.gov number, NCT02871882, NCT02033876.FundingResearch support and drug was provided by Satiogen Pharmaceuticals (San Diego, CA). AA, MC, and NFL report grants (AA- C-Sig P30DK84567, K23 DK114460; MC- NIH R01 DK67071; NFL- R01 DK057993) from the NIH. JR was supported by an Early Career Grant from Society for Endocrinology.

Dataset Information

Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis.

Background and aims

Methods

Results

Conclusion

Publications

Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis.

Similar Datasets

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