The Metabolic Profile of Intrahepatic Cholestasis of Pregnancy Is Associated With Impaired Glucose Tolerance, Dyslipidemia, and Increased Fetal Growth

Martineau, Marcus; Raker, Christina; Dixon, Peter H.; Chambers, Jenny; Machirori, Mavis; M.King, Nicole; Hooks, Melissa L.; Manoharan, Ramya; Chen, Kenneth; Powrie, Raymond; Williamson, Catherine

doi:10.2337/dc14-2143

Cited by 117 publications

(116 citation statements)

References 45 publications

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“…It is suggested that during gestation if the homeostasis of one mentioned substances is dysregulated it might correlate with higher risk of abnormal levels of another. One of the prospective study of 31 patients with ICP reported a significantly higher blood glucose level while oral glucose tolerance testing (OGTT) [6].…”

Section: Introductionmentioning

confidence: 99%

Association between intrahepatic cholestasis in pregnancy and gestational diabetes mellitus. A retrospective analysis

et al. 2019

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Objectives: Intrahepatic cholestasis of pregnancy (ICP) is a liver specific disorder affecting 0.08%-27.6% pregnant women. It is characterized by reduced expression of the primary bile acid farnesoid receptor (FXR). In recent studies, it has been showed that FXR has an impact on normal glucose homeostasis. Based on that it was suggested that the level of bile acids correlates with glucose level. The aim of the study was to evaluate the association between ICP and gestational diabetes mellitus (GDM).Material and methods: 102 singleton patients complicated by ICP were included to the study and divided into two groups: non-GDM group (74 patients) and GDM group (28 patients). ICP was diagnosed based on the serum bile acids level > 10 μmol/L and GDM with the 75 g oral glucose tolerance test and FIGO guidelines. Demographic and clinical outcome data (including maternal age, BMI and infant weight) and ICP and GDM biochemical markers were collected. Results:The incidence of GDM in ICP patients was 27.45%. 73% of women included to the study developed mild cholestasis. Lower levels of serum bile acids were correlated with GDM group. When compared mean total bilirubin level was significantly higher in non-GDM group. Transaminases (ALT, AST) and neonate condition including mean birth weight revealed no significant difference between the groups. On the other hand, prevalence of large for gestational age was significantly higher in non-GDM group (p < 0.00001). Conclusions:The incidence of ICP is higher in women with GDM.

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Section: Introductionmentioning

confidence: 99%

Association between intrahepatic cholestasis in pregnancy and gestational diabetes mellitus. A retrospective analysis

et al. 2019

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“…Specifically, studies in late pregnant rats have demonstrated increased mRNA expression and activity of hormone-sensitive lipase in white adipose tissue [8]. Additionally, it has been shown that the levels and the activity of adipose tissue LPL are reduced in women and rats with late pregnancy [9], thereby decreasing the deposit of lipids in maternal adipocytes.…”

Section: Catabolic Phasementioning

confidence: 99%

Metabolic Adaptations in Pregnancy: A Review

Zeng

Liu²,

Li³

2017

Ann Nutr Metab

184

135

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Background: Pregnancy is a dynamic state involving multiple adaptations that are necessary in order to ensure a continuous supply of essential metabolites to support the growth and the development of the fetus. Objectives: This review article is aimed to discuss important adaptations in metabolism that take place during non-complicated pregnancy. Materials and Methods: We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting the importance of metabolic adaptations during a non-complicated pregnancy. The preferred language was English and the most recent reports were selected to get an updated review. Results: It was observed clearly in the searched literature that metabolic adaptations are a crucial part of pregnancy, as they provide the mother with sufficient energy stores to meet the demands of pregnancy. These adaptions also help in preparing the mother for lactation and also help in providing proper environment for the proper growth of fetus in the womb. Moreover, multiple biomolecules including glucose, fatty acids, ketone bodies, hormones collectively contribute toward these metabolic adaptations. Conclusions: This review article concludes that metabolic adaptations are crucial for proper fetus development.

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“…The drug ursodeoxycholic acid (UDCA) improves itch severity and alters the composition of the serum bile acid pool in ICP 8,9 . Previous studies have suggested that UDCA may be of additional benefit for women with ICP, for example by normalising the ICP-related fall in glucagon-like peptide 1 (GLP1) release following a meal 6 . Indeed, murine studies have demonstrated that UDCA treatment can lower blood glucose concentrations in mice fed a high-fat diet 10 .…”

mentioning

confidence: 99%

Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy

Ovadia

Perdones-Montero

Fan

et al. 2020

Sci Rep

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Ursodeoxycholic acid (UDcA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in icp to alter enterohepatic signalling. the gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDcA (fisher's exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDcA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. these demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19.The serum and faecal bile acid composition is intimately related to biotransformation of bile acids by intestinal bacteria, and their subsequent enterohepatic circulation. Deconjugation of primary bile acids by bacterial bile salt hydrolase (BSH) enables unconjugated bile acids to be modified to secondary bile acids. Bile acids act as signalling molecules for many different end organs (e.g. liver, pancreas, adipose tissue, inflammatory cells), with individual bile acid species of differing ligand potency for different receptors (e.g. farnesoid X receptor (FXR), Takeda G-protein-coupled receptor 5 (TGR5)) 1-3 .Intrahepatic cholestasis of pregnancy (ICP) is predominantly a liver disorder specific to pregnancy, defined by pruritus and elevated serum bile acids beyond the normal asymptomatic hypercholanaemia of pregnancy. Fetal adverse outcomes are related to the extent of elevation of serum concentrations of total bile acids 4,5 . Women with ICP have increased rates of impaired glucose tolerance, gestational diabetes mellitus, and dyslipidaemia 6,7 .

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The Metabolic Profile of Intrahepatic Cholestasis of Pregnancy Is Associated With Impaired Glucose Tolerance, Dyslipidemia, and Increased Fetal Growth

Cited by 117 publications

References 45 publications

Association between intrahepatic cholestasis in pregnancy and gestational diabetes mellitus. A retrospective analysis

Association between intrahepatic cholestasis in pregnancy and gestational diabetes mellitus. A retrospective analysis

Metabolic Adaptations in Pregnancy: A Review

Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy

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