Association between serum bile acid profiles and gestational diabetes mellitus: A targeted metabolomics study

Gao, Jieying; Xu, Bo; Zhang, Xiaoqing; Cui, Yue; Deng, Linlin; Shi, Zhenghu; Shao, Yina; Ding, Min

doi:10.1016/j.cca.2016.05.026

Cited by 52 publications

(47 citation statements)

References 49 publications

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“…Changing habits of population may lead in the nearest future to increased rate of this condition. Based on our results and other studies it may also have an impact on rate of intrahepatic cholestasis of pregnancy [6,20].…”

Section: Discussionsupporting

confidence: 78%

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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: Discussionsupporting

confidence: 78%

“…It is thought, that bile acids are involved in the regulation of hepatic glucose metabolism by FXR-mediated pathways [21,22]. Based on that some studies searched whether ICP might increase risk of GDM [20]. Martineau et al evaluated the incidence of GDM in ICP patients is higher than in general population and the rate by then is 13.6% [23].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…The alteration of BA metabolome may indicate intestinal flora imbalance and glucose metabolic disorders in GDM state. Another BA metabolomics studied in Chinese subjects reported that THDCA levels were similarly higher in GDM patients, but the changes in CA, HDCA and LCA levels were not found (24). UDCA has been frequently reported to be closely associated with lipid and glucose metabolism (25,26), but UDCA concentrations were comparable between the two groups.…”

Section: Discussionmentioning

confidence: 96%

Development of Multimarker Diagnostic Models from Metabolomics Analysis for Gestational Diabetes Mellitus (GDM)

Hou

Meng

Zhao

et al. 2018

Molecular & Cellular Proteomics

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Although metabolomics are desirable to understand the pathophysiology of gestational diabetes mellitus (GDM), comprehensive metabolomic studies of GDM are rare. We aimed to offer a holistic view of metabolites alteration in GDM patients and investigate the possible multimarker models for GDM diagnosis. Biochemical parameters and perinatal data of 131 GDM cases and 138 controls were collected. Fasting serum samples at 75 g oral glucose tolerance test were used for metabolites by ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry, ultra performance liquid chromatography-triple triple-quadrupole-mass spectrometry and gas chromatography- time-of- flight mass spectrometry platforms. Significant changes were observed in free fatty acids, bile acids, branched chain amino acids, organic acids, lipids and organooxygen compounds between two groups. In receiver operating characteristic (ROC) analysis, different combinations of candidate biomarkers and metabolites in multimarker models achieved satisfactory discriminative abilities for GDM, with the values of area under the curve (AUC) ranging from 0.721 to 0.751. Model consisting of body mass index (BMI), retinol binding protein 4 (RBP4), n-acetylaspartic acid and C16:1 (cis-7) manifested the best discrimination [AUC 0.751 (95% CI: 0.693-0.809), < 0.001], followed by model consisting of BMI, Cystatin C, acetylaspartic acid and 6,7-diketoLCA [AUC 0.749 (95% CI: 0.691-0.808), < 0.001]. Metabolites alteration reflected disorders of glucose metabolism, lipid metabolism, amino acid metabolism, bile acid metabolism as well as intestinal flora metabolism in GDM state. Multivariate models combining clinical markers and metabolites have the potential to differentiate GDM subjects from healthy controls.

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“…In humans, early studies showed that MCAs were unable to be synthesized because of a lack of specific enzymes . However, MCAs also have been recently detected by many clinical studies in humans and have been used as new biomarkers for several diseases . Although the processes have not been fully understood, there is evidence suggesting that MCAs are converted from CDCAs by the human liver microsome CYP450 system .…”

Section: Discussionmentioning

confidence: 99%

Ratio of Conjugated Chenodeoxycholic to Muricholic Acids is Associated with Severity of Nonalcoholic Steatohepatitis

Chen

Zheng

Liu

et al. 2019

Obesity

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Objective Bile acids (BAs) are important molecules in the progression of nonalcoholic fatty liver disease. This study aimed to investigate BA profile alterations in Chinese nonalcoholic steatohepatitis (NASH) patients. Methods BA profiles in serum and liver tissues were determined by ultraperformance liquid chromatography coupled to tandem mass spectrometry in patients from two different clinical centers. Results A total of 134 participants were enrolled in this study to serve as the training (n = 87) and validation (n = 47) cohorts. The ratio of circulating conjugated chenodeoxycholic acids to muricholic acids (P = 0.001) was elevated from healthy controls to non‐NASH individuals to NASH individuals in a stepwise manner in the training cohort and was positively associated with the histological severity of NASH: steatosis (R2 = 0.12), lobular inflammation (R2 = 0.12), ballooning (R2 = 0.11), and fibrosis stage (R2 = 0.18). The ratio was elevated in the validation cohort of NASH patients (P < 0.001), and it was able to predict NASH (area under the receiver operating characteristic curve: 75%) and significant fibrosis (area under the receiver operating characteristic curve: 71%) in these two cohorts. Moreover, this elevated ratio and impaired farnesoid X receptor signaling were found in the NASH liver. Conclusions Altered BA profile in NASH is closely associated with the severity of liver lesions, and it has the potential for predicting NASH development.

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Association between serum bile acid profiles and gestational diabetes mellitus: A targeted metabolomics study

Cited by 52 publications

References 49 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

Development of Multimarker Diagnostic Models from Metabolomics Analysis for Gestational Diabetes Mellitus (GDM)

Ratio of Conjugated Chenodeoxycholic to Muricholic Acids is Associated with Severity of Nonalcoholic Steatohepatitis

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