Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: A nested case-control study

Abstract

Background Bile acid metabolism plays an important role in metabolism but it is uncertain whether bile acid metabolites in early pregnancy are associated with risk of gestational diabetes mellitus (GDM). Methods We organized a 1:1 case-control study nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in China: 243 women with GDM were matched with 243 non-GDM controls on age (±1 year). Conditional logistic regression and restricted cubic spline were used to examine full-range associations of bile acid metabolites with GDM. Findings All the 9 detectable bile acids were inversely associated with the risk of GDM, among them, 8 in nonlinear and one in largely linear manners in multivariable analysis. Glycoursodeoxycholic acid (GUDCA) at ≤0.07 nmol/mL and deoxycholic acid (DCA) at ≤0.28 nmol/mL had threshold effects and their decreasing levels below the cutoff points were associated with rapid rises in the risk of GDM. In traditional risk factor model, the stepwise procedure identified that GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.280 nmol/mL were still significant (OR: 6.84, 95%CI: 1.10–42.48 & 2.06, 1.26–3.37), while other bile acids were not. Inclusion of the two bile acids in the model increased the area under operating characteristic's curve from 0.69 to 0.76 (95% CI: 0.71–0.80) ( P < .05). Interpretation Serum GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.28 nmol/mL in early pregnancy were independently associated with increased risk of GDM in Chinese pregnant women. Funding Talent Recruitment Scheme grant of Tianjin Medical University and National Key Research and Development Program, etc.

Circulating Lysophosphatidylcholines in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women

“…The selection procedure of the nested case-control study has been published in a previous study (13). In brief, 2991 women were enrolled and provided overnight fasting venous blood samples at their first antenatal care visit (median [interquartile range]: 10 [9-11] gestational weeks).…”

“…For example, a study found that plasma LPCs were positively associated with the risk of diabetes (11), but another study showed that plasma LPCs were inversely associated with diabetes risk (12). Our group reported that decreased bile acids, i.e., deoxycholic acid (DCA) and glycoursodeoxycholic acid (GUDCA), were independently associated with the risk of GDM (13). In this connection, several metabolomics studies found that abnormal bile acid metabolism was associated with phospholipid disorders and both of them can be used as biomarkers of diabetes (14,15).…”

Metabolomic Profiling After a Meal Shows Greater Changes and Lower Metabolic Flexibility in Cardiometabolic Diseases

“…In our study, the response of bile acid metabolite (chenodeoxycholic acid glycine conjugate or glycoursodeoxycholic acid) in a meal challenge differed by CMD status. Prior studies have found associations between glycoursodeoxycholic acid and diabetes treatment (metformin) [ 53 ] as well as outcomes (gestational diabetes) [ 54 ]. Metformin upregulates conjugated bile acids such as glycoursodeoxycholic acid, which is hypothesized to explain the lower circulating cholesterol concentrations observed with metformin treatment [ 53 ].…”

Declined Maternal GDCA is Correlated With Insulin Resistance and β-Cell Compensation in GDM: A Cross-Sectional Study in Chinese Pregnant Women

“…Research conducted on a large cohort of Chinese pregnant women in early pregnancy found that fasting serum levels of GUDCA ≤ 0.07 nmol/mL and DCA ≤ 0.28 nmol/mL were independently associated with an increased risk for development of GDM [31].Untargeted metabolomics administrated in pregnant women's fasting serum during OGTT screening period spot that CA, ios-DCA and dehydio-LCA decreased in GDM [32]. In this research, GDCA and TDCA declined obviously in GDM.…”