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. 2018 Sep;35:317-324.
doi: 10.1016/j.ebiom.2018.08.015. Epub 2018 Aug 14.

Bile Acid Metabolites in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women: A Nested Case-Control Study

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Free PMC article

Bile Acid Metabolites in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women: A Nested Case-Control Study

Jing Li et al. EBioMedicine. .
Free PMC article

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.

Keywords: Bile acids; Early-onset marker; Gestational diabetes mellitus; Metabolism; Metabolomics.

Figures

Fig. 1
Fig. 1
Flow diagram of selection of the study women in the nested case-control study.
Fig. 2
Fig. 2
Associations between individual bile acids and the risk of gestational diabetes mellitus (GDM) in Chinese women. Abbreviations: CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; GUDCA, glycoursodeoxycholic acid; OR, odds ratio. The upper (dotted, black) lines were derived from univariable analyses, the middle (crossed, blue) lines were derived from multivariable analyses (See Table 2, multivariable model 1 for the list of adjusted variables) and the bottom (red, straight) lines were the reference line at OR = 1.
Fig. 3
Fig. 3
Receiver operating characteristic curves of traditional risk factors, bile acids and traditional risk factors plus bile acids for gestational diabetes mellitus in Chinese women. Abbreviations: DCA, deoxycholic acid; GUDCA, glycoursodeoxycholic acid; ROC: receiver operating characteristic curve. Legends: The blue (solid) curve stands for the DCA and GUDCA model; the green (dash-dot) curve for the traditional risk factor model (Multivariable Model 1 in Table 2 for the list of variables), the black (dashed) curve for the traditional risk factor plus DCA and GUDCA model. The area under the operating characteristic curve (AUC) was 0.69 (95% CI: 0.64–0.73) for the DCA and GUDCA model, 0.69 (95% CI: 0.64–0.74) for the traditional risk factors model and 0.76 (95% CI: 0.71–0.80) for the traditional risk factor plus DCA and GUDCA model (P < .0001 for comparison of the traditional risk factor plus DCA and GUDCA model with either of the other two models).

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