Association of Serum Levels of Trace Elements in Early Pregnancy with Bile Acid Metabolism and Gestational Diabetes Mellitus:A Nested Case-Control Study / 华中科技大学学报(医学版)

ABSTRACT

Objective To explore the association between serum trace element levels in early pregnancy and gestational dia-betes mellitus(GDM),and the mediating effect of bile acid metabolism changes in this association.Methods A nested case-con-trol study was designed based on the Guangxi Zhuang Birth Cohort.A total of 248 pregnant women(case group=124,control group=124)were included from June 2015 to July 2019 in Nanning city.The concentrations of 8 trace elements and 31 bile acids in serum were measured in early pregnancy.Conditional logistic regression and BKMR models were used to analyze the associa-tion and combined effect between trace elements and GDM risk,respectively.Orthogonal partial least squares-discriminant anal-ysis(OPLS-DA)was used to screen potential bile acid biomarkers associated with GDM,and then conditional logistic regression was used to determine the association between specific bile acid levels and GDM risk.Multiple linear regression was used to e-valuate the association of serum trace element concentrations with differential bile acid metabolites.Mediation analysis was used to evaluate the mediating role of bile acids in the relationship between trace element exposure and GDM.Results After adjus-ting for confounding factors,serum vanadium(V)was found to be positively associated with the risk of GDM,while chromium(Cr),manganese(Mn),zinc(Zn),selenium(Se)and molybdenum(Mo)were negatively correlated with the risk of GDM(all P＜0.05).The OPLS-DA model and conditional Logistic regression analysis showed that taurocholic acid(TCA),glycochenodeoxy-cholic acid 3-sulfate(GCDCA-3S),glycochenodeoxycholic acid-3-O-β-glucuronide(GCDCA-3Gln),glycoursodeoxycholic acid-3-sulfate(GUDCA-3S),taurodeoxycholic acid-3-sulfate(TDCA-3S),and chenodeoxycholic acid(CDCA)might be potential bile acid metabolic markers of GDM(all P＜0.05).The concentrations of multiple trace elements were also significantly correlated with the levels of specific bile acids(all P＜0.05).Mediation analysis showed that GCDCA-3Gln and TCA mediated the associa-tion between serum Zn and Se and GDM risk,respectively(all P＜0.05).Conclusion Serum trace elements such as V and Cr are significantly associated with the risk of GDM in early pregnancy,and changes in bile acid metabolism may precede the occur-rence of GDM.It is suggested that the effect of trace elements on the metabolism of bile acids,especially conjugated bile acids,may be one of the mechanisms affecting the risk of GDM.