Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism

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BACKGROUND: Gestational diabetes mellitus (GDM) is common complication in pregnancy. Most studies on the relationship between metal and GDM have centered on a single metal or a few metals mixed, and it remains unclear whether bile acids are associated with this relationship. OBJECTIVE: To investigate the association between exposure to multiple metals in early pregnancy and GDM risk, and the mediating role of serum bile acids. METHODS: Based on a Guangxi Zhuang Birth Cohort, 650 pregnant women recruited were included in the study. Multiple machine models were used to explore the key metal variables and estimate the effects of mixed metal exposure. Then, a nested case-control study was designed with 1:1 individual matching by maternal age and gestational age (n = 304). Mediation analysis was used to assess the mediating role of serum bile acids between metal exposure and GDM. RESULTS: Mo and Sb were found to be negatively associated with GDM risk, while Cd was positively associated with GDM risk. The BKMR model showed that mixed exposure to Mo, Cd and Sb were negatively correlated with GDM risk. Besides, multiple bile acids (such as glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA)) and nine bile acid ratios were correlated with GDM risk. Mo, Cd and Sb were significantly correlated with bile acid levels. The TCA/CA and TCDCA/CDCA played a mediating role in Sb exposure and GDM risk. CONCLUSIONS: Our findings indicate that exposure to Mo, Cd and Sb is significantly associated with the risk of GDM, and bile acids may play a mediating role in this.

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