Metal Exposure during Early Pregnancy and Risk of Gestational Diabetes Mellitus: Mixture Effect and Mediation by Phospholipid Fatty Acids

妊娠期糖尿病 调解 化学 内科学 妊娠期 内分泌学 产科 怀孕 医学 生物 遗传学 政治学 法学
作者
Fengjiang Sun,Xiong‐Fei Pan,Yongxia Hu,Jinxin Xie,Wenxuan Cui,Yi‐Xiang Ye,Yi Wang,Xue Yang,Ping Wu,Jiaying Yuan,Yan Yang,An Pan,Da Chen
出处
期刊:Environmental Science & Technology [American Chemical Society]
卷期号:57 (37): 13778-13792 被引量:11
标识
DOI:10.1021/acs.est.3c04065
摘要

Despite existing studies exploring the association between metal exposure and gestational diabetes mellitus (GDM), most of them have focused on a single metal or a small mixture of metals. Our prospective work investigated the joint and independent effects of early gestational exposure to 17 essential and nonessential metals on the GDM risk and potential mediation by plasma phospholipid fatty acids (PLFAs) based on a nested case-control study established with 335 GDM cases and 670 randomly matched healthy controls. The Bayesian kernel machine regression (BKMR) and quantile g-computation analyses demonstrated a joint effect from metal co-exposure on GDM risk. BKMR with hierarchical variable selection indicated that the group of essential metals was more strongly associated with GDM than the group of nonessential metals with group posterior inclusion probabilities (PIPs) of 0.979 and 0.672, respectively. Cu (0.988) and Ga (0.570) had the largest conditional PIPs within each group. We also observed significant mediation effects of selected unsaturated PLFAs on Cu-GDM and Ga-GDM associations. KEGG enrichment analysis further revealed significant enrichment in the biosynthesis of unsaturated PLFAs. C18:1 n-7 exhibited the largest proportion of mediation in both associations (23.8 and 22.9%). Collectively, our work demonstrated the joint effect of early gestational metal exposure on GDM risk and identified Cu and Ga as the key species to the joint effect. The findings lay a solid ground for further validation through multicenter investigations and mechanism exploration via laboratory studies.
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