PMID- 37656932 OWN - NLM STAT- MEDLINE DCOM- 20230920 LR - 20230925 IS - 1520-5851 (Electronic) IS - 0013-936X (Linking) VI - 57 IP - 37 DP - 2023 Sep 19 TI - Metal Exposure during Early Pregnancy and Risk of Gestational Diabetes Mellitus: Mixture Effect and Mediation by Phospholipid Fatty Acids. PG - 13778-13792 LID - 10.1021/acs.est.3c04065 [doi] AB - 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. FAU - Sun, Fengjiang AU - Sun F AUID- ORCID: 0000-0002-9002-0173 AD - School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, Guangdong, China. FAU - Pan, Xiong-Fei AU - Pan XF AD - Section of Epidemiology and Population Health & Department of Gynecology and Obstetrics, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, and National Medical Product Administration Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, West China Second University Hospital, Sichuan University and Shuangliu Institute of Women's and Children's Health, Shuangliu Maternal and Child Health Hospital, Chengdu 610041, Sichuan, China. FAU - Hu, Yongxia AU - Hu Y AD - School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, Guangdong, China. FAU - Xie, Jinxin AU - Xie J AD - School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, Guangdong, China. FAU - Cui, Wenxuan AU - Cui W AD - School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, Guangdong, China. FAU - Ye, Yi-Xiang AU - Ye YX AD - Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. FAU - Wang, Yi AU - Wang Y AD - Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. FAU - Yang, Xue AU - Yang X AUID- ORCID: 0000-0002-9775-5009 AD - Section of Epidemiology and Population Health & Department of Gynecology and Obstetrics, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, and National Medical Product Administration Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, West China Second University Hospital, Sichuan University and Shuangliu Institute of Women's and Children's Health, Shuangliu Maternal and Child Health Hospital, Chengdu 610041, Sichuan, China. FAU - Wu, Ping AU - Wu P AD - Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. FAU - Yuan, Jiaying AU - Yuan J AD - Department of Science and Education, Shuangliu Maternal and Child Health Hospital, Chengdu 610200, Sichuan, China. FAU - Yang, Yan AU - Yang Y AUID- ORCID: 0000-0001-9592-8327 AD - School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, Guangdong, China. AD - Synergy Innovation Institute of GDUT, Shantou 515041, Guangdong, China. FAU - Pan, An AU - Pan A AD - Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. FAU - Chen, Da AU - Chen D AUID- ORCID: 0000-0001-5563-0091 AD - School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, Guangdong, China. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20230901 PL - United States TA - Environ Sci Technol JT - Environmental science & technology JID - 0213155 RN - 0 (Fatty Acids) RN - 0 (Phospholipids) RN - 0 (Metals) SB - IM MH - Female MH - Pregnancy MH - Humans MH - *Fatty Acids MH - Phospholipids MH - *Diabetes, Gestational/chemically induced/epidemiology MH - Bayes Theorem MH - Case-Control Studies MH - Prospective Studies MH - Metals OTO - NOTNLM OT - gestational diabetes mellitus OT - joint effect OT - mediation OT - metals OT - phospholipid fatty acids EDAT- 2023/09/01 18:42 MHDA- 2023/09/20 06:42 CRDT- 2023/09/01 16:03 PHST- 2023/09/20 06:42 [medline] PHST- 2023/09/01 18:42 [pubmed] PHST- 2023/09/01 16:03 [entrez] AID - 10.1021/acs.est.3c04065 [doi] PST - ppublish SO - Environ Sci Technol. 2023 Sep 19;57(37):13778-13792. doi: 10.1021/acs.est.3c04065. Epub 2023 Sep 1.