{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T18:23:41Z","timestamp":1782411821704,"version":"3.54.5"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103821"],"award-info":[{"award-number":["82103821"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Minerals and trace elements were involved in the pathogenesis and progression of diabetes. However, the association of mixed exposure to essential elements and toxic elements with gestational diabetes mellitus (GDM) is poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to examine the associations between serum calcium (Ca), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and cadmium (Cd) concentrations in early pregnancy and GDM risk in Chinese pregnant women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A total of 1,168 pregnant women were included in this prospective cohort study. The concentrations of serum elements were measured using the polarography method before 14 gestational weeks and an oral glucose tolerance test was conducted at 24\u201328 gestational weeks to diagnose GDM. Binary logistic regression analysis and restricted cubic spline were applied to evaluate the association between serum individual element and GDM. Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to assess the associations between mixed essential elements and Cd exposure and GDM risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean concentrations of Zn (124.65 vs. 120.12\u2009\u03bcmol\/L), Fe (135.26 vs. 132.21\u2009\u03bcmol\/L) and Cu (23.33 vs. 23.03\u2009\u03bcmol\/L) in the GDM group were significantly higher than those in the control group. Single-element modeling results suggested that second and fourth-quartile maternal Zn and Fe concentration, third and fourth-quartile Cu concentration and fourth-quartile Ca concentration were associated with an increased risk of GDM compared to first-quartile values. Restricted cubic spline analysis showed U-shaped and non-linear relationships between Cd and GDM. According to the BKMR models and WQS analyses, a six-element mixture was significantly and positively associated with the risk of GDM. Additionally, Cd, Zn, and Cu contributed the most strongly to the association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serum Zn, Cu, Fe, and Ca exposure during early pregnancy showed a positive association with GDM in the individual evaluation. The multiple-evaluation showed that high levels of elements mixture, particularly Cd, Zn, and Cu, may promote the development of GDM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2023.1278617","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T08:09:17Z","timestamp":1701850157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Combined exposure to multiple essential elements and cadmium at early pregnancy on gestational diabetes mellitus: a prospective cohort study"],"prefix":"10.3389","volume":"10","author":[{"given":"Guifang","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhuan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhe","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S81","DOI":"10.2337\/dc14-S081","article-title":"Diagnosis and classification of diabetes mellitus","volume":"37","year":"2013","journal-title":"Diabetes Care"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1515\/jpm-2012-0015","article-title":"The prevalence of gestational diabetes in advanced economies","volume":"40","author":"Schneider","year":"2012","journal-title":"J Perinat Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/jdi.12854","article-title":"Prevalence of gestational diabetes mellitus in mainland China: a systematic review and meta-analysis","volume":"10","author":"Gao","year":"2019","journal-title":"J Diabetes Investig"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"675","DOI":"10.2337\/diacare.24.12.2160","article-title":"Antepartum and early postpartum predictors of type 2 diabetes development in women with gestational diabetes mellitus","volume":"27","author":"Dalfr\u00e0","year":"2001","journal-title":"Diabetes Metab"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"676","DOI":"10.2337\/dc09-1848","article-title":"International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy","volume":"33","author":"Metzger","year":"2010","journal-title":"Diabetes Care"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e49","DOI":"10.1097\/aog.0000000000002501","article-title":"ACOG Practice Bulletin No. 190: gestational diabetes mellitus","volume":"131","year":"2018","journal-title":"Obstet Gynecol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/nu12061864","article-title":"Role of minerals and trace elements in diabetes and insulin resistance","volume":"12","author":"Dubey","year":"2020","journal-title":"Nutrients"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/2251-6581-13-16","article-title":"Metals in the pathogenesis of type 2 diabetes","volume":"13","author":"Khan","year":"2014","journal-title":"J Diabetes Metab Disord"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1007\/s12020-013-0032-x","article-title":"Zinc and insulin in pancreatic beta-cells","volume":"45","author":"Li","year":"2014","journal-title":"Endocrine"},{"key":"ref10","first-page":"47","article-title":"Magnesium metabolism and its disorders","volume":"24","author":"Swaminathan","year":"2003","journal-title":"Clin Biochem Rev"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"106770","DOI":"10.1016\/j.envint.2021.106770","article-title":"Associations between endocrine-disrupting heavy metals in maternal hair and gestational diabetes mellitus: a nested case-control study in China","volume":"157","author":"Jia","year":"2021","journal-title":"Environ Int"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"124412","DOI":"10.1016\/j.chemosphere.2019.124412","article-title":"Multiple metal concentrations and gestational diabetes mellitus in Taiyuan, China","volume":"237","author":"Wang","year":"2019","journal-title":"Chemosphere"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"105370","DOI":"10.1016\/j.envint.2019.105370","article-title":"Exposure to multiple metals in early pregnancy and gestational diabetes mellitus: a prospective cohort study","volume":"135","author":"Wang","year":"2020","journal-title":"Environ Int"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.scitotenv.2018.11.422","article-title":"Exposure to heavy metals during pregnancy related to gestational diabetes mellitus in diabetes-free mothers","volume":"656","author":"Soomro","year":"2019","journal-title":"Sci Total Environ"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"111854","DOI":"10.1016\/j.ecoenv.2020.111854","article-title":"Prospective association of metal levels with gestational diabetes mellitus and glucose: a retrospective cohort study from South China","volume":"210","author":"Zhou","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"4295","DOI":"10.1210\/jc.2019-00109","article-title":"A prospective study of early pregnancy essential metal(loid)s and glucose levels late in the second trimester","volume":"104","author":"Zheng","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"126829","DOI":"10.1016\/j.jtemb.2021.126829","article-title":"Plasma levels of trace element status in early pregnancy and the risk of gestational diabetes mellitus: a nested case-control study","volume":"68","author":"Zhu","year":"2021","journal-title":"J Trace Elem Med Biol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.3390\/nu12041108","article-title":"First trimester microelements and their relationships with pregnancy outcomes and complications","volume":"12","author":"Lewandowska","year":"2020","journal-title":"Nutrients"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1002\/fsn3.2561","article-title":"Effect of magnesium supplementation on pregnancy outcome in gestational diabetes mellitus patients: a meta-analysis of randomized controlled trials","volume":"10","author":"Qu","year":"2022","journal-title":"Food Sci Nutr"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.numecd.2015.02.013","article-title":"Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: a prospective study","volume":"25","author":"Zaccardi","year":"2015","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"157819","DOI":"10.1016\/j.scitotenv.2022.157819","article-title":"Cadmium induces ferroptosis mediated inflammation by activating Gpx4\/Ager\/P65 axis in pancreatic \u03b2-cells","volume":"849","author":"Hong","year":"2022","journal-title":"Sci Total Environ"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00420-018-1367-7","article-title":"Association between maternal blood cadmium and lead concentrations and gestational diabetes mellitus in the Japan environment and children\u2019s study","volume":"92","author":"Oguri","year":"2019","journal-title":"Int Arch Occup Environ Health"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.envint.2018.01.001","article-title":"Relation between cadmium exposure and gestational diabetes mellitus","volume":"113","author":"Xing","year":"2018","journal-title":"Environ Int"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/S0278-6915(01)00048-5","article-title":"Interactions between cadmium and zinc in the organism","volume":"39","author":"Brz\u00f3ska","year":"2001","journal-title":"Food Chem Toxicol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1097\/mop.0000000000000877","article-title":"Environmental mixtures and children\u2019s health: identifying appropriate statistical approaches","volume":"32","author":"Tanner","year":"2020","journal-title":"Curr Opin Pediatr"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"107161","DOI":"10.1016\/j.envint.2022.107161","article-title":"Exposure to multiple trace elements and miscarriage during early pregnancy: a mixtures approach","volume":"162","author":"Lu","year":"2022","journal-title":"Environ Int"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"112615","DOI":"10.1016\/j.envres.2021.112615","article-title":"Association between prenatal exposure to metal mixtures and early childhood allergic diseases","volume":"206","author":"Ruan","year":"2022","journal-title":"Environ Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1186\/s12884-018-2131-4","article-title":"Prevalence and risk factors of gestational diabetes mellitus in Asia: a systematic review and meta-analysis","volume":"18","author":"Lee","year":"2018","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1080\/14767058.2020.1754395","article-title":"Prevalence of gestational diabetes mellitus and its determinants among pregnant women in Beijing","volume":"35","author":"Wang","year":"2022","journal-title":"J Matern Fetal Neonatal Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1289\/ehp.97105s4817","article-title":"Factors influencing susceptibility to metals","volume":"105","author":"Gochfeld","year":"1997","journal-title":"Environ Health Perspect"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1097\/00001648-199901000-00008","article-title":"Causal diagrams for epidemiologic research","volume":"10","author":"Greenland","year":"1999","journal-title":"Epidemiology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.envint.2018.11.076","article-title":"Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: comparison of three statistical models","volume":"123","author":"Zhang","year":"2019","journal-title":"Environ Int"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"105728","DOI":"10.1016\/j.envint.2020.105728","article-title":"Prenatal exposure to per- and polyfluoroalkyl substances and maternal and neonatal thyroid function in the project viva cohort: a mixtures approach","volume":"139","author":"Preston","year":"2020","journal-title":"Environ Int"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.envint.2018.01.016","article-title":"Association between prenatal exposure to multiple insecticides and child body weight and body composition in the Vhembe South African birth cohort","volume":"113","author":"Coker","year":"2018","journal-title":"Environ Int"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"047004","DOI":"10.1289\/EHP5838","article-title":"A quantile-based G-computation approach to addressing the effects of exposure mixtures","volume":"128","author":"Keil","year":"2020","journal-title":"Environ Health Perspect"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1385\/bter:88:2:113","article-title":"Elemental contents in serum of pregnant women with gestational diabetes mellitus","volume":"88","author":"Wang","year":"2002","journal-title":"Biol Trace Elem Res"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"131809","DOI":"10.1016\/j.chemosphere.2021.131809","article-title":"Exposure to metals and metalloids among pregnant women from Spain: levels and associated factors","volume":"286","author":"Lozano","year":"2022","journal-title":"Chemosphere"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1007\/s002540000224","article-title":"Geographical variations of trace elements in sediments of the major rivers in eastern China","volume":"39","author":"Chen","year":"2000","journal-title":"Environ Geol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1177\/15648265020233s124","article-title":"Dietary intake of essential minor and trace elements from Asian diets","volume":"23","author":"Iyengar","year":"2002","journal-title":"Food Nutr Bull"},{"key":"ref40","first-page":"157","article-title":"Estimation of serum zinc, copper and magnesium levels in Bangladeshi women with gestational diabetes mellitus attending in a tertiary care hospital","volume":"28","author":"Mishu","year":"2019","journal-title":"Mymensingh Med J"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1152\/physrev.00018.2001","article-title":"Free radicals in the physiological control of cell function","volume":"82","author":"Dr\u00f6ge","year":"2002","journal-title":"Physiol Rev"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e0251554","DOI":"10.1371\/journal.pone.0251554","article-title":"Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia","volume":"16","author":"Tokuyama","year":"2021","journal-title":"PLoS One"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.mam.2005.07.015","article-title":"Copper, oxidative stress, and human health","volume":"26","author":"Uriu-Adams","year":"2005","journal-title":"Mol Asp Med"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0009-8981(92)90220-k","article-title":"Copper metabolism\u2014a factor in gestational diabetes?","volume":"213","author":"Loven","year":"1992","journal-title":"Clin Chim Acta"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1007\/s00592-007-0250-x","article-title":"Maternal-foetal status of copper, iron, molybdenum, selenium and zinc in obese gestational diabetic pregnancies","volume":"44","author":"Al-Saleh","year":"2007","journal-title":"Acta Diabetol"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5402\/2012\/470419","article-title":"A comparative study of relationship between micronutrients and gestational diabetes","volume":"2012","author":"Akhlaghi","year":"2012","journal-title":"ISRN Obstet Gynecol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"2922","DOI":"10.1016\/j.clnu.2018.12.032","article-title":"Association between plasma concentration of copper and gestational diabetes mellitus","volume":"38","author":"Li","year":"2019","journal-title":"Clin Nutr"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s12011-016-0877-y","article-title":"Copper in diabetes mellitus: a meta-analysis and systematic review of plasma and serum studies","volume":"177","author":"Qiu","year":"2017","journal-title":"Biol Trace Elem Res"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/0002-9378(87)90259-6","article-title":"Effect of calcium supplementation on the vascular sensitivity to angiotensin II in pregnant women","volume":"156","author":"Lopez-Jaramillo","year":"1987","journal-title":"Am J Obstet Gynecol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1002\/fsn3.2118","article-title":"Association of dietary calcium, magnesium, and vitamin D with type 2 diabetes among us adults: National Health and Nutrition Examination Survey 2007\u20132014-a cross-sectional study","volume":"9","author":"Shah","year":"2021","journal-title":"Food Sci Nutr"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.3945\/ajcn.2008.27182","article-title":"Dietary calcium and magnesium intakes and the risk of type 2 diabetes: the Shanghai women\u2019s health study","volume":"89","author":"Villegas","year":"2009","journal-title":"Am J Clin Nutr"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1007\/s00198-015-3444-z","article-title":"Serum calcium and incident diabetes: an observational study and meta-analysis","volume":"27","author":"Sing","year":"2016","journal-title":"Osteoporos Int"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"105527","DOI":"10.1016\/j.envint.2020.105527","article-title":"Association of urinary cadmium, circulating fatty acids, and risk of gestational diabetes mellitus: a nested case-control study in China","volume":"137","author":"Li","year":"2020","journal-title":"Environ Int"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.jinorgbio.2019.03.013","article-title":"The essential metals for humans: a brief overview","volume":"195","author":"Zoroddu","year":"2019","journal-title":"J Inorg Biochem"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"289","DOI":"10.7727\/wimj.2015.017","article-title":"Investigation of the prevalence rate of gestational diabetes mellitus with diagnostic criteria of IADPSG and the analysis of its risk factors","volume":"23","author":"Li","year":"2015","journal-title":"Chin J Diabetes"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1278617\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T08:09:21Z","timestamp":1701850161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1278617\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":55,"alternative-id":["10.3389\/fnut.2023.1278617"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2023.1278617","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]},"article-number":"1278617"}}