Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Environ Int. 2021 Oct;155:106690. doi: 10.1016/j.envint.2021.106690. Epub 2021 Jun 10.
Metals are involved in glucose metabolism, and some may alter glycemic regulation. However, joint effects of essential and non-essential metals on glucose concentrations during pregnancy are unclear. This study explored the joint associations of pregnancy exposures to essential (copper, magnesium, manganese, selenium, zinc) and non-essential (arsenic, barium, cadmium, cesium, lead, mercury) metals with gestational glucose concentrations using 1,311 women enrolled 1999-2002 in Project Viva, a Boston, MA-area pregnancy cohort. The study measured erythrocyte metal concentrations from 1 trimester blood samples and used glucose concentrations measured 1 h after non-fasting 50-gram glucose challenge tests (GCT) from clinical gestational diabetes screening at 26-28 weeks gestation. Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation were applied to model the associations of metal mixtures-including their interactions-with glucose concentrations post-GCT. We tested for reproducibility of BKMR results using generalized additive models. The BKMR model showed an inverse U-shaped association for barium and a linear inverse association for mercury. Specifically, estimated mean glucose concentrations were highest around 75th percentile of barium concentrations [2.1 (95% confidence interval: -0.2, 4.4) mg/dL higher comparing to the 25th percentile], and each interquartile range increase of erythrocyte mercury was associated with 1.9 mg/dL lower mean glucose concentrations (95% credible interval: -4.2, 0.4). Quantile g-computation showed joint associations of all metals, essential-metals, and non-essential metals on gestational glucose concentrations were all null, however, we observed evidences of interaction for barium and lead. Overall, we found early pregnancy barium and mercury erythrocytic concentrations were associated with altered post-load glucose concentrations in later pregnancy, with potential interactions between barium and lead.
金属参与葡萄糖代谢,其中一些可能会改变血糖调节。然而,关于妊娠期间必需和非必需金属对血糖浓度的联合影响尚不清楚。本研究使用 1999-2002 年在波士顿 MA 地区妊娠队列项目 Viva 中招募的 1311 名女性,探讨了妊娠期间暴露于必需(铜、镁、锰、硒、锌)和非必需(砷、钡、镉、铯、铅、汞)金属与妊娠 1 小时后血糖浓度的联合关联。该研究从 1 个孕期的血液样本中测量了红细胞金属浓度,并使用了 26-28 周时的非空腹 50 克葡萄糖挑战试验(GCT)后的 1 小时血糖浓度进行了临床妊娠糖尿病筛查。贝叶斯核机器回归(BKMR)和基于分位数的 g 计算被应用于模型金属混合物(包括它们的相互作用)与 GCT 后血糖浓度的关联。我们使用广义加性模型测试了 BKMR 结果的重现性。BKMR 模型显示,钡呈反 U 形关联,汞呈线性负相关。具体来说,与第 25 百分位数相比,钡浓度第 75 百分位数左右的估计平均血糖浓度最高[高 2.1(95%置信区间:-0.2,4.4)mg/dL],每增加一个四分位距的红细胞汞与平均血糖浓度降低 1.9mg/dL 相关[95%可信区间:-4.2,0.4]。分位数 g 计算显示,所有金属、必需金属和非必需金属对妊娠血糖浓度的联合关联均为零,但我们观察到钡和铅之间存在相互作用的证据。总的来说,我们发现妊娠早期的红细胞钡和汞浓度与妊娠后期负荷后血糖浓度的改变有关,钡和铅之间可能存在相互作用。