Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Environ Res. 2024 Dec 1;262(Pt 1):119810. doi: 10.1016/j.envres.2024.119810. Epub 2024 Aug 16.
Certain endocrine-disrupting chemicals (EDCs) are widespread in consumer products and may alter glucose metabolism. However, the impact of EDC exposures on glucose and insulin regulation during pregnancy is incompletely understood, despite potential adverse consequences for maternal and infant health. We estimated associations between 37 urinary biomarkers of EDCs and glucose-insulin traits among pregnant women.
Seventeen phthalate or phthalate substitute metabolites, six environmental phenols, four parabens, and ten organophosphate ester metabolites were quantified in mid-pregnancy urine from 298 participants in the Healthy Start Study. Fasting blood glucose, insulin, and hemoglobin A1c were assessed concurrently, and Homeostasis Model Assessment 2-Insulin Resistance (HOMA2-IR) was calculated. Gestational diabetes diagnoses and screening results were obtained from medical records for a subset of participants. We estimated associations between each EDC and outcome separately using linear and robust Poisson regression models and analyzed EDC mixture effects.
The EDC mixture was positively associated with glucose, insulin, and HOMA2-IR, although overall associations were attenuated after adjustment for maternal BMI. Two mixture approaches identified di(2-ethylhexyl) phthalate (DEHP) metabolites as top contributors to the mixture's positive associations. In single-pollutant models, DEHP metabolites were positively associated with fasting glucose, fasting insulin, and HOMA2-IR even after adjustment for maternal BMI. For example, each interquartile range increase in log-transformed mono(2-ethyl-5-oxohexyl) phthalate was associated with 2.4 mg/dL (95% confidence interval (CI): 1.1, 3.6) higher fasting glucose, 11.8% (95%CI: 3.6, 20.5) higher fasting insulin, and 12.3% (95%CI: 4.2, 21.1) higher HOMA2-IR. Few EDCs were associated with hemoglobin A1c or with a combined outcome of impaired glucose tolerance or gestational diabetes.
Exposures to phthalates and particularly DEHP during pregnancy are associated with altered glucose-insulin regulation. Disruptions in maternal glucose metabolism during pregnancy may contribute to adverse pregnancy outcomes including gestational diabetes and fetal macrosomia, and associated long-term consequences for maternal and child health.
某些内分泌干扰化学物质（EDCs）广泛存在于消费产品中，可能会改变葡萄糖代谢。然而，尽管对母婴健康可能存在不良后果，但人们对孕期 EDC 暴露对葡萄糖和胰岛素调节的影响仍了解甚少。我们估计了 37 种尿内分泌干扰物生物标志物与孕妇葡萄糖-胰岛素特征之间的关联。
在健康起点研究中，对 298 名参与者的妊娠中期尿液中 17 种邻苯二甲酸酯或邻苯二甲酸酯替代代谢物、6 种环境酚类、4 种对羟基苯甲酸酯和 10 种有机磷酸酯代谢物进行了定量检测。同时检测空腹血糖、胰岛素和糖化血红蛋白，并计算稳态模型评估 2 胰岛素抵抗（HOMA2-IR）。对于部分参与者，从病历中获得了妊娠期糖尿病的诊断和筛查结果。我们分别使用线性和稳健泊松回归模型估计每种内分泌干扰物与结局之间的关联，并分析内分泌干扰物混合物的作用。
尽管在调整了母体 BMI 后，总体关联减弱，但内分泌干扰物混合物与葡萄糖、胰岛素和 HOMA2-IR 呈正相关。两种混合物方法均发现邻苯二甲酸二（2-乙基己基）酯（DEHP）代谢物是混合物呈正相关的主要贡献者。在单污染物模型中，DEHP 代谢物与空腹血糖、空腹胰岛素和 HOMA2-IR 呈正相关，即使在调整了母体 BMI 后也是如此。例如，每增加一个对数变换的单（2-乙基-5-氧己基）邻苯二甲酸酯的四分位距与空腹血糖升高 2.4mg/dL（95%置信区间（CI）：1.1，3.6）、空腹胰岛素升高 11.8%（95%CI：3.6，20.5）和 HOMA2-IR 升高 12.3%（95%CI：4.2，21.1）有关。很少有内分泌干扰物与糖化血红蛋白或葡萄糖耐量受损或妊娠期糖尿病的综合结局有关。
孕期邻苯二甲酸酯特别是邻苯二甲酸二（2-乙基己基）酯的暴露与葡萄糖-胰岛素调节的改变有关。孕期母体葡萄糖代谢紊乱可能导致妊娠结局不良，包括妊娠期糖尿病和胎儿巨大儿，并对母婴健康产生相关的长期影响。
