Ministry of Education -Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Environ Int. 2021 Nov;156:106621. doi: 10.1016/j.envint.2021.106621. Epub 2021 May 11.
Humans are widely exposed to environmental perfluoroalkyl substances (PFAS), which may affect glucose homeostasis. However, research linking PFAS exposure to glucose homeostasis during pregnancy is limited and the results were inconsistent. We aimed to investigate the association between PFAS exposure and glucose homeostasis in pregnancy in a large prospective cohort.
A total of 2747 pregnant women who participated in the Shanghai Birth Cohort, had blood samples in early pregnancy and completed a 75 g oral glucose tolerance test (OGTT) at 24-28 gestational weeks were included. 10 PFAS were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples in early pregnancy. Logistic regression was used to explore the associations between PFAS concentrations and gestational diabetes mellitus (GDM), while multiple linear regression was used to model the associations between PFAS and OGTT fasting, 1-h and 2-h glucose levels. Potential confounders were adjusted. Bayesian kernel machine regression (BKMR) and a quantile-based g-computation approach (qgcomp) were employed to explore the joint and independent effects of PFAS on glucose homeostasis.
The incidence of GDM was 11.8%. One log-unit increment in plasma concentrations in early pregnancy was associated with an increased risk of GDM for perfluorobutane sulfonate (PFBS) (adjusted odd ratio (aOR) = 1.23, 95% confidence interval (95% CI): 1.05, 1.44) and perfluoroheptanoic acid (PFHpA) (aOR = 1.25, 95% CI: 1.07, 1.46). Perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonate (PFHxS) and PFHpA were positively correlated with 1-h and 2-h glucose levels. Results of the mixed exposure model showed that the joint effects of PFAS were significantly associated with abnormal glucose homeostasis; In the BKMR model, PFAS mixture exposure was positively associated with the GDM incidence, 1-h and 2-h glucose levels and negatively correlated with FBG level. A similar trend could be observed in qgcomp and the positive correlation between PFAS and 2-h glucose level was significant (β = 0.12, 95% CI: 0.04, 0.20). PFOS, PFNA and PFHpA may be the main contributors after controlling for other PFAS congeners. PFOS was significantly correlated with GDM incidence and 2-h glucose level, and PFHpA was significantly associated with FBG and 2-h glucose levels. The above associations were more prominent among women with a normal prepregnant BMI.
Environmental exposure to PFAS may affect glucose homeostasis in pregnancy and increase the risk of GDM, especially in normal weight women.
人类广泛接触环境中的全氟烷基物质（PFAS），这可能会影响葡萄糖稳态。然而，将 PFAS 暴露与妊娠期间葡萄糖稳态联系起来的研究有限，且结果不一致。我们旨在通过一项大型前瞻性队列研究，调查 PFAS 暴露与妊娠期间葡萄糖稳态之间的关系。
共纳入了 2747 名参加上海出生队列的孕妇，她们在孕早期采集了血样，并在 24-28 孕周完成了 75g 口服葡萄糖耐量试验（OGTT）。使用高效液相色谱/串联质谱法（HPLC/MS-MS）在孕早期的血浆样本中检测了 10 种 PFAS。使用 logistic 回归来探讨 PFAS 浓度与妊娠期糖尿病（GDM）之间的关联，而多元线性回归则用于建立 PFAS 与 OGTT 空腹、1 小时和 2 小时血糖水平之间的关系。调整了潜在的混杂因素。采用贝叶斯核机器回归（BKMR）和基于分位数的 g 计算方法（qgcomp）来探讨 PFAS 对葡萄糖稳态的联合和独立影响。
GDM 的发病率为 11.8%。孕早期血浆浓度每增加一个对数单位，与全氟丁烷磺酸（PFBS）（调整后的比值比（aOR）=1.23，95%置信区间（95%CI）：1.05，1.44）和全氟庚酸（PFHpA）（aOR=1.25，95%CI：1.07，1.46）的 GDM 风险增加相关。全氟辛烷磺酸（PFOS）、全氟壬酸（PFNA）、全氟癸酸（PFDA）、全氟己烷磺酸（PFHxS）和 PFHpA 与 1 小时和 2 小时血糖水平呈正相关。混合暴露模型的结果表明，PFAS 的联合作用与异常葡萄糖稳态显著相关；在 BKMR 模型中，PFAS 混合物暴露与 GDM 发病率、1 小时和 2 小时血糖水平呈正相关，与 FBG 水平呈负相关。在 qgcomp 中也可以观察到类似的趋势，并且 PFAS 与 2 小时血糖水平之间的正相关具有统计学意义（β=0.12，95%CI：0.04，0.20）。PFOS、PFNA 和 PFHpA 可能是在控制其他 PFAS 同系物后主要的贡献物质。PFOS 与 GDM 发病率和 2 小时血糖水平显著相关，而 PFHpA 与 FBG 和 2 小时血糖水平显著相关。上述关联在体重正常的女性中更为明显。
环境中 PFAS 的暴露可能会影响妊娠期间的葡萄糖稳态，并增加 GDM 的风险，尤其是在体重正常的女性中。
