Exposure to Bisphenol a Substitutes and Gestational Diabetes Mellitus: A Prospective Cohort Study in China

ORIGINAL RESEARCH published: 30 April 2019 doi: 10.3389/fendo.2019.00262 Exposure to Bisphenol a Substitutes and Gestational Diabetes Mellitus: A Prospective Cohort Study in China Wenxin Zhang 1 , Wei Xia 1 , Wenyu Liu 1 , Xinping Li 1 , Jie Hu 1 , Bin Zhang 2 , Shunqing Xu 1 , Yanqiu Zhou 3 , Jiufeng Li 3 , Zongwei Cai 3* and Yuanyuan Li 1* 1 Key Laboratory of Environment and Health (HUST), Ministry of Education and Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 2 Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 3 State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China Background: The association of bisphenol A (BPA) and gestational diabetes mellitus (GDM) has been investigated in only a small number of studies, and research on the associations between BPA substitutes and GDM is scarce. Edited by: Wei Bao, The University of Iowa, United States Reviewed by: Buyun Liu, The University of Iowa, United States Todd Hagobian, California Polytechnic State University, United States *Correspondence: Zongwei Cai Yuanyuan Li Specialty section: This article was submitted to Diabetes, a section of the journal Frontiers in Endocrinology Received: 30 June 2018 Accepted: 08 April 2019 Published: 30 April 2019 Citation: Zhang W, Xia W, Liu W, Li X, Hu J, Zhang B, Xu S, Zhou Y, Li J, Cai Z and Li Y (2019) Exposure to Bisphenol a Substitutes and Gestational Diabetes Mellitus: A Prospective Cohort Study in China. Front. Endocrinol. 10:262. doi: 10.3389/fendo.2019.00262 Objective: We aimed to investigate the associations of four bisphenols [bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF)] levels in urine sample with the risk of gestational diabetes mellitus (GDM) and plasma glucose levels. Methods: A total of 1,841 pregnant women from a cohort study were recruited at their first prenatal examination between 2013 and 2015 in Wuhan, China. Concentrations of four bisphenols (BPA, BPS, BPF, BPAF) were measured in first-trimester urine samples using Ultra-high performance liquid chromatography system coupled to a Triple Quadrupole mass spectrometer (UHPLC-TQMS). An oral glucose tolerance test (OGTT) was performed at 24–28 gestational weeks and GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. We used multivariable logistic regression models to examine the associations of urinary bisphenols with the risk of GDM, and multiple linear regression models to determine the associations between bisphenols exposure and plasma glucose levels. Results: Urinary BPAF was associated with increased odds of GDM among women with normal pre-pregnancy BMI [adjusted odds ratio (aOR) = 1.70 (95% CI: 1.08, 2.67) for the highest group compared to the lowest group], and the association remained significant after additional adjustment for other bisphenols [aOR = 1.68 (95% CI: 1.03, 2.72)]. No significant associations were observed for other bisphenols and GDM. Consistent with the result of GDM, women in the highest BPAF category had a mean of 0.05 mmol/L (95% CI: 0.01, 0.09) higher fasting plasma glucose (FPG) levels than women in the lowest category. For BPA and plasma glucose, non-linear associations were observed between urinary BPA and FPG and the sum of the PG z-score among women who were overweight (p for non-linear association <0.05). We also found that the per-unit increase in natural log transformed specific gravity adjusted BPS [ln (SG-adj BPS)] was associated with a 0.03 mmol/L (95% CI: 0.01, 0.04) increase in FPG levels and the associations might Frontiers in Endocrinology | www.frontiersin.org 1 April 2019 | Volume 10 | Article 262 Zhang et al. Bisphenols and GDM be modified by fetal sex (p for interaction <0.05). Among women with female fetus, a per-unit increase in ln (SG-adj BPS) was associated with a 0.04 mmol/L (95% CI: 0.02, 0.06) increase in FPG, a 0.11 mmol/L (95% CI: 0.04, 0.17) increase in 1 h-PG and a 0.19 mmol/L (95% CI: 0.08, 0.30) increase in the sum of PG z-score. Conclusions: Our results provide evidence that BPAF and BPS might be potential risk factors of GDM, which require to be studied further. Keywords: gestational diabetes, bisphenol A, bisphenol S, bisphenol F, bisphenol AF, plasma glucose, endocrine disrupting chemicals INTRODUCTION homeostasis of these BPA substitutes, which were used more and more widely and frequently in our daily life, are still unknown. Since findings on the associations between BPA exposure and the risk of GDM were inconsistent, and little was known on the endocrine-disrupting effects on human metabolism of BPA substitutes, we conducted the prospective cohort study to investigate the potential disrupting effects of bisphenols exposure on glucose metabolism. In this prospective study, we examined concentrations of four typical and widely used bisphenols (BPA, BPS, BPF, BPAF) in first-trimester urine samples of pregnant women and estimated the associations of the four bisphenols with GDM and plasma glucose levels in a population of pregnant women in central China. Meanwhile, it was reported that women with a different BMI before pregnancy or who were carrying a fetus of a different sex have different endocrine environments (32–34), so we carried out a further stratified analysis by prepregnancy BMI and fetal sex. Gestational diabetes mellitus (GDM) is a common complication during pregnancy and is defined as “any degree of glucose intolerance with onset or first recognition during pregnancy” (1, 2). GDM and hyperglycemia during pregnancy have been reported to be associated with adverse maternal, neonatal, and postnatal outcomes; thus, it is important to find potential risk factors for GDM. Except for the common-known risk factors (a high maternal age, being overweight before pregnancy, a family history of type 2 diabetes, a history of diabetes before pregnancy, etc.), concerns are increasingly being raised on the environmental factors for developing GDM, especially for some environmental chemicals that have endocrine-disrupting effects (3–5). Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl)-propane), a typical endocrine disruptor, is widely used in the production of polycarbonate plastics and epoxy resins used in numerous consumer products, to which human beings are widely exposed to in daily life. Increasing evidence has indicated that BPA may be harmful to human health, especially with regard to endocrine metabolism (6–9). Evidence from animal studies has suggested that BPA exposure may disrupt glucose homeostasis and contribute to metabolic disorders; thus, BPA may be a risk factor for the development of diabetes (10–1 (...truncated)