Growing evidence suggests that exposure to endocrine disruptors are associated with obesity and diabetes. One such endocrine disruptor, which humans are widely exposed to, is bisphenol-A (BPA). BPA production has increased in the last decade. Although animal studies demonstrate that BPA induces metabolic changes that lead to altered glucose homeostasis, no prospective human studies have examined the association between BPA and incident type 2 diabetes (T2DM) or gestational diabetes (GDM). GDM complicates 7 to 10% of pregnancies in the U.S. and its incidence has increased 35-90% in the past decade. Women with GDM are at high risk of T2DM and their offspring are more likely to develop obesity and T2DM during childhood. To assess a potential causal association between urinary levels of BPA in pregnancy and the onset of GDM, adverse changes in biomarkers of insulin resistance and liver enzymes, the proposed study will enroll 3,350 ethnically diverse pregnant women early in gestation and follow them prospectively until delivery. The baseline in-person study visit will coincide with the routine integrated screening blood test (10-13 weeks). The visit will include a blood draw for markers of insulin resistance and liver enzymes, urine specimen collection, anthropometric measurements, and questionnaires to assess exposure to BPA and other covariates. Women will be asked to mail a second urine specimen one month later (14-17 weeks). We will average the 2 measurements of BPA to help account for variability in the exposure. During the routine screening for GDM (24-28 weeks) additional blood samples will be collected for measurements of markers of insulin resistance and liver enzyme. Given the high cost of measuring BPA and metabolic biomarkers (glucose, insulin, adiponectin, GGT and ALT);we will obtain these measurements from 300 GDM cases and 600 controls to conduct a prospective, nested case-control study (cases will be matched to controls on age, race-ethnicity and gestational age at the GDM screening). This nested case-control study will address the following hypotheses: a) higher early pregnancy urinary levels of BPA are associated with an increased risk of GDM (Aim 1);b) higher early pregnancy urinary levels of BPA are associated with adverse changes in adiponectin and insulin levels and the liver enzymes GGT and ALT (Aims 2 and 3);c) markers of insulin resistance and liver enzymes partially mediate the association between BPA and GDM (Aim 4);and d) higher urinary levels of BPA will be associated with an increased risk of having a LGA infant, and the association may be partially mediated by GDM (Aim 5). This study will allow for the examination of potential mediating factors and exploration of the mechanisms underlying the association between BPA exposure and GDM risk and to address an important public health concern: the potentially harmful effects of BPA on pregnancy glucose metabolism and diabetes. Findings from this study might help in developing policies for the regulation of BPA use and be translated into prevention strategies for diabetes.

Public Health Relevance

Bisphenol-A (BPA) production has increased in the last decade. Although animal studies demonstrate that BPA induces metabolic changes that lead to altered glucose metabolism, no prospective human studies have examined the association between BPA and gestational diabetes (GDM). To assess a potential causal association between urinary levels of BPA in pregnancy and the onset of GDM, adverse changes in biomarkers of insulin resistance and liver enzymes, the proposed study will enroll ethnically diverse pregnant women early in gestation and follow them prospectively until delivery. This study will allow for the examination of potential mediating factors and exploration of the mechanisms underlying the association between BPA exposure and GDM risk and to address an important public health concern: the potentially harmful effects of BPA on pregnancy glucose metabolism and diabetes. Findings from this study might help in developing policies for the regulation of BPA use and be translated into prevention strategies for diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES019196-01A1
Application #
8440084
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Gray, Kimberly A
Project Start
2012-11-20
Project End
2017-10-31
Budget Start
2012-11-20
Budget End
2013-10-31
Support Year
1
Fiscal Year
2013
Total Cost
$610,786
Indirect Cost
$191,786
Name
Kaiser Foundation Research Institute
Department
Type
DUNS #
150829349
City
Oakland
State
CA
Country
United States
Zip Code
94612