Prenatal Bisphenol A Exposure and Risk of Gestational Diabetes

产前双酚 A 暴露与妊娠期糖尿病的风险

• 批准号: 8440084
• 负责人: ASSIAMIRA FERRARA
• 金额: $ 61.08万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-11-20 至 2017-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8440084
• 关键词: Accounting; Address; Adipocytes; Adipose tissue; Age; Alcohol consumption; Animals; Biological Markers; Blood; Blood Tests; Blood specimen; Body mass index; Case-Control Studies; Childhood; Cohort Studies; Cost Measures; Diabetes Mellitus; Diet; Endocrine Disruptors; Enrollment; Enzymes; Ethnic Origin; Etiology; Exposure to; Family history of; Future; Gene Expression; Gestational Age; Gestational Diabetes; Glucose; Health; Hepatocyte; Human; Incidence; Infant; Insulin; Insulin Resistance; Lead; Link; Liver; Mails; Measurement; Measures; Mediating; Metabolic; Metabolic Marker; Mothers; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Perinatal; Persons; Physical activity; Policies; Pregnancy; Pregnant Women; Prevalence; Prevention strategy; Production; Propane; Prospective Studies; Public Health; Questionnaires; Race; Regulation; Reporting; Resources; Risk; Smoking; Specimen; Translating; Triglycerides; Urine; Visit; Weight Gain; Woman; Youth; adiponectin; biobank; bisphenol A; blood glucose regulation; exposed human population; glucose metabolism; high risk; lipid metabolism; liver function; obesity in children; offspring; parity; prenatal; prospective; public health relevance; sample collection; screening; urinary

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：越来越多的证据表明，暴露于内分泌干扰物与肥胖和糖尿病有关。 Bisphenol-A（BPA），人类广泛暴露于人类的一种这种内分泌破坏者。在过去的十年中，BPA产量有所增加。尽管动物研究表明，BPA诱导了代谢变化，导致葡萄糖稳态改变，但没有前瞻性人类研究检查BPA与2型型糖尿病（T2DM）或妊娠糖尿病（GDM）之间的关联。 GDM在美国的怀孕中有7至10％的妊娠复杂化，在过去的十年中，其发病率增加了35-90％。具有GDM的妇女的T2DM风险很高，其后代更有可能在儿童时期发展肥胖和T2DM。 为了评估妊娠中BPA尿液水平与GDM发作之间的潜在因果关系，胰岛素抵抗和肝酶的生物标志物的不利变化，拟议的研究将在妊娠妊娠早期招募3,350名种族多样化的孕妇，并前瞻性地跟随她们直至分娩。基线面对面的研究访问将与常规的综合筛查血液测试（10-13周）一致。这次访问将包括胰岛素抵抗和肝酶标记，尿液标本收集，人体测量测量和问卷调查的鲜血，以评估对BPA和其他协变量的接触。一个月后（14-17周）将要求妇女邮寄第二次尿液标本。我们将平均BPA的2个测量值，以帮助解决暴露量的可变性。在常规筛选GDM（24-28周）期间，将收集其他血液样本，以测量胰岛素抵抗和肝酶的标记。鉴于测量BPA和代谢生物标志物的高成本（葡萄糖，胰岛素，脂联素，GGT和ALT）；我们将从300例GDM病例和600个对照中获得这些测量值，以进行前瞻性的病例对照研究（病例将与GDM筛查时的年龄，种族种族和妊娠年龄对照相匹配）。这项嵌套的病例对照研究将解决以下假设：a）较高的早期妊娠尿液水平与GDM的风险增加有关（AIM 1）； b）较高的早期妊娠尿液水平BPA与脂联素和胰岛素水平以及肝酶GGT和ALT的不良变化有关（目标2和3）； c）胰岛素抵抗和肝酶的标记部分介导了BPA和GDM之间的关联（AIM 4）； d）较高的BPA水平将与患有LGA婴儿的风险增加有关，并且该关联可能由GDM部分介导（AIM 5）。这项研究将允许检查潜在的中介因素，并探索BPA暴露与GDM风险之间关联的机制，并解决重要的公共卫生问题：BPA对怀孕葡萄糖代谢和糖尿病的潜在有害影响。这项研究的结果可能有助于制定调节BPA使用的政策，并将其转化为糖尿病的预防策略。