CHILDHOOD DIOXIN EXPOSURE AND ENERGY HOMEOSTASIS DYSREGULATION

儿童二恶英暴露和能量稳态失调

基本信息

批准号：
7904960
负责人：
JANE S BURNS
金额：
$ 8.09万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7904960
关键词：
9 year old Adipocytes Adolescence Adult Age Air Animals Biochemical Biological Markers Birth Weight Blood Blood Glucose Blood specimen Body fat Body mass index Cardiovascular Diseases Cattle Chemicals Child Childhood Cholesterol Cities Clinical Cohort Studies Collection Communities Data Collection Development Diabetes Mellitus Diet Dioxins Dyslipidemias Energy Intake Enrollment Environmental Exposure Epidemiologic Studies Exposure to Family Fasting Fatty acid glycerol esters General Population Genetic Predisposition to Disease Glucose Growth Homeostasis Human Human Milk Hypertriglyceridemia Incidence Insulin Insulin Resistance Leptin Link Lipids Measurement Measures Medical Medical Records Metabolic Metabolism Modeling Non-Insulin-Dependent Diabetes Mellitus Obesity Outcome Physical Examination Physical activity Play Polychlorinated Biphenyls Population Study Prediabetes syndrome Puberty Reporting Research Research Personnel Risk Risk Factors Role Russia Serum Soil Time Triglycerides adipokines adiponectin boys density design diabetes risk dibenzo(1,4)dioxin electric impedance environmental chemical fasting glucose glucose metabolism high risk indexing insight obesity in children polychlorinated dibenzofurans prospective public health relevance waist circumference

项目摘要

DESCRIPTION (provided by investigator): Recent epidemiologic studies have reported associations of serum concentrations of polychlorinated dibenzo- p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) with elevated serum glucose and insulin, and greater risk of type 2 diabetes mellitus (T2DM). Most of these studies have been cross-sectional and were unable to establish a temporal association or identify critical exposure periods between serum PCDDs and PCDFs (herein referred to as dioxins) and PCBs with these outcomes. None of these studies were conducted among children. In the last two decades, the incidence of childhood obesity and T2DM has increased substantially. Contributory factors include diet, physical activity, and genetic predisposition. Epidemiological studies suggest environmental exposures such as dioxins and PCBs may also play a role. Obesity and T2DM are associated with impaired glucose metabolism, dyslipidemia, and altered serum adipokines. Recent research suggests that alterations in these biomarkers of energy homeostasis in children may precede and promote the development of obesity and T2DM. We propose to incorporate measurements of metabolic abnormalities into an ongoing longitudinal cohort study evaluating the associations of serum dioxins and PCBs with growth and pubertal development in 499 boys in Chapaevsk, Russia. We are in the fourth year of this study in which the boys, enrolled at 8 to 9 years old, are evaluated yearly, and will be followed through puberty to adulthood. At enrollment, the boys provided blood samples for dioxin and PCB analyses, permitting us to measure peri-pubertal exposure. We perform annual physical examinations that include anthropomorphic measurements, and collect detailed family medical, dietary, and residential information. We propose to extend the original aims of this study to evaluate whether higher peri- pubertal serum dioxins and PCB levels are associated with dysregulation of energy homeostasis, with a specific focus on glucose, lipid, and adipocyte metabolism, and adiposity. We will prospectively evaluate these associations from peri-puberty through adolescence, using medical record information for birth weight and ponderal index, annual physical exams and biennial serum analysis for biochemical biomarkers. Our comprehensive data collection will enable us to assess the interactions of these exposures and factors such as caloric intake and physical activity on the outcomes. The application's prospective design will permit us to evaluate whether exposure to elevated dioxins and PCBs during the peri-pubertal period is associated with subsequent glucose dysregulation, altered fat and adipokine metabolism, and increased adiposity. PUBLIC HEALTH RELEVANCE: Although diet and physical activity are well-known risk factors for obesity and diabetes, there is increasing evidence that environmental exposure to chemicals may also play a role. Dioxins and polychlorinated biphenyls (PCBs) have been linked with increased risk of diabetes in human studies, and to greater body fat in animal studies. This application will assess whether higher blood levels of dioxins and PCBs in Russian boys are associated with increased risk of higher blood glucose, insulin, and low density cholesterol as well as greater body fat, which will provide important scientific insights into the role of environmental chemicals in the development of diabetes and obesity.

描述（由研究者提供）：最近的流行病学研究报告了多氯二苯并-对二恶英 (PCDD)、多氯二苯并呋喃 (PCDF) 和多氯联苯 (PCB) 的血清浓度与血糖和胰岛素升高以及较高类型风险之间的关联2 型糖尿病（T2DM）。这些研究大多数都是横断面的，无法建立时间关联或确定血清 PCDD 和 PCDF（本文称为二恶英）和 PCB 与这些结果之间的关键暴露期。这些研究均不是在儿童中进行的。在过去二十年中，儿童肥胖和 T2DM 的发病率大幅增加。影响因素包括饮食、体力活动和遗传倾向。流行病学研究表明，二恶英和多氯联苯等环境暴露也可能起到一定作用。肥胖和 T2DM 与葡萄糖代谢受损、血脂异常和血清脂肪因子改变有关。最近的研究表明，儿童能量稳态生物标志物的改变可能先于并促进肥胖和 T2DM 的发展。我们建议将代谢异常的测量纳入一项正在进行的纵向队列研究中，该研究评估了俄罗斯恰帕耶夫斯克 499 名男孩的血清二恶英和 PCB 与生长和青春期发育的关系。这项研究已进入第四年，每年对 8 至 9 岁的男孩进行评估，并跟踪他们从青春期到成年。入组时，男孩们提供了血液样本进行二恶英和多氯联苯分析，使我们能够测量青春期前后的暴露情况。我们每年进行一次体检，包括拟人化测量，并收集详细的家庭医疗、饮食和居住信息。我们建议扩展本研究的最初目标，以评估青春期周围血清二恶英和 PCB 水平是否与能量稳态失调相关，特别关注葡萄糖、脂质、脂肪细胞代谢和肥胖。我们将利用出生体重和体重指数的病历信息、年度体检和每两年一次的生化生物标志物血清分析，前瞻性地评估从青春期到青春期的这些关联。我们全面的数据收集将使我们能够评估这些暴露和热量摄入和体力活动等因素对结果的相互作用。该应用程序的前瞻性设计将使我们能够评估在青春期期间接触升高的二恶英和多氯联苯是否与随后的葡萄糖失调、脂肪和脂肪代谢改变以及肥胖增加有关。公共卫生相关性：尽管饮食和体力活动是肥胖和糖尿病的众所周知的危险因素，但越来越多的证据表明，环境中化学物质的暴露也可能发挥作用。在人类研究中，二恶英和多氯联苯 (PCB) 与糖尿病风险增加有关，在动物研究中，二恶英和多氯联苯 (PCB) 与体脂肪增加有关。该应用程序将评估俄罗斯男孩血液中较高的二恶英和多氯联苯含量是否与较高的血糖、胰岛素、低密度胆固醇以及较高的体脂风险增加有关，这将为了解环境化学物质在儿童发育中的作用提供重要的科学见解。糖尿病和肥胖症。