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：
7739401
负责人：
JANE S BURNS
金额：
$ 8.18万
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 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7739401
关键词：
9 year old Adipocytes Adolescence 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（研究者提供）：最近的流行病学研究报告了血清浓度的多氯联苯二苯甲酸二恶英（PCDDS），多氯联苯（PCDFS）和多氯的双氯苯基（PCB）与升高的血清葡萄糖和胰岛素和胰岛素和胰岛素2型糖尿病和胰岛素2型和胰岛素2糖的风险（PCBS）的关联。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之间的关键暴露期（此处称为二恶英）和具有这些结果的PCB。这些研究都没有在儿童中进行。在过去的二十年中，儿童肥胖和T2DM的发病率大大增加。贡献因素包括饮食，体育活动和遗传倾向。流行病学研究表明，诸如二恶英和PCB之类的环境暴露也可能发挥作用。肥胖和T2DM与葡萄糖代谢，血脂异常和血清脂肪因子改变有关。最近的研究表明，儿童能量稳态的这些生物标志物的改变可能在肥胖和T2DM的发展之前。我们建议将代谢异常的测量纳入正在进行的纵向同伴研究中，该研究评估了俄罗斯Chapaevsk的499名男孩的血清二恶英与PCB与增长和青春期发展的关联。我们正处于这项研究的第四年中，每年评估了8至9岁的男孩，并将遵循青春期到成年。入学时，男孩提供了用于二恶英和PCB分析的血液样本，使我们可以测量聚会周期的暴露。我们进行年度身体检查，包括拟人化测量，并收集详细的家庭医疗，饮食和住宅信息。我们建议扩展本研究的最初目标，以评估较高的青春期血清二恶英和PCB水平是否与能量稳态失调有关，并特别关注葡萄糖，脂质和脂肪细胞代谢和脂肪。我们将使用出生体重和肺部指数，年度体格检查和生化生物标志物的年度体育锻炼，年度身体检查和双年展的血清分析，前瞻性地评估这些关联到青春期到青春期的关联。我们的综合数据收集将使我们能够评估这些暴露量和因素摄入量和体育锻炼等因素的相互作用。该应用程序的前瞻性设计将使我们能够评估在毕伯伯尔伯伯氏院期间接触升高的二恶英和PCB，这是否与随后的葡萄糖失调，脂肪和脂肪因子代谢的改变以及肥胖性增加有关。公共卫生相关性：尽管饮食和体育锻炼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，环境暴露于化学物质也可能发挥作用。二恶英和多氯联苯（PCB）与人类研究中的糖尿病风险增加有关，并且在动物研究中与体内脂肪更大有关。该申请将评估俄罗斯男孩中较高的血液二氧化碳和PCB是否与增加血糖，胰岛素和低密度胆固醇以及更大的体内脂肪的风险增加有关，这将为环境化学物质在糖尿病和肥胖的发展中的作用提供重要的科学见解。