Effects of Arsenic on Adolescent Growth and Metabolic Health

砷对青少年生长和代谢健康的影响

• 批准号: 8985676
• 负责人: JANE S BURNS
• 金额: $ 8.08万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-11 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8985676
• 关键词: 19 year old; Adolescence; Adolescent; Adult; Age; Air; Area; Arsenic; Bangladesh; Biological; Biological Markers; Blood; Blood Pressure; Body Composition; Body fat; Cardiovascular Diseases; Chemical Weapons; Chemicals; Chickens; Child; Child health care; Childhood; Chlorinated Hydrocarbons; Cholesterol; Cities; Cohort Studies; Collection; Consumption; Country; Data; Development; Diet; Disease; Dust; Dyslipidemias; Endocrine; Endocrine Disruptors; Endocrine disruption; Energy Metabolism; Enrollment; Environmental Exposure; Epidemiologic Studies; Exposure to; Fasting; Food; Food Contamination; Fruit; Growth; Health; Height; Hypertension; Hypertriglyceridemia; Individual; Industry; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Lead; Leptin; Link; Low Birth Weight Infant; Measurement; Measures; Medical History; Metabolic; Metabolic Diseases; Metabolism; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Pathway interactions; Physical activity; Play; Poison; Population; Prevalence; Puberty; Public Health; Reducing diet; Reporting; Research; Rice; Risk; Risk Factors; Role; Russia; Sampling; Secondary to; Serum; Socioeconomic Status; Soil; System; Time; Toxic Environmental Substances; Urine; Water; Water consumption; Weight; boys; cohort; density; disease registry; electric impedance; environmental chemical; exposed human population; fasting glucose; food consumption; glucose metabolism; insight; lewisite; muscle form; prenatal; prepuberty; residence; urinary; young adult

DESCRIPTION (provided by applicant): The prevalence of insulin resistance, dyslipidemia, and high blood pressure has increased substantially among children in recent decades. These conditions track into adulthood, and predispose to subsequent development of type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD). Recent evidence shows that exposure to endocrine disrupting chemicals (EDCs) during key developmental periods may be a risk factor for metabolic disorders independent of diet and physical activity. Inorganic arsenic (iAs), an EDC, has been linked to low birth weight, and poor childhood growth (e.g. lower height and weight). Children are considered especially vulnerable to iAs, because of their rapid physical growth and maturing endocrine and metabolic systems. However, most epidemiologic studies assessing iAs effects on children's health have been cross-sectional, conducted in areas with high iAs groundwater levels not representative of most population exposures, and lacking in diet and/or individual exposure measures. We propose to prospectively examine the associations of prepubertal urinary iAs with adolescent growth, blood pressure, and serum biomarkers of growth and metabolism. We will also evaluate environmental and dietary predictors of urinary concentrations of arsenic species and metabolites. We will leverage our ongoing longitudinal cohort study examining the association of organochlorine compounds (OCs) and lead with growth and sexual maturity among 499 boys in Chapaevsk, Russia by measuring urinary arsenic species and metabolites in this population. Chapaevsk is an industrial city with arsenic and OC contamination secondary to environmental releases of chlorinated and other chemicals, including the organo-arsenic chemical weapon lewisite, by local industry. Our preliminary data demonstrate that the boys' urine iAs levels are higher than the U.S. population but much lower than high water iAs regions such as Bangladesh. Boys enrolled at ages 8-9 years were followed until 18 -19 years old. At entry, boys provided blood and urine samples for prepubertal exposure assessment, and detailed data was collected on medical history, socioeconomic status, residential proximity to the primary industrial polluter, and diet. Boys underwent annual physical exams, bio-electric impedance measures, and collection of urine; blood was collected biennially. These extensive prospectively collected outcome and covariate measures will provide us with a unique opportunity to assess the effect of iAs exposure during the vulnerable prepubertal period with adolescent growth and blood pressure, a time when manifestations of altered growth may be particularly evident. Furthermore, by virtue of unusual local industrial contamination with iAs and the cohort's prevalent consumption of locally grown foods, diet's role in iAs exposure and iAs exposure effects will be assessed. Finally, our study will be the first to assess urinary iAs associations with serum biomarkers of adolescent growth and energy metabolism, providing insight into the underlying biological mechanisms of iAs associations with adult T2D and CVD.

描述（由申请人提供）：近几十年来，儿童的胰岛素抵抗，血脂异常和高血压的流行率大大增加。这些条件追踪到成年期，并易于随后发展2型糖尿病（T2D）和心血管疾病（CVD）。最近的证据表明，在关键发育期间暴露于内分泌破坏化学物质（EDC）可能是独立于饮食和体育锻炼的代谢疾病的危险因素。 EDC无机砷（IAS）与低出生体重和儿童期生长（例如高度和体重较低）有关。由于儿童的身体生长快速，内分泌和代谢系统，因此被认为特别容易受到IAS的影响。但是，大多数评估IAS对儿童健康影响的流行病学研究都是横断面的，在IAS高地下水位水平高的地区进行，不代表大多数人口暴露，并且缺乏饮食和/或个人暴露措施。我们建议前瞻性地检查青春期前IAS与青少年生长，血压以及生长和代谢的血清生物标志物的关联。我们还将评估砷和代谢物的尿液浓度的环境和饮食预测指标。我们将利用我们正在进行的纵向队列研究研究，研究有机氯化合物（OCS）的关联，并通过测量该人群的尿砷和代谢物，在俄罗斯查普斯克的499名男孩中与生长和性成熟。查普斯克（Chapaevsk）是一个工业城市，其继发于氯化和其他化学物质的环境释放的砷和OC污染，包括当地工业，包括有机疗法的化学武器路易斯特。我们的初步数据表明，男孩的尿液IAS水平高于美国人口，但远低于孟加拉国等高水IAS地区。在8-9岁时入学的男孩一直遵循直到18 -19岁。进入时，男孩提供了血液和尿液样本进行青春期前的暴露评估，并收集了有关病史，社会经济状况，与初级工业污染者的住宅邻近性和饮食的详细数据。男孩接受了年度体格检查，生物电阻抗措施和尿液收集；两年一次收集血液。这些广泛的前瞻性收集结果和协变量措施将为我们提供一个独特的机会，以评估脆弱的青春期前时期IAS暴露的影响，并以青春期的生长和血压和血压和血压，这一时期可能特别明显。此外，由于与IAS的异常局部工业污染以及该队列对本地种植的食物的普遍消费，饮食在IAS暴露中的作用和IAS暴露效应将得到评估。最后，我们的研究将是第一个评估与青少年生长和能量代谢的血清生物标志物相关的研究，从而洞悉了IAS与成人T2D和CVD的基本生物学机制。