Exposure to Multipollutants and Obesity, Type-2 Diabetes and Metabolic Syndrome

接触多种污染物与肥胖、2 型糖尿病和代谢综合征

• 批准号: 9322520
• 负责人: Sung Kyun Park
• 金额: $ 61.7万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9322520
• 关键词: Address; Affect; Age-Years; Aging; Anti-Bacterial Agents; Arsenic; Beta Cell; Biological; Biological Availability; Blood Pressure; Body Composition; Body fat; Body mass index; C-reactive protein; Cell physiology; Chemicals; Clinical; Cohort Studies; Complex; Data; Disease; Dose; Educational workshop; Environment; Environmental Exposure; Environmental Health; Environmental Pollutants; Environmental Risk Factor; Epidemiology; Etiology; Exposure to; Fatty acid glycerol esters; Flame Retardants; Functional disorder; Goals; Health; Heavy Metals; Homeostasis; Hormonal Change; Human; Impact evaluation; Incidence; Individual; Institute of Medicine (U.S.); Insulin Resistance; Intervention; Leptin; Life; Lipids; Longitudinal Studies; Longitudinal cohort study; Medicine; Menopause; Metabolic; Metabolic Diseases; Metabolic syndrome; Methods; Mission; Modeling; National Institute of Environmental Health Sciences; Natural History; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organophosphates; Outcome; Pathogenesis; Pathway interactions; Pesticides; Phenols; Play; Polychlorinated Biphenyls; Population; Predisposition; Prospective Studies; Public Health; Research; Risk; Risk Factors; Role; Sampling; Scientific Advances and Accomplishments; Serum; Site; Study of Women' s Health Across the Nation; Urine; Variant; Visit; Weight Gain; Woman; Women' s Health; adipokines; adiponectin; base; bisphenol A; cohort; cost; cost efficient; design; disorder risk; epidemiology study; follow-up; health data; healthy aging; high dimensionality; high risk; improved; innovation; insight; middle age; organochlorine pesticide; phthalates; pollutant; pollutant interaction; prospective; proteostasis; public health relevance; repository; response; stressor; trait; waist circumference

 DESCRIPTION (provided by applicant): A growing body of evidence suggests that environmental pollutants, such as polychlorinated biphenyls (PCBs), bisphenol-A, phthalates and arsenic, may play an important role in the pathophysiology of type-2 diabetes mellitus (T2DM), obesity, and metabolic syndrome (MetS). While the evidence supports the role of environmental pollutants as potential risk factors for metabolic diseases, several important challenges remain to establish causality in human populations: 1) there have been few prospective longitudinal cohort studies, raising concerns related to causal inferences and problems of reverse causality; 2) data on emerging pollutants widespread in our environment such as brominated flame retardants and antibacterial agents and preservatives is lacking; 3) data on underlying mechanisms in human populations is lacking; and 4) data on combined effects of multiple pollutants in relation to metabolic diseases is lacking due to statistical challenges. Although women become more susceptible to cardio-metabolic disorders during the menopausal transition due to the hormonal changes, little is known about the role of environmental pollutants in metabolic diseases during this critical window of susceptibility. This new epidemiologic study in a multi-ethnic cohort of women seeks to address these research gaps and improve our understanding of how exposure to multiple pollutants affects the risks of developing T2DM, obesity and MetS. We propose 1) to identify potential environmental pollutants associated with incident T2DM, obesity and MetS; 2) to assess the associations of environmental pollutants with longitudinal changes in intermediate metabolic traits including blood pressure, body composition (e.g., fat mass and percent body fat), lipid profiles, insulin resistance and C-reactive protein, and with cross-sectional associations with adipokines (e.g., leptin and adiponectin); and 3) to examine the combined effects of multiple pollutants on T2DM, obesity and MetS evaluated simultaneously and construct an Environmental Risk Score. We will also explore potential pollutant-pollutant interactions in relation to metabolic outcomes. We will conduct a case-cohort study (n=950; 382 new cases of T2DM, obesity and/or MetS occurred between 1999 and 2010 and a random subcohort of 753 women (185 overlap with new cases)) in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-ethnic cohort of midlife women who are at increased metabolic risk, evaluated annually or bi-annually for more than 10 years. We will evaluate more than 120 environmental pollutants such as PCBs, organochlorine pesticides, flame retardants, organophosphate pesticides and metabolites, heavy metals, phthalates, bisphenol-A, and other phenolic compounds assessed in either serum or urine samples. This project addresses strategic priorities of the National Institute of Environmental Health Sciences (NIEHS), including identifying common biological pathways and understanding disease pathogenesis by combined environmental exposures. We will address these issues using innovative analytic approaches likely to yield new insights on the study of multiple pollutants and human health.

 描述（由适用提供）：越来越多的证据表明，环境污染物（例如多氯二苯基（PCB），双苯酚A，邻苯二甲酸酯和砷可能在2型糖尿病类型的病理生理学中起重要作用，在糖尿病（T2DM），OBESITY和METSBOLOM（METS）中起重要作用。尽管证据支持环境污染物作为代谢疾病的潜在危险因素的作用，但在人口中建立偶然性仍然存在的一些重要挑战：1）很少有前瞻性纵向队列研究，引发了与偶然的推论和反向伤亡有关的问题； 2）缺乏有关我们环境中新兴污染物宽度的数据，例如损坏的阻燃剂和抗菌剂和防腐剂； 3）缺乏有关人口中潜在机制的数据； 4）由于统计挑战，缺乏有关多种污染物相对于代谢疾病的组合作用的数据。尽管由于荷尔蒙变化，在更年期过渡期间，女性变得更容易受到心脏代谢疾病的影响，但在这种关键的敏感性窗口中，环境污染物在代谢性疾病中的作用知之甚少。这项新的流行病学研究在众多妇女队列中旨在解决这些研究差距，并提高我们对暴露于多种污染物的暴露方式的理解，影响开发T2DM，肥胖和Mets的风险。我们建议1）确定与T2DM，肥胖和Mets相关的潜在环境污染物； 2）评估环境污染物与中间代谢特征的纵向变化的关联，包括血压，身体组成（例如脂肪质量和体内脂肪百分比），脂质特征，胰岛素抵抗和C反应性蛋白质，以及与脂肪因子的横截面关联（例如，leptin和leptiponectin和adiponectin）； 3）检查多种污染物对T2DM的综合作用，简单地评估肥胖和Mets并构建环境风险评分。我们还将探索与代谢结果有关的潜在污染物 - 污染物相互作用。 We will conduct a case-cohort study (n=950; 382 new cases of T2DM, obesity and/or MetS occurred between 1999 and 2010 and a random subcohort of 753 women (185 overlap with new cases)) in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-ethnic cohort of midlife women who are at increased metabolic risk, evaluated annually or bi-annually for more than 10 年。我们将评估120多种环境污染物，例如PCB，有机氯农药，阻燃剂，有机磷酸盐农药和代谢物，重金属，邻苯二甲酸盐，双苯酚-A以及其他在血清或尿液样品中评估的酚类化合物。该项目涉及国家环境健康科学研究所（NIEHS）的战略重点，包括确定常见的生物学途径并通过联合环境暴露来理解疾病发病机理。我们将使用可能对多种污染物和人类健康的研究产生新的见解来解决这些问题。