Environmental Triggers of Cardiometabolic Disease

心血管代谢疾病的环境诱因

• 批准号: 8223143
• 负责人: Sanjay Rajagopalan
• 金额: $ 42.43万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-04 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8223143
• 关键词: Acute; Address; Adult; Air; Air Pollutants; Air Pollution; Animals; Area; Asia; Attention; Autonomic nervous system; Blood Pressure; Breathing; Caliber; Carbon Black; Cardiovascular Diseases; Cardiovascular system; China; Chronic; Chronic Disease; Cities; Country; Data; Developing Countries; Development; Diet; Disease; Environment; Environmental Exposure; Environmental Hazards; Environmental Pollutants; Environmental Risk Factor; Epidemic; Equilibrium; Exposure to; Food; Functional disorder; Future; Genetic; Goals; Health; Health Policy; Human; Hypertension; India; Individual; Inflammatory; Insulin Resistance; Intervention; Investigation; Latin America; Lead; Life; Life Style; Link; Locales; Measures; Mediating; Metabolic; Metabolic syndrome; Methodology; Metric; Monitor; Morbidity - disease rate; Motivation; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Measure; Particulate; Particulate Matter; Pathway interactions; Phenotype; Play; Policies; Pollution; Predisposition; Protocols documentation; Public Health; Research; Resistance development; Resources; Risk; Risk Factors; Role; Societies; Source; Specific qualifier value; Structure; Syndrome; Techniques; Testing; Time; United States; Urbanization; Variant; Vasodilation; Water; base; cardiovascular risk factor; diet and exercise; functional outcomes; insight; instrument; insulin sensitivity; mortality; novel; pollutant; primary outcome; prognostic; public health relevance; research study; secondary outcome; sedentary

DESCRIPTION (provided by applicant): Chronic cardiometabolic (CM) diseases such as obesity and type 2 diabetes (T2DM) are the leading cause of morbidity and mortality in urbanized societies. While poor diet, exercise and genetics have been the primary suspects, the link between chronic exposure to environmental pollutants has only gained recent attention. Recent compelling evidence from our group has suggested that environmental exposures to ambient particulate matter <2.5 (PM2.5) may cause insulin resistance and promote the development of several features of the metabolic syndrome such as elevated blood pressure and endothelial dysfunction. If such links were demonstrated to be true in humans, then it may provide insights into the epidemic of T2DM and cardiovascular disease in developing countries which sit at the confluence of high exposures to such pollutants over a life time and inadequate resources to study/respond to them. We posit that a multi-national collaborative effort with focused investigations in environments with the highest levels of exposure (developing countries such as China and India), are likely to provide new and much needed data on the risk posed by these variables on an individuals life-time risk for T2DM and cardiovascular complications. We will test this hypothesis through the establishment of a network that would lead studies on the links between exposure and adverse CM effects and propose doing this in this as part of 3 specific aims. In aim 1, we propose to establish feasibility of such an effort in Beijing, China, an effort that will involve implementation of novel exposure assessment methodologies simultaneously with the ability to execute key surrogate outcome measures of importance in cardiovascular risk with CM diseases. In Aim 2, the association between functional cardiovascular risk variables [insulin sensitivity, BP, endothelial function] and acute and sub-acute variations in personal black carbon and ambient PM2.5 levels among 100 individuals with the CM syndrome will be investigated. In Aim 3, we will examine potential biologic pathways of importance in the proposed functional outcomes. Specifically we will determine the association between ambient PM2.5 levels and alterations in (a) adipocytokines/inflammatory variables and autonomic nervous system (ANS) balance. If such links between PM and T2DM cardiovascular risk can be demonstrated, they will present a unique opportunity for public health policy changes on limiting environmental exposures to inhaled particulates. PUBLIC HEALTH RELEVANCE: In this project we will set up a research network to conduct investigations on environmental factors and cardiovascular risk in developing countries. Our broader motivation is to create a framework to investigate the role of environmental factors in conferring risk susceptibility for chronic diseases, a traditionally under- investigated and poorly understood area. As part of demonstrating feasibility in this proposal, we will explore the link between personal black carbon exposure, ambient particulate matter <2.5 microns (PM2.5) levels and measures of metabolic insulin sensitivity, blood pressure, alterations in adipocytokines and autonomic nervous system balance. If such links can be demonstrated, they will present a unique opportunity for public health intervention and policy changes.

描述（由申请人提供）：肥胖和 2 型糖尿病 (T2DM) 等慢性心脏代谢 (CM) 疾病是城市化社会发病和死亡的主要原因。虽然不良饮食、锻炼和遗传是主要嫌疑人，但长期接触环境污染物之间的联系最近才引起人们的关注。我们小组最近的令人信服的证据表明，环境暴露于<2.5（PM2.5）的环境颗粒物可能会导致胰岛素抵抗，并促进代谢综合征的一些特征的发展，例如血压升高和内皮功能障碍。如果这种联系在人类身上得到证实，那么它可能会为发展中国家 T2DM 和心血管疾病的流行提供深入的了解，因为这些国家一生中高度暴露于此类污染物，而研究/应对这些污染物的资源不足。我们认为，在暴露水平最高的环境（中国和印度等发展中国家）开展重点调查的多国合作努力，可能会提供新的、急需的数据，说明这些变量对个人 T2DM 和心血管并发症的终生风险造成的风险。我们将通过建立一个网络来检验这一假设，该网络将引导研究暴露与 CM 不良影响之间的联系，并建议将其作为 3 个具体目标的一部分。在目标 1 中，我们建议在中国北京建立此类工作的可行性，这项工作将涉及实施新型暴露评估方法，同时能够执行对 CM 疾病心血管风险具有重要意义的关键替代结果测量。在目标 2 中，将研究 100 名 CM 综合征患者的功能性心血管风险变量 [胰岛素敏感性、血压、内皮功能] 与个人黑碳和环境 PM2.5 水平的急性和亚急性变化之间的关联。在目标 3 中，我们将研究对所提出的功能结果具有重要意义的潜在生物学途径。具体来说，我们将确定环境 PM2.5 水平与 (a) 脂肪细胞因子/炎症变量和自主神经系统 (ANS) 平衡的变化之间的关联。如果 PM 和 T2DM 心血管风险之间的这种联系能够得到证实，将为改变限制吸入颗粒物环境暴露的公共卫生政策提供独特的机会。 公共卫生相关性：在这个项目中，我们将建立一个研究网络，对发展中国家的环境因素和心血管风险进行调查。我们更广泛的动机是创建一个框架来研究环境因素在赋予慢性病风险易感性方面的作用，这是一个传统上研究不足且知之甚少的领域。作为论证该提案可行性的一部分，我们将探讨个人黑碳暴露、环境颗粒物 <2.5 微米 (PM2.5) 水平与代谢胰岛素敏感性、血压、脂肪细胞因子变化和自主神经系统平衡测量之间的联系。如果能够证明这种联系，将为公共卫生干预和政策改变提供独特的机会。