Environmental Triggers of Cardiometabolic Disease

描述（由申请人提供）：慢性心脏代谢（CM）疾病，如肥胖和2型糖尿病（T2 DM）是城市化社会发病率和死亡率的主要原因。虽然不良的饮食，运动和遗传是主要的嫌疑人，但长期暴露于环境污染物之间的联系只是最近才得到关注。我们小组最近的令人信服的证据表明，环境暴露于<2.5的环境颗粒物（PM2.5）可能会导致胰岛素抵抗，并促进代谢综合征的几个特征的发展，如血压升高和内皮功能障碍。如果这种联系在人类中被证明是真实的，那么它可能会提供对发展中国家T2 DM和心血管疾病流行的见解，这些国家处于一生中高暴露于此类污染物和研究/应对资源不足的汇合点。我们认为，在暴露水平最高的环境中（中国和印度等发展中国家）进行重点研究的多国合作努力，可能会提供有关这些变量对T2 DM和心血管并发症个体终身风险构成的风险的新的和急需的数据。我们将通过建立一个网络来测试这一假设，该网络将导致对暴露和不良CM效应之间联系的研究，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这种努力的可行性，这项努力将涉及实施新的暴露评估方法，同时能够执行CM疾病心血管风险的重要性的关键替代结局指标。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相关性。在目标3中，我们将研究在拟议的功能结局中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）平衡的改变之间的关联。如果能够证明PM和T2 DM心血管风险之间的这种联系，它们将为限制环境暴露于吸入颗粒物的公共卫生政策变化提供一个独特的机会。

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.