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.