Arsenic Exposure, Diabetes and Atherosclerosis

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 DESCRIPTION (provided by applicant): This resubmission will investigate the associations between exposure to arsenic and other environmental exposures on vascular function and platelet activity among newly diagnosed untreated patients with type 2 diabetes (T2D). Candidate: The primary objective of this application is to support Dr. Jonathan Newman's career development into an independent translational cardiovascular physician-scientist in the field of environmental medicine, diabetes and cardiovascular disease (CVD). Dr. Newman's career goal is to integrate environmental medicine with cardiovascular care such that cardiovascular outcomes can be improved, particularly for patients with T2D and an elevated risk of CVD. His proposed training plan focuses on 4 areas: (1) research methods and analysis; (2) translational laboratory methods; (3) vascular structure and function; 4) environmental medicine and epidemiology. Environment: New York University (NYU) Medical Center is a national leader in research and is one of the top 20 medical schools in NIH funding. The Department of Environmental Medicine at NYU is one of the nation's oldest and foremost centers for research into the health effects of environmental pollution. The Division of Cardiology is a top-ranked division nationally, with the largest research budget in the Department of Medicine at NYU. Research: The population of patients with T2D continues to grow. CVD is the leading cause of morbidity and mortality in patients with T2D. There remains an unmet clinical need to identify modifiable risk factors for CVD in patients with T2D. Exposure to inorganic arsenic and other environmental toxicants may be novel targets for CVD risk reduction for these patients. However, there have been no clinical studies of environmental exposures on vascular function and thrombotic risk among untreated patients newly diagnosed with T2D. To investigate the role of inorganic arsenic and other environmental exposures on vascular function and platelet activity in an urban T2D population, we propose to study a prospective cohort of 100 newly diagnosed individuals with T2D, without the confounding effects of diabetes treatment. Our specific aims are to: (1) evaluate the association between inorganic arsenic exposure and measures of vascular function; (2) evaluate the association between inorganic arsenic exposure and measures of thrombotic risk; and (3) explore the independent association between environmental exposures other than arsenic and measures of vascular function and thrombotic risk. Our proposed innovative study will prospectively assess the association between biomarkers of vascular and platelet function and environmental exposures, a potential novel risk factor for CVD in patients with T2D. The proposed study will support a robust training plan in translational research and environmental and cardiovascular disease epidemiology, and will support the development of the PI into an independent translational physician-scientist. There is an unmet need to address the excess risk of CVD among patients with T2D, and this study represents an innovative approach to a novel class of risk factors.