Arsenic Exposure, Diabetes and Atherosclerosis

 描述（由申请方提供）：本次重新提交将研究砷暴露和其他环境暴露对新诊断的未经治疗的2型糖尿病（T2 D）患者血管功能和血小板活性的影响。候选人：该申请的主要目的是支持Jonathan纽曼博士的职业发展成为环境医学，糖尿病和心血管疾病（CVD）领域的独立翻译心血管医生科学家。纽曼博士的职业目标是将环境医学与心血管护理相结合，从而改善心血管结局，特别是对于患有T2 D和CVD风险升高的患者。他提出的培训计划侧重于4个领域：（1）研究方法和分析;（2）转化实验室方法;（3）血管结构和功能;（4）环境医学和流行病学。环境：纽约大学（NYU）医学中心是全国领先的研究，是美国国立卫生研究院资助的前20所医学院之一。纽约大学环境医学系是美国历史最悠久、最重要的研究环境污染对健康影响的中心之一。心脏病科是全国排名第一的部门，在纽约大学医学系拥有最大的研究预算。研究：T2 D患者人数持续增长。CVD是T2 D患者发病和死亡的主要原因。在T2 D患者中识别CVD的可改变风险因素的临床需求仍未得到满足。暴露于无机砷和其他环境毒物可能是降低这些患者心血管疾病风险的新目标。然而，目前还没有关于环境暴露对新诊断为T2 D的未经治疗患者的血管功能和血栓形成风险的临床研究。为了研究无机砷和其他环境暴露对城市T2 D人群血管功能和血小板活性的作用，我们建议研究100名新诊断的T2 D患者的前瞻性队列，没有糖尿病治疗的混杂效应。我们的具体目标是：（1）评价无机砷暴露与血管功能指标之间的关系;（2）评价无机砷暴露与血栓形成风险指标之间的关系;（3）探索砷以外的环境暴露与血管功能和血栓形成风险指标之间的独立关系。我们提出的创新研究将前瞻性地评估血管和血小板功能的生物标志物与环境暴露之间的相关性，这是T2 D患者CVD的潜在新风险因素。拟议的研究将支持转化研究以及环境和心血管疾病流行病学方面的强大培训计划，并将支持PI发展为独立的转化医生-科学家。在T2 D患者中，有一个未满足的需求来解决CVD的过度风险，这项研究代表了一类新的风险因素的创新方法。

 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.