Arsenic Exposure, Diabetes and Atherosclerosis

 描述(由申请人提供)：这项重新提交将调查暴露于砷和其他环境暴露对新诊断的未经治疗的2型糖尿病(T2D)患者的血管功能和血小板活性的关系。候选人：此申请的主要目标是支持乔纳森·纽曼博士的职业发展，使其成为环境医学、糖尿病和心血管疾病(CVD)领域的独立翻译心血管内科医生兼科学家。纽曼博士的职业目标是将环境医学与心血管护理相结合，以改善心血管结果，特别是对于患有T2D和心血管疾病风险增加的患者。他提出的培训计划集中在4个领域：(1)研究方法和分析；(2)转换实验室方法；(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)医学中心在研究方面是全国领先的，也是NIH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、最重要的环境污染对健康影响研究中心之一。心脏病学部是全国排名最高的学部，在纽约大学医学系拥有最大的研究预算。研究：T2D患者的人数持续增长。心血管疾病是T2D患者发病率和死亡率的主要原因。在T2D患者中识别CVD的可改变危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靶点。然而，在新诊断为T2D的未经治疗的患者中，还没有关于环境暴露对血管功能和血栓风险的临床研究。为了研究无机砷和其他环境暴露对城市T2D人群血管功能和血小板活性的影响，我们建议对100名新诊断的T2D患者进行前瞻性队列研究，不考虑糖尿病治疗的混杂影响。我们的具体目标是：(1)评估无机砷暴露与血管功能测量之间的关联；(2)评估无机砷暴露与血栓形成风险测量之间的关联；以及(3)探索除砷以外的环境暴露与血管功能测量与血栓形成风险测量之间的独立关联。我们提出的创新性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关系，环境暴露是T2D患者心血管疾病的潜在新危险因素。拟议的研究将支持在翻译研究以及环境和心血管疾病流行病学方面的强有力的培训计划，并将支持将PI发展为独立的翻译内科科学家。在T2D患者中，有一个尚未得到满足的需求来解决心血管疾病的额外风险，这项研究代表了一种针对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.