Vascular Alterations in the Prediabetic Condition

糖尿病前期的血管改变

• 批准号: 6891031
• 负责人: Cynthia Cheng
• 金额: $ 14.92万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6891031
• 关键词: albumins; blood chemistry; blood pressure; cardiovascular disorder; clinical research; disease /disorder onset; glucose tolerance test; human subject; hypertension; insulin sensitivity /resistance; limbs; metabolic syndrome; microscopy; patient oriented research; peripheral blood vessel; prediabetic state; urinalysis; vascular resistance; vasodilation

DESCRIPTION (provided by applicant): Cynthia Cheng MD, PhD is an instructor in Family Medicine. She holds a doctoral degree in Pharmacology. Dr. Cheng's career goal is to become an established investigator in cardiovascular disease research; specifically, she is interested in the early phase of vascular injury in diabetes and hypertension. Together with her mentor Dr. Falkner, Dr. Cheng has developed a concept derived from three well established observations: 1) The morbidity and mortality suffered by patients with diabetes are consequences of vascular disease; 2) Patients with high blood pressure (a disorder of the vasculature) have a greater risk for development of type 2 diabetes; and 3) Insulin resistance precedes type 2 diabetes and is common among patients with hypertension. Therefore, patients with high blood pressure and insulin resistance may have underlying vascular disease that precedes and contributes to the expression of diabetes. Accordingly, the overall hypothesis for this project is: Microvascular disease precedes the onset of clinical diabetes. Subjects with both high blood pressure and the prediabetic condition of insulin resistance plus impaired fasting glucose will have alterations in microvascular structure. The Research Specific Aims are to: 1. Develop a cohort of adults that includes a sample with high blood pressure (130-160 mmHg systolic) who also have insulin resistance, and a sample of age/race/sex matched adults with normal blood pressure (<130 mmHg systolic) and insulin sensitivity. 2. Measure small vessel structure in peripheral nail beds using capillaroscopy. 3. Measure vascular function by forearm blood flow and determine forearm vascular resistance at maximal vasodilation. 4. Determine if there are other markers of vessel injury in the cohort by assessing urinary albumin excretion. To conduct this research plan, Dr Cheng will work in Dr. Falkner's laboratory to master the established procedures on metabolic assessment and forearm blood flow, and Dr. Cheng will develop the methodology to examine microvascular structure by intravital capillary microscopy. Data generated in this project will be utilized to construct hypothesis driven research applications to continue Dr. Cheng's investigations in this area of clinical research. Data obtained from investigations of the early phase of vascular injury may reduce cardiovascular disease morbidity by contributing to improved strategies to identify, prevent and reverse the vascular pathology of diabetes and hypertension.

描述（由申请人提供）： Cynthia Cheng医学博士是家庭医学的讲师。她拥有药理学博士学位。郑博士的职业目标是成为心血管疾病研究领域的知名研究者;具体而言，她对糖尿病和高血压的早期血管损伤感兴趣。郑博士与她的导师Falkner博士共同发展了一个概念，这个概念来自三个公认的观察：1）糖尿病患者的发病率和死亡率是血管疾病的后果; 2）高血压患者（血管系统疾病）有更大的风险发展为2型糖尿病;胰岛素抵抗先于2型糖尿病，在高血压患者中很常见。因此，患有高血压和胰岛素抵抗的患者可能具有先于糖尿病并促成糖尿病表达的潜在血管疾病。因此，本项目的总体假设是：微血管疾病先于临床糖尿病发作。患有高血压和胰岛素抵抗加上空腹血糖受损的糖尿病前期状况的受试者将具有微血管结构的改变。本研究的具体目标是：1。建立一个成年人队列，其中包括一个患有高血压（收缩压130-160 mmHg）且同时患有胰岛素抵抗的样本，以及一个年龄/种族/性别匹配的血压正常（收缩压<130 mmHg）且胰岛素敏感性正常的成年人样本。2.使用毛细血管镜测量周边甲床中的小血管结构。3.通过前臂血流量测量血管功能，并确定最大血管舒张时的前臂血管阻力。4.通过评估尿白蛋白排泄，确定队列中是否存在其他血管损伤标志物。为了进行这项研究计划，郑博士将在Falkner博士的实验室工作，以掌握代谢评估和前臂血流的既定程序，而郑博士将发展通过活体毛细血管显微镜检查微血管结构的方法。本项目中生成的数据将用于构建假设驱动的研究应用程序，以继续郑博士在该临床研究领域的研究。从血管损伤的早期阶段的调查中获得的数据可以通过有助于改进识别、预防和逆转糖尿病和高血压的血管病理学的策略来降低心血管疾病的发病率。