Vascular Alterations in the Prediabetic Condition

描述(由申请人提供)： 辛西娅·程，医学博士，家庭医学讲师。她拥有药理学博士学位。程博士的职业目标是成为心血管疾病研究领域的知名研究员；具体地说，她对糖尿病和高血压的血管损伤早期阶段感兴趣。郑博士和她的导师Falkner博士从三个公认的观察结果中形成了一个概念：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(一种血管系统疾病)患者患2型糖尿病的风险更高；3)胰岛素抵抗是2型糖尿病的先兆，在高血压患者中很常见。因此，高血压和胰岛素抵抗的患者可能有潜在的血管疾病，这些疾病先于糖尿病的表达，并有助于糖尿病的表达。因此，该项目的总体假设是：微血管疾病先于临床糖尿病的发病。既有高血压，又有糖尿病前期胰岛素抵抗加上空腹血糖受损的受试者，将会有微血管结构的改变。研究的具体目标是：1.开发一组成年人，包括一名患有高血压(130-160毫米汞柱收缩压)但也有胰岛素抵抗的样本，以及一名年龄/种族/性别匹配、血压(&lt；130毫米汞收缩压)和胰岛素敏感性正常的成年人样本。2.用毛细支气管镜测量周围甲床小血管结构。3.用前臂血流量测定血管功能，测定最大血管扩张时的前臂血管阻力。4.通过评估尿白蛋白排泄量来确定队列中是否还有其他血管损伤的标志物。为了执行这项研究计划，郑博士将在Falkner博士的实验室工作，掌握代谢评估和前臂血流的既定程序，并将开发利用活体毛细血管显微镜检查微血管结构的方法。在这个项目中产生的数据将被用于构建假设驱动的研究应用程序，以继续郑博士在这一临床研究领域的研究。从血管损伤早期阶段的调查中获得的数据可能有助于改进识别、预防和逆转糖尿病和高血压的血管病变的策略，从而降低心血管疾病的发病率。

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.