Determinants of Insulin Mediated Glucose uptake in South Asians

南亚人胰岛素介导的葡萄糖摄取的决定因素

• 批准号: 8601069
• 负责人: THEMISTOCLES LEONARD ASSIMES
• 金额: $ 18.09万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8601069
• 关键词: Abdomen; Accounting; Address; Adipocytes; Adipose tissue; Adult; Advisory Committees; Age; Asians; Atherosclerosis; Award; Biometry; Body fat; Cardiopulmonary; Cardiovascular system; Clinical Research; Collaborations; Complex; Development; Diabetes Mellitus; Dual-Energy X-Ray Absorptiometry; Epidemiology; Ethnic group; Europe; European; Exercise stress test; Fatty acid glycerol esters; Functional disorder; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Genotype; Glucose; Gold; Grant; Heart; Heart Diseases; Hepatocyte; Hispanics; Hospitals; Human; Human Genetics; Inherited; Insulin; Insulin Resistance; International; Knowledge; Light; MRI Scans; Magnetic Resonance Imaging; Measures; Mediating; Medicine; Mentors; Methods; Mexican; Molecular Biology; Monitor; Muscle Cells; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxygen; Pathway interactions; Physical Fitness; Physical activity; Physicians; Physiological; Plant Roots; Population; Population Sciences; Predisposition; Questionnaires; Race; Recruitment Activity; Regression Analysis; Research; Research Personnel; Research Proposals; Resources; Risk; Sampling; Scanning; Scientist; Secondary Prevention; South Asian; Stress Tests; Symptoms; Taiwan; Techniques; Testing; Tissues; United States National Institutes of Health; Universities; Visceral; Work; adverse outcome; base; cardiovascular disorder risk; career development; cohort; design; experience; genetic epidemiology; genome wide association study; genome-wide; glucose uptake; high risk; human subject; improved; innovation; insight; insulin sensitivity; insulin sensitizing drugs; interest; knowledge base; next generation; novel; professor; public health relevance; racial and ethnic; research study; sex; standard measure; subcutaneous; tool; trait; uptake

DESCRIPTION (provided by applicant): The purpose of this award is to provide Dr. Themistocles (Tim) Assimes, Assistant Professor of Medicine at Stanford University, the support necessary to transition him from a junior investigator to an independent physician scientist studying the genetic determinants of various human complex traits related to cardiovascular medicine. Dr. Assimes is an adult cardiologist with an advanced degree in epidemiology and biostatistics and significant experience conducting human genetic studies using existing sample sets. Career development activities focus on consolidating his expertise by 1) designing and implementing his first human subjects clinical research study involving handling of biospecimens, 2) increasing his involvement in several international genetic epidemiology collaborations, and 3) attending didactic courses to expand his knowledge base in contemporary genetics, molecular biology, advanced statistical genetics and the pathophysiology of insulin resistance (IR). An advisory committee, which includes his mentors, Drs. Thomas Quertermous and Gerald Reaven, will carefully monitor his progress towards independence. The research proposal builds on ongoing efforts in the candidate's division to identify the root causes of IR by studying South Asians, a racial/ethnic group known to be strongly predisposed to IR and its adverse consequences for unclear reasons. In this context, Specific Aim 1 proposes to quantify IR and its primary established determinants of adiposity and physical fitness in ~330 South Asians and ~100 white/Europeans using 'gold standard' measuring tools. These include an insulin suppression test to assess insulin mediated glucose uptake, DXA and abdominal MRI scans to determine total and regional body fat, pedometers to estimate current physical activity, and a symptom limited cardiopulmonary stress test to estimate maximum oxygen uptake (max VO2). A new research partnership between the non-profit South Asian Heart Center at El Camino Hospital, Mountain View, CA, and Division of Cardiovascular Medicine at Stanford University will facilitate recruitment. This aim will test the hypothesis that a predisposition to IR in South Asians is evident even after taking into account significant differences between the two racial/ethnic groups in adiposity and physical fitness not captured by more traditional methods of assessment of these variables (e.g., BMI and physical activity questionnaires). In Specific Aim 2, the candidate will perform genome wide genotyping in ~400 South Asians followed by gene/SNP set pathway analyses using innovative analytical techniques developed by collaborators at SAGE Bionetworks. The same analytical techniques will be applied to multiple other sample sets with GWAS and direct measures of IR representing 3 other race/ethnic groups including Europeans, East Asians, and Hispanics. This aim will compare and contrast pathways associated with IR across all groups and test the hypothesis that South Asians are more IR because they have inherited a relatively inefficient cellular mechanism of handling glucose compared to other racial/ethnic groups. PUBLIC HEALTH RELEVANCE: Insulin resistance is a physiologic state where fat, muscle and liver cells lose their ability to respond to insulin. The resulting high levels of insulin predispose to the development of diabetes, heart disease, and other serious conditions. Work proposed in this grant aims to identify the reasons some populations are particularly high risk of insulin resistance and its consequences.

描述（由申请人提供）：该奖项的目的是为斯坦福大学医学助理教授Themistocles（Tim）Assimes博士提供，这是将他从初级研究者转变为研究与心血管医学相关的各种人类复杂性特征的遗传决定因素的独立医师科学家所必需的支持。 Assimes博士是一名成人心脏病专家，拥有流行病学和生物统计学的高级学位，并且使用现有样本集进行人类遗传研究。职业发展活动的重点是通过1）设计和实施他的第一个人类学科的临床研究研究，涉及处理生物测量，2）增加他参与了几种国际遗传流行病学合作，以及3）参加教学课程，以扩大他的遗传学，分子遗传学和统计学的统计学，统计学和统计学学位，以下是统计学的遗传学和统计学。咨询委员会，包括他的导师，博士。 Thomas Quermentous和Gerald Reaven将仔细监视他在独立方面的进步。这项研究提案以候选人部门的持续努力为基础，通过研究南亚人来识别IR的根本原因，这是一个已知的种族/族裔群体，由于不明确的原因，人们强烈倾向于IR及其不利后果。在这种情况下，特定的目标1提议使用“黄金标准”测量工具量化IR及其主要建立的肥胖和身体健康的决定因素和〜100位白人/欧洲人。其中包括一项胰岛素抑制测试，以评估胰岛素介导的葡萄糖摄取，DXA和腹部MRI扫描，以确定全部和区域体内脂肪，估计当前身体活动的计步器以及有限的心肺应激测试，以估计最大的氧气摄取（最大VO2）。加利福尼亚州山景城El Camino医院的非营利性南亚心脏中心与斯坦福大学心血管医学部的新研究合作伙伴关系将有助于招募。该目标将检验以下假设：即使考虑到两个种族/族裔群体之间在肥胖和身体健康方面存在显着差异，南亚人在南亚人的倾向也很明显，而不是通过评估这些变量的更传统的方法来捕获的（例如，BMI和体育活动问卷）。在特定的目标2中，候选人将使用由Sage Bionetworks的合作者开发的创新分析技术进行〜400个南亚人，然后进行基因/SNP设置途径分析。相同的分析技术将应用于其他多个带有GWAS的样本集和代表其他3种种族/种族群体的IR的直接措施，包括欧洲人，东亚人和西班牙裔。该目标将比较所有组中与IR相关的IR相关的途径，并检验以下假设：与其他种族/族裔群体相比，与其他种族/族裔相比，他们遗传了处理葡萄糖的相对效率低下的细胞机制。 公共卫生相关性：胰岛素抵抗是一种生理状态，脂肪，肌肉和肝细胞失去对胰岛素反应的能力。由此产生的高水平的胰岛素容易发生糖尿病，心脏病和其他严重疾病的发展。该赠款中提出的工作旨在确定某些人群抗胰岛素抵抗及其后果的高风险。