Novel Type 2 Diabetes Mellitus Preventive Therapies

新型 2 型糖尿病预防疗法

• 批准号: 7687386
• 负责人: Carine M Lenders
• 金额: $ 17.69万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687386
• 关键词: Adherence; Adolescent; Adult; Affect; Age; Amino Acids; Antidiabetic Drugs; Area; Award; Basic Science; Biological Markers; Body fat; Boston; Branched-Chain Amino Acids; Cereals; Childhood; Chronic; Clinical; Clinical Trials; Cohort Studies; Controlled Clinical Trials; Coupled; Data; Development; Dietary intake; Double-Blind Method; Education; Ensure; Evaluation; Family; Family history of; Fiber; Foundations; Future; Glutamine; Goals; Grant; Hispanics; In Vitro; Insulin Resistance; Intake; Intervention; Leucine; Life Style; Longitudinal Studies; Measures; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Metformin; Non-Insulin-Dependent Diabetes Mellitus; Nurses; Nurses' Health Study; Nutritional; Obesity; Outcome; Pediatrics; Placebo Control; Placebos; Preventive; Proteins; Public Health; Randomized; Recruitment Activity; Regulation; Relative (related person); Research; Research Design; Risk; Risk Factors; Role; Safety; Scientist; Supplementation; Testing; Toes; Translational Research; Universities; Weight; Weight Gain; Woman; Work; Youth; cohort; combat; diabetes risk; diabetic; efficacy testing; energy balance; experience; in vivo; indexing; insight; lifestyle intervention; longitudinal analysis; medical schools; middle age; novel; obesity risk; prevent; professor; prospective; skills; trend; Adherence; Adolescent; Adult; Affect; Age; Amino Acids; Antidiabetic Drugs; Area; Award; Basic Science; Biological Markers; Body fat; Boston; Branched-Chain Amino Acids; Cereals; Childhood; Chronic; Clinical; Clinical Trials; Cohort Studies; Controlled Clinical Trials; Coupled; Data; Development; Dietary intake; Double-Blind Method; Education; Ensure; Evaluation; Family; Family history of; Fiber; Foundations; Future; Glutamine; Goals; Grant; Hispanics; In Vitro; Insulin Resistance; Intake; Intervention; Leucine; Life Style; Longitudinal Studies; Measures; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Metformin; Non-Insulin-Dependent Diabetes Mellitus; Nurses; Nurses' Health Study; Nutritional; Obesity; Outcome; Pediatrics; Placebo Control; Placebos; Preventive; Proteins; Public Health; Randomized; Recruitment Activity; Regulation; Relative (related person); Research; Research Design; Risk; Risk Factors; Role; Safety; Scientist; Supplementation; Testing; Toes; Translational Research; Universities; Weight; Weight Gain; Woman; Work; Youth; cohort; combat; diabetes risk; diabetic; efficacy testing; energy balance; experience; in vivo; indexing; insight; lifestyle intervention; longitudinal analysis; medical schools; middle age; novel; obesity risk; prevent; professor; prospective; skills; trend

DESCRIPTION (provided by applicant): The candidate for this K-23 award is Carine Lenders, MD, MS, an Assistant Professor of Pediatrics at Boston University School of Medicine/Boston Medical Center. My area of expertise and early research has focused on nutritional issues, specially the role of amino acids, in the development of obesity in adolescents. Over the past two decades, type 2 diabetes mellitus (T2DM) has emerged from relative obscurity to become one of the most serious complications of obesity in Hispanic obese populations, especially among those with a family history of T2DM. Few therapies have demonstrated long term efficacy in combating obesity and risk of T2DM in youth. This K23 Award application outlines a mentored 5-year education and research plan, centered on the use of amino acids as pharmacologic agents to prevent T2DM among Hispanic adolescents. Given the emerging evidence that glutamine and leucine (building blocks of protein) may affect energy partition and thus diabetes risk, and that the relationship of glutamine and diabetic risk has been further evaluated in one adult observational cohort study but data on leucine are lacking, we plan to conduct two studies: one to examine the relationship of leucine and T2DM using an observational adult study and one clinical trial to determine the efficacy of glutamine to reduce insulin resistance, a diabetes risk factor. The short- and long-term educational goals of this application are: 1) To increase my understanding of applied longitudinal analysis; 2) To gain insight in translational research and experience in the presentation of clinical trials; and, 3) To gain valuable mentorship to ensure progress towards becoming an independent clinical scientist. The long term goal of this K23 Award application is to apply ideas from basic sciences and longitudinal studies in the clinical setting using a single agent or a combination of agents to prevent T2DM. The primary specific aims of the research plan are: 1) to use a cohort of 70,356 middle-aged women followed for 18 years to examine the relationship of leucine to T2DM risk and weight gain; 2) to conduct a randomized, double-blind, placebo controlled, clinical trial to test the efficacy of 6 months supplements of glutamine in reducing biomarkers for insulin resistance and weight gain among 56 obese Hispanic adolescents age 13-17.9 with a BMI at or above the 95th percentile and a family history of T2DM. At the end of the grant period, I will have obtained sufficient research, design skills, and preliminary data to plan pivotal clinical trials of glutamine, and possibly leucine, coupled with or without lifestyle changes.

描述（由申请人提供）： 该K-23奖的候选人是波士顿大学医学院/波士顿医学中心的儿科助理教授Carine Lenders，MD，MS。我的专业知识领域和早期研究集中在营养问题上，尤其是氨基酸的作用，在青少年肥胖发展中。 在过去的二十年中，2型糖尿病（T2DM）已经从相对晦涩的角度出现，成为西班牙裔肥胖人群中肥胖最严重的并发症之一，尤其是在具有T2DM家族史的人中。很少有疗法在对抗青年人的肥胖和T2DM风险方面具有长期疗效。该K23奖项申请概述了一项指导的5年教育和研究计划，以使用氨基酸作为药理剂来防止西班牙裔青少年中T2DM的使用。鉴于新出现的证据表明，谷氨酰胺和亮氨酸（蛋白质的组成部分）可能会影响能量分配，从而影响糖尿病的风险，并且在一项成人观察同量研究中，已经进一步评估了谷氨酰胺和糖尿病风险的关系，但对Leucine的数据进行了研究，但缺乏对leucine和T2D的临床研究的研究，我们计划进行两项研究：一项研究。谷氨酰胺可降低胰岛素抵抗，这是一种糖尿病风险因素。 该应用程序的短期和长期教育目标是：1）增加我对应用纵向分析的理解； 2）在临床试验的介绍中获得转化研究和经验的见解； 3）获得宝贵的指导，以确保成为一名独立临床科学家的进步。该K23奖励申请的长期目标是使用单个代理或代理组合在临床环境中应用基础科学和纵向研究的想法，以防止T2DM。 研究计划的主要特定目的是：1）使用70,356名中年妇女的队列跟踪了18年，以检查亮氨酸与T2DM风险和体重增加的关​​系； 2）进行一项随机，双盲，安慰剂控制的临床试验，以测试谷氨酰胺在减少生物标志物减少生物标志物的6个月补充剂中，以在56名肥胖西班牙裔青少年中以13-17.9岁的胰岛素抵抗和体重增加，并在95％的BMI上或以上是95个百分位和T2DM的家族史。在赠款期结束时，我将获得足够的研究，设计技能和初步数据，以计划谷氨酰胺的关键临床试验，甚至可能没有生活方式的改变。