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.
