Prevention of Type 2 Diabetes through Diet and Metabolomics

项目摘要 2型糖尿病影响美国每11个成年人中的1个，并且是死亡的主要原因。高质量 饮食摄入与2型糖尿病风险降低独立且强烈相关。代谢 然而，饮食摄入和糖尿病之间的联系仍不清楚。了解这些生物 饮食摄入和糖尿病之间的过程可以帮助建立新的和有效的个性化目标 来治疗和预防。与代谢和细胞过程相关的化合物的表达是 叫做代谢组学本提案的目的是确定与以下物质相关的代谢物的身份： 低糖尿病风险的饮食模式，以调查这些代谢物与糖尿病发病的关联，以及 与这些代谢物的作用相关的因果途径，并检查这些代谢物水平的变化。 在一项试验性饮食干预中使用低糖尿病风险食物来检测代谢物。目标1将使用数据和生物标本 从多种族研究的动脉粥样硬化（梅萨），调解人的动脉粥样硬化在南亚人的生活 美国MASALA研究和鹿特丹研究（RS），以确定低糖尿病风险 已知和新型代谢物的饮食模式。我们将验证新发现的代谢物， 电波队列。目的2将这些新发现的代谢物与糖尿病发病联系起来， 它们在多大程度上介导了饮食和糖尿病之间的关系。它还将代谢物置于 使用网络分析技术的生物背景。AIM 3使用现有试点的数据和生物标本 在糖尿病前期患者中进行短期核桃补充剂的试验，以评估代谢物的变化， 干预。 这个指导以病人为导向的研究职业发展奖的候选人，Meghana Gadgil博士， 是一个普通内科医生和助理教授在一般内科在大学 来自加州的弗朗西斯科。Gadgil博士是一位具有丰富营养学背景的医生调查员， 糖尿病在这个提案中，她将研究饮食摄入量、代谢物表达 和2型糖尿病发病率之间的关系。这项工作将作为她总体职业目标的基础： 成为一名独立的临床研究者，专注于预防高危人群中的糖尿病， 饮食干预的使用。Gadgil博士将致力于结构化的教学培训和指导研究 在以下领域的经验：1）代谢组学分析和解释技术; 2）网络和 路径分析; 3）临床试验设计和管理; 4）职业发展技能。 这项研究是相关和及时的，因为糖尿病及其危险因素的发病率都在持续上升， 用于预防的个性化饮食策略很少。拟议的调查将有助于 了解、新知识和预防糖尿病饮食干预的潜在目标。

PROJECT SUMMARY Type 2 diabetes affects 1 in every 11 adults in the United States, and is a leading cause of death. High quality dietary intake is independently and strongly associated with lower risk of type 2 diabetes. The metabolic processes connecting dietary intake and diabetes, however, remain unclear. Understanding these biological processes between dietary intake and diabetes can help to establish new and effective individualized targets for treatment and prevention. The expression of compounds related to metabolism and cellular processes is called metabolomics. The objective of this proposal is to determine the identity of metabolites associated with a low-diabetes-risk dietary pattern, to investigate the association of these metabolites with incident diabetes, and the causal pathways related to the action of these metabolites, and to examine changes in the levels of these metabolites in a pilot dietary intervention with a low-diabetes-risk food. Aim 1 will use data and biospecimens from the Multi-Ethnic Study of Atherosclerosis (MESA), the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study and the Rotterdam Study (RS) to determine the association of a low-diabetes-risk dietary pattern with known and novel metabolites. We will validate newly discovered metabolites within the Airwave cohort. Aim 2 associates these newly identified metabolites with incident diabetes and examines the extent to which they mediate the relationship between diet and diabetes. It also places the metabolites within a biological context using network analysis techniques. Aim 3 uses data and biospecimens from an existing pilot trial of a short-term walnut supplement in individuals with prediabetes to evaluate changes in metabolites with the intervention. The candidate for this Mentored Patient-Oriented Research Career Development Award, Dr. Meghana Gadgil, is a General Internist and an Assistant Professor in the Division of General Internal Medicine at the University of California, San Francisco. Dr. Gadgil is a physician-investigator with a strong background in nutrition and diabetes. In this proposal, she will examine novel associations between dietary intake, metabolite expression and type 2 diabetes incidence. This work will serve as the foundation for her overarching career goal: to become an independent clinical investigator focused on prevention of diabetes in high-risk populations through the use of dietary interventions. Dr. Gadgil will commit to structured didactic training and mentored research experience in the areas of 1) techniques for metabolomic analysis and interpretation; 2) training in network and pathway analysis; 3) clinical trial design and management; and 4) career development skills. This study is relevant and timely, as the incidence of both diabetes and its risk factors continues to rise, and personalized dietary strategies for prevention are few. The proposed investigations will contribute understanding, new knowledge, and potential targets of dietary intervention for diabetes prevention.