Prevention of Type 2 Diabetes through Diet and Metabolomics

项目总结 在美国，每11个成年人中就有一个患有2型糖尿病，是导致死亡的主要原因。高品质 饮食摄入量独立且与较低的2型糖尿病风险密切相关。新陈代谢 然而，饮食摄入和糖尿病之间的联系仍不清楚。了解这些生物学特性 饮食摄入和糖尿病之间的过程有助于建立新的、有效的个体化目标 用于治疗和预防。与新陈代谢和细胞过程有关的化合物的表达是 称为新陈代谢组学。这项建议的目的是确定与 低糖尿病风险饮食模式，以调查这些代谢物与糖尿病发病的关系，以及 与这些代谢物的作用有关的因果途径，并检查这些水平的变化 一种低糖尿病风险食物的试验性饮食干预中的代谢物。目标1将使用数据和生物质谱学 来自对动脉粥样硬化的多种族研究(MESA)，生活在南亚人中的动脉粥样硬化的介体 在美国(Masala)和鹿特丹研究(RS)确定低风险糖尿病之间的联系 饮食模式与已知和新的代谢物。我们将验证新发现的代谢物在 电波队列。AIM 2将这些新发现的代谢物与糖尿病发病联系起来，并检查 它们在多大程度上调节了饮食和糖尿病之间的关系。它还将代谢物放在一个 使用网络分析技术的生物学背景。AIM 3使用现有飞行员的数据和生物质谱学 对糖尿病前期患者短期补充核桃以评估代谢产物变化的试验 干预行动。 这项以患者为导向的导师研究职业发展奖的候选人Meghana Gadgil博士， 是该大学普通内科医生和普通内科助理教授 加利福尼亚州，旧金山。Gadgil博士是一名医生兼研究员，在营养学和 糖尿病。在这项提案中，她将研究饮食摄入量、代谢物表达之间的新关联 和2型糖尿病的发病率。这项工作将成为她总体职业目标的基础： 成为专注于预防高危人群糖尿病的独立临床调查员 饮食干预的使用。Gadgil博士将致力于有组织的教学培训和有指导的研究 具有以下领域的经验：1)代谢分析和解释技术；2)网络和 途径分析；3)临床试验设计和管理；4)职业发展技能。 这项研究是相关的和及时的，因为糖尿病及其危险因素的发病率持续上升，以及 用于预防的个性化饮食策略很少。拟议的调查将有助于 糖尿病饮食干预的认识、新知识和潜在目标。

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.