Prevention of Type 2 Diabetes through Diet and Metabolomics

通过饮食和代谢组学预防 2 型糖尿病

• 批准号: 10450899
• 负责人: MEGHANA DIPTI GADGIL
• 金额: $ 7.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450899
• 关键词: Adherence; Adult; Affect; Americas; Analytical Chemistry; Area; Aromatic Amino Acids; Atherosclerosis; Award; Biological; Biological Process; Branched-Chain Amino Acids; California; Carbohydrates; Cause of Death; Cell physiology; Clinical Investigator; Clinical Trials Design; Cohort Studies; Consumption; Data; Diabetes Mellitus; Diabetes prevention; Diet; Dietary Component; Dietary Fiber; Dietary Intervention; Dietary Practices; Dietary intake; Eating; Enrollment; Fishes; Food; Food Supplements; Foundations; Future; Goals; Health Food; Homocysteine; Incidence; Individual; Insulin Resistance; Intake; Internal Medicine; Internist; Intervention; Intervention Studies; Intervention Trial; Investigation; Juglans; Knowledge; Lead; Life; Link; Longitudinal cohort study; Measures; Meat; Mediating; Mediator of activation protein; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Metabolism; Monitor; Multi-Ethnic Study of Atherosclerosis; Non-Insulin-Dependent Diabetes Mellitus; Nuts; Obesity; Participant; Pathway Analysis; Pathway interactions; Pattern; Persons; Physicians; Pilot Projects; Plants; Population; Prediabetes syndrome; Prevention; Prevention strategy; Processed Meats; Prospective cohort; Proteins; Public Health; Randomized; Research; Research Personnel; Risk; Risk Factors; Role; San Francisco; Source; South Asian; Standardization; Structure; Techniques; Time; Training; United States; Universities; Validation; Work; base; career; career development; cohort; design; diabetes risk; dietary; experience; fruits and vegetables; high risk population; improved; metabolic abnormality assessment; metabolomics; modifiable risk; mortality; novel; nutrition; personalized therapeutic; pilot trial; precision nutrition; prevent; professor; response; skill acquisition; therapeutic target; therapy design; trial design

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.

项目概要 在美国，每 11 名成年人中就有 1 人患有 2 型糖尿病，并且是导致死亡的主要原因。高质量 饮食摄入量与较低的 2 型糖尿病风险独立且密切相关。新陈代谢 然而，饮食摄入与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有助于建立新的有效的个体化目标 用于治疗和预防。与代谢和细胞过程相关的化合物的表达是 称为代谢组学。该提案的目的是确定与某种物质相关的代谢物的身份。 低糖尿病风险饮食模式，研究这些代谢物与糖尿病发生的关联，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 使用低糖尿病风险食物进行试点饮食干预中的代谢物。目标 1 将使用数据和生物样本 来自动脉粥样硬化多种族研究 (MESA)，南亚人生活中动脉粥样硬化的介质 美国 (MASALA) 研究和鹿特丹研究 (RS) 以确定低糖尿病风险之间的关联 含有已知和新代谢物的饮食模式。我们将验证新发现的代谢物 电波队列。目标 2 将这些新发现的代谢物与糖尿病发生相关联，并检查 它们在多大程度上介导饮食与糖尿病之间的关系。它还将代谢物置于 使用网络分析技术的生物背景。目标 3 使用现有试点的数据和生物样本 对糖尿病前期患者进行短期核桃补充剂试验，以评估代谢物的变化 的干预。 本次以患者为导向的研究职业发展奖的候选人 Meghana Gadgil 博士， 是大学普通内科的普通内科医生和助理教授 加利福尼亚州、旧金山。 Gadgil 博士是一位具有丰富营养学背景的医师研究员 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 型糖尿病发病率。这项工作将成为她总体职业目标的基础： 成为一名独立的临床研究者，专注于通过以下方式预防高危人群的糖尿病 使用饮食干预措施。 Gadgil 博士将致力于结构化的教学培训和指导研究 1) 代谢组学分析和解释技术方面的经验； 2）网络培训 途径分析； 3）临床试验设计和管理； 4) 职业发展技能。 这项研究是相关且及时的，因为糖尿病及其危险因素的发病率持续上升，并且 用于预防的个性化饮食策略很少。拟议的调查将有助于 糖尿病预防饮食干预的理解、新知识和潜在目标。