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: 10164615
• 负责人: MEGHANA DIPTI GADGIL
• 金额: $ 19.32万
• 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/10164615
• 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.

项目摘要 2型糖尿病会影响美国每11名成年人中的1个，并且是死亡的主要原因。高质量 饮食摄入量独立且与较低的2型糖尿病风险相关。代谢 但是，连接饮食摄入和糖尿病的过程尚不清楚。了解这些生物学 饮食摄入和糖尿病之间的过程可以帮助建立新的有效的个性化目标 用于治疗和预防。与代谢和细胞过程有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A相关的代谢物的身份 低糖尿病风险饮食模式，以研究这些代谢产物与入射糖尿病的关联，以及 与这些代谢物的作用相关的因果途径，并检查这些代谢水平的变化 在试验性饮食干预中，代谢物和低糖尿病风险食物。 AIM 1将使用数据和生物测量 从动脉粥样硬化的多民族研究（MESA）中，南亚人的动脉粥样硬化介体 在美国（Masala）研究和鹿特丹研究（RS），以确定低糖尿病风险的关联 饮食模式，具有已知和新型代谢物。我们将验证在 空波队列。 AIM 2伴侣这些新近鉴定的代谢产物与入射糖尿病，并检查 它们介导饮食与糖尿病之间的关系的程度。它还将代谢物置于 使用网络分析技术的生物环境。 AIM 3使用现有飞行员的数据和生物测量 在糖尿病前患者中对短期核桃补充剂的试验，以评估代谢物的变化 干预。 这项受过指导的以患者为导向的研究职业发展奖的候选人Meghana Gadgil博士， 是大学普通内科医学系的普通内科医生和助理教授 加利福尼亚州，旧金山。 Gadgil博士是一名医师评论者，营养和 糖尿病。在此提案中，她将研究饮食摄入，代谢物表达之间的新型关联 和2型糖尿病发病率。这项工作将成为其总体职业目标的基础： 成为专注于预防高风险人群中糖尿病的独立临床研究者 使用饮食干预措施。 Gadgil博士将承诺进行结构化的教学培训并指导研究 在1）代谢组分析和解释的技术方面的经验； 2）网络培训和 途径分析； 3）临床试验设计和管理； 4）职业发展技巧。 这项研究是相关且及时的，因为糖尿病及其危险因素的发生率持续上升，并且 个性化预防饮食策略很少。拟议的调查将做出贡献 理解，新知识和饮食干预的潜在糖尿病预防目标。