Metabolomics and Type 2 Diabetes in a Cohort of Older Puerto Ricans

项目摘要 这个为期4年的K 01职业发展奖旨在提供必要的资源和培训， 候选人Shilpa N Bhupathiraju博士将在营养领域开展独立的研究事业， 慢性病流行病学培训计划包括教学课程工作，动手实践， 实验室培训、代谢组学讲习班、研讨会、咨询委员会会议、职业充实 方案，并出席全国会议。其目的是向布帕蒂拉朱博士提供 代谢组学和系统流行病学新兴领域的必要技能。Bhupathiraju博士是一位 积极主动、有能力的年轻研究人员，在该领域的研究生产力方面有着良好的记录 饮食和生活方式的决定因素。然而，为了实现研究独立， 她将需要掌握营养流行病学的新分析工具，如系统流行病学， 代谢组学拟议的项目将在哈佛T. H.实施。公共卫生学院。 学校毗邻广泛的研究和医疗机构，使Bhupathiraju博士能够获得 一个巨大的范围和深度的科学专业知识，资源和机会，以促进她的职业生涯， 建立研究独立性。拟议的项目是独特和及时的，因为它是有史以来第一次评估 一组老年波多黎各人中2型糖尿病（T2 D）的新的和未探索的代谢生物标志物。之间 在所有西班牙裔亚组中，波多黎各人的健康状况最差，2型糖尿病患病率过高， 代谢综合征、高血压和肥胖症。他们有独特的饮食模式，可能有助于T2 D 风险来自波士顿波多黎各健康研究的储存基线样本将用于测量有希望的 与T2 D风险相关的代谢物，包括肠道微生物群代谢物、尿素循环代谢物、2-氨基己二酸 酸、2-羟基丁酸、支链和芳香族氨基酸和β-氨基异丁酸， 120例T2 D流行病例和120例匹配对照的有效病例对照研究设计。通过利用 在基线和2年时已经测量的心脏代谢生物标志物中，该项目还将评估 候选代谢物和T2 D中间标志物之间的横断面和前瞻性关联。 其次，这些目标，候选人还将1）确定与T2 D相关的途径和签名， 2)检查关键代谢物的饮食来源。波士顿波多黎各健康研究非常适合 检查这些研究问题，因为它已经储存了生物标本和饮食，生活方式， 和种族特定的变量，如文化适应和感知压力。拟议研究的结果 这可能有助于确定新的生物标志物和预防T2 D的策略。世界级的指导团队， 是各自领域的领导者，加上丰富的科学环境和资源，将确保 Bhupathiraju博士成功和顺利地转变为营养学独立研究者， 代谢组学和慢性病流行病学。

PROJECT SUMMARY This 4-year K01 career development award was designed to provide the necessary resources and training to the candidate, Dr. Shilpa N Bhupathiraju, to launch an independent research career in the field of nutrition and chronic disease epidemiology. The training plan includes a mixture of didactic course work, hands-on laboratory training, metabolomics workshops, seminars, advisory committee meetings, career enrichment programs, and attendance at national conferences. It is intended to provide Dr. Bhupathiraju with the necessary skill set in the emerging fields of metabolomics and systems epidemiology. Dr. Bhupathiraju is a highly motivated and capable young researcher with an established record of research productivity in the area of dietary and lifestyle determinants of chronic diseases. However, in order to achieve research independence, she will need to master novel analytic tools in nutritional epidemiology such as systems epidemiology and metabolomics. The proposed project will be implemented at the Harvard T.H. Chan School of Public Health. The school is adjacent to a wide range of research and medical institutions giving Dr. Bhupathiraju access to an enormous range and depth of scientific expertise, resources, and opportunities to advance her career and establish research independence. The proposed project is unique and timely as it is the first ever to evaluate novel and unexplored metabolic biomarkers of type 2 diabetes (T2D) in a group of older Puerto Ricans. Among all Hispanic sub-groups, Puerto Ricans experience the poorest health with excessive prevalence of T2D, metabolic syndrome, hypertension, and obesity. They have unique dietary patterns that may contribute to T2D risk. Stored baseline samples from the Boston Puerto Rican Health Study will be used to measure promising metabolites related to T2D risk, including gut microbiota metabolites, urea cycle metabolites, 2-aminoadipic acid, 2-hydroxybutanoic acid, branched chain and aromatic amino acids, and β-aminoisobutyric acid in an efficient case-control study design of 120 prevalent T2D cases and 120 matched controls. By taking advantage of already measured cardiometabolic biomarkers at baseline and 2-years, the project will also evaluate the cross-sectional and prospective associations between candidate metabolites and intermediate markers of T2D. Secondary to these aims, the candidate will also 1) identify pathways and signatures associated with T2D, and 2) examine dietary sources of key metabolites. The Boston Puerto Rican Health Study is well-suited to examine these research questions as it has stored biospecimens and well-validated measures of diet, lifestyle, and ethnic-specific variables such as acculturation and perceived stress. Findings from the proposed research may help identify novel biomarkers and prevention strategies for T2D. The world-class mentoring team who are leaders in their respective fields together with the rich scientific environment and resources will ensure the successful and seamless transition of Dr. Bhupathiraju into an independent investigator in nutrition, metabolomics, and chronic disease epidemiology.