Metabolomics and type 2 diabetes risk among high-risk women with a history of gestational diabetes

有妊娠糖尿病史的高危女性的代谢组学和 2 型糖尿病风险

基本信息

批准号：
8923268
负责人：
Deirdre Kay Tobias
金额：
$ 13.63万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8923268
关键词：
Address Amino Acids Aminoisobutyric Acids Archives Area Aromatic Amino Acids Betaine Biological Biological Markers Boston Branched-Chain Amino Acids Cardiovascular Diseases Choline Chronic Disease Communities Data Development Diabetes Mellitus Diabetic Diet Diet Dietary Factors Disease Epidemic Epidemiologic Methods Epidemiologic Studies Epidemiologist Epidemiology Fasting Functional disorder Future Gestational Diabetes Glucose Intolerance Glutamates Glutamine Goals Health High Risk Woman Individual Institution Investigation K-Series Research Career Programs Kidney Life Style Link Measurement Measures Meat Medical Mentors Metabolic Non-Insulin-Dependent Diabetes Mellitus Nurses&apos Health Study Nutritional Obesity Pathway Analysis Pathway interactions Physical activity Plasma Play Population Positioning Attribute Pregnancy Prevention Preventive Intervention Public Health Public Health Schools Recording of previous events Research Research Methodology Research Personnel Research Project Grants Resources Retinal Diseases Risk Risk Factors Role Sampling Series Source System Techniques Training Training Programs United States Water Woman Work analytical tool career cohort cost design diabetes risk experience follow-up high risk high throughput technology insight lifestyle factors lifestyle intervention metabolomics modifiable risk multidisciplinary novel novel marker nutrition population health prevent prospective responsible research conduct skills small molecule symposium trimethyloxamine

项目摘要

DESCRIPTION (provided by applicant): This K01 Career Development Award application proposes a multidisciplinary 4-year training program to provide the candidate, Dr. Deirdre K. Tobias, with the experience and resources necessary to launch a successful career as an independent nutrition and diabetes epidemiologist. The training plan, developed closely with primary mentor Dr. JoAnn Manson and co-mentor Dr. Frank B. Hu, will broaden Dr. Tobias' repertoire of research methodologies, including biomarker analysis, metabolomics, and systems epidemiology, and significantly strengthen her chronic disease epidemiology skill set. Dr. Tobias is an emerging and prolific epidemiologic researcher of nutritional and lifestyle determinants of gestational diabetes (GDM) and type 2 diabetes; however, additional training in important analytical tools is necessary to achieve her long-term goals of being an independent and successful researcher in population health. Additionally, these activities will give her extensive training in project management, which is essential for her future independent research endeavors. The Harvard School of Public Health is a leading research and academic institution within the large Boston-area medical community. This network will provide vast resources and opportunities for Dr. Tobias during this important developmental period, including cutting-edge seminar series, relevant advanced coursework, training in the responsible conduct of research, and scientific conferences. The proposed research project offers the candidate an outstanding opportunity to become proficient in the novel area of metabolomics research by evaluating the role of promising individual metabolites with diabetes risk among high risk women with prior GDM in the Nurses' Health Study II. Stored fasting plasma samples from the NHS II cohort will be used to measure a well-validated panel of water soluble and amino acid metabolites, including branched chain and aromatic amino acids, gut flora metabolites (e.g., choline, TMAO), glutamate, glutamine, and the recently cited β-aminoisobutyric acid (BAIBA). From this, an efficient prospective nested case-control design is proposed to analyze 200 diabetes cases and 200 matched controls with a history of GDM to identify metabolites associated with incident type 2 diabetes. Additionally, the project includes investigation of the known dietary sources for several of these metabolites with type 2 diabetes risk, among the 6,400 women with GDM in NHS II. This cohort is uniquely well-suited to assess these relationships, due to repeated dietary and lifestyle measures and 25 years of follow-up. Findings from the research proposed in this application may inform public health strategies to prevent type 2 diabetes in a high risk population, while increasing our understanding of the mechanisms by which diet confers diabetes risk among women with a history of GDM. The outstanding training opportunities in novel research areas such as metabolomics and systems epidemiology with key leaders in the fields will greatly enhance the skills and capabilities of the candidate, and position her for a successful and productive career as a nutrition and diabetes epidemiologist.

描述（由应用程序提供）：这项K01职业发展奖申请提案提案一项多学科的4年培训计划，旨在为候选人Deirdre K. Tobias博士提供，以成功地成为独立营养和糖尿病流行病学家所必需的经验和资源。该培训计划与主要导师乔恩·曼森（Joann Manson）博士和同事Frank B. Hu博士紧密制定，Tobias博士的研究方法曲目，包括生物标志物分析，代谢组学和系统流行病学，并显着增强了她的慢性疾病疾病流行病学技能。 Tobias博士是妊娠糖尿病（GDM）和2型糖尿病的营养和生活方式的新兴和多产的流行病学研究者。但是，必须对重要的分析工具进行额外的培训，以实现她成为人口健康领域独立和成功研究人员的长期目标。此外，这些活动将为她提供广泛的项目管理培训，这对于她未来的独立研究努力至关重要。哈佛大学公共卫生学院是波士顿地区大型医学界的领先研究和学术机构。该网络将为Tobias博士提供大量的资源和机会，在这个重要的发展时期，包括尖端的研讨会系列，相关的高级课程，负责任的研究进行培训以及科学会议。拟议的研究项目为候选人提供了一个很棒的机会，可以通过评估在护士健康研究中具有先前GDM的高风险妇女中有希望的个体代谢物风险的个人代谢产物的作用来精通代谢组学研究的新领域。来自NHS II队列的存储的空腹血浆样品将用于测量验证良好的水固体和氨基酸代谢物，包括分支链和芳香氨基酸，肠道菌群代谢物（例如Choline，Choline，TMAO），谷氨酸，谷氨酰胺，谷氨酰胺以及最近引用的β-氨基抗体（BAIB）（BAIB）。由此，提出了有效的前瞻性病例对照设计，以分析200例糖尿病病例和200个具有GDM病史的匹配对照，以识别与2型型糖尿病相关的代谢物。此外，该项目还包括针对其中几种具有2型糖尿病风险的代谢产物的已知饮食来源，在NHS II中有6,400名GDM的女性中。由于一再进行饮食和生活方式措施以及25年的随访，该队列非常适合评估这些关系。本应用程序中提出的研究的发现可能会为公共卫生策略提供依据，以防止高风险人群中的2型糖尿病，同时增加我们对饮食赋予GDM史的糖尿病风险的机制的理解。在新型研究领域（例如代谢组学和系统流行病学）与主要领导者的杰出培训机会将极大地提高候选人的技能和能力，并将她定位为成功和产品职业，作为营养和糖尿病的流行病学家。