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

• 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
• 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' 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

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（由申请人提供）：本 K01 职业发展奖申请提出了一项为期 4 年的多学科培训计划，旨在为候选人 Deirdre K. Tobias 博士提供作为独立营养和糖尿病医生开启成功职业生涯所需的经验和资源。该培训计划由主要导师 JoAnn Manson 博士和联合导师 Frank B. Hu 博士密切制定，将拓宽 Tobias 博士的研究方法，包括生物标志物。 Tobias 博士是一位新兴且多产的妊娠期糖尿病 (GDM) 和 2 型糖尿病营养和生活方式决定因素的流行病学研究员，她在分析、代谢组学和系统流行病学方面拥有丰富的经验，并显着增强了她的慢性病流行病学技能。分析工具对于实现她成为人口健康领域独立且成功的研究人员的长期目标是必要的。此外，这些活动将为她提供项目管理方面的广泛培训，这对于她未来的独立研究工作至关重要。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，该网络将为托比亚斯博士在这一重要的发展时期提供大量资源和机会，包括尖端研讨会系列、相关高级课程、拟议的研究项目通过评估有前途的个体代谢物在糖尿病高风险女性中的作用，为候选人提供了一个精通代谢组学研究新领域的培训。护士健康中的既往 GDM研究 II. 来自 NHS II 队列的储存的空腹血浆样本将用于测量一组经过充分验证的水溶性和氨基酸代谢物，包括支链和芳香氨基酸、肠道菌群代谢物（例如胆碱、TMAO）、谷氨酸、谷氨酰胺和最近引用的 β-氨基异丁酸 (BAIBA) 由此提出了一种有效的前瞻性巢式病例对照设计来分析 200 例糖尿病病例。和 200 名具有 GDM 病史的对照对照，以识别与 2 型糖尿病相关的代谢物。此外，该项目还包括在 NHS II 的 6,400 名 GDM 女性中调查其中几种具有 2 型糖尿病风险的代谢物的已知饮食来源。由于反复的饮食和生活方式测量以及本申请中提出的研究结果 25 年的跟踪，该队列非常适合评估这些关系。在代谢组学和系统流行病学等新研究领域，与该领域的主要领导者进行培训的机会将大大增加。候选人的技能和能力，使她能够成为一名成功且富有成效的营养和糖尿病流行病学家。