Periodontal Infections and Type 2 Diabetes Mellitus Risk

描述(由申请人提供)：本职业发展提案旨在为Demmer博士从博士后研究职位过渡到独立的终身教职职位提供必要的保护研究时间和培训。该提案包括两个阶段：1)指导阶段，侧重于加强候选人的出版记录，并在候选人现有专业知识之外的研究领域获得额外培训；2)在采购研究跟踪教员职位后进行综合研究项目。拟议的培训将在哥伦比亚大学医学中心的梅尔曼公共卫生学院进行。具体地说，指导博士后阶段将提供以下四个模块的高级培训机会：模块1)高级测量方法，重点是量化感染作为慢性疾病病因暴露的方法；模块2)2型糖尿病流行病学和病理生理学；模块3)基因组学，重点是生物信息学和基因表达研究；模块4)传播科学成果和撰写补助金。这项独立的阶段研究旨在验证牙周感染是2型糖尿病(DM)发展的一个病因因素的假设。Demmer博士建议研究在两年的纵向随访中，基线暴露于已知牙周病原体是否与DM危险因素的进展有关。Demmer博士和他的同事将评估空腹血糖、胰岛素抵抗和β细胞功能障碍的两年进展，并在选定牙周病原体定植水平高和低的参与者之间比较这些进展率。这将使用纵向队列设计，在基线登记年龄为30-55岁的三族男女人口中的n=300名参与者中实现这一目标。拟议的设计将仔细控制潜在的混杂因素，如空腹血糖、胰岛素、血脂、肥胖、饮食、年龄、吸烟、种族和性别。这项拟议的研究可以通过提供适合于解决时间性(即牙周感染是否先于糖尿病发病)的强有力的研究设计，来推进关于牙周感染和2型糖尿病之间众所周知的联系的科学知识。此外，关于感染对糖尿病基本病理的独立贡献的数据可以第一次使用基于人群的慢性感染模型来处理。独立阶段研究项目将大大提高申请者在未来R-01申请中担任首席调查员的资格-这是该资助机制的明确目标。

DESCRIPTION (provided by applicant): This career development proposal aims to provide the necessary protected research time and training for Dr. Demmer to transition from his postdoctoral research position to an independent tenure track faculty position. The proposal is comprised of two phases: 1) A mentored phase focused on strengthening the candidate's publication record and obtaining additional training in research areas outside of the candidate's current expertise; and 2) a comprehensive research project to be carried out upon procurement of a research track faculty position. The proposed training will be carried out in the Mailman School of Public Health at Columbia University Medical Center. Specifically, the mentored postdoctoral phase will provide opportunities for advanced training in the following four modules: Module 1) Advanced measurement methods with focus on methodological approaches to quantifying infection as an etiologic exposure for chronic disease; Module 2) Type 2 diabetes mellitus epidemiology and pathophysiology; Module 3) Genomics, with an emphasis in bioinformatics and gene expression studies; Module 4) Dissemination of scientific findings and grant writing. The independent phase research aims to test the hypothesis that periodontal infection is an etiologic factor in the development of type 2 diabetes mellitus (DM). Dr. Demmer proposes to study whether baseline exposure to known periodontal pathogens is associated with progression of DM risk factors over two years of longitudinal follow-up. Dr. Demmer and colleagues will assess the two year progression of fasting glucose, insulin resistance and beta-cell dysfunction and compare these progression rates between participants with high vs. low colonization levels of selected periodontal pathogens. This will be achieved using a longitudinal cohort design among n=300 participants in a population of tri-ethnic men and women aged 30 - 55 years at baseline enrollment. The proposed design will carefully control for potential confounders such as baseline levels of fasting glucose, insulin, lipids, obesity, diet, age, smoking, ethnicity and gender. The proposed research can advance the scientific knowledge regarding the well-known association between periodontal infection and type 2 diabetes mellitus through its provision of a powerful study design appropriate for addressing temporality (i.e., do periodontal infections precede the onset of diabetes pathology). In addition, data on the independent contribution of infections to the underlying pathology of diabetes can be addressed for the first time using a population based, chronic infection model. The independent phase research project will significantly enhance the applicant's qualifications to serve as principal investigator on a future R-01 application - an explicit aim of this funding mechanism.