Periodontal Infections and Type 2 Diabetes Mellitus Risk

描述（由申请人提供）：本职业发展建议旨在为Demmer博士提供必要的受保护的研究时间和培训，以便从博士后研究职位过渡到独立的终身教职职位。该提案由两个阶段组成：1）指导阶段，重点是加强候选人的出版记录，并在候选人目前的专业知识之外的研究领域获得额外的培训;和2）在采购研究跟踪教师职位时进行的综合研究项目。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。具体而言，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，重点是将感染量化为慢性疾病的病因暴露的方法学方法;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）科学发现的传播和赠款的写作。本研究旨在验证牙周感染是2型糖尿病（DM）发病的一个致病因素这一假设。Demmer博士建议研究已知牙周病原体的基线暴露是否与DM风险因素的进展相关，并进行为期两年的纵向随访。Demmer博士及其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，并比较选定牙周病原体定植水平高与低的参与者之间的进展率。这将在基线入组时年龄为30 - 55岁的三种族男性和女性人群中使用n=300名受试者的纵向队列设计来实现。拟定设计将仔细控制潜在混杂因素，如空腹血糖、胰岛素、血脂、肥胖、饮食、年龄、吸烟、种族和性别的基线水平。拟议的研究可以通过提供一个强大的研究设计来促进关于牙周感染和2型糖尿病之间众所周知的关联的科学知识，该研究设计适合于解决时间性（即，牙周感染是否先于糖尿病病理学的发作）。此外，关于感染对糖尿病潜在病理学的独立贡献的数据可以首次使用基于人群的慢性感染模型来解决。独立阶段的研究项目将大大提高申请人的资格，作为未来R-01申请的主要研究者-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.