Subgingival microbial community structure and insulin resistance

描述（由申请方提供）：本提案将研究龈下微生物群落组成与胰岛素抵抗之间的关联。这将在参加PI的NIH资助的R 00职业发展奖的300名无糖尿病参与者中完成：口腔感染，葡萄糖不耐症和胰岛素抵抗研究（ORIGINS）。2型糖尿病是一个重要的公共卫生问题，包括牙周感染在内的慢性感染被认为是胰岛素抵抗和糖尿病发生的潜在危险因素。然而，所报告的关联的时间性和机制尚不清楚。我们的工作通过证明牙周感染可以预测健康无糖尿病参与者中的糖尿病事件以及血红蛋白A1 c（HbA 1c）的进展，从而使该主题变得更加清晰。这些是首次报道慢性感染与糖尿病发展风险之间纵向相关性的研究。然而，我们以前的研究是基于临床措施，并没有直接研究口腔微生物群落特征。因此，我们建议使用微生物鉴定微阵列和454焦磷酸测序方法直接研究从无糖尿病参与者收集的生物膜样品的微生物组成。ORIGINS是一个年龄在20 - 55岁之间的多种族工作男性和女性样本，他们是纽约市哥伦比亚大学医学中心SEIU 1199工会的成员。这项研究的结果将确定特定的微生物群落特征与胰岛素抵抗的横截面和纵向。在此过程中，我们将在ORIGINS队列的计划长期随访期间获得关键知识，用于集中先验假设检验，以评估在本研究中观察到的与胰岛素抵抗相关的微生物群落特征是否也可以预测临床2型糖尿病的发展。此外，在短期内，这些研究结果也可以告知适当的资格标准和治疗目标的小型集中干预试验，以调查抗感染牙周治疗是否可以减少胰岛素抵抗的风险个体。

DESCRIPTION (provided by applicant): This proposal will investigate the association between subgingival microbial community composition and insulin resistance. This will be accomplished among 300 diabetes-free participants enrolled in the PI's NIH funded R00 career development award: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS). Type 2 diabetes mellitus is an important public health problem and chronic infections, including periodontal infections, have been suggested as a potential risk factor for insulin resistance and diabetogenesis. However the temporality and mechanism(s) of reported associations are unclear. Our work has brought some clarity to the topic by demonstrating that periodontal infections predict both incident diabetes as well as the progression of hemoglobin A1c (HbA1c) among healthy, diabetes-free participants. These represent the first studies to report on longitudinal associations between a chronic infection and risk for diabetes development. However, our previous studies were based on clinical measures and did not study oral microbial community characteristics directly. Therefore we propose to use both a microbe identification microarray and 454 pyrosequencing methods to directly study the microbial composition of biofilm samples collected from diabetes-free participants. ORIGINS is a multi-ethnic sample of working men and women aged 20 - 55 years with membership in the SEIU1199 union at Columbia University Medical Center, in New York City. Results from this study will identify specific microbial community characteristics associated with insulin resistance both cross-sectionally and longitudinally. In doing so, we will have critical knowledge for focused a priori hypothesis testing during the planned long term follow-up of the ORIGINS cohort to evaluate whether microbial community characteristics observed to be related to insulin resistance in the present study can also predict the development of clinical type 2 diabetes. Moreover, in the near-term these findings can also inform the appropriate eligibility criteria and therapy targets fr small focused intervention trials to investigate whether anti-infective periodontal therapy can reduce insulin resistance in at-risk individuals.