Subgingival microbial community structure and insulin resistance

龈下微生物群落结构与胰岛素抵抗

• 批准号: 8385439
• 负责人: Ryan T. Demmer
• 金额: $ 24万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-20 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8385439
• 关键词: Academic Medical Centers; Age; Air; Anti-Infective Agents; Bacteria; Bioinformatics; C-reactive protein; Characteristics; Chronic; Clinical; Cohort Studies; Communities; Data Analyses; Data Collection; Dental; Development; Diabetes Mellitus; Diet; Eligibility Determination; Enrollment; Ethnic Origin; Exposure to; Funding; Gender; Glucose Intolerance; Glycosylated hemoglobin A; Goals; Grouping; Health Policy; High Prevalence; Human; Individual; Infection; Inflammation; Inflammation Mediators; Inflammatory; Insulin; Insulin Resistance; Interleukin-6; Intervention Trial; K-Series Research Career Programs; Knowledge; Link; Lipids; Measurement; Measures; Mediator of activation protein; Medical; Methodology; Methods; Microbe; Microbial Biofilms; Modeling; New York City; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Participant; Pathology; Periodontal Diseases; Periodontal Infection; Population; Prevention; Protocols documentation; Public Health; Reporting; Research Infrastructure; Risk; Risk Factors; Role; Sampling; Smoking; Source; Stimulus; Structure; TNF gene; Testing; Tobacco; Translations; United States National Institutes of Health; Universities; Variant; White Blood Cell Count procedure; Work; Working Women; adiponectin; aged; base; clinical practice; cohort; cost; diabetes risk; fasting glucose; fasting plasma glucose; follow-up; holistic approach; microbial; microbial community; novel; oral infection; primary outcome; subgingival biofilm; working men

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. PUBLIC HEALTH RELEVANCE: The identification of a role for periodontal bacteria in the development of T2DM could have substantial public health impact. Even modest increases in T2DM risk associated with periodontal infection would be important given the high prevalence of treatable and preventable periodontal infections. The existence of an infrastructure for prevention and treatment of oral infection could allow for rapid translation of findings into both medical and dental clinical practice as well as public health policy.

描述（由申请人提供）：该提案将调查亚生物群落组成和胰岛素抵抗之间的关联。这将在300名无糖尿病参与者中完成，该参与者参加了PI的NIH资助R00职业发展奖：口腔感染，葡萄糖不耐症和胰岛素抵抗研究（起源）。 2型糖尿病是重要的公共卫生问题，慢性感染（包括牙周感染）被认为是胰岛素抵抗和糖尿病发生的潜在危险因素。但是，报告关联的时间和机制尚不清楚。我们的工作通过证明牙周感染可以预测入射糖尿病以及血红蛋白A1C（HBA1C）的进展，从而使该主题有所清楚。这些代表了报告慢性感染与糖尿病发育风险之间的纵向关联的最初研究。但是，我们以前的研究基于临床指标，并未直接研究口腔微生物社区特征。因此，我们建议同时使用微生物鉴定微阵列和454种焦磷酸测序方法来直接研究从无糖尿病参与者中收集的生物膜样品的微生物组成。 Origins是一个多民族的样本，包括20至55岁的工作男女，并在纽约市哥伦比亚大学医学中心的SEIU1199联盟中会员资格。这项研究的结果将在横截面和纵向上确定与胰岛素抵抗相关的特定微生物群落特征。在此过程中，我们将拥有关键的知识，以重点在计划的长期随访期间进行先验假设检验，以评估本研究中观察到的微生物群落特征是否与胰岛素抵抗有关，还可以预测2型临床2型糖尿病的发展。此外，在短期内，这些发现还可以告知适当的资格标准和治疗目标，以小型重点干预试验，以研究抗感染的牙周治疗是否可以降低处于危险中的个体中的胰岛素抵抗。 公共卫生相关性：确定牙周细菌在T2DM开发中的作用可能会产生重大的公共卫生影响。鉴于可治疗和可预防的牙周感染的高流行率，与牙周感染相关的T2DM风险的适度增加也很重要。对于预防和治疗口腔感染的基础设施的存在可能可以使发现快速转化为医学和牙科临床实践以及公共卫生政策。