Oral Infection in the Pathogenesis of Gestational Diabetes

口腔感染在妊娠糖尿病发病机制中的作用

基本信息

批准号：
7500138
负责人：
LYNNAE Karen MILLAR Sauvage
金额：
$ 18.8万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2010-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7500138
关键词：
Affect Animal Pregnancy Area Under Curve Asians Biological Assay Biopsy Specimen Birth Birth Weight Blood Blood specimen Body mass index C-reactive protein Calibration Caring Chronic Clinic Clinical Clinical Research Clinical Trials Clinical Trials Design Collaborations Communities Condition Coupled DNA DNA Methylation Data Data Collection Dental Development Diabetes Mellitus Diagnosis Discipline of obstetrics Disease Early Diagnosis Enrollment Environment Epigenetic Process Ethnic Origin Exposure to Faculty Family history of Fetal Growth Fetal Weight Funding Future Gender Genes Genitourinary system Gestational Age Gestational Diabetes Glucola Glucose Glucose tolerance test Goals Grant Growth Factor Hawaii Hepatic Hour House Staffs Human Human Resources IGF1 gene IGFBP3 gene Immunoglobulin M Incidence Individual Infection Inflammatory Institution Insulin Resistance Insulin-Like Growth Factor Binding Protein 3 Insulin-Like Growth Factor I Insulin-Like Growth Factor II Interleukin-6 Interview Investigation Joints Laboratories Leadership Leukocytes Life Link Longitudinal Studies Lymphocyte Marital Status Maternal Age Measures Mediating Medical Methylation Microbe Minority Modeling Molecular Morbidity - disease rate Neonatal Non-Insulin-Dependent Diabetes Mellitus North Carolina OGTT Odds Ratio Oral Oral health Organism Outcome Pacific Island Americans Pathogenesis Patient Recruitments Patient currently pregnant Pattern Perinatal Periodontal Diseases Periodontal Infection Periodontitis Pilot Projects Population Postpartum Period Pregnancy Pregnancy Complications Pregnant Women Premature Birth Prematurity of fetus Prevalence Private Practice Production Protocols documentation Race Rate Recruitment Activity Regulation Regulatory Element Research Research Design Research Infrastructure Research Proposals Research Training Resources Risk Risk Factors Role Sample Size Sampling School Dentistry Serum Serum Markers Severities Small for Gestational Age Infant Smoking Somatomedins Stress Testing Thinking Third Pregnancy Trimester Tissues Training Umbilical Cord Blood Universities Week Weight Weight Gain Woman abstracting base case control cohort data management demographics design diabetic experience fetal glucose tolerance glycemic control imprint indexing insulin sensitivity isoprostaglandin F2alpha type-III mRNA Expression maternal diabetes maternal serum neonate non-diabetic novel oral infection oral pathogen performance site programs respiratory sample collection stressor

项目摘要

DESCRIPTION (provided by applicant): Project Summary/Abstract: Gestational diabetes mellitus (GDM) is associated with significant perinatal morbidity, fetal growth abnormalities and in the development of Type 2 diabetes later in life in affected offspring. We have recently demonstrated that severe periodontal infection is increased in gestational diabetics compared to non-diabetic Asian and Pacific Islander (API) women. Since API women are disproportionately affected by GDM, we have the unique opportunity to study the mechanisms underlying the documented association between oral infection and GDM in a high risk cohort. Our specific aims are: (1) to determine whether fetal-placental exposure to maternal oral organisms is associated with a decrease in insulin-like growth factor-2 (IGF2) in maternal serum and/or fetal cord blood at delivery and to demonstrate fetal IgM seropositivity and IGF2 suppression are intermediary explanatory variables in the association between maternal periodontal status and glycemic control; (2) to determine whether maternal periodontal disease is associated with a decrease in the level of IGF1 in maternal serum and to demonstrate IGF1 suppression is an intermediary variable in the association between maternal periodontal status and glycemic control; and (3) to establish necessary infrastructure and support to conduct a longitudinal clinical trial from < 16 weeks gestational age until 3 months postpartum. A cohort of 200 pregnant API women will be recruited and followed to determine the association between periodontal disease, IGF1, IGF2, and glycemic control. Data collection will include: demographics, antepartum care, labor, delivery, and neonatal outcomes, and glycemic control. Interviews and periodontal exams will be performed at baseline, at delivery, and at 3 months postpartum. Maternal blood will be obtained for glucose and IGF1 assays. Fetal cord blood samples will measure IGF2 and IgM levels to 18 oral microbes. Maternal blood, fetal cord blood, plaque, and placental samples will be stored for additional assays, if indicated. We anticipate our investigation will demonstrate IGF1 and IGF2 are decreased in women with moderate-severe periodontal disease and impaired glycemic control. This pilot project will additionally enable us to establish the infrastructure to conduct a large longitudinal clinical trial designed to demonstrate that periodontal disease increases the incidence and severity of GDM and persistence of insulin resistance postpartum; and to further study the mechanism of that effect. Narrative We hypothesize that periodontal disease associated inflammatory stressors contribute to insulin resistance through a fundamental alteration in the maternal-fetal IGF (insulin-like growth factor) axis.

描述（由申请人提供）：项目摘要/摘要：妊娠糖尿病（GDM）与严重的围产期发病率，胎儿生长异常以及后期患者的生命后期2型糖尿病的发展有关。我们最近证明，与非糖尿病亚洲和太平洋岛民（API）妇女相比，妊娠糖尿病患者的严重牙周感染增加了。由于API妇女受GDM的影响不成比例，因此我们有独特的机会研究高风险队列中口腔感染与GDM之间有记录关联的机制。我们的具体目的是：（1）确定胎儿对产妇口服生物的暴露是否与孕产妇血清和/或胎儿血液中胰岛素样生长因子-2（IGF2）的降低有关，并在分娩时表现出胎儿IgM血清血清素质和IGF2抑制作用的周期性均具有变化性的变量。（2）确定母体牙周疾病是否与母体血清中IGF1水平的降低相关并证明IGF1抑制是孕产妇牙周地位与血糖控制之间关联的中间变量；（3）建立必要的基础设施和支持，以进行纵向临床试验，从胎龄<16周到产后3个月。将招募200名怀孕API妇女的队列，并遵循确定牙周疾病，IGF1，IGF2和血糖控制之间的关联。数据收集将包括：人口统计学，天前护理，人工，分娩和新生儿结局以及血糖控制。访谈和牙周检查将在基线，交货和产后3个月进行。将获得葡萄糖和IGF1测定法的产妇血液。胎儿血液样品将测量IGF2和IGM水平为18个口腔微生物。如果指示，孕产妇的血液，胎儿血液，斑块和胎盘样品将用于其他测定。我们预计我们的研究将证明中度严重牙周疾病和血糖控制受损的女性IGF1和IGF2降低。该试点项目还将使我们能够建立基础设施，以进行大型纵向临床试验，旨在证明牙周疾病会增加GDM的发病率和严重性以及产后胰岛素抵抗的持续性；并进一步研究该作用的机制。叙述我们假设牙周疾病相关的炎症应激源通过母体 - 狂热IGF（胰岛素样生长因子）轴的基本改变而导致胰岛素抵抗。