Prenatal Conditions and the Pathway to Obesity and Diabetes in Children

产前状况以及儿童肥胖和糖尿病的途径

基本信息

批准号：
8668775
负责人：
STEVEN D CHERNAUSEK
金额：
$ 25.65万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-04 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8668775
关键词：
4 year old Adult Affect Age-Months American Indians Angiogenic Factor Basal metabolic rate Biological Assay Birth Birth Intervals Body Composition Body fat Cardiovascular Diseases Characteristics Child Childhood Clinical Cohort Studies Cytosine DNA Data Collection Development Diabetes Mellitus Disease Dual-Energy X-Ray Absorptiometry Dyslipidemias Enrollment Epigenetic Process Event Fatty acid glycerol esters Fetus Funding Future Gene Expression Gene Targeting Gene-Modified Genetic Genome Glucose Goals Growth Health Hispanics Hormonal Hypertension Indirect Calorimetry Individual Infant Inflammation Inflammatory Insulin Insulin Resistance Interleukins Intervention Label Lead Leptin Leukocytes Life Lipids Low Birth Weight Infant Magnetic Resonance Imaging Maps Measures Metabolic Metabolic syndrome Metabolism Methylation Minority Modification Monitor Mothers Native Americans Non-Insulin-Dependent Diabetes Mellitus Nursery Schools Obesity Outcome Oxidative Stress Parents Pathogenesis Pathway interactions Phenotype Physiological Placenta Placental Growth Factor Plasma Population Pre-Eclampsia Predisposing Factor Predisposition Pregnancy Pregnant Women Recruitment Activity Risk Risk Factors Roentgen Rays Role Serum Surrogate Markers Testing Umbilical Cord Blood United States National Institutes of Health Variant Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factors Woman Youth adiponectin aged cohort cytokine design endothelial dysfunction fetal genome wide association study high risk indexing infancy inflammatory marker insight maternal diabetes obesity risk offspring prenatal prevent programs prospective

项目摘要

DESCRIPTION (provided by applicant): Pre-eclampsia (PE) is associated with an increased risk for diabetes mellitus (DM) for both mother and child. Similarly, the risk for DM and metabolic syndrome (MS) is increased for the offspring of women with DM during pregnancy. This is especially problematic among American Indian and Hispanic women who are at much higher risk for T2DM and PE and surely contributes to the growing problem of T2DM in Hispanic and American Indian youth. The overarching hypothesis is that the effects of maternal DM and PE combine to compound the risk of DM/MS in offspring by changing gene expression via epigenetic mechanisms and altering circulating factors. This effectively "programs" the offspring for later DM/MS. To test this, selected offspring of pregnant women with DM and at high risk for PE will be studied from birth to age 4 years. The first aim examines the effect of maternal T2DM alone and complicated by PE on growth, body composition, and metabolic indices. Standard anthropometric measures are obtained along with assessment of body composition by dual energy X-ray absorptiometry and magnetic resonance imaging. Serum glucose, insulin and lipid concentrations are determined along with measures of metabolic rate. The second aim tests the hypothesis that an infant born to DM mother ( PE) is exposed to repertoire of cytokines/inflammatory factors before birth that leads to unfavorable metabolic indices and body composition. The third aim maps epigenetic modifications in order to identify relevant target genes. The HELP assay is employed to identify variation in cytosine methylation at specific genetic loci in placental and leukocyte DNA. Defining the mechanisms, risk factors, and surrogate markers of future DM can lead new ways to prevent DM in high risk populations.

描述（由申请人提供）：先兆子痫 (PE) 与母亲和孩子患糖尿病 (DM) 的风险增加有关。同样，怀孕期间患有糖尿病的女性的后代患糖尿病和代谢综合征 (MS) 的风险也会增加。这在美洲印第安人和西班牙裔女性中尤其成问题，她们患 T2DM 和 PE 的风险要高得多，并且肯定会加剧西班牙裔和美洲印第安人青年中日益严重的 T2DM 问题。总体假设是，母体 DM 和 PE 的影响通过表观遗传机制改变基因表达并改变循环因素，共同增加后代 DM/MS 的风险。这有效地为后代“编程”以供以后的 DM/MS 使用。为了测试这一点，将对患有 DM 且患有 PE 高风险的孕妇的选定后代进行从出生到 4 岁的研究。第一个目标是检查母亲 T2DM 单独和并发 PE 对生长、身体成分和代谢指标的影响。通过双能 X 射线吸收测量法和磁共振成像评估身体成分，获得标准人体测量数据。血清葡萄糖、胰岛素和脂质浓度与代谢率的测量一起确定。第二个目标检验以下假设：DM 母亲 (PE) 所生的婴儿在出生前暴露于一系列细胞因子/炎症因子，导致不利的代谢指标和身体成分。第三个目标是绘制表观遗传修饰图，以识别相关的靶基因。 HELP 测定用于识别胎盘和白细胞 DNA 中特定基因位点的胞嘧啶甲基化变化。定义未来 DM 的机制、风险因素和替代标记可以为高危人群预防 DM 提供新的方法。