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）：explampsia（PE）与母亲和儿童的糖尿病（DM）风险增加有关。同样，怀孕期间DM的后代增加了DM和代谢综合征（MS）的风险。在美洲印第安人和西班牙裔妇女中，这尤其有问题，这些妇女面临T2DM和PE的风险更高，并且肯定会导致西班牙裔和美洲印第安人青年的T2DM日益增长的问题。总体假设是，通过表观遗传机制改变基因表达并改变循环因子，母体DM和PE结合了后代DM/MS的风险。这有效地“编程”了以后的DM/MS的后代。为了测试这一点，将研究从出生到4岁的DM和高风险的孕妇的选定后代。第一个目的研究了单独使用母体T2DM的影响，并且PE对生长，身体组成和代谢指数的影响很复杂。通过双能量X射线吸收仪和磁共振成像评估人体组成以及人体组成的评估。确定血清葡萄糖，胰岛素和脂质浓度以及代谢率的度量。第二个目的检验了以下假设：DM母亲（PE）出生的婴儿在出生前暴露于细胞因子/炎症因素的曲目，这会导致不利的代谢指数和身体组成。第三个目标映射表观遗传修饰，以识别相关的靶基因。使用帮助测定法确定胎盘和白细胞DNA在特定遗传基因座的胞嘧啶甲基化的变化。定义未来DM的机制，危险因素和替代标志物可以引导新的方法来防止高风险人群中的DM。