Exploring the Fetal Origins Hypothesis in Diverse Youth

探索不同青年的胎儿起源假说

• 批准号: 8503606
• 负责人: Dana Dabelea
• 金额: $ 53.1万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-14 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8503606
• 关键词: 19 year old; Address; Adipose tissue; Affect; Attenuated; Beta Cell; Biochemical Markers; Birth; Blood Pressure; Body Weight Changes; Breast Feeding; Cardiovascular Abnormalities; Cell physiology; Child; Childhood; Cohort Studies; Colorado; DNA; DNA Methylation; Development; Diabetic intrauterine environment; Diet; Dyslipidemias; Energy Intake; Environment; Epidemic; Epidemiologic Studies; Epigenetic Process; Ethnic group; Event; Exhibits; Exposure to; Fatty acid glycerol esters; Feeding Patterns; Feeding behaviors; Functional disorder; Genes; Gestational Diabetes; Goals; Grant; Growth; Growth and Development function; Health Planning; Hepatic; Individual; Insulin Resistance; Intake; Lead; Leptin; Leptin resistance; Life; Liver; Mediating; Metabolic; Metabolic Diseases; Mothers; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Measure; Participant; Pathway interactions; Pattern; Perinatal; Perinatal Exposure; Positioning Attribute; Pregnancy; Prevention; Puberty; Race; Relative (related person); Risk; Signal Transduction; Visceral; Visit; Youth; aged; carbohydrate metabolism; cardiovascular risk factor; cohort; critical developmental period; fetal; follow-up; in utero; indexing; inflammatory marker; insulin secretion; insulin signaling; lipid metabolism; member; novel; nutrition; obesity in children; obesity risk; offspring; postnatal; prenatal; prenatal exposure; programs; rapid growth; saturated fat

DESCRIPTION (provided by applicant): Obesity now affecting one in five children in the U.S. and gestational diabetes (GDM) increasing among all racial and ethnic groups, it is becoming increasing important to understand how events that happen early in life, even before birth, can alter the obesity trajectory of individuals. The fetal over-nutrition hypothesis posits that intrauterine environment of diabetic and obese pregnancies may permanently alter the offspring's long- term risk for obesity and metabolic diseases, through developmental programming. Although several epidemiologic studies have provided evidence in support of this hypothesis there are many unanswered questions, including the biologic mechanisms responsible for these effects, and the relative contribution of the postnatal environment. The EPOCH (Exploring Perinatal Outcomes in CHildren) Study, a retrospective cohort study completing it's first five year grant cycle, is proposing to address some of these questions. EPOCH participants were 604 children (and their mothers) aged 6-13 years in 2006-2010, who were offspring of singleton pregnancies. The mother-child pairs were members of the Kaiser Permanente of Colorado Health plan (KPCO) at birth (B) and at first EPOCH visit (T1). EPOCH findings provided novel evidence that fetal over- nutrition is operating among contemporary US children, and possible avenues for prevention. EPOCH offspring are now entering puberty, another critical developmental period, associated with rapid growth, alterations in fat patterning, and development of insulin resistance. The goal of this renewal of RO1 DK068001-6 is to continue to follow this cohort for another five years, when participating youth will be 12-19 years (T2) to determine if the detrimental effects conferred by intrauterine over-nutrition become more evident during transition through puberty. The specific aims for this follow-up period are: Aim1: Follow the EPOCH cohort of youth exposed and not exposed to GDM in utero to explore the effects of fetal over-nutrition on: a) childhood growth, development and distribution of adiposity; b) cardiovascular (CV) risk factors; and c) metabolic abnormalities that are precursorsof type 2 diabetes (T2D), among 12-19 year old youth. Explore how postnatal feeding patterns (breastfeeding, high energy, high saturated fat intake) influence these associations. Aim No. 2. To explore the hypothesis of defective leptin signaling through which fetal over-nutrition could increase the risk of obesity in children. Aim 3: To examine the epigenetic DNA methylation profiles (using offspring DNA collected at T1) in specific genes according to fetal exposure status and assess whether DNA methylation profiles mediate the association between exposure to maternal GDM in utero and childhood outcomes.

描述（由申请人提供）：肥胖症现在影响美国五分之一的儿童，妊娠糖尿病（GDM）在所有种族和族裔群体中都增加了，对于了解即使在出生前的早期发生早期发生的事件，也可以改变个人的肥胖轨迹，这变得越来越重要。胎儿过度营政假设认为，糖尿病和肥胖妊娠的宫内环境可能会通过发育节目永久改变后代肥胖和代谢性疾病的长期风险。尽管一些流行病学研究提供了支持这一假设的证据，但仍有许多未解决的问题，包括负责这些影响的生物学机制以及产后环境的相对贡献。一项回顾性队列研究完成了其第一个五年赠款周期，这是一项回顾性队列研究，这是一项回顾性的研究，这是一个时代（探索儿童围产期结果），正在提议解决其中一些问题。 Epoch参与者是2006 - 2010年6-13岁的604名儿童（及其母亲），他们是单身妊娠的后代。母子对是科罗拉多州健康计划（KPCO）出生时（b）和初次访问（T1）的Kaiser Permanente（KPCO）的成员。时期的发现提供了新的证据，表明胎儿过度营养在当代美国儿童中正在运作，并可能用于预防途径。时代后代现在正在进入青春期，这是一个与快速增长，脂肪模式变化相关的另一个关键发育时期， 和胰岛素抵抗的发展。 RO1 DK068001-6续约的目标是继续跟随该队列五年，参加年轻人将为12-19岁 （T2）确定在通过青春期过渡期间，宫内过度营养所带来的有害影响是否变得更加明显。该随访期的具体目的是：AIM1：遵循暴露于子宫内GDM的年轻人的时代队列，以探索胎儿过度努力的影响： b）心血管（CV）风险因素； c）在12-19岁的青年中，是2型糖尿病（T2D）的代谢异常。探索产后进食模式（母乳喂养，高能量，高饱和脂肪摄入量）如何影响这些关联。目的2。探索有缺陷的瘦素信号传导的假设，胎儿过度营养可以增加儿童肥胖的风险。 AIM 3：根据胎儿暴露状态检查特定基因的表观遗传DNA甲基化谱（使用在T1处收集的后代DNA），并评估DNA甲基化谱是否介导了子宫和儿童期成果中的母体GDM之间的关联。