Exploring the Fetal Origins Hypothesis in Diverse Youth

描述（由申请人提供）：胎儿期被认为是暴露可能产生终身影响的关键（或敏感）时期之一。晚年肥胖的增加似乎发生在出生体重谱的两端：出生体重较高的全身性肥胖和出生体重较低时内脏脂肪增加及其代谢后果。这些表型是否在暴露的儿童中可检测到，以及它们是否具有共同的生物学途径是本提案的重点。本提案的具体目的是：目的1：同时研究不同种族儿童在宫内暴露于营养过剩（产妇糖尿病）和营养不足（生长限制）对儿童体重、脂肪模式和胰岛素抵抗标志物的长期影响。目标2。探讨子宫内激素“编程”的假设，胎儿暴露于激素会增加儿童肥胖和胰岛素抵抗的风险。

DESCRIPTION (provided by applicant): Fetal life is considered one of the critical (or sensitive) periods when an exposure may have lifelong effects. Increased adiposity in later life seems to occur at both ends of the birth weigh spectrum: generalized obesity with higher birth weight and increased visceral adiposity and its metabolic consequences at lower birth weights. Whether or not these phenotypes are detectable in exposed children and whether or not they have common biologic pathways is a focus of this proposal. The specific aims of this proposal are: Aim No. 1: To examine in parallel the long-term consequences of intrauterine exposure to excess nutrition (maternal diabetes) and under nutrition (growth restriction) on/childhood body size, fat patterning and markers of insulin resistance, among children of different ethnic groups. Aim No. 2. To explore hypothesis of intrauterine hormonal "programming" through which fetal exposures could increase the risk of obesity and insulin resistance in children. The proposed project is a prospective study proposing to enroll a total of 810 eight to eleven-year old offspring of diabetic pregnancies (exposed group-1), offspring of non-diabetic pregnancies with intrauterine growth restraint (exposed group-2), and control children (unexposed group), as well as their biological mothers, in three ethnic groups (non-Hispanic whites, Hispanics, and African-Americans). Comparison of exposed and unexposed groups will allow assessment and disentangling of the effects of exposure to diabetes mellitus in utero and intrauterine growth restraint on body size, fat patterning and insulin resistance markers and features later in childhood. The proposed research should also help understand whether these exposures have direct biological influences or are mediated through lifestyle choices. Such studies could ultimately lead to the development of strategies for early life prevention of future chronic disorders.