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）期之一。在以后的生活中，肥胖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的内脏肥胖及其代谢后果增加。这些表型是否在暴露的儿童中可检测到，以及他们是否具有共同的生物学途径是本提案的重点。该提案的具体目标是：目标1：在不同种族群体的儿童中，平行审查宫内暴露于营养过剩（母亲糖尿病）和营养不足（生长受限）对儿童体型、脂肪模式和胰岛素抵抗标志物的长期后果。目标二。探讨宫内激素“程序化”假说，胎儿暴露可增加儿童肥胖和胰岛素抵抗的风险。 拟议的项目是一项前瞻性研究，计划在三个种族群体（非西班牙裔白人、西班牙裔和非洲裔美国人）中共招募810名8至11岁的糖尿病妊娠后代（暴露组-1）、非糖尿病妊娠宫内生长受限的后代（暴露组-2）和对照儿童（未暴露组）及其亲生母亲。通过比较暴露组和未暴露组，将能够评估和弄清子宫内糖尿病暴露和宫内生长限制对儿童期以后的体型、脂肪模式和胰岛素抵抗标志物和特征的影响。拟议中的研究还应有助于了解这些暴露是否具有直接的生物学影响或通过生活方式的选择介导。这些研究最终可能导致制定预防未来慢性疾病的早期策略。

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.