ANCESTRAL ADMIXTURE AND INSULIN

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 非裔美国人（AA）和墨西哥人的糖尿病患病率较高 美国人（MA）vs欧洲人（EA）。这些差异不能完全由人口和/或健康相关变量解释，这表明遗传因素参与其中。 除了有限的例外，大多数关于糖尿病相关特征人群差异的观察结果都涉及EA和AA成年人。然而，一些研究表明，胰岛素相关表型的种族差异起源于儿童时期，使青春期前人群成为研究的适当目标。因此，本研究旨在调查不同种族群体的儿童。出于各种原因，研究青春期前的儿童非常重要。首先，通过研究这个样本，我们将研究早期的病理生理因素，在许多环境和行为因素对疾病风险产生影响之前。此外，了解儿童糖尿病相关特征的病因将有助于在生命早期阶段制定干预策略，从而增加疾病预防。本研究的主要目的是研究遗传和环境参数对胰岛素分泌和作用方面种族/民族差异的影响。 具体的假设是：1）较低水平的欧洲混合物（ADM）与较高的空腹胰岛素、较低的胰岛素敏感性（Si）和较高的急性胰岛素对葡萄糖的反应（AIRg）相关; 2）在具有较低水平的欧洲ADM的儿童中，较低水平的体力活动将部分解释较低水平的Si和较高水平的空腹胰岛素和AIRg;在欧洲ADM水平较低的儿童中，食物摄入和社会经济地位（SES）都不会对空腹胰岛素、Si和AIRg的测量产生影响; 3）由祖先信息标记代表的基因组中的DNA序列将与空腹胰岛素、Si和AIRg显著相关。将在两次过夜GCRC访视期间进行检测，其中包括采集血液用于遗传混合物分析;频繁采样的静脉内葡萄糖耐量试验用于测定胰岛素敏感性和分泌;以及膳食耐量试验用于检查GI衍生的促胰岛素激素。身体成分，脂肪分布，SES，饮食摄入量和身体健康也将进行评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The prevalence of diabetes is higher among African-Americans (AA) and Mexican Americans (MA) vs European Americans (EA). These differences are not completely explained by demographic and/or health-related variables, suggesting that genetic factors are involved. With limited exceptions, the majority of observations regarding population differences in diabetes-related traits refer to EA and AA adults. However, several studies have demonstrated that racial differences in insulin-related phenotypes have their origin in childhood, making the prepubertal population an appropriate target for study. Hence, this study has been designed to investigate children of different racial groups. Studying prepubertal children is extremely important for a variety of reasons. First, by studying this sample we will be looking at the early pathophysiological factors, before many environmental and behavioral factors exert an influence in disease risk. In addition, understanding the etiology of diabetes-related traits in children will allow the development of intervention strategies at early stages of life that will increase disease prevention. The main objective of this study is to investigate the effect of genetic and environmental parameters on racial/ethnic differences in aspects of insulin secretion and action. The specific hypotheses to be tested are that, 1) Lower levels of European admixture (ADM) are associated with higher fasting insulin, lower insulin sensitivity (Si), and higher acute insulin response to glucose (AIRg); 2) In children with lower levels of European ADM, lower levels of physical activity will explain, in part, lower levels of Si and higher levels of fasting insulin and AIRg; in children with lower levels of European ADM, neither food intake nor socioeconomic status (SES) will have an effect on measures of fasting insulin, Si and AIRg; 3) Sequences of DNA across the genome represented by ancestry informative markers will be significantly associated with fasting insulin, Si, and AIRg. Testing will be conducted during two overnight GCRC visits, which will include collection of blood for genetic admixture analysis; a frequently sampled intravenous glucose tolerance test for determination of insulin sensitivity and secretion; and a meal tolerance test for examination of GI-derived insulinotropic hormones. Body composition, fat distribution, SES, dietary intake, and physical fitness also will be assessed.