Mitochondrial Function in Pediatric Obesity

描述（由申请人提供）：肥胖症和2型糖尿病在美国和世界范围内呈流行趋势。据估计，未来25年全球糖尿病负担将翻一番。虽然已知肥胖与胰岛素抵抗和糖尿病相关，但对因果关系和机制的了解有限。肥胖程度并不能直接预测胰岛素抵抗的程度，也不是所有胰岛素抵抗的人都会发展成糖尿病。因此，胰岛素抵抗的原因是一个备受科学关注的领域。越来越多的证据表明，线粒体的改变有助于人类糖尿病的发展。这些数据的强度为探索糖尿病风险个体的线粒体功能提供了支持。儿童2型糖尿病正以前所未有的速度增长。肥胖儿童有发生胰岛素抵抗、相对胰岛素缺乏和2型糖尿病的风险。目前还没有准确的预测模型来评估哪些儿童会患上这种慢性衰弱性疾病。因此，探索线粒体功能障碍作为儿童糖尿病的潜在预测因子是很重要的。拟议方案的目的是探索与健康对照儿童相比，肥胖儿童的线粒体功能。使用一种新的非侵入性成像技术将允许线粒体活性的功能体内评估。横断面和随后的纵向设计将调查年龄、身体组成和青春期状态的变化对胰岛素抵抗发展的贡献以及与线粒体功能障碍的关系。候选人的背景、指导和机构承诺的力量提供了一个独特的非常适合的环境来进行这项研究计划，并支持儿童胰岛素抵抗和糖尿病领域独立儿科临床研究者的职业发展。

DESCRIPTION (provided by applicant): Obesity and type 2 diabetes are occurring at epidemic rates in the United States and worldwide. The global burden of diabetes is estimated to double over the next 25 years. Although obesity is known to correlate with insulin resistance and diabetes, there is limited knowledge as to causality and mechanism. The level of obesity does not directly predict the level of insulin resistance, and not all insulin resistant individuals will progress to diabetes. Therefore, the cause of insulin resistance is an area of intense scientific interest. There is increasing evidence that alterations in mitochondria contribute to the development of diabetes in humans. The strength of these data provides support for the exploration of mitochondrial function in individuals at risk for the development of diabetes. Pediatric type 2 diabetes is increasing at unprecedented rates. Obese children are at risk for the development of insulin resistance, relative insulin deficiency and type 2 diabetes mellitus. There are currently no accurate predictive models to evaluate which children will develop this chronic debilitating illness. Therefore, it is important to explore mitochondrial dysfunction as a potential predictor of diabetes in children. The aims of the proposed protocol are to explore mitochondrial function in children with obesity compared to healthy control children. The use of a novel non-invasive imaging technique will allow for a functional in vivo assessment of mitochondrial activity. The cross-sectional and subsequent longitudinal design will investigate the contribution of alterations in age, body composition, and pubertal status to the development of insulin resistance and the relationship to mitochondrial dysfunction. The strength of the candidate's background, mentorship and institutional commitment provide a uniquely well suited environment to conduct this research proposal and to support the career development of an independent pediatric clinical investigator in the area of childhood insulin resistance and diabetes. In summary, the proposed project will investigate mitochondrial function, using MRI based technology, as a non-invasive predictive marker for the development of insulin resistance and type 2 diabetes mellitus in children. The study of mitochondrial dysfunction in children may both identify those at risk for disease and provide a molecular target for prevention and treatment.