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以流行病的速度发生。据估计，全球糖尿病的负担在未来25年将翻一番。虽然众所周知，肥胖与胰岛素抵抗和糖尿病有关，但人们对其因果关系和机制知之甚少。肥胖程度并不能直接预测胰岛素抵抗的程度，也不是所有的胰岛素抵抗个体都会发展成糖尿病。因此，胰岛素抵抗的原因是一个引起强烈科学兴趣的领域。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。这些数据的力量为探索糖尿病高危人群的线粒体功能提供了支持。儿科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、相对胰岛素缺乏症和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。该方案的目的是探索肥胖儿童与健康对照儿童的线粒体功能。一种新的非侵入性成像技术的使用将允许在体内对线粒体活性进行功能性评估。横断面和随后的纵向设计将调查年龄、身体成分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、指导和机构承诺的优势提供了一个独特的、非常适合进行这项研究提案的环境，并支持儿童胰岛素抵抗和糖尿病领域的独立儿科临床调查员的职业发展。 总之，拟议的项目将使用基于MRI的技术来研究线粒体功能，将其作为儿童胰岛素抵抗和2型糖尿病发展的非侵入性预测标记。对儿童线粒体功能障碍的研究既可以识别疾病的风险人群，也可以为预防和治疗提供分子靶点。

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.