Mitochondrial Function in Pediatric Obesity

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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.