Intensive Exercise to Improve Mitochondrial Dysfunction in Pediatric Obesity

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.
Obese children are at risk for the development of insulin resistance, relative insulin
deficiency and type 2 diabetes mellitus (DM). The prevention of type 2 DM is hindered by the
lack of a non-invasive predictive test, knowledge as to individual risk and effective
preventative measures. There is increasing evidence that alterations in mitochondria
contribute to the development of diabetes in humans. Therefore, it is important to explore
mitochondrial dysfunction as a potential predictor of diabetes in children and a potential
target for prevention. The aims of the proposed protocol are to determine whether an
intensive exercise intervention can improve mitochondrial function in children identified as
having mitochondrial dysfunction and insulin resistance. The use of a non-invasive imaging
technique will allow for a functional in vivo assessment of mitochondrial activity. The
investigators propose the investigation of an intensive exercise protocol designed to
improve mitochondrial function in children who are insulin resistant and have documented
mitochondrial dysfunction by magnetic resonance spectroscopy. The study is designed to
investigate the plasticity of abnormal mitochondrial function in high risk children. In
summary, the proposed projects will investigate mitochondrial function as a non-invasive
predictive marker for the development of insulin resistance and type 2 diabetes mellitus in
children and attempt to modify mitochondrial function with an intensive exercise
intervention. The study of mitochondrial dysfunction in children may both identify those at
risk for disease and provide a molecular therapeutic target for prevention and treatment.

The investigators hypothesize that children with insulin resistance and mitochondrial
dysfunction who are randomized to intensive exercise versus standard lifestyle advice will
show improvement in mitochondrial function and insulin sensitivity.