This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The current epidemic of childhood obesity is associated with an increased risk for type 2 diabetes T2D and cardiovascular disease CVD. Through our preliminary study we have demonstrated differences in inflammatory markers, serum soluble adhesion molecules and lipids between obese O children with risk factors for T2D and lean L children. This protocol will evaluate the role of inflammation and oxidative stress OS as potential underlying mechanisms leading to insulin resistance IR and increased risk for atherosclerosis in obese O children. This will determine if O children exhibit a state of low-grade chronic inflammation and increased OS compared with L children, determine if O children exhibit increased CV risk. Furthermore, we will determine if differences observed between O and L children are related to IR; and through a 6-month intervention program we will determine if therapy with metformin or an intensive lifestyle modification program, both known to improve insulin sensitivity, will lead to an associated improvement on inflammation and OS in O children. All O children who complete the baseline evaluation and are not diagnosed with impaired glucose tolerance or T2D, will be randomized to one of 3 intervention arms: metformin therapy, intensive lifestyle modification program or 'usual care' advice on dietary changes and increasing physical activity given only at baseline. Findings from this study could help us identify new screening tools that may be useful in clinical practice to identify those O children at highest risk to develop T2D and atherosclerosis.
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