MECHANISMS OF VASCULAR DYSFUNCTION IN OBESITY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Childhood obesity has increased dramatically in the U.S. in the last decade. Unfortunately, these overweight children are at risk for target organ damage, adult diabetes, heart disease and stroke. One of the pathways by which obesity may induce target organ damage involves adiponectin (APN) an adipose-tissue derived cytokine. APN has direct vascular protective effects. However, it is found in reduced levels in obesity, obesity related inflammation and in coronary artery disease. Low levels are associated with insulin resistance and the dyslipidemia found as part of the metabolic syndrome. Therefore, we propose a cross-sectional study of school aged adolescents to study relationships between obesity and vascular function. Analyses will be performed to determine if the mechanisms underlying arterial dysfunction may relate to abnormal levels of CV risk factors, inflammation and APN. Brachial Artery Distensibility, BMI, BP, lipids, high sensitivity CRP, and APN will be measured in the ongoing 'Landmarks in the Progression to Type 2 Diabetes' study currently being conducted in the Princeton School District (N=2000). A sample of this cohort (n=450) will also undergo brachial flow mediated dilatation, measurement of augmentation index & pulse wave velocity. Contrasts in laboratory and vascular measures will be made among normals, obese subjects with normal insulin levels and obese adolescents with hyperinsulinemia. Showing that metabolic abnormalities related to overweight lead to blood vessel dysfunction in children will help doctors identify high risk children for early treatment to prevent future heart attack and stroke.