Nutritional Treatment of Overweight Adolescents with Cardiovascular Risk Factors

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DESCRIPTION (provided by applicant): The applicant, Dr. Sarah de Ferranti, is a pediatric cardiologist and Instructor in Pediatrics at Harvard University. Her long term goal is to become an independent clinician researcher in the assessment of vascular dysfunction and reduction of cardiovascular risk in children. Dr. de Ferranti has a longstanding interest in prevention; the pediatric obesity epidemic has focused her attention on adolescents with cardiovascular risk factors typical of the adult metabolic syndrome. Children with cardiovascular risk factors are likely to have cardiovascular and metabolic disease as adults. The proposed career development plan is necessarily multi-disciplinary, incorporating aspects of inflammatory physiology, nutritional lifestyle modification, and the conduct of an interventional clinical trial. Importantly, she will become proficient in vascular functional testing as a way of assessing pre-clinical atherosclerosis, allowing her to combine two areas of expertise rarely seen together, pediatric preventive cardiology and non-invasive vascular testing. Under the mentorship of Dr. David Ludwig, a pediatric endocrinologist experienced in obesity and nutrition, and Dr. Jane Newburger, a pediatric cardiologist with expertise in preventive cardiology and research, the applicant will investigate the effect of two nutritional strategies on cardiovascular risk factors. Using a feeding study design, the applicant will test the hypothesis that dietary strategy, independent of weight loss, affects cardiovascular risk factors. The protocol randomly assigns 46 overweight adolescents age 12-19 years with cardiovascular risk factors typical of the metabolic syndrome to receive either a low-fat diet or a low-glycemic load diet designed to induce a 5% weight loss over a period of 8 weeks. The primary outcome will be changes from baseline in insulin sensitivity as measured with an intravenous glucose tolerance test; other outcomes will include inflammation, coagulopathy, dyslipidemia, blood pressure, central obesity and body composition by DEXA. A secondary hypothesis to be tested is that vascular function measured by brachial artery reactivity and peripheral arterial tonometry will improve with weight loss, with larger changes from baseline in the low glycemic load group than the low fat diet. To our knowledge, this would be the first well- controlled feeding study to be conducted in overweight adolescents. The high prevalence of pediatric obesity in the United States makes greater understanding of the pediatric cardiovascular consequences essential.