Nutritional Treatment of Overweight Adolescents with Cardiovascular Risk Factors

描述（由申请人提供）：申请人Sarah de Ferranti博士是哈佛大学的儿科心脏病专家和儿科讲师。她的长期目标是成为一名独立的临床研究人员，评估血管功能障碍和降低儿童心血管风险。de Ferranti博士对预防有着长期的兴趣;儿童肥胖症的流行使她将注意力集中在具有成人代谢综合征典型心血管危险因素的青少年身上。有心血管危险因素的儿童成年后可能患心血管和代谢疾病。拟议的职业发展计划必须是多学科的，包括炎症生理学，营养生活方式的改变，以及干预性临床试验的进行。重要的是，她将精通血管功能测试作为评估临床前动脉粥样硬化的一种方式，使她能够联合收割机结合两个领域的专业知识很少看到在一起，儿科预防心脏病学和非侵入性血管测试。在肥胖和营养方面经验丰富的儿科内分泌学家大卫路德维希博士和具有预防心脏病学和研究专长的儿科心脏病学家简纽伯格博士的指导下，申请人将研究两种营养策略对心血管风险因素的影响。使用喂养研究设计，申请人将检验饮食策略（不依赖于体重减轻）影响心血管风险因素的假设。该方案随机分配了46名年龄在12-19岁之间的超重青少年，他们具有典型的代谢综合征心血管风险因素，接受低脂饮食或低血糖负荷饮食，旨在诱导8周内体重减轻5%。主要结局将是通过静脉内葡萄糖耐量试验测量的胰岛素敏感性相对于基线的变化;其他结局将包括炎症、凝血障碍、血脂异常、血压、向心性肥胖和DEXA测定的身体组成。待检验的次要假设是，通过肱动脉反应性和外周动脉张力测定法测量的血管功能将随着体重减轻而改善，低血糖负荷组较基线的变化大于低脂饮食组。据我们所知，这将是第一个在超重青少年中进行的控制良好的喂养研究。美国儿童肥胖的高患病率使得更好地了解儿童心血管后果至关重要。

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.