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，评估儿童血管功能障碍和降低心血管风险。德·费兰蒂博士长期以来一直对预防感兴趣；儿童肥胖症的流行使她的注意力集中在患有心血管风险因素的青少年身上，这些风险因素是成人代谢综合征的典型特征。有心血管危险因素的儿童成年后很可能患有心血管和代谢性疾病。拟议的职业发展计划必须是多学科的，包括炎症生理学、营养生活方式改变和进行干预性临床试验等方面。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，使她能够结合两个罕见的专业领域：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专家简·纽伯格博士的指导下，申请者将调查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，申请者将检验饮食策略与体重减轻无关，影响心血管危险因素的假设。该方案随机分配了46名12-19岁的超重青少年，他们患有典型的代谢综合征心血管危险因素，接受低脂肪饮食或低血糖负荷饮食，旨在8周内使体重减轻5%。主要结果将是通过静脉葡萄糖耐量测试测量的胰岛素敏感性基线的变化；其他结果将包括炎症、凝血障碍、血脂异常、血压、中心性肥胖和DEXA的身体成分。有待检验的第二个假设是，通过臂动脉反应性和外周动脉血压测量测量的血管功能将随着体重减轻而改善，低血糖负荷组比低脂肪饮食组比基线变化更大。据我们所知，这将是第一个在超重青少年中进行的良好控制喂养研究。儿童肥胖症在美国的高流行率使得对儿童心血管后果的更多了解变得至关重要。

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.