A Novel Diet-Phenotype Interaction Affecting Body Weight

描述（由申请人提供）：近年来，组成广泛变化的饮食已用于治疗肥胖症。虽然这些饮食都没有产生持续的，长期的减肥效果，但几乎所有类型的饮食都有一些人做得非常好。个体之间这种差异的一种解释是动机和行为的差异。然而，潜在的生物学差异也可能发挥重要作用。以前的工作已经确定胰岛素分泌（通过标准75克口服葡萄糖负荷后30分钟的血清胰岛素浓度进行定量）是一个重要的生物决定因素。这项随机对照的多中心试验旨在验证胰岛素分泌将预测哪种类型的饮食对每个人最有效的假设。共有160名肥胖的年轻人（18至40岁）将被分配到两种饮食之一：低脂（60%碳水化合物，20%脂肪，20%蛋白质）或低血糖负荷（45%碳水化合物，35%脂肪，20%蛋白质）。参与者将在两个地点（波士顿儿童医院或北卡罗来纳大学教堂山分校）招募，并根据基线胰岛素分泌状态分配到饮食组。该方案将包括6个月的强化干预期和12个月的随访期。注册营养师将在小组研讨会和预定电话中提供营养教育和行为咨询。为了避免混淆，将密切关注组间治疗强度、体力活动处方和行为方法的控制。主要终点将是DXA扫描的体脂百分比。次要终点将包括心血管和糖尿病风险因素。重复的24小时饮食和体力活动回忆访谈将提供过程数据。将对已鉴定的代谢物进行代谢组学分析和分子分析，以表征表型并探索潜在的生理机制。

DESCRIPTION (provided by applicant): In recent years, diets of widely varying composition have been used in the treatment of obesity. While none of these diets has produced consistent, long-term weight loss, some individuals on virtually all types of diets do remarkably well. One explanation for this variation among individuals is differences in motivation and behavior. However, underlying biological differences may also play an important role. Previous work has identified insulin secretion (as quantified by serum insulin concentration at 30 minutes following a standard 75-gram oral glucose load) as an important biological determinant. This randomized-controlled, multi-center trial aims to test the hypothesis that insulin secretion will predict which type of diet will work best for each individual. A total of 160 obese young adults (18 to 40 years) will be assigned to one of two diets: low-fat (60% carbohydrate, 20% fat, 20% protein) or low-glycemic load (45% carbohydrate, 35% fat, 20% protein). Participants will be enrolled at two sites (Children's Hospital Boston or University of North Carolina-Chapel Hill) and assigned to diet groups according to baseline insulin secretion status. The protocol will include an intensive 6-month intervention period and a 12-month follow-up period. Registered dietitians will provide nutrition education and behavioral counseling during group workshops and scheduled telephone calls. In an effort to avoid confounding, close attention will be paid to control for treatment intensity, physical activity prescriptions, and behavioral methods between groups. The primary endpoint will be percent body fat by DXA scan. Secondary endpoints will include cardiovascular and diabetes risk factors. Repeated, 24-hour dietary and physical activity recall interviews will provide process data. Metabolomic profiling and molecular analysis of identified metabolites will be conducted to characterize phenotype and explore potential physiological mechanisms.