Weight Loss and Exercise in Frail Obese Elderly Subjects

摘要：肥胖会导致严重的医疗并发症，影响生活质量。此外，在老年人中，肥胖会加剧与衰老和缺乏身体活动相关的力量、耐力、平衡和行动能力的下降，从而导致身体虚弱。老年人肥胖的适当治疗是有争议的，因为老年人的相对健康风险随着体重指数的增加而降低，体重减轻对骨骼健康和肌肉质量的潜在有害影响。本研究的主要目的是评估减肥和运动对身体功能、身体成分、骨骼和肌肉代谢以及虚弱、肥胖的老年男性和女性的生活质量的独立和联合影响。核心假设是，在虚弱肥胖的老年受试者中，减肥将改善身体功能和生活质量，而增加锻炼不仅会增加这些结果的改善，还会减轻减肥对骨骼和肌肉质量的不利影响。为了验证这一假设，100名身体虚弱的老年（65-85岁）肥胖男性和女性（BMI > 30 kg/m2）将被随机分为4个治疗组：1)对照组，2)10%减肥组，3)运动训练组，4)10%减肥加运动训练组。身体机能测量（体能测试，基于体能的力量、柔韧性、耐力、平衡和运动控制测试，以及评估功能状态的问卷调查）、身体组成（通过双能x线吸收仪评估全身脂肪和无脂质量，通过磁共振成像测量腹部脂肪和大腿肌肉质量）、将在52周治疗干预之前、期间和之后确定骨密度（BMD）和骨周转率（结合骨形成和吸收标志物的全身和局部骨密度）、肌肉蛋白合成（使用稳定同位素示踪技术的肌纤维蛋白合成率）以及与健康相关的生活质量（短期健康调查和体重对生活质量的影响问卷）。受试者被随机分为减重组和减重加运动组，将参加华盛顿大学体重管理中心的综合体重管理计划。随机分配到运动组或减肥加运动组的受试者将参加一个有监督的运动训练计划（每次90分钟，每周3天，持续52周）。一项为期一年的试点研究的令人鼓舞的结果表明，生活方式改变计划对改善体弱肥胖老年人身体功能的可行性和有效性。这项随机对照试验产生的数据将最终为越来越多的体弱肥胖老年男性和女性建立适当的治疗指南。

Abstract: Obesity causes serious medical complications and impairs quality of life. Moreover, in elderly persons, obesity can lead to frailty by exacerbating the decline in strength, endurance, balance and mobility associated with aging and physical inactivity. Appropriate treatment for obesity in elderly persons is controversial because of the decreased relative health risks with increasing body mass index in the elderly and the potential harmful effects of weight loss on bone health and muscle mass. The primary objectives of the proposed research are to evaluate the independent and combined effects of weight loss and exercise on physical function, body composition, bone and muscle metabolism, and quality of life in frail, obese elderly men and women. The central hypothesis is that in frail obese elderly subjects, weight loss will improve physical function and quality of life, while the addition of exercise will not only augment improvement in these outcomes, but also attenuate the adverse effects of weight loss on bone and muscle masses. To test this hypothesis, 100 elderly (65-85 years old) obese men and women (BMI > 30 kg/m2) with physical frailty will be randomized to 4 treatment groups: 1) control, 2) 10% weight loss, 3) exercise training, and 4) 10% weight loss plus exercise training. Measures of physical function (physical performance test, performance-based tests of strength, flexibility, endurance, balance, and motor control, and questionnaires that evaluate functional status), body composition (total body fat and fat-free mass evaluated by dual energy x-ray absorptiometry, abdominal fat and thigh muscle mass measured by magnetic resonance imaging), bone mineral density (BMD) and bone turnover (total body and regional BMD in conjunction with markers of bone formation and resorption), muscle protein synthesis (myofibrillar protein synthesis rate using stable isotope tracer techniques), and health related quality-of-life (Short-Form Health Survey and Impact of Weight on Quality of Life questionnaires) will be determined before, during, and after a 52-week treatment intervention. Subjects randomized to weight loss and weight loss plus exercise group will participate in a comprehensive weight management program at the Washington University Weight Management Center. Subjects randomized to exercise or weight loss plus exercise will participate in a supervised exercise-training program (90-min sessions, 3 days/week for 52 weeks). Encouraging results from a 1-year pilot study suggest the feasibility and efficacy of a lifestyle modification program towards improving physical function in frail obese elderly subjects. The data generated from this proposed randomized controlled trial will ultimately establish appropriate treatment guidelines for the increasing number of frail obese elderly men and women.