Weight Loss and Exercise in Frail Obese Elderly Subjects

摘要：肥胖会导致严重的医疗并发症，并影响生活质量。此外，在老年人中，肥胖会加剧与衰老和缺乏体力活动相关的力量、耐力、平衡性和灵活性的下降，从而导致虚弱。老年人肥胖的适当治疗是有争议的，因为随着老年人体重指数的增加，相对健康风险降低，而且体重减轻对骨健康和肌肉质量有潜在的有害影响。这项拟议研究的主要目标是评估减肥和锻炼对虚弱、肥胖的老年男性和女性的身体功能、身体成分、骨骼和肌肉代谢以及生活质量的独立和综合影响。中心假设是，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，而额外的锻炼不仅会增强这些结果的改善，还会减弱减肥对骨骼和肌肉质量的不利影响。为了验证这一假设，将100名身体虚弱的老年肥胖(BMI和GT；30 kg/m2)男性和女性随机分为4组：1)对照组，2)10%减重，3)运动训练，4)10%减重+运动训练。测量身体功能(体能测试、力量、灵活性、耐力、平衡和运动控制的性能测试，以及评估功能状态的问卷)、身体成分(用双能x射线吸收测量仪评估全身脂肪和脱脂质量，用磁共振成像测量腹部脂肪和大腿肌肉质量)、骨密度(BMD)和骨转换(全身和局部骨密度，结合骨形成和吸收的标志)，肌肉蛋白质合成(使用稳定同位素示踪剂技术的肌原纤维蛋白合成率)，与健康相关的生活质量(简明健康调查和体重对生活质量的影响问卷)将在52周的治疗干预之前、期间和之后确定。被随机分为减肥和减肥加运动组的受试者将参加华盛顿大学体重管理中心的综合体重管理计划。随机接受锻炼或减肥加锻炼的受试者将参加有监督的锻炼计划(每次90分钟，每周3天，共52周)。一项为期一年的初步研究的令人鼓舞的结果表明，生活方式改变计划对改善虚弱肥胖老年受试者的身体功能是可行的和有效的。这项拟议的随机对照试验产生的数据最终将为越来越多的虚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.