WEIGHT LOSS--BONE & SKELETAL MUSCLE HOMEOSTASIS IN NIDDM

患有2型糖尿病的严重肥胖女性（BMI 35至40）骨骼质量增加。他们也有一个增加的无脂肪质量，大概包括增加骨骼肌。这些女性不断尝试减肥，以改善糖尿病控制。过去，减肥的尝试通常是通过医学手段进行的，但严重肥胖的妇女越来越频繁地接受减肥手术。随着体重的减轻，无论通过何种方式，医疗或手术，脂肪量都会减少。此外，有证据表明，骨骼和骨骼肌中的钙也会丢失。我们计划调查两组2型糖尿病女性在减肥过程中骨矿物质和骨骼肌的损失，一组通过低热量饮食减肥，另一组通过胃旁路手术减肥。待检验的假设是，随着体重减轻：1）两组骨骼肌都会丢失; 2）如果受试者适当补充钙和维生素D，骨钙不会丢失; 3）骨转换的生化标志物会升高; 4）手术组胃肠道钙吸收会受损; 5）生活质量将与减肥量成比例地提高。我们将研究BMI范围为35至40，年龄为25至45岁的绝经前糖尿病女性。使用核心A&B生化标志物测量身体组成，并在基线、6个月、1年和2年时测量生活质量。将比较两组这些参数的变化以及血糖控制（HgbA 1c）、血压和血脂的改善。核心C将用于数据存储、数据分析和结果的统计评价。随着严重肥胖糖尿病女性减肥尝试的发生率越来越高，以及减肥手术干预的增加，是否会对骨骼和肌肉产生不良影响对于估计此类尝试的风险-受益比非常重要。目前还没有足够的关于2型糖尿病患者对胃旁路反应的骨丢失和肌肉质量的数据，因此该提案是及时的，具有公共卫生重要性。

Severely obese women (BMI 35 to 40) with type 2 diabetes mellitus have an increased skeletal mass. They also have an increased fat-free mass, presumably including increased skeletal muscle. These women are continually attempting to lose weight in order to improve their diabetes control. Attempts at weight loss have generally been carried out medically in the past, but severely obese women are undergoing bariatric surgery more and more frequently. With weight loss, by whatever means, medical or surgical, fat mass is lost. In addition, there is some evidence that calcium from bone and skeletal muscle mass is also lost. We plan to investigate the loss of bone mineral and skeletal muscle during weight loss in two groups of women with type 2 diabetes, one group losing weight on a hypocaloric diet and another group losing weight with gastric by-pass surgery. The hypotheses to be tested are that, with weight loss: 1) skeletal muscle will be lost in both groups; 2) bone calcium will not be lost if subjects are appropriately supplemented with calcium and vitamin D; 3) biochemical markers of bone turnover will be elevated; 4) gastrointestinal calcium absorption will be impaired in the surgical group; 5) quality of life will improve in proportion to amount of weight loss. We will study pre-menopausal diabetic women with a BMI range of 35 to 40, aged 25 to 45 years. Measures of body composition using Core A&B biochemical markers, and quality of life will be taken at baseline, 6 months, one year, and two years. The two groups will be compared for changes in these parameters and also for improvement in glucose control (HgbA1c), blood pressure, and blood lipids. Core C will be used for data storage, data analysis, and statistical evaluation of results. With the great incidence of weight loss attempts in this country by severely obese diabetic women, and with the increasing bariatric surgery interventions, whether adverse effects on bone and muscle occur is important in estimating the risk-benefit ratio of such attempts. There are no adequate data on bone loss and one on muscle mass in response to gastric by-pass in type 2 diabetic patients, so that the proposal is timely and has public health importance.