OBESITY, GLUCOSE METABOLISM AND DIET IN OLDER WOMEN

候选人是一名运动生理学家，其最初的研究 并资助了一些试点项目，重点关注饮食和 运动对久坐正常人的肥胖和葡萄糖代谢的影响， 糖尿病患者。拟议中的MRSDA将使她获得 在肌肉和脂肪代谢方面的训练， 研究衰老和葡萄糖代谢的相互作用， 患糖尿病风险高的女性。调研： 糖尿病（GDM）每年影响90，000名女性， 在怀孕的10-20年内，40-65%的这些妇女发展 非胰岛素依赖型糖尿病（NIDDM）;一种与 肥胖，缺乏运动， 葡萄糖和脂肪酸代谢。我们假设女性 有GDM病史且存在葡萄糖耐量受损 (IGT)或NIDDM绝经后会久坐不动，有内脏 肥胖和葡萄糖、脂肪和肌肉异常 新陈代谢.一个结构化的减肥和有氧运动计划 (WL+AEX）将比单独减肥（WL）更有效， 减少内脏肥胖和增加有氧能力1） 降低游离脂肪酸（FFA）水平，增加脂肪氧化; 2)增加肌肉GLUT-4蛋白和糖原储存;和3） 增强胰岛素敏感性，从而改善葡萄糖耐量。 本研究旨在探讨IGT或NIDDM患者的血糖稳态 （N=80）绝经后女性（50-60岁），有GDM病史。 将在基线和WL 6个月后进行测量 或WL+AEX。患者随访将在术后1年进行， 评估患者葡萄糖耐量的干预，身体 组成和VO 2 max。总体和局部体脂百分比，脂肪 体重、瘦组织重量和骨矿物质含量将被确定 通过双能X线吸收法计算机断层扫描将 量化“腹内和皮下脂肪组织面积， 大腿中部肌肉和脂肪组织区域。将测量VO 2 max 进行渐进式跑步机测试高胰岛素-血糖正常 带有氚化葡萄糖的夹子将评估葡萄糖利用率， 胰岛素敏感性，并定量肝脏的作用， 关于葡萄糖的生产。在钳夹过程中，血浆FFA水平 并测定脂肪氧化。股肌活检 将获得外侧肌用于测量纤维 特征、GLUT-4转运蛋白和氧化酶水平。 WL或WL+AEX方案对糖耐量低减患者血糖稳态的影响 或NIDDM绝经后妇女与先前GDM是未知的。的 预计的研究将提供宝贵的信息，以帮助 制定代谢控制管理指南， 肥胖型糖耐量异常和糖尿病患者。工作环境： 在Goldberg博士和Nagey博士的指导下接收本MSRDA 将允许候选人在老年学研究中开展职业生涯 NIDDM高危女性的葡萄糖稳态紊乱， 并研究WL或WL+AEX改善的机制 碳水化合物代谢跨学科的环境， 医学院提供优良的培训和资源， 在老年学和新陈代谢方面的高级学习。拟议工作 将为候选人提供必要的技能和培训 开始独立的研究生涯

The candidate is an Exercise Physiologist whose initial research and funded pilot projects focused on the effects of diet and exercise on obesity and glucose metabolism in sedentary normals and patients with diabetes. The proposed MRSDA will allow her to gain training in the areas of muscle and fat metabolism while investigating the interactions of aging and glucose metabolism in women with a high risk of developing diabetes. Research: Gestational diabetes mellitus (GDM) affects 90,000 women per yr in the U.S. Within 10-20 y of pregnancy, 40-65% of these women develop non-insulin dependent diabetes mellitus (NIDDM); a disease linked to obesity, physical inactivity and characterized by abnormalities in glucose and fatty acid metabolism. We hypothesize that women with a history of GDM who present with impaired glucose tolerance (IGT) or NIDDM after the menopause will be sedentary, have visceral obesity and abnormalities in their glucose, fat and muscle metabolism. A structured weight loss and aerobic exercise program (WL+AEX) will be more effective than weight loss (WL) alone in reducing visceral obesity and increasing aerobic capacity to 1) decrease free fatty acid (FFA) levels and increase fat oxidation; 2) increase muscle GLUT-4 protein and glycogen storage; and 3) enhance insulin sensitivity thereby improving glucose tolerance. This study will investigate glucose homeostasis in IGT or NIDDM (N=80) postmenopausal women (50-60 y) with a history of GDM. Measurements will be performed at baseline and after 6 months of WL or WL+AEX. Follow-up of patients will occur 1 yr after the intervention(s) to evaluate the patient's glucose tolerance, body composition and VO2max. Total and regional percent body fat, fat mass, lean tissue mass and hone mineral content will be determined by dual-energy x-ray absorptiometry. Computed tomography will quantify' intraabdominal and subcutaneous adipose tissue areas and mid-thigh muscle and adipose tissue area. VO2 max will be measured during a progressive treadmill test. Hyperinsulinemic-euglycemic clamps with tritiated glucose will assess glucose utilization, insulin sensitivity, and quantitate the role of the liver with respect to glucose production. During the clamp, plasma FFA levels and fat oxidation will be determined. Muscle biopsies of the vastus lateralis will be obtained for measurement of fiber characteristics, GLUT-4 transporters, and oxidative enzyme levels. The effects of WL or WL+AEX program on glucose homeostasis in IGT or NlDDM postmenopausal women with prior GDM are unknown. The projected study will contribute valuable information to help develop guidelines for the management of the metabolic control in the obese glucose intolerant and diabetic patient. Environment: Receipt of this MSRDA with the guidance of Drs. Goldberg and Nagey will allow the candidate to launch a career in gerontology studying disorders of glucose homeostasis in women at a high risk for NIDDM, and investigate the mechanisms by which WL or WL+AEX improve carbohydrate metabolism. The interdisciplinary environment in the School of Medicine provides excellent training and resources for advanced learning in gerontology and metabolism. The proposed work will provide the candidate with the requisite skills and training to embark on an independent research career.