OBESITY, GLUCOSE METABOLISM AND DIET IN OLDER WOMEN

候选人是一位运动生理学家，他的初步研究 并资助了侧重于饮食和营养的影响的试点项目 运动对久坐健康人肥胖和糖代谢的影响 糖尿病患者。拟议的MRSDA将使她获得 肌肉和脂肪代谢方面的训练，同时 老年人衰老与糖代谢的相互作用 患糖尿病风险较高的女性。研究： 妊娠期糖尿病(GDM)每年影响90,000名妇女 在美国，在怀孕10-20年内，这些女性中有40%-65%的人 非胰岛素依赖型糖尿病(NIDDM)； 肥胖，缺乏运动，并以异常为特征 在葡萄糖和脂肪酸代谢方面。我们假设女性 有妊娠期糖尿病病史，表现为糖耐量受损 (IGT)或NIDDM绝经后会久坐不动，有脏腑 肥胖和血糖、脂肪和肌肉的异常 新陈代谢。有组织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，将有氧能力提高到1) 降低游离脂肪酸(FFA)水平，增加脂肪氧化； 2)增加肌肉GLUT-4蛋白和糖原储备；3) 增强胰岛素敏感性，从而改善糖耐量。 这项研究将研究IGT或NIDDM患者的血糖稳态 80例有妊娠期糖尿病病史的绝经后妇女(50~60岁)。 测量将在基线和WL的6个月后执行 或WL+AEX。患者的随访将在1年后进行 干预(S)评估患者的糖耐量，身体 成分和最大摄氧量。总体脂和区域体脂百分比， 将测定体重、瘦组织质量和骨矿物质含量 采用双能X射线吸收计量法。计算机断层扫描将 量化腹内和皮下脂肪组织面积和 大腿中部肌肉和脂肪组织区域。将测量最大摄氧量 在一次渐进的跑步机测试中。高胰岛素-正常血糖 含氚葡萄糖的钳夹将评估葡萄糖的利用， 胰岛素敏感性，并量化肝脏的作用 关于葡萄糖的生产。在钳夹期间，血浆FFA水平 脂肪氧化将被确定。股肌活组织检查 测量纤维时将获得侧位。 特性、GLUT-4转运体和氧化酶水平。 WL或WL+AEX方案对糖耐量低减患者血糖稳态的影响 或者绝经后有妊娠期糖尿病的妇女是未知的。这个 计划中的研究将有助于提供有价值的信息 制定新陈代谢控制管理指南 肥胖、糖耐量低减和糖尿病患者。环境： 在Goldberg和Nagey博士的指导下收到这份MSRDA 将允许应聘者开始老年学研究的职业生涯 NIDDM高危女性的血糖稳态紊乱， 并探讨了WL或WL+AEX改善的机制 碳水化合物代谢。中国的跨学科环境 医学院提供优秀的培训和资源 在老年学和新陈代谢方面的高级学习。拟议中的工作 将为应聘者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.