Metformin and Muscle in Insulin-resistant Older Veterans

描述（由申请人提供）： 此拨款申请是为克莉丝汀李，医学博士，MS的VA临床科学研究与发展（CSR&D）职业发展奖（CDA-2），她的培训目标是成为一个独立的临床和翻译研究人员在肌肉减少症研究领域。职业发展计划包括以下学习目标：（1）干预性临床试验的实施和分析经验，（2）肌肉生理学的知识和研究技术，以及（3）了解研究肌肉生物学的概念和实验室技术。李博士将从一个由流行病学、临床和翻译研究人员组成的跨学科导师团队获得科学和职业指导，该团队在胰岛素抵抗和肌肉骨骼衰老方面具有专业知识。波特兰退伍军人管理医疗中心、俄勒冈州临床和转化研究所、俄勒冈州健康与科学大学生物化学和分子生物学系以及骨和矿物质单位以及匹兹堡大学的关键教学、临床和实验室资源将协助李博士的培训和完成她的研究项目。拟议的研究利用临床和转化研究方法，不仅为Lee博士提供实现上述职业目标的机会，而且还为肌肉减少症研究领域做出贡献。肌肉减少症与力量下降、残疾增加、更多福尔斯和骨折相关，并且存在于超过50%的80岁以上的美国成年人中。目前很少有干预措施来预防或治疗肌肉减少症，并且对肌肉减少症的机制缺乏了解。鉴于65岁以上的退伍军人越来越多，预防肌肉减少症及其导致的残疾的研究对这一人群的健康，独立和福祉至关重要。Lee博士的初步数据显示，空腹血糖受损和糖尿病的老年男性肌肉损失加速，但糖尿病男性接受二甲双胍治疗除外。本提案的科学目的是进一步研究这一发现，试图（1） 确定二甲双胍是否可以预防肌肉质量和身体机能的损失;（2）检查与二甲双胍治疗相关的肌肉组织学特征的变化。了解预防肌肉减少症的机制的目标可能会导致更有效的方法来保护日益增长的老龄退伍军人的功能。研究肌肉的临床和转化研究技能的增加将使李博士成为肌肉减少症研究社区的重要成员。

DESCRIPTION (provided by applicant): This grant application is for a VA Clinical Science Research and Development (CSR&D) Career Development Award (CDA-2) for Christine Lee, MD, MS. Her training goal is to become an independent clinical and translational researcher in the field of sarcopenia research. The career development plan includes the following learning objectives: (1) experience in the conduct and analysis of interventional clinical trials, (2) knowledge and research techniques in muscle physiology and (3) understanding of concepts and lab techniques for studying muscle biology. Dr. Lee will receive scientific and career guidance from an interdisciplinary mentorship team comprising epidemiologic, clinical and translational researchers with expertise in insulin resistance and musculoskeletal aging. Key didactic, clinical and laboratory resources at the Portland Veteran's Administration Medical Center, the Oregon Clinical and Translational Research Institute, the Department of Biochemistry and Molecular Biology and Bone and Mineral Unit at the Oregon Health & Science University, and the University of Pittsburgh will assist in Dr. Lee's training and completion of her research projects. The proposed study utilizes clinical and translational research approaches to not only provide Dr. Lee with opportunities to reach the career goals delineated above, but also to contribute to the field of sarcopenia research. Sarcopenia is associated with decreased strength, increased disability, more falls and fractures and is present in over 50% of U.S. adults past the age of 80. There are currently few interventions to prevent or treat sarcopenia and a poor understanding of the mechanisms for sarcopenia. Given the growing number of veterans over the age of 65, studies to prevent sarcopenia and resulting disability are important for the health, independence and well-being of this population. Dr. Lee's preliminary data showed that older men with impaired fasting glucose and diabetes had accelerated muscle loss, except when men with diabetes were treated with metformin. The scientific aims of this proposal further investigates this finding by attempting (1) to determine whether metformin can prevent the loss in muscle mass and physical performance and (2) to examine changes in muscle histologic characteristics associated with metformin treatment. The goal to understand mechanisms for preventing sarcopenia may lead to more effective methods for preserving function for the growing population of aging veterans. The addition of clinical and translational research skills for studying muscle will allow Dr. Lee to become a valuable member of the sarcopenia research community.