Metformin and Muscle in Insulin-resistant Older Veterans

描述(由申请人提供)： 这项资助申请是为医学博士Christine Lee颁发的退伍军人事务部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石棺减少症研究领域的一名独立的临床和翻译研究人员。职业发展计划包括以下学习目标：(1)进行和分析干预性临床试验的经验，(2)肌肉生理学的知识和研究技术，(3)了解肌肉生物学的概念和实验室技术。Lee博士将接受一个跨学科指导团队的科学和职业指导，该团队由在胰岛素抵抗和肌肉骨骼老化方面具有专业知识的流行病学、临床和翻译研究人员组成。波特兰退伍军人管理医疗中心、俄勒冈临床和翻译研究所、俄勒冈健康与科学大学生物化学和分子生物学系、骨与矿物部以及匹兹堡大学的主要教学、临床和实验室资源将协助Lee博士进行培训并完成她的研究项目。这项拟议的研究利用临床和转化性研究方法，不仅为Lee博士提供了实现上述职业目标的机会，还为骨质疏松症研究领域做出了贡献。骨质疏松症与力量下降、残疾增加、更多的跌倒和骨折有关，超过50%的80岁以上的美国成年人存在这种情况。目前，很少有干预措施来预防或治疗石棺减少症，而且对石棺减少症的机制了解很少。鉴于65岁以上的退伍军人人数不断增加，预防骨质疏松症和由此导致的残疾的研究对这一人群的健康、独立和福祉非常重要。Lee博士的初步数据显示，除糖尿病患者接受二甲双胍治疗外，空腹血糖受损且患有糖尿病的老年男性肌肉流失速度加快。该提案的科学目的通过尝试(1)进一步调查这一发现。 确定二甲双胍是否可以防止肌肉质量和体能的丧失，以及(2)检查与二甲双胍治疗相关的肌肉组织学特征的变化。了解预防骨质疏松症的机制的目标可能会导致为日益增长的老年退伍军人保留功能的更有效的方法。增加研究肌肉的临床和翻译研究技能将使李博士成为石棺减少症研究社区中有价值的一员。

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.