Long Duration Activity and Metabolic Control after Spinal Cord Injury

脊髓损伤后的长期活动和代谢控制

• 批准号: 9478256
• 负责人: RICHARD K. SHIELDS
• 金额: $ 31.64万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9478256
• 关键词: Address; Biogenesis; C-reactive protein; Cardiovascular Diseases; Carrier Proteins; Cell Respiration; Chronic; Clinic; Clinical; Cost Savings; Diabetes Mellitus; Dose; Electric Stimulation; Electron Transport; Endocrine Glands; Energy Metabolism; Enzymes; Exercise; Fatigue; Fiber; Fostering; Frequencies; Gene Expression Regulation; Gene Proteins; General Population; Genes; Glucagon; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Health; Home environment; Homeostasis; Hour; Human; Individual; Inflammation; Insulin; Interleukin-6; Intervention; Limb structure; Measures; Metabolic; Metabolic Control; Metabolic Diseases; Metabolic syndrome; Metabolism; Methods; Mitochondria; Muscle; Muscle Fatigue; Muscle Fibers; Muscle Mitochondria; Musculoskeletal; Musculoskeletal System; OGTT; OPA1 gene; Obesity; Paralysed; Pathway interactions; Patient Self-Report; Patients; Phenotype; Physiologic pulse; Physiological; Play; Population; Property; Protective Agents; Proteins; Protocols documentation; Quality of life; Regulation; Rehabilitation therapy; Reporting; Research; Resistance; Risk; Role; Skeletal Muscle; Spinal cord injury; Stimulus; Stress; Testing; Therapeutic; Time; Tissues; Training; Translating; Wheelchairs; base; blood glucose regulation; cohort; cost; cost effective; cytokine; exercise program; experience; fibroblast growth factor 21; glucose metabolism; health related quality of life; human model; improved; innovation; metabolic rate; mortality; novel; physical inactivity; prevent; public health relevance; rehabilitation strategy; standard care; total energy expenditure; transcription factor

 DESCRIPTION (provided by applicant): Skeletal muscle is the largest endocrine organ in the body, playing an indispensable role in glucose homeostasis. Spinal cord injury (SCI) prevents skeletal muscle from carrying out this important function. Dysregulation of glucose metabolism precipitates high rates of metabolic syndrome, diabetes, and other secondary health conditions (SHCs) of SCI. These SHCs exert a negative influence on health-related quality of life (HRQOL). New discoveries support that a low level of activity throughout the day offers a more effective metabolic stimulus than brief, episodic exercise bouts. The proposed study will translate this emerging concept to the population of individuals with SCI by using low-force, long-duration electrical muscle stimulation to subsidize daily activity levels. Recently, we demonstrated that this type of stimulation up-regulates key genes that foster an oxidative, insulin-sensitive phenotype in paralyzed muscle. We will now test whether this type of activity can improve glucose homeostasis and metabolic function in patients with chronic paralysis. We hypothesize that improvements in metabolic function will be accompanied by a reduction in SHCs and a concomitant improvement in self-reported HRQOL. Three specific aims will address these hypotheses. Aim 1 will compare 2 doses of non-tetanizing stimulation (1 and 3 Hz) on muscle fatigue resistance and cellular adaptations in pathways that promote oxidative metabolism, muscle fiber type and mitochondrial biogenesis. Aim 2 will compare the effects of these same 2 frequencies of stimulation on clinically-important metrics of metabolic function and systemic inflammation. Finally, Aim 3 will measure SHCs and HRQOL in the training cohorts versus individuals who receive standard care (no muscular activation). We hypothesize that metabolic improvements achieved in Specific Aim 2 will be associated with fewer SHCs and higher self-reported HRQOL in patients with chronic SCI. The long-term goal of this research is to develop a rehabilitation strategy to protect the musculoskeletal health, metabolic function, and health-related quality of life of people living with complete SCI. This study is novel because it uses an intervention that is feasible, low-cost, and is rated to be convenient and unobtrusive by our pilot subjects. This intervention has excellent potential for efficacy and is likely to be economical and easily integrated into the daily lives of individuals with SCI.

 描述（由适用提供）：骨骼肌是体内最大的内分泌器官，在葡萄糖稳态中起着必不可少的作用。脊髓损伤（SCI）可防止骨骼肌执行这一重要功能。葡萄糖代谢的失调会导致SCI的代谢综合征，糖尿病和其他继发健康状况（SHC）的高率。这些SHC对与健康相关的生活质量（HRQOL）产生负面影响。新发现支持全天低水平的活动提供了比简短的，情节性运动更有效的代谢刺激。拟议的研究将通过使用低强度的，长期的电肌肉刺激来补贴日常活动水平，将这一新兴概念转化为SCI患者的人群。最近，我们证明，这种刺激上调了关键基因，从而促进了瘫痪肌肉中一种氧化，胰岛素敏感的表型。现在，我们将测试这种活动是否可以改善慢性瘫痪患者的葡萄糖稳态和代谢功能。我们假设代谢功能的改善将通过减少SHC和自我报告的HRQOL的伴随改善来实现。三个具体目标将解决这些假设。 AIM 1将比较2剂在促进氧化代谢，肌肉纤维类型和线粒体生物发生的途径中，在肌肉疲劳耐药性和细胞适应中，对2剂的非四分化刺激（1和3 Hz）进行比较。 AIM 2将比较这些2种相同的刺激频率对代谢功能和全身注射的临床重要指标的影响。最后，AIM 3将在训练队列中与接受标准护理的个人（无肌肉激活）中的SHC和HRQOL测量。我们假设在特定目标2中实现的代谢改善将与慢性SCI患者的SHC较少和自我报告的HRQOL有关​​。这项研究的长期目标是制定一种康复策略，以保护肌肉骨骼健康，代谢功能和与健康相关的生活质量的生活质量。这项研究之所以新颖，是因为它使用了可行的，低成本的干预措施，并且被我们的飞行员受试者评为方便且不引人注目。这种干预具有巨大的效率潜力，并且很可能是经济的，并且很容易融入SCI患者的日常生活中。