Long Duration Activity and Metabolic Control after Spinal Cord Injury

 说明(申请人提供)：骨骼肌是体内最大的内分泌器官，在维持血糖平衡方面起着不可或缺的作用。脊髓损伤(SCI)阻碍了骨骼肌执行这一重要功能。糖代谢失调会导致代谢综合征、糖尿病和其他SCI继发性健康状况(SHCS)的高发生率。这些SHC对健康相关的生活质量(HRQOL)产生了负面影响。新的发现支持，与短暂的间歇性运动相比，全天的低水平活动提供了更有效的新陈代谢刺激。这项拟议的研究将通过使用低强度、长时间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脊髓损伤患者群体。最近，我们证明，这种类型的刺激上调了关键基因的表达，这些基因促进了瘫痪肌肉中氧化的、胰岛素敏感的表型。我们现在将测试这种类型的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，代谢功能的改善将伴随着SHCS的减少和自我报告的HRQOL的改善。三个具体目标将解决这些假设。目的1将比较2种剂量的非破伤风刺激(1和3赫兹)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对肌肉疲劳抗性和细胞适应的影响。目标2将比较这两种相同频率的刺激对代谢功能和全身炎症的临床重要指标的影响。最后，目标3将测量训练队列中的SHCS和HRQOL与接受标准护理(不激活肌肉)的个人的SHC和HRQOL。我们假设，在特定目标2中实现的代谢改善将与慢性脊髓损伤患者较少的SHCS和较高的自我报告的HRQOL相关。这项研究的长期目标是开发一种康复策略，以保护完全性脊髓损伤患者的肌肉骨骼健康、代谢功能和与健康相关的生活质量。这项研究是新颖的，因为它使用了一种可行的、低成本的干预措施，并且被我们的试点受试者评价为方便和不引人注目。这种干预具有极好的疗效潜力，很可能是经济的，很容易融入脊髓损伤患者的日常生活。

 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.