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

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：骨骼肌是体内最大的内分泌器官，在葡萄糖稳态中发挥着不可或缺的作用。脊髓损伤（SCI）阻止骨骼肌执行这一重要功能，导致葡萄糖代谢失调。代谢综合征、糖尿病和 SCI 的其他继发性健康状况 (SHC) 这些 SHC 对健康相关的生活质量 (HRQOL) 产生负面影响。新的发现表明，全天低水平的活动比短暂的、间歇性的运动能提供更有效的代谢刺激。拟议的研究将通过使用低强度、长时间的电流将这一新兴概念应用到患有 SCI 的人群中。最近，我们证明这种类型的刺激会上调促进瘫痪肌肉氧化、胰岛素敏感表型的关键基因。我们现在将测试这种类型的活动是否可以改善葡萄糖稳态和代谢。我们探索了代谢功能的改善将伴随着 SHC 的减少以及自我报告的 HRQOL 的改善，目标 1 将比较 2 种非破伤风剂量。刺激（1 和 3 Hz）对肌肉抗疲劳性和促进氧化代谢、肌纤维类型和线粒体生物合成途径的细胞适应的影响，目标 2 将比较这 2 种相同频率的刺激对的影响。最后，目标 3 将测量训练组与接受标准护理（无肌肉激活）的个体的 SHC 和 HRQOL。我们发现，特定目标 2 中实现的代谢改善将与此相关。慢性 SCI 患者的 SHC 更少，自我报告的 HRQOL 更高这项研究的长期目标是制定康复策略，以保护人们的肌肉骨骼健康、代谢功能和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、低成本的干预措施，并且被我们的试点受试者评价为方便且不引人注目，并且可能是经济且容易的。融入 SCI 患者的日常生活。