Long Duration Activity and Metabolic Control after Spinal Cord Injury

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 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.