Muscle Atrophy, Physical Performance and Glucose Tolerance Post-Stroke

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DESCRIPTION (provided by applicant): Stroke, a leading cause of disability, can promote metabolic dysfunction that increases the risk for diabetes, subsequent stroke recurrence, and cardiovascular disease complications. We have shown a marked loss of muscle mass in the paretic leg and a fiber type shift in stroke survivors with a stroke latency of approximately 3 years. These skeletal muscle changes in chronic stroke are associated with gait deficit severity. The fundamental hypothesis of this study is that skeletal muscle atrophy and fiber type shift occurs rapidly after a stroke and these changes are accompanied by a decline in physical performance and a worsening of glucose tolerance in hemiparetic stroke survivors. The aims of this 2-year pilot study are the following: 1) To determine immediate, 2, 4, and 6 month changes in paretic and nonparetic skeletal muscle composition (mass, volume, intramuscular fat by DXA and CT) and skeletal muscle histology (fiber type proportions) during sub-acute stroke recovery in veteran stroke survivors; 2) To assess functional deficit (short physical performance battery or SPPB, six minute walk, gait and balance, strength), and glucose tolerance (glucose and insulin concentrations by OGTT) during sub-acute stroke recovery and determine whether changes in skeletal muscle are associated with functional performance and glucose tolerance. To accomplish these aims, 30 hemiparetic ischemic stroke subjects aged 45- 75 years, BMI 20-40 kg/m2 will undergo body composition tests, fine-needle muscle biopsies, function deficit tests, and measurement of glucose tolerance ~2 weeks post stroke, and at 2, 4, and 6 months in the sub-acute stroke period. This proposal would be the first to investigate the trajectory of the skeletal muscle atrophy and abnormal glucose metabolism that occurs in stroke survivors. Knowledge of the skeletal muscle changes that occur in the early phases after stroke is essential to create new guidelines which incorporate exercise rehabilitation, much like cardiac rehabilitation, in order to facilitate and improve the health care of veteran stroke survivors. Results of this current pilot study will allow the development of a larger project that evaluates either an aerobic exercise (treadmill), strength (resistive), or gait and balance training program or a combination of these during the stroke recovery period. The results could effectively change the current guidelines for the care of stroke survivors during the acute recovery period and have a significant impact on the health of veterans. PUBLIC HEALTH RELEVANCE: Stroke, a leading cause of disability in the veteran population, increases the risk for diabetes, subsequent stroke recurrence, and cardiovascular disease complications. The downsizing of private and federal health care resources, along with the anticipated increase in stroke rates as our veteran population ages, mandate that alternative strategies be developed to reduce the public health burden of stroke. This pilot study may facilitate our knowledge of the timing of paretic leg muscle atrophy, fiber type shift, and the progression of worsening of glucose tolerance after stroke. Knowledge of the skeletal muscle changes occurring in the sub-acute stroke period is essential to create new guidelines incorporating exercise rehabilitation, much like cardiac rehabilitation, in order to facilitate and improve the health care of veteran stroke survivors.