Muscle Atrophy, Physical Performance and Glucose Tolerance Post-Stroke

描述（由申请人提供）： 中风是导致残疾的主要原因，可促进代谢功能障碍，从而增加糖尿病、随后中风复发和心血管疾病并发症的风险。我们已经发现，中风存活者的瘫痪腿肌肉质量明显减少，并且中风潜伏期约为3年。这些骨骼肌的变化与慢性中风步态缺陷的严重程度有关。本研究的基本假设是，中风后骨骼肌萎缩和纤维类型的转变迅速发生，这些变化伴随着偏瘫中风幸存者的体能下降和葡萄糖耐量恶化。这项为期2年的初步研究的目的如下：1）确定麻痹和非麻痹骨骼肌组成的即刻、2、4和6个月的变化（DXA和CT测量的质量、体积、肌内脂肪）和骨骼肌组织学（纤维类型比例）在亚急性中风恢复期的退伍军人中风幸存者; 2）评估功能缺陷（短期体能测试组合或SPPB，6分钟步行，步态和平衡，力量），和糖耐量（通过OGTT的葡萄糖和胰岛素浓度），并确定骨骼肌的变化是否与功能表现和葡萄糖耐量相关。为了实现这些目标，30例年龄为45- 75岁、BMI为20-40 kg/m2的轻偏瘫缺血性卒中受试者将在卒中后约2周以及亚急性卒中期的2、4和6个月时接受身体组成测试、细针肌肉活检、功能缺陷测试和葡萄糖耐量测量。 这一建议将是第一个调查的轨迹骨骼肌萎缩和异常葡萄糖代谢发生在中风幸存者。了解中风后早期发生的骨骼肌变化对于制定新的指南至关重要，这些指南将运动康复纳入其中，就像心脏康复一样，以促进和改善中风幸存者的健康护理。目前的试点研究结果将允许开发一个更大的项目，评估中风恢复期间的有氧运动（跑步机），力量（阻力）或步态和平衡训练计划或这些的组合。研究结果可以有效地改变目前急性恢复期中风幸存者护理的指南，并对退伍军人的健康产生重大影响。 公共卫生相关性： 中风是退伍军人残疾的主要原因，会增加糖尿病、随后中风复发和心血管疾病并发症的风险。私人和联邦卫生保健资源的缩减，沿着随着退伍军人人口年龄的增长，中风率预计会增加，这要求开发替代策略以减少中风的公共卫生负担。这项初步研究可能有助于我们了解中风后轻瘫腿部肌肉萎缩、纤维类型转移和葡萄糖耐量恶化的时间。了解亚急性卒中期间发生的骨骼肌变化对于制定纳入运动康复的新指南至关重要，就像心脏康复一样，以促进和改善退伍军人卒中幸存者的健康护理。

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.