Denver VA Medical Center, Clermont Street, Denver, CO 80220, USA.
Rev Endocr Metab Disord. 2013 Mar;14(1):77-86. doi: 10.1007/s11154-012-9234-4.
Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.
身体适应性的限制，在 1 型和 2 型糖尿病患者中都是一致的发现，与心血管疾病和全因死亡率密切相关。这些限制可能会显著导致影响该人群的持续心血管疾病死亡率过高。即使血糖控制良好且没有明显的临床并发症，VO2 峰值和 VO2 动力学的运动损伤也会在糖尿病早期出现。亚临床心脏功能障碍常常存在，但不能完全解释糖尿病患者观察到的运动能力缺陷。部分原因是由于运动挑战时的灌注减少导致心脏限制。这是一种可逆转的缺陷。同样，在骨骼肌中，营养血流的损伤与运动动力学的减缓（或低效）以及运动能力的下降相关。有几个相关性突出了内皮特异性损伤作为糖尿病运动功能障碍的介质的可能性，包括胰岛素抵抗、内皮功能障碍、心肌灌注减少、组织血红蛋白氧饱和度减慢以及线粒体功能障碍。运动训练和针对改善胰岛素敏感性和内皮功能的治疗都能提高 2 型糖尿病患者的身体适应性。优化糖尿病患者的运动功能对预防糖尿病和降低死亡率风险具有重要意义。了解糖尿病内皮功能障碍的分子细节可能为纠正这一缺陷提供特定的治疗靶点。正在研究测试这一假设的大鼠模型。
