OBJECTIVE Long before clinical complications of type 1 diabetes (T1D) develop, oxygen supply and use can be altered during activities of daily life. We examined in patients with uncomplicated T1D all steps of the oxygen pathway, from the lungs to the mitochondria, using an integrative ex vivo (muscle biopsies) and in vivo (during exercise) approach. RESEARCH DESIGN AND METHODS We compared 16 adults with T1D with 16 strictly matched healthy control subjects. We assessed lung diffusion capacity for carbon monoxide and nitric oxide, exercise-induced changes in arterial O2 content (SaO2, PaO2, hemoglobin), muscle blood volume, and O2 extraction (via near-infrared spectroscopy). We analyzed blood samples for metabolic and hormonal vasoactive moieties and factors that are able to shift the O2-hemoglobin dissociation curve. Mitochondrial oxidative capacities were assessed in permeabilized vastus lateralis muscle fibers. RESULTS Lung diffusion capacity and arterial O2 transport were normal in patients with T1D. However, those patients displayed blunted exercise-induced increases in muscle blood volume, despite higher serum insulin, and in O2 extraction, despite higher erythrocyte 2,3-diphosphoglycerate. Although complex I- and complex II-supported mitochondrial respirations were unaltered, complex IV capacity (relative to complex I capacity) was impaired in patients with T1D, and this was even more apparent in those with long-standing diabetes and high HbA1c. [Formula: see text]O2max was lower in patients with T1D than in the control subjects. CONCLUSIONS Early defects in microvascular delivery of blood to skeletal muscle and in complex IV capacity in the mitochondrial respiratory chain may negatively impact aerobic fitness. These findings are clinically relevant considering the main role of skeletal muscle oxidation in whole-body glucose disposal.

中文翻译：

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从环境空气到线粒体呼吸链的1型糖尿病中的肌肉氧气供应和使用：是否存在限制步骤？

目的在1型糖尿病（T1D）的临床并发症出现之前，日常生活中的供氧和使用可能会发生变化。我们采用综合的离体（肌肉活检）和体内（运动过程）方法，对患有简单T1D的患者进行了从肺部到线粒体的氧气通路所有步骤的检查。研究设计和方法我们将16名成人T1D患者与16名严格匹配的健康对照受试者进行了比较。我们评估了肺对一氧化碳和一氧化氮的扩散能力，运动引起的动脉血氧含量（SaO2，PaO2，血红蛋白），肌肉血容量和血氧提取（通过近红外光谱）的变化。我们分析了血液样本中的代谢和激素血管活性部分以及能够改变O2-血红蛋白解离曲线的因素。在透化的股外侧肌纤维中评估线粒体的氧化能力。结果T1D患者的肺扩散能力和动脉血O2转运正常。然而，尽管血清胰岛素含量较高，但尽管红细胞2,3-二磷酸甘油酯含量较高，但这些患者的运动导致肌肉血容量增加的作用减弱。尽管复杂的I和复杂的II支持的线粒体呼吸没有改变，但是复杂的IV容量（相对于复杂的I容量）在T1D患者中受损，这在患有长期糖尿病和高HbA1c的患者中更为明显。[公式：见正文] T1D患者的O2max低于对照组。结论血液向骨骼肌微血管输送的早期缺陷以及线粒体呼吸链的复杂IV容量可能会对有氧适应性产生负面影响。考虑到骨骼肌氧化在全身葡萄糖处置中的主要作用，这些发现与临床相关。