Dissociation of local and global skeletal muscle oxygen transport metrics in type 2 diabetes.

AIMS: Exercise capacity is impaired in type 2 diabetes, and this impairment predicts excess morbidity and mortality. This defect appears to involve excess skeletal muscle deoxygenation, but the underlying mechanisms remain unclear. We hypothesized that reduced blood flow, reduced local recruitment of blood volume/hematocrit, or both contribute to excess skeletal muscle deoxygenation in type 2 diabetes. METHODS: In patients with (n=23) and without (n=18) type 2 diabetes, we recorded maximal reactive hyperemic leg blood flow, peak oxygen utilization during cycling ergometer exercise (VO2peak), and near-infrared spectroscopy-derived measures of exercise-induced changes in skeletal muscle oxygenation and blood volume/hematocrit. RESULTS: We observed a significant increase (p<0.05) in skeletal muscle deoxygenation in type 2 diabetes despite similar blood flow and recruitment of local blood volume/hematocrit. Within the control group skeletal muscle deoxygenation, local recruitment of microvascular blood volume/hematocrit, blood flow, and VO2peak are all mutually correlated. None of these correlations were preserved in type 2 diabetes. CONCLUSIONS: These results suggest that in type 2 diabetes 1) skeletal muscle oxygenation is impaired, 2) this impairment may occur independently of bulk blood flow or local recruitment of blood volume/hematocrit, and 3) local and global metrics of oxygen transport are dissociated.

Impaired Tissue Oxygenation in Metabolic Syndrome Requires Increased Microvascular Perfusion Heterogeneity.

Metabolic syndrome (MS) in obese Zucker rats (OZR) is associated with impaired skeletal muscle performance and blunted hyperemia. Studies suggest that reduced O2 diffusion capacity is required to explain compromised muscle performance and that heterogeneous microvascular perfusion distribution is critical. We modeled tissue oxygenation during muscle contraction in control and OZR skeletal muscle using physiologically realistic relationships. Using a network model of Krogh cylinders with increasing perfusion asymmetry and increased plasma skimming, we predict increased perfusion heterogeneity and decreased muscle oxygenation in OZR, with partial recovery following therapy. Notably, increasing O2 delivery had less impact on VO2 than equivalent decreases in O2 delivery, providing a mechanism for previous empirical work associating perfusion heterogeneity and impaired O2 extraction. We demonstrate that increased skeletal muscle perfusion asymmetry is a defining characteristic of MS and must be considered to effectively model and understand blood-tissue O2 exchange in this model of human disease.