Type 2 diabetes (T2DM) is the most prevalent form of diabetes, affecting nearly 22 million people in the United States. It is well established that functional exercise tolerance and peak oxygen uptake are reduced in T2DM compared with healthy counterparts. However, the mechanisms contributing to this exercise defect remain unclear. Our long-term goal is to determine the factors contributing to the exercise intolerance and reduced submaximal exercise capacity in the T2DM population. In this study, we hypothesize that both a failure to adequately increase muscle oxygen delivery following the onset of exercise and reduced oxidative function of skeletal muscle contribute to the acute oxygen deficit and diminished exercise function described in T2DM.
The specific aims this proposal will address two questions: 1) Is the oxygen deficit in T2DM revealed by exercise due to limitation in muscle oxygen delivery, muscle utilization or both?; and 2) How is muscle oxidative function related to defects in functional exercise capacity observed in T2DM? This study will utilize a unique combination of measurements to evaluate the potential muscle oxygen delivery impairment and abnormalities of mitochondrial function in relation to the impaired oxygen uptake responses during exercise in T2DM. More broadly and from a practical standpoint, these data will advance our understanding of the interaction between skeletal muscle metabolism and muscle blood flow in the exercise responses in health and T2DM where O2 transport and muscle oxidative function may be critical factors. Functional exercise capacity is reduced in type 2 diabetes mellitus (T2DM), and a low exercise capacity is associated with mortality in the T2DM population. The mechanisms leading to this exercise deficit remain largely unknown, but insulin resistance and endothelial dysfunction correlate with this defect suggesting abnormalities in exercise blood flow and muscle oxidative metabolism may dictate the functional exercise impairment. The results of this study will address the mechanisms of impaired muscle oxygen delivery and muscle oxidative dysfunction as they relate to the observed exercise impairment in T2DM. ? ? ?
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| Nadeau, Kristen J; Zeitler, Phillip S; Bauer, Timothy A et al. (2009) Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity. J Clin Endocrinol Metab 94:3687-95 |
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