Skeletal muscle metabolism in patients with severe chronic obstructive pulmonary disease : A study of carbohydrate and fat metabolism

Sammanfattning: In chronic obstructive pulmonary disease (COPD) deterioration of skeletal muscle metabolism is reported in both respiratory and non-respiratory muscles. This deterioration may contribute to both the development of respiratory failure and general disability often seen in severe COPD patients. The aim of this study was to obtain more information on carbohydrate and fat metabolism in advanced, stable COPD patients and to investigate the possible association between muscle glycogen and estimates of malnuttition. Furthermore, the effect of long-term oxygen therapy on the metabolic state was studied. Using the needle biopsy technique, muscle specimens were obtained from the quadriceps femoris muscle for analysis of muscle metabolites, glycolytic and oxidative enzyme activities and skeletal muscle fibre composition. Blood fuel metabolites were studied at rest, during exercise and recovery. Lipolysis was studied using a tracer technique and the response of lipolysis to insulin, as well as insulin resistance in peripheral tissues were studied using the euglycaernic, hyperinsulinaernic glucose clamp technique.Depletion of glycogen, A TP and creatine phosphate and increased concentrations of creatine and lactate were observed in the quadriceps femoris muscle. Metabolite concentrations correlated to anerial blood gas values- the lower the Pa02 and the higher the PaC02 the greater the deterioration of the metabolic state. Muscle glycogen concentration correlated to estimates of malnuttition. The correlation between glycogen concentration and prealbumin concentration was strong - the lower the glycogen concentration the lower the prealbumin concentration. After 8 months of long-term oxygen therapy (L TOT) the high energy phosphate state had improved. There was a verylow percentage "oxidative" Type I muscle fibres in the quadriceps femoris muscle. Analysis of enzyme activity also showed adaptation in the form of augmented glycolysis and decreased aerobic metabolism. No changes in enzyme activity were observed after 7 months of LTOT. The turnover rate of free fatty acids (FFA) and plasma FFA concentration were increased in the fasting state. There was a significant positive  correlation between turnover rate ofFFA and FFA concentration in arterial plasma. The results also suggest a reduction in the inhibitory effect of inulin on lipolysis. A few hours after a light breakfast FFA, glycerol and 3-hydroxybutyrate concentrations were lower in COPD patients with chronic respiratory failure (CRF) that in COPD patients without CRF at rest, during exercise and recovery, indicating decreased lipolysis in the CRF patients compared to COPD patients without CRF. In patients with severe COPD and muscle glycogen depletion no resistance to insulin in peripheral tissues was observed.In conclusion, skeletal muscle depletion exists in patients with severe, stable COPD. Skeletal muscle glycogen concentration is associated with concentrations of serum proteins. Adaptation of muscle metabolism in the form of augmented glycolysis and reduced aerobic metabolism was observed. Lipolysis is increased in the fasting state and the results suggest a reduction in the inhibitory effect of insulin on lipolysis. No resistance to insulin in peripheral tissues was found. LTOT may improve the muscle energy state of hypoxaemic COPD patients.