Decreased insulin action in skeletal muscle from patients with McArdle's disease

1 Copenhagen Muscle Research Center, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, DK-2400 Copenhagen; 2 Copenhagen Muscle Research Center, Department of Neurology, Rigshospitalet, DK-2100 Copenhagen, Denmark; 3 Institute for Exercise and Environmental Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75216; and 4 Diabetes Research Laboratory, Winthrop University Hospital, Mineola, New York 11501 Insulin action is decreased by high muscle glycogen concentrations in skeletal muscle. Patients with McArdle's disease have chronic high muscle glycogen levels and might therefore be at risk of developing insulin resistance. In this study, six patients with McArdle's disease and six matched control subjects were subjected to an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp. The muscle glycogen concentration was 103 ± 45% higher in McArdle patients than in controls. Four of six McArdle patients, but none of the controls, had impaired glucose tolerance. The insulin-stimulated glucose utilization and the insulin-stimulated increase in glycogen synthase activity during the clamp were significantly lower in the patients than in controls (51.3 ± 6.0 vs. 72.6 ± 13.1 µmol · min 1 · kg lean body mass 1 , P