Bed-rest-induced insulin resistance occurs primarily in muscle

Treatment of trauma victims and patients with severe illness may contribute to their metabolic derangements by severely restricting physical activity. We sought to quantitate the impact of absolute bed rest alone on insulin regulation of glucose metabolism in six healthy subjects. Six to seven days of strict bed rest resulted in moderate deterioration in oral glucose tolerance and increased both fasting plasma insulin concentration and the insulin response to an oral glucose challenge by more than 40%. Euglycemic insulin clamp studies demonstrated the development of resistance to insulin's stimulation of whole-body glucose utilization. This change was characterized by a rightward shift of the insulin dose-response curve (insulin concentration at which 50% of maximal stimulation occurred was 45 +/- 3 (SE) microU/mL in the base line period and 78 +/- 8 microU/mL after seven days of bed rest, P less than .01) with little alteration in the maximal response in the rate of glucose uptake (baseline 15.4 +/- 1.4 mg/kg.min and bed rest 14.0 +/- 1.3 mg/kg.min). In contrast to the shift of sensitivity of whole-body glucose utilization to insulin, suppression of hepatic glucose output by insulin was unchanged by seven days of bed rest. Insulin binding to circulating mononuclear cells was not changed by bed rest. These studies demonstrate that the limited physical activity dictated by bed rest for as little as seven days is associated with substantial resistance to insulin's effects on glucose metabolism. Further, the data suggest that these effects occur primarily in skeletal muscle with little change in insulin action on the liver.