Insulin action in insulin-dependent diabetes mellitus (type I): Measurement during constant and changing insulin concentrations

To test the hypothesis that insulin resistance in type I diabetes mellitus is characterized by a decrease in the rate as well as the amplitude of response to insulin, seven patients with diabetes mellitus and 12 subjects without diabetes were given an identical amount of insulin on two occasions: once as a primed constant and once as a variable eight-step infusion. On both occasions plasma glucose concentrations were maintained in the euglycemic range by means of an exogenous glucose infusion. The amplitude of stimulation of glucose utilization was decreased (p < 0.05) in the type I patients compared with the subjects without diabetes during both a constant and a variable insulin infusion, whether measured as the peak (2.24 ± 0.11 mg/kg/min vs 3.18; ± 0.18 mg/kg/min constant and 2.80 ± 0.30 mg/kg/min vs 3.54 ± 0.23 mg/kg/min variable) or integrated response above basal (54 ± 2 mg/kg vs 115 ± 26 mg/kg constant and 60 ± 26 mg/kg vs 147 ± 21 mg/kg, variable). In addition, the rate of activation of glucose utilization (slope 0 to 90 minutes) was decreased (p < 0.02) in the type I patients compared with subjects without diabetes during both the constant (0.003 ± 0.001 mg/kg/min² vs 0.008 ± 0.002 mg/kg/min²) and variable (0.006 ± 0.002 mg/kg/min² vs 0.015 ± 0.002 mg/kg/min²) insulin infusions. Insulin antibody binding did not correlate with the severity of insulin resistance. We conclude that insulin resistance in patients with insulin-dependent diabetes mellitus is attributable to a decrease in both the rate and amplitude of response to insulin.