Insulin sensitivity was assessed using the euglycaemic clamp technique in eight type I diabetic patients (after overnight
blood glucose normalization with an
artificial pancreas) and in six healthy subjects. Basal
insulin concentrations were higher in diabetic patients (25 +/- 4 microU/ml) than in control subjects (17 +/- 1 microU/ml; P less than 0.05).
Insulin infusion of 0.5, 1.0, 2.0 and 5.0 mU/kg per min during subsequent 2-h periods resulted in similar mean steady-state
insulin concentrations in both groups. The mean
dextrose requirements during the last 40 min of each period were nevertheless decreased in diabetic patients (1.6 +/- 0.5, 3.5 +/- 0.8, 6.5 +/- 0.7, 10.2 +/- 0.7 mg/kg per min) as compared with control subjects (4.7 +/- 0.3, 8.2 +/- 0.9, 10.2 +/- 0.9, 12.4 +/- 0.9 mg/kg per min). At low
insulin concentrations
dextrose requirements were diminished in all diabetic subjects. At the highest
insulin levels, individual dose-response curves from only four patients were within the normal range. Under basal conditions, the monocyte receptor number was significantly reduced in diabetic patients (17,500 +/- 2,800 sites/cell) as compared with control subjects (26,700 +/- 2,500 sites/cell; P less than 0.05), whereas there were no differences regarding empty site affinities. Receptor data did not differ in patients with normal and decreased maximal
dextrose requirements.
Insulin resistance is apparently a common feature of type I diabetes at serum
insulin concentrations of approximately 100 microU/ml. Normalization of the
insulin effect by higher
insulin concentrations is not possible in all patients.
Insulin antibodies at concentrations observed in this study (less than 0.16 mU/ml) do not contribute significantly to
insulin resistance; receptor and postreceptor defects are possibly more important.