Characterization of insulin resistance in type I diabetes.
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose