Effect of insulin antibodies and their kinetic characteristics on plasma free insulin dynamics in patients with diabetes mellitus.

To determine the influence of insulin antibodies (and their equilibrium kinetic properties) on the pharmacokinetics of insulin, we examined the relationship between insulin antibody binding and the initial rate of increase, time to peak, and return to baseline of therapeutic doses of insulin injected subcutaneously (0.15 U/kg) and the half-life, distribution space, and metabolic clearance rate of intravenously infused insulin (2 mU/kg/min) in insulin-treated patients with diabetes mellitus. Compared to age-weight-matched nondiabetic subjects, the diabetic subjects had reduced initial rates of increase (0.33 +/- 0.2 v 0.44 +/- 0.03 microU/mL/min, P less than 0.05), delayed time to peak (130 +/- 12 v 86 +/- 8 min, p less than 0.02), and prolonged return to baseline (485 +/- 37 v 313 +/- 13 min, P less than 0.01) of plasma free insulin levels after subcutaneous injection of insulin, and a prolonged half-life (19.8 +/- 5.8 v 4.3 +/- 0.3 min, P less than 0.02), increased distribution space (904 +/- 284 v 109 +/- 10 mL/kg, P less than 0.001), and augmented metabolic clearance rate (28.5 +/- 1.8 v 17.3 +/- 0.7 mL/kg/min, P less than 0.001) after intravenously infused insulin. All of these abnormal parameters were significantly correlated with binding of insulin to insulin antibodies at tracer insulin concentrations (Bo) and with the high affinity of insulin antibody binding sites as determined by Scatchard analysis. However, patients with 125I insulin antibody binding (Bo) less than 10 percent had normal or near normal plasma free insulin pharmacokinetics.(ABSTRACT TRUNCATED AT 250 WORDS)