The influence of insulin antibodies on the pharmacokinetics of NPH insulin in patients with type 1 diabetes treated with human insulin.

Abstract

The influence of insulin binding antibodies on the pharmacokinetics of NPH insulin was studied in Type 1 diabetic patients on human insulin. Insulin-antibody binding (B(o) was measured during a screening procedure in 155 Type 1 diabetic patients. In 36 patients, B(o) was < 1.5%, and in 38 patients B(o) was > 10.0%. Of these, 6 patients, group 1 (B(o) < 1.5%) and 8 patients, group 2 (B(o) > 10.0%), respectively, subsequently participated in a pharmacokinetic study. Free insulin and the glucose infusion rate were measured using a euglycaemic clamp after subcutaneous injection of NPH insulin (0.4 U kg-1). The areas under the curve (AUC) of free insulin concentration were smaller for group 2 (p = 0.01) than for group 1 (212.2 +/- 22.0 vs 316.8 +/- 25.3 mU l-1h). The AUCs of the glucose infusion rate were also smaller for group 2 (p < 0.05) than for group 1 (2.50 +/- 0.32 vs 3.58 +/- 0.36 g kg-1). A significant negative correlation exists between the AUCs for free insulin concentration and insulin-antibody binding B(o) (r = 0.76, p = 0.001). The daily insulin dosage was higher in group 2 (p = 0.02) than in group 1 (0.66 +/- 0.03 vs 0.53 +/- 0.03 U kg-1). We conclude that insulin antibodies influence the pharmacokinetics of NPH human insulin. The demonstrable influence on the kinetics of free insulin and glucose utilization leads to a slight increase in daily total insulin requirements.