The Influence of Insulin Antibodies on the Pharmacokinetics of NPH Insulin in Patients with Type 1 Diabetes treated with Human Insulin

Publisher Website
Google Scholar
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 (Bo) was measured during a screening procedure in 155 Type 1 diabetic patients. In 36 patients, Bo was 10.0%. Of these, 6 patients, group 1 (Bo < 1.5%) and 8 patients, group 2 (Bo > 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−1 h). 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 Bo (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.