title: 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.
authors.affiliation: Department of Internal Medicine, Medical University of Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Peters
authors.forename: O
authors.initials: O
authors.lastname: Klose
authors.forename: R
authors.initials: R
authors.lastname: Hefty
authors.forename: F
authors.initials: F
authors.lastname: Keck
authors.forename: W
authors.initials: W
authors.lastname: Kerner
mesh_terms: D000328:Adult; D000936:Antigen-Antibody Complex; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D007330:Insulin Antibodies / Q000097:blood*; D007336:Insulin, Isophane / Q000493:pharmacokinetics*; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012016:Reference Values
chemical_list: D000936:Antigen-Antibody Complex; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D007330:Insulin Antibodies; D007336:Insulin, Isophane; D011994:Recombinant Proteins