Prolonged Action of Regular Insulin in Diabetic Patients: Lack of Relationship to Circulating Insulin Antibodies*

We previously reported that in insulin-treated diabetic subjects the time course of action of regular insulin injected sc is different from that reported in standard textbooks. The present studies evaluated the role of insulin antibodies (Abs) in the altered pharmacokinetics of regular insulin by comparing the time course of insulin action in 10 patients receiving chronic insulin therapy and having insulin Abs with that in 15 previously untreated patients without detectable Abs. After an overnight fast, the patients were given an infusion of 5% dextrose in water at 100 ml/h. Regular insulin (15 U) was then injected sc in the deltoid region of the arm. The onset of action of sc insulin, as indicated by a 10% fall in serum glucose, was similar in both patient groups [1.9 ± 0.1 (±SEM) hour in Ab-negative and 1.8 ± 0.1 h in Ab-positive patients]. The peak effect of insulin action, as determined by the nadir of serum glucose, was 4.6 ± 0.2 h in the previously untreated patients, not significantly different fro...