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

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Abstract
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 from the value in the diabetic patients with insulin Abs (5.2 ± 0.4 h). The duration of action of insulin was also similar in both groups (14.7 ± 0.7 vs. 14.4 ± 1.0 h). No significant correlations were found between insulin Ab levels and any of these 3 parameters of insulin action. However, the peak effect and total duration of insulin action were significantly correlated with the baseline serum glucose levels. A possible role of insulin Abs was evaluated in these patients by repeating the studies over a 2-year period. During this time, the previously untreated patients were treated with highly purified pork insulin, to which they developed low titers of insulin Abs. The diabetic patients who had been chronically treated with insulin were changed from less purified insulin to highly purified pork insulin, and all had a significant reduction in their Ab titers. No changes in insulin pharmacokinetics were found in either group. These studies demonstrate that the prolonged action of sc injected regular insulin in diabetic patients is not related to the effect of circulating insulin Abs