The pharmacokinetics of subcutaneous regular insulin in type I diabetic patients: assessment using a glucose clamp...

We recently reported that the peak effect and duration of action of regular insulin injected sc were prolonged in diabetic patients and were not related to the presence of insulin antibodies. The results suggested that the ambient level of plasma glucose might be an important factor in determining the pharmacokinetics of regular insulin. In the present study we used a glucose clamp technique, which minimizes interference by counterregulatory phenomena, to study the pharmacokinetics of regular insulin injected sc at 2 different blood glucose concentrations [276 +/- 7 (+/- SEM) and 130 +/- 5 mg/dl] in 10 insulin-dependent diabetic patients. The patient's blood glucose concentration was maintained constant by means of a variable rate iv infusion of 20% dextrose in water after sc injection of regular insulin (0.2 U/kg) in the deltoid region of the arm. The onset of insulin action occurred at similar times at both glucose concentrations (0.6 +/- 0.1 h at 276 mg/dl vs. 0.5 +/- 0.1 h at 130 mg/dl; P greater than 0.05). Peak insulin action (determined from the time of the maximal glucose infusion rate) was delayed in the studies done at 276 mg/dl (4.7 +/- 0.2 h) compared to that in studies done at mean glucose concentrations of 130 mg/dl (4.3 +/- 0.2 h; P less than 0.05). The duration of insulin action was also significantly prolonged in the studies done at the higher glucose concentrations (9.1 +/- 0.3 h at 276 mg/dl vs. 7.7 +/- 0.2 h at 130 mg/dl; P less than 0.01). These results confirm previous reports of prolonged insulin action in diabetic patients, especially in the presence of hyperglycemia.