Validation of closed-loop subcutaneous insulin infusion algorithm--application of subcutaneous insulin absorption kinetics.

For long-term glycemic normalization with a closed-loop control system, a subcutaneous insulin infusion algorithm has been developed based on the pharmacokinetics of subcutaneously administered insulin. A 3-compartmental model was applied to mathematically express the relation between the insulin injected subcutaneously as an input and the plasma insulin response as an output. A computer simulation study using this model showed that the following insulin infusion algorithm is feasible for closed-loop glycemic control by selecting appropriate parameters (Kp/Kd/Kc = 0.0056/0.92/-0.11), IIR(t) = Kp G(t)+Kd d G(t)/dt+Kc, where IIR(t) is the subcutaneous insulin infusion rate at time t (min), G(t) is the blood glucose concentration and Kp, Kd, Kc are the constants. In 5 pancreatectomized dogs, subcutaneous insulin infusion with this algorithm made it possible to keep postprandial glycemic levels after oral glucose load (2 g/kg) at 168 +/- 14 mg/dl (mean +/- SEM) in 60 min and maintained normoglycemia from 180 to 300 min with the total amount of infused insulin being 0.14 +/- 0.019 U/kg. In 5 insulin-dependent diabetic patients, the peaks of postprandial glycemic levels after meal load (450 kcal) were controlled to 176 +/- 36 mg/dl at 90 min and were reduced to 98 +/- 13 mg/dl at 300 min with the total amount of infused insulin being 0.172 +/- 0.063 U/kg. The mean peak plasma insulin level was 49 +/- 11 microU/ml at 90 min. These results indicate the clinical controllability of postprandial glycemia with the closed-loop subcutaneous insulin infusion algorithm in diabetic patients.