INTRAVENOUS, INTRA-PERITONEAL, AND SUBCUTANEOUS ROUTES OF INSULIN DELIVERY IN DIABETIC MAN

Successful implantation of an artificial pancreas requires the infusion of insulin into an appropriate anatomic site. Three sites being actively investigated include intravenous (i.v.), intraperitoneal (i.p.), and subcutaneous (s.c.). This study compared the rate, magnitude, and duration of insulin absorption from these 3 absorption sites as assessed by the appearance of 'free' insulin into the plasma of 10 insulin-dependent diabetic subjects. The biologic effectiveness of insulin was assessed by the suppression of plasma glucose concentration following a 750-calorie meal. The results suggest that i.v. delivered insulin provides the most rapid increase in plasma free insulin concentration, followed by the i.p. and s.c. routes, respectively. In contrast, the elevation of plasma free insulin concentration was most prolonged with the s.c. route, followed by i.p. and i.v. routes, respectively. Compared with the i.v. and s.c. routes of insulin delivery, only 50% of the i.p. delivered insulin appeared in the plasma. The onset of the biologic activity of the insulin delivered by the 3 different routes during the 4.5-h observation period was most rapid for the i.v. and least rapid for the s.c. route. These results suggest that all three routes may be appropriate sites for delivery of insulin from an artificial pancreas. However, because of the difference in absorption kinetics and the onset of biologic effectiveness of the delivered insulin, different quantities and timing of insulin delivery may be needed.