The Intravenous, Intraperitoneal, and Subcutaneous Routes of Insulin Delivery in Diabetic Man

Abstract

Successful implantation of an artificial pancreas requires the infusion of insulin into an appropriate anatomic site. Three sites being actively investigated include (1) intravenous (i.V.), (2) intraperitoneal (i.p.), and (3) subcutaneous (s.c). This study compared the rate, magnitude, and duration of insulin absorption from these three 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. Our 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 three different routes during the 4½-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.

The Artificial Pancreas: A Dynamic Challenge

“…The insulin that is not absorbed by the liver enters the systemic circulation and causes an increase in glucose uptake in the various tissues, thereby leading to a secondary BGL response. The overall result is a glucose lowering effect that is almost comparable to intravenous infusion in terms of bandwidth, and with a latency comparable to that of the glucose increasing effect of food intake (Schade et al 1979). Consequently, it is possible to counteract the trend of an increasing BGL with a faster and increased glucose lowering effect of a given amount of insulin without increasing the risk of subsequent hypoglycemia compared to the risk associated with I SC delivery.…”

“…Physiologically, this option is quite appealing, and it has a fast dynamic effect. The pancreas secretes insulin to the liver via the portal vein, and a significant proportion of the insulin is absorbed by the liver ("first passage effect") within a few seconds after secretion before the rest enters the systemic circulation according to studies in animals (Matsuo et al 2003, Micossi et al 1986, Radziuk et al 1994, Schade et al 1979, Schade et al 1980, Schade et al 1981, Selam et al 1990) and humans (Widerøe et al 1996). I IP gives close to physiological insulin levels both in the liver and other tissues (Nelson et al 1982).…”

“…an obstruction of the infusion set. One could argue that the faster insulin uptake from the IP infusion site to the blood stream (Schade et al 1979, Schade et al 1980) makes it more dangerous, because insulin delivered this way affects the BGL more rapidly and with a stronger peak effect. On the other hand, the faster effect allows for a higher closed-loop bandwidth, which in normal situations implies smaller transient BGL deviations and thus generally improves safety and robustness.…”

Intraperitoneal insulin infusion: on the way to the artificial pancreas

“…Фармакокинетику и фармакодинамику инсулина при различных способах введения исследовали и у пациентов с СД1 [62]. Биологический эффект (фар-макодинамику) инсулина оценивали по снижению концентрации глюкозы в плазме после приема пищи, содержащей 750 ккал (рис.…”

Implantable insulin pumps and metabolic control

“…However, the work on implantable insulin delivery systems continued. Two different access routes were investigated, the intravenous, with the advantage of an immediate response to insulin, and the intraperitoneal route which was shown to deliver the hormone essentially to the portal system and which was likely to have less clinical complications [9].…”