Comparison between closed-loop portal and peripheral venous insulin delivery systems for an artificial endocrine pancreas

Abstract

To establish the ideal insulin delivery route for an artificial endocrine pancreas, we examined the effectiveness of closed-loop portal insulin delivery. We investigated the effects of the route of insulin delivery on net hepatic glucose balance (NHGB) in dogs under pancreatic clamp conditions with somatostatin plus basal glucagon and insulin infusions. A constant rate of suprabasal insulin was infused via the portal vein or a peripheral vein, and glucose was infused into the portal vein for 180 min. The mean net hepatic glucose uptake (NHGU) values in the portal insulin infusion group (PI group) were significantly greater than those in the peripheral venous insulin infusion group (VI group); the changes from the baseline values at 180 min were 3.54 +/- 0.66 and 2.45 +/- 0.82 mg kg(-1) min(-1) in the PI and VI groups, respectively, P < 0.05. Furthermore, dogs under pancreatic clamp conditions were controlled after a 2-g/kg oral glucose load by applying the closed-loop intraportal (PO) or intravenous (IV) insulin infusion algorithm. There were no significant differences in glycemic control and insulin requirements between these algorithms. However, the maximum peripheral venous and arterial plasma insulin concentrations with the PO algorithm were significantly lower than those with the IV algorithm [305.1 +/- 68.9 and 468.1 +/- 66.9 pmol/l (peripheral vein) and 305.3 +/- 62.9 and 469.6 +/- 85.1 pmol/l (artery) with the PO and IV algorithms, respectively, P < 0.05]. On the other hand, the maximum portal plasma insulin concentration with the PO algorithm was significantly higher than that with the IV algorithm (619.9 +/- 101.7 and 414.3 +/- 79.9 pmol/l with the PO and IV algorithms, respectively, P < 0.05). The mean NHGU values with the PO algorithm were significantly greater than those with the IV algorithm. Our results confirmed that closed-loop portal insulin delivery is feasible with regard to both insulin profiles and hepatic glucose handling in vivo, and indicated that the portal vein is the most suitable insulin delivery route for the artificial endocrine pancreas.

Feasibility of Automating Insulin Delivery for the Treatment of Type 1 Diabetes

“…This component (Fig. 1) creates a response analogous to the ␤-cells firstphase insulin secretion (7,(12)(13)(14) and has been used to aid many closed-loop intravenous insulin delivery systems (15)(16)(17)(18)(19), including those of the Biostator (20 -22). However, the system being evaluated here relies on subcutaneous insulin delivery, which adds a substantial delay to the appearance of insulin in plasma.…”

Evaluation of the Effect of Gain on the Meal Response of an Automated Closed-Loop Insulin Delivery System

“…Previous closed-loop studies in diabetic dogs have used phases analogous to P(t) and D(t), with intravenous insulin delivery, to show that meal excursions could be obtained that were actually lower than those observed in normal dogs (10,11). More recent studies using insulin analogs have evaluated other administration routes (12)(13)(14). The main difference between the algorithms in these earlier studies (10 -14) and the algorithm used here is that the proposed ␤-cell model has an integral component [I(t)] (Eq.…”

“…Early studies in the diabetic canine, using intravenous insulin (10,11), showed promising results, delivering insulin in proportion to glucose above or below target and its rate of change, and later work extended these results with rapidacting insulin analogs and alternate sites of delivery (12)(13)(14).…”

The Artificial Pancreas: How Sweet Engineering Will Solve Bitter Problems

“…6 These studies included no more than twelve subjects and lasted no more than 48 hours, [3][4][5][6][7][8][9][10][11][12] except for one trial that was reported to last for 14 days. …”

“…They have delivered insulin subcutaneously and intraperitoneally with a PD controller. 6,9,[73][74][75][76] Their results, however, were not replicated by an English group that used the same control method.…”