Strict glycemic control in diabetic dogs with closed-loop intraperitoneal insulin infusion algorithm designed for an artificial endocrine pancreas

Abstract

 The ultimate goal of the development of an artificial endocrine pancreas is to achieve long-term strict glycemic regulation. To establish the physiological insulin delivery route of the artificial endocrine pancreas, intraperitoneal insulin infusion may be important. For this purpose, we tried to develop a closed-loop intraperitoneal insulin infusion algorithm by analyzing the pharmacokinetics of intraperitoneal regular insulin absorption using a mathematical model. The parameters for this algorithm were calculated to simulate the plasma insulin profile after intraperitoneal insulin injection as closely as possible. To evaluate the appropriateness of this algorithm, we tried glycemic control after an oral glucose load of 2 g/kg or a meal load of 80 kcal/kg in diabetic dogs by applying the algorithm. With the use of the subcutaneous insulin lispro infusion algorithm, which we have previously reported, alloxan-induced diabetic dogs exhibited postprandial hyperglycemia and delayed hyperinsulinemia, followed by hypoglycemia after an oral glucose load of 2 g/kg. However, by using the intraperitoneal insulin infusion algorithm, excellent glycemic control (postprandial blood glucose levels of 9.1 ± 0.8 mmol/l at 70 min and 3.8 ± 0.3 mmol/l at 240 min, respectively) could be achieved without any associated delayed hyperinsulinemia or hypoglycemia. Glycemic excursion after a meal load of 80 kcal/kg was also controlled from 3.9 to 10.1 mmol/l. Our results confirm that the intraperitoneal insulin infusion algorithm in vivo is feasible and that this algorithm can be superior to the subcutaneous insulin lispro infusion algorithm in the regulation of blood glucose.