The evaluation of glucagon infusion algorithms for a counterregulatory system in artificial endocrine pancreas

As counterregulatory system of artificial endocrine pancreas, glucagon infusion algorithm has been developed and its usefulness has been examined in pancreatectomized dogs and a pancreatectomized diabetic patient. Glucagon infusion rate (G1nIR(t)) was determined depending on proportional plus derivative action to blood glucose concentration (BG(t] with the time delay (tau) to start infusion as follows. G1nIR(t) = Gp(BGp- BG(t-tau)) + Gd(-dBG(t-tau)) + Gc where BGp is the projected value of blood glucose concentration, Gp, and Gd are the coefficients and Gc is the constant for basal glucagon supplement. Glucagon infusions based only on proportional action (Gp/Gd/Gc/tau) = (0.2/0/0.4/10 or 0.4/0/0.4/10) failed in simulating the pattern of blood glucose or glucagon response seen in normal dogs. Glucagon infusion based on proportional plus derivative action (Gp/Gd/Gc/tau = 0.2/0.4/0.4/10) successfully mimicked the pattern of blood glucose concentration and plasma glucagon profile seen in normal dogs. This glucagon infusion algorithm has been applied to control insulin-induced hypoglycemia in a pancreatectomized patient with the same infusion parameters. Hypoglycemia was recovered to normoglycemia in 80 min and the plasma glucagon patterns showed no significant difference from those in healthy volunteers. These data indicate that glucagon infusion algorithm thus developed is effective to render hypoglycemia to normoglycemia and mimic plasma glucagon response seen in normal subjects.