Standard-of-care insulin therapies for regulating blood glucose in diabetes typically involve either multiple daily subcutaneous injections or subcutaneous infusion with an insulin pump. In the case of the former, daily boluses of long-acting insulin formulations, which release slowly into the blood stream, are used to provide the subject's basal metabolic insulin requirement and boluses of rapid-acting insulin formulations, which absorb rapidly into the blood stream, are used to provide insulin for meals or to treat hyperglycemia. In the case of insulin pump therapy, either regular human recombinant insulin is used or, more typically, one of several rapid-acting insulin formulations is used to provide both basal and bolus therapy. In this case, a pre-programmed basal insulin infusion rate (or a preprogrammed daily “profile” containing several different basal insulin infusion rates that vary throughout the day) is prescribed and administered automatically by the insulin pump throughout the day, and individual boluses to insulin for meals or to treat hyperglycemia are administered with the insulin pump manually by the subject as needed. The preprogrammed basal insulin infusion rate (or pre-programmed daily basal insulin infusion rate profile) can be changed to (or temporarily overridden with) a different infusion rate by the subject, but once implemented, will execute the prescribed infusion rate without knowledge of, or regard to, instantaneous glucose levels from a continuous glucose monitoring device.
Clemens & Hough (U.S. Pat. No. 4,464,170) introduced the idea of using glucose-sensor data (obtained from a device capable of frequently sampling blood glucose concentration levels) to modulate the basal infusion rate relative to a previously prescribed basal insulin infusion rate during online operation of an autonomous glucose control system. Their strategy attempts to control drift in blood glucose away from a set point blood glucose value by considering the slope of the least squares fit to past blood glucose values. The method is described in the context of intravenous insulin infusion in an in-patient setting and implicitly assumes that insulin administered by the controller appears instantly in blood.