Closed-Loop Glycemic Control with a Wearable Artificial Endocrine Pancreas Variations in Daily Insulin Requirements to Glycemic Response

Abstract

We succeeded in miniaturizing a needle-type glucose monitoring system with characteristics suitable for application in a wearable, closed-loop control system. A wearable artificial endocrine pancreas (12 × 15 × 6 cm, 400 g) consisting of a sensor, a microcomputer system that calculates insulin and glucagon infusion rates, and two roller pumps was developed. Continuous glucose monitoring by a glucose sensor inserted in the subcutaneous tissue of the forearm or abdomen of healthy and diabetic volunteers revealed that glucose concentrations in subcutaneous tissue were 10% lower than, but were highly correlated with, blood glucose concentrations in the range of 49–388 mg/dl. Glycemic control was established in diabetic patients by intravenously infusing insulin in response to measured glucose concentrations on a moment-to-moment basis for a period of several days. By comparing the glycemic control obtained in each patient treated with multiple insulin injections or open-loop subcutaneous insulin infusion, the superiority of feedback control with the system was clearly demonstrated. During continuous glycemic regulation, day-to-day variations of insulin requirements were recognized in both basal insulin infusion and postprandial insulin infusion rates in response to identical meals and exercise. These data suggest the feasibility of long-term glycemic control in diabetic subjects with a wearable artificial endocrine pancreas, and indicate that to overcome changes in individual metabolic characteristics on a moment-to-moment basis, a closed-loop glycemic control system may be essential for ambulatory diabetic patients.