Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery

Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery Feasibility study testing a new model for the artificial pancreas Eric Renard , MD, PHD 1 , Jerome Place , MSC 1 , Martin Cantwell , BSC 2 , Hugues Chevassus , PHARMD 3 and Cesar C. Palerm , PHD 2 1 Endocrinology Department, Le Centre Hospitalier Universitaire Montpellier and Unité Mixte de Recherche Centre National de la Recherche Scientifique 5232, University of Montpellier, Montpellier, France; 2 Medtronic Diabetes, Northridge, California; 3 INSERM Clinical Investigation Centre 001, Le Centre Hospitalier Universitaire Montpellier, Montpellier, France. Corresponding author: Eric Renard, renard.amtim{at}wanadoo.fr . Abstract OBJECTIVE Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm. RESEARCH DESIGN AND METHODS Two-day closed-loop therapy (except for a 15-min premeal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean ± SEM percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was significantly higher (39.1 ± 4.5 vs. 27.7 ± 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4–6.6 mmol/l range (46.3 ± 5.3 vs. 28.6 ± 7.4, P = 0.025) and lower mean blood glucose levels (6.9 ± 0.3 vs. 7.9 ± 0.6 mmol/l, P = 0.036). Time spent with blood glucose