title: Blood glucose control using a novel continuous blood glucose monitor and repetitive intravenous insulin boluses: exploiting natural insulin pulsatility as a principle for a future artificial pancreas.
abstract: The aim of this study was to construct a glucose regulatory algorithm by employing the natural pulsatile pattern of insulin secretion and the oscillatory pattern of resting blood glucose levels and further to regulate the blood glucose level in diabetic pigs by this method. We developed a control algorithm based on repetitive intravenous bolus injections of insulin and combined this with an intravascular blood glucose monitor. Four anesthetized pigs were used in the study. The animals developed a mildly diabetic state from streptozotocin pretreatment. They were steadily brought within the blood glucose target range of 4.5-6.0 mmol/L in 21 to 121 min and kept within that range for 128 to 238 min (hypoglycemic values varied from 2.9 to 51.1 min). The study confirmed our hypotheses regarding the feasibility of this new principle for blood glucose control, and the algorithm was constantly improved during the study to produce the best results in the last animals. The main obstacles were the drift of the IvS-1 sensor and problems with the calibration procedure, which calls for an improvement in the sensor stability before this method can be applied fully in new studies in animals and humans.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, MTFS, Postbox 8905, 7491 Trondheim, Norway ; Department of Anesthesiology and Intensive Care Medicine, Trondheim University Hospital, Postbox 3250 Sluppen, 7006 Trondheim, Norway.
authors.forename: Nils K
authors.initials: NK
authors.lastname: Skjaervold
authors.affiliation: Invivosense Norway Ltd., c/o NTNU Technology Transfer, Sem Saelands Vei 14, 7034 Trondheim, Norway.
authors.forename: Dan
authors.initials: D
authors.lastname: Ostling
authors.affiliation: Invivosense Norway Ltd., c/o NTNU Technology Transfer, Sem Saelands Vei 14, 7034 Trondheim, Norway ; Department of Electronics and Telecommunications, Faculty of Information Technology, Mathematics and Electrical Engineering, Norwegian University of Science and Technology, 7491 Trondheim, Norway ; Faculty of Technology, Sør-Trøndelag University College, Postbox 2320, 7004 Trondheim, Norway.
authors.forename: Dag R
authors.initials: DR
authors.lastname: Hjelme
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, 7491 Trondheim, Norway ; Department of Clinical Pharmacology, Trondheim University Hospital, Postbox 3250 Sluppen, 7006 Trondheim, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Spigset
authors.affiliation: Unit of Comparative Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Oddveig
authors.initials: O
authors.lastname: Lyng
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, MTFS, Postbox 8905, 7491 Trondheim, Norway ; Department of Anesthesiology and Intensive Care Medicine, Trondheim University Hospital, Postbox 3250 Sluppen, 7006 Trondheim, Norway.
authors.forename: Petter
authors.initials: P
authors.lastname: Aadahl