title: Closed-loop subcutaneous insulin infusion algorithm with a short-acting insulin analog for long-term clinical application of a wearable artificial endocrine pancreas.
abstract: Considering the management and safety of the insulin delivery route when a wearable artificial endocrine pancreas is applied to ambulatory diabetic patients on a long-term basis, we developed a s.c. insulin infusion algorithm by analyzing the dynamics of a s.c. injected short-acting insulin analog (Insulin Lispro) by a three-compartment model. Principally the insulin infusion algorithm was developed as a transfer function with the first-order delay in both proportional and derivative actions to blood glucose concentrations. The parameters for this algorithm were calculated to simulate a physiological plasma insulin profile as closely as possible. By applying this algorithm with regular insulin, diabetic patients showed a 2 h postprandial hyperglycemia and a delayed hyperinsulinemia, followed by hypoglycemic episodes 4-5 h after oral glucose load, just as observed in the computer simulation study. However, using Insulin Lispro, a near-physiological glycemic control (postprandial blood glucose of 153.1 +/- 8.3 mg/100 ml at 60 min and 90.3 +/- 7.1 mg/100 ml at 180 min, respectively) could be achieved without showing any delayed hyperinsulinemia or hypoglycemia. Daily glycemic excursions were also controlled near-physiologically and although the daily insulin requirement (731.7 +/- 160.5 mU/kg/day) was slightly higher, it was not significantly different from that with i.v. insulin infusion (622.3 +/- 142.6 mU/kg/day). These results indicate that the application of s.c. insulin infusion algorithm with Insulin Lispro is feasible for long-term glycemic control with a wearable artificial endocrine pancreas in ambulatory diabetic patients.
authors.affiliation: Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimoda
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: M
authors.initials: M
authors.lastname: Sakakida
authors.forename: Y
authors.initials: Y
authors.lastname: Konno
authors.forename: K
authors.initials: K
authors.lastname: Ichinose
authors.forename: M
authors.initials: M
authors.lastname: Uehara
authors.forename: T
authors.initials: T
authors.lastname: Nowak
authors.forename: M
authors.initials: M
authors.lastname: Shichiri
mesh_terms: D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000032:analysis; D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D061268:Insulin Lispro; D013677:Medical Laboratory Science / Q000379:methods*; D008991:Monitoring, Physiologic / Q000379:methods
chemical_list: D001786:Blood Glucose; D007328:Insulin; D061268:Insulin Lispro