title: Model-based closed-loop glucose control in type 1 diabetes: the DiaCon experience.
abstract: BACKGROUND
  To improve type 1 diabetes mellitus (T1DM) management, we developed a model predictive control (MPC) algorithm for closed-loop (CL) glucose control based on a linear second-order deterministic-stochastic model. The deterministic part of the model is specified by three patient-specific parameters: insulin sensitivity factor, insulin action time, and basal insulin infusion rate. The stochastic part is identical for all patients but identified from data from a single patient. Results of the first clinical feasibility test of the algorithm are presented.
  
  
  METHODS
  We conducted two randomized crossover studies. Study 1 compared CL with open-loop (OL) control. Study 2 compared glucose control after CL initiation in the euglycemic (CL-Eu) and hyperglycemic (CL-Hyper) ranges, respectively. Patients were studied from 22:00-07:00 on two separate nights.
  
  
  RESULTS
  Each study included six T1DM patients (hemoglobin A1c 7.2% ± 0.4%). In study 1, hypoglycemic events (plasma glucose < 54 mg/dl) occurred on two OL and one CL nights. Average glucose from 22:00-07:00 was 90 mg/dl [74-146 mg/dl; median (interquartile range)] during OL and 108 mg/dl (101-128 mg/dl) during CL (determined by continuous glucose monitoring). However, median time spent in the range 70-144 mg/dl was 67.9% (3.0-73.3%) during OL and 80.8% (70.5-89.7%) during CL. In study 2, there was one episode of hypoglycemia with plasma glucose <54 mg/dl in a CL-Eu night. Mean glucose from 22:00-07:00 and time spent in the range 70-144 mg/dl were 121 mg/dl (117-133 mg/dl) and 69.0% (30.7-77.9%) in CL-Eu and 149 mg/dl (140-193 mg/dl) and 48.2% (34.9-72.5%) in CL-Hyper, respectively.
  
  
  CONCLUSIONS
  This study suggests that our novel MPC algorithm can safely and effectively control glucose overnight, also when CL control is initiated during hyperglycemia.
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Kettegård Alle 30, 2650 Hvidovre, Denmark. signe.schmidt@regionh.dk.
authors.forename: Signe
authors.initials: S
authors.lastname: Schmidt
authors.forename: Dimitri
authors.initials: D
authors.lastname: Boiroux
authors.forename: Anne Katrine
authors.initials: AK
authors.lastname: Duun-Henriksen
authors.forename: Laurits
authors.initials: L
authors.lastname: Frøssing
authors.forename: Ole
authors.initials: O
authors.lastname: Skyggebjerg
authors.forename: John Bagterp
authors.initials: JB
authors.lastname: Jørgensen
authors.forename: Niels Kjølstad
authors.initials: NK
authors.lastname: Poulsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Madsen
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Kirsten
authors.initials: K
authors.lastname: Nørgaard
mesh_terms: D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000032:analysis; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation* / Q000379:methods*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D015918:Infusion Pumps, Implantable; D007328:Insulin / Q000008:administration & dosage; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D019397:Pancreas, Artificial; D014584:User-Computer Interface
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin