title: A simulation model of glucose regulation in the critically ill.
abstract: Focused research is underway to improve the delivery of tight glycaemic control at the intensive care unit. A major component is the development of safe, efficacious and effective insulin titration algorithms, which are normally evaluated in time-consuming resource-demanding clinical studies. Simulation studies with virtual critically ill patients can substantially accelerate the development process. For this purpose, we created a model of glucoregulation in the critically ill. The model includes five submodels: a submodel of endogenous insulin secretion, a submodel of insulin kinetics, a submodel of enteral glucose absorption, a submodel of insulin action and a submodel of glucose kinetics. Model parameters are estimated utilizing prior knowledge and data collected routinely at the intensive care unit to represent the high intersubject and temporal variation in insulin needs in the critically ill. Bayesian estimation combined with the regularization method is used to estimate (i) time-invariant model parameters and (ii) a time-varying parameter, the basal insulin concentration, which represents the temporal variation in insulin sensitivity. We propose a validation process to validate virtual patients developed for the purpose of testing glucose controllers. The parameter estimation and the validation are exemplified using data collected in six critically ill patients treated at a medical intensive care unit. In conclusion, a novel glucoregulatory model has been developed to create a virtual population of critically ill facilitating in silico testing of glucose controllers at the intensive care unit.
authors.affiliation: Institute of Metabolic Science, Metabolic Research Laboratories, Level 4, Box 289, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK. rh347@cam.ac.uk
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
authors.forename: Ludovic J
authors.initials: LJ
authors.lastname: Chassin
authors.forename: Martin
authors.initials: M
authors.lastname: Ellmerer
authors.forename: Johannes
authors.initials: J
authors.lastname: Plank
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
mesh_terms: D000368:Aged; D000465:Algorithms; D001499:Bayes Theorem; D003198:Computer Simulation; D016638:Critical Illness; D005260:Female; D005947:Glucose / Q000502:physiology*; D006207:Half-Life; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics; D007328:Insulin / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose