title: A subcutaneous insulin pharmacokinetic model for computer simulation in a diabetes decision support role: model structure and parameter identification.
abstract: OBJECTIVE
  The goal of this study was to develop a unified physiological subcutaneous (SC) insulin absorption model for computer simulation in a clinical diabetes decision support role. The model must model the plasma insulin appearance of a wide range of current insulins, especially monomer insulin and insulin glargine, utilizing common chemical states and transport rates, where appropriate.
  
  
  METHODS
  A compartmental model was developed with 13 patient-specific model parameters covering six diverse insulin types [rapid-acting, regular, neutral protamine Hagedorn (NPH), lente, ultralente, and glargine insulin]. Model parameters were identified using 37 sets of mean plasma insulin time-course data from an extensive literature review via nonlinear optimization methods.
  
  
  RESULTS
  All fitted parameters have a coefficient of variation <100% (median 51.3%, 95th percentile 3.6-60.6%) and can be considered a posteriori identifiable.
  
  
  CONCLUSIONS
  A model is presented to describe SC injected insulin appearance in plasma in a diabetes decision support role. Clinically current insulin types (monomeric insulin, regular insulin, NPH, insulin, and glargine) and older insulin types (lente and ultralente) are included in a unified framework that accounts for nonlinear concentration and dose dependency. Future work requires clinical validation using published pharmacokinetic studies.
authors.affiliation: Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand. xww10@student.canterbury.ac.nz
authors.forename: Jason
authors.initials: J
authors.lastname: Wong
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Chase
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Hann
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lotz
authors.forename: Jessica
authors.initials: J
authors.lastname: Lin
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Le Compte