title: In silico simulation of long-term type 1 diabetes glycemic control treatment outcomes.
abstract: OBJECTIVE
  The goals of this study were to develop (1) a safe and effective protocol for the clinical control of type 1 diabetes using conventional self-monitoring blood glucose (SMBG) measurements and multiple daily injections with insulin analogues, and (2) an in silico simulation tool of type 1 diabetes to predict long-term glycemic control outcomes of clinical interventions.
  
  
  METHODS
  The virtual patient method was used to develop a simulation tool for type 1 diabetes using data from a type 1 diabetes patient cohort (n = 40). The tool was used to test the adaptive protocol (AC) and a conventional intensive insulin therapy (CC) against results from a representative control cohort. Optimal and suboptimal basal insulin replacements were evaluated as a function of SMBG frequency in conjunction with the (AC and CC) prandial control protocols.
  
  
  RESULTS
  In long-term glycemic control, the AC protocol significantly decreased hemoglobin A1c in conditions of suboptimal basal insulin replacement for SMBG frequencies > or = 6/day, and reduced the occurrence of mild and severe hypoglycemia by 86-100% over controls, over all SMBG frequencies in conditions of optimal basal insulin.
  
  
  CONCLUSIONS
  A simulation tool to predict long-term glycemic control outcomes from clinical interventions has been developed to test a novel, adaptive control protocol for type 1 diabetes. The protocol is effective and safe compared to conventional intensive insulin therapy and controls. As fear of hypoglycemia is a large psychological barrier to glycemic control, the AC protocol may represent the next evolution of intensive insulin therapy to deliver increased glycemic control with increased safety. Further clinical or experimental validation is needed to fully prove the concept.
authors.affiliation: Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand. xww10@student.canterbury.ac.nz
authors.forename: Xing-Wei
authors.initials: XW
authors.lastname: Wong
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Chase
authors.forename: Christopher
authors.initials: C
authors.lastname: E Hann
authors.forename: Thomas
authors.initials: T
authors.lastname: F Lotz
authors.forename: Jessica
authors.initials: J
authors.lastname: Lin
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Le Compte
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Shaw