title: In silico evaluation of an artificial pancreas combining exogenous ultrafast-acting technosphere insulin with zone model predictive control.
abstract: BACKGROUND
  Because of the slow pharmacokinetics of subcutaneous (SC) insulin, avoiding postprandial hyperglycemia has been a major challenge for an artificial pancreas (AP) using SC insulin without a meal announcement.
  
  
  METHODS
  A semiautomated AP with Technosphere® Insulin (TI; MannKind Corporation, Valencia, CA) was designed to combine pulmonary and SC insulin. Manual inhalation of 10 U ultrafast-absorbing TI at mealtime delivers the first, or cephalic, phase of insulin, and an SC insulin pump controlled by zone model predictive controller delivers second-phase and basal insulin. This AP design was evaluated on 100 in silico subjects from the University of Virginia/Padova metabolic simulator using a protocol of two 50 g carbohydrate (CHO) meals and two 15 g CHO snacks.
  
  
  RESULTS
  Simulation analysis shows that the semiautomated AP with TI provides 32% and 16% more time in the controller target zone (80-140 mg/dl) during the 4 h postprandial period, with 39 and 20 mg/dl lower postprandial blood glucose peak on average than the pure feedback AP and the AP with manual feed-forward SC bolus, respectively. No severe hypoglycemia (<50 mg/dl) was observed in any cases.
  
  
  CONCLUSIONS
  The semiautomated AP with TI provides maximum time in the clinically accepted region when compared with pure feedback AP and AP with manual feed-forward SC bolus. Furthermore, the semiautomated AP with TI provides a flexible operation (optional TI inhalation) with minimal user interaction, where the controller design can be tailored to specific user needs and abilities to interact with the device.
authors: Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, California 93106-5080, USA.
authors: Justin J
authors: JJ
authors: Lee
authors: Eyal
authors: E
authors: Dassau
authors: Howard
authors: H
authors: Zisser
authors: Rebecca A
authors: RA
authors: Harvey
authors: Lois
authors: L
authors: Jovanovič
authors: Francis J
authors: FJ
authors: Doyle
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage*; D019397:Pancreas, Artificial; D013997:Time Factors
chemical_list: D007328:Insulin