title: A closed-loop artificial pancreas based on risk management.
abstract: BACKGROUND
  Control algorithms that regulate blood glucose (BG) levels in individuals with type 1 diabetes mellitus face several fundamental challenges. Two of these are the asymmetric risk of clinical complications associated with low and high glucose levels and the irreversibility of insulin action when using only insulin. Both of these nonlinearities force a controller to be more conservative when uncertainties are high. We developed a novel extended model predictive controller (EMPC) that explicitly addresses these two challenges.
  
  
  METHODS
  Our extensions to model predictive control (MPC) operate in three ways. First, they explicitly minimize the combined risk of hypoglycemia and hyperglycemia. Second, they integrate the effect of prediction uncertainties into the risk. Third, they understand that future control actions will vary if measurements fall above or below predictions. Using the University of Virginia/Padova Simulator, we compared our novel controller (EMPC) against optimized versions of a proportional-integral-derivative (PID) controller, a traditional MPC, and a basal/bolus (BB) controller, as well as against published results of an independent MPC (IMPC). The BB controller was optimized retrospectively to serve as a bound on the possible performance.
  
  
  RESULTS
  We tuned each controller, where possible, to minimize a published blood glucose risk index (BGRI). The simulated controllers (PID/MPC/EMPC/BB) provided BGRI values of 2.99/3.05/2.51/1.27 as compared to the published IMPC BGRI value of 4.10. These correspond to 73/79/84/92% of BG values lying in the euglycemic range (70-180 mg/dl), respectively, with mean BG levels of 151/156/147/140 mg/dl.
  
  
  CONCLUSIONS
  The EMPC strategy extends MPC to explicitly address the issues of asymmetric glycemic risk and irreversible insulin action using estimated prediction uncertainties and an explicit risk function. This controller reduces the avoidable BGRI by 56% (p < .05) relative to a published MPC algorithm studied on a similar population.
authors.affiliation: Department of Aeronautics and Astronautics, Stanford University, Stanford, California, USA. fmccamer@yahoo.com
authors.forename: Fraser
authors.initials: F
authors.lastname: Cameron
authors.forename: B Wayne
authors.initials: BW
authors.lastname: Bequette
authors.forename: Darrell M
authors.initials: DM
authors.lastname: Wilson
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Buckingham
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Lee
authors.forename: Günter
authors.initials: G
authors.lastname: Niemeyer
mesh_terms: D000465:Algorithms; D001786:Blood Glucose / Q000032:analysis*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007003:Hypoglycemia / Q000097:blood; D007328:Insulin / Q000097:blood; D007332:Insulin Infusion Systems; D015233:Models, Statistical; D019397:Pancreas, Artificial; D011237:Predictive Value of Tests; D012306:Risk; D012308:Risk Management
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human