title: Sensitivity of the Predictive Hypoglycemia Minimizer System to the Algorithm Aggressiveness Factor.
abstract: BACKGROUND
  The Predictive Hypoglycemia Minimizer System ("Hypo Minimizer"), consisting of a zone model predictive controller (the "controller") and a safety supervision module (the "safety module"), aims to mitigate hypoglycemia by preemptively modulating insulin delivery based on continuous glucose monitor (CGM) measurements. The "aggressiveness factor," a pivotal variable in the system, governs the speed and magnitude of the controller's insulin dosing characteristics in response to changes in CGM levels.
  
  
  METHODS
  Twelve adults with type 1 diabetes were studied in closed-loop in a clinical research center for approximately 24 hours. This analysis focused primarily on the effect of the aggressiveness factor on the automated insulin-delivery characteristics of the controller, and secondarily on the glucose control results.
  
  
  RESULTS
  As aggressiveness increased from "conservative" to "medium" to "aggressive," the controller recommended less insulin (-3.3% vs -14.4% vs -19.5% relative to basal) with a higher frequency (5.3% vs 14.4% vs 20.3%) during the critical times when the CGM was reading 90-120 mg/dl and decreasing. Blood glucose analyses indicated that the most aggressive setting resulted in the most desirable combination of the least time spent <70 mg/dl and the most time spent 70-180 mg/dl, particularly in the overnight period. Hyperglycemia, diabetic ketoacidosis, or severe hypoglycemia did not occur with any of the aggressiveness values.
  
  
  CONCLUSIONS
  The Hypo Minimizer's controller took preemptive action to prevent hypoglycemia based on predicted changes in CGM glucose levels. The most aggressive setting was quickest to take action to reduce insulin delivery below basal and achieved the best glucose metrics.
authors.affiliation: Animas Corporation, Chesterbrook, PA, USA dfinan@its.jnj.com.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Finan
authors.affiliation: University of California, Santa Barbara, Santa Barbara, CA, USA Sansum Diabetes Research Institute, Santa Barbara, CA, USA.
authors.forename: Eyal
authors.initials: E
authors.lastname: Dassau
authors.affiliation: University of Virginia, Center for Diabetes Technology, Charlottesville, VA, USA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Breton
authors.affiliation: University of Virginia, Center for Diabetes Technology, Charlottesville, VA, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Patek
authors.affiliation: Animas Corporation, Chesterbrook, PA, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McCann
authors.affiliation: University of Virginia, Center for Diabetes Technology, Charlottesville, VA, USA.
authors.forename: Boris P
authors.initials: BP
authors.lastname: Kovatchev
authors.affiliation: University of California, Santa Barbara, Santa Barbara, CA, USA Sansum Diabetes Research Institute, Santa Barbara, CA, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Doyle
authors.affiliation: Animas Corporation, Chesterbrook, PA, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Levy
authors.affiliation: Animas Corporation, Chesterbrook, PA, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Venugopalan
mesh_terms: D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D015918:Infusion Pumps, Implantable; D007328:Insulin / Q000008:administration & dosage*; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D019397:Pancreas, Artificial
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Aggressiveness factor; algorithm; artificial pancreas; closed-loop control; model predictive control; type 1 diabetes