title: Effect of algorithm aggressiveness on the performance of the Hypoglycemia-Hyperglycemia Minimizer (HHM) System.
abstract: The Hypoglycemia-Hyperglycemia Minimizer (HHM) System aims to mitigate glucose excursions by preemptively modulating insulin delivery based on continuous glucose monitor (CGM) measurements. The "aggressiveness factor" is a key parameter in the HHM System algorithm, affecting how readily the system adjusts insulin infusion in response to changing CGM levels. Twenty adults with type 1 diabetes were studied in closed-loop in a clinical research center for approximately 26 hours. This analysis focused on the effect of the aggressiveness factor on the insulin dosing characteristics of the algorithm and, to a lesser extent, on the glucose control results observed. As the aggressiveness factor increased from conservative to medium to aggressive: the maximum observed insulin dose delivered by the algorithm—which is designed to give doses that are corrective in nature every 5 minutes—increased (1.00 vs 1.15 vs 2.20 U, respectively); tendency to adhere to the subject's nominal basal dose decreased (61.9% vs 56.6% vs 53.4%); and readiness to decrease insulin below basal also increased (18.4% vs 19.4% vs 25.2%). Glucose analyses by both CGM and Yellow Springs Instruments (YSI) indicated that the aggressive setting of the algorithm resulted in the least time spent at levels >180 mg/dL, and the most time spent between 70-180 mg/dL. There was no severe hyperglycemia, diabetic ketoacidosis, or severe hypoglycemia for any of the aggressiveness values investigated. These analyses underscore the importance of investigating the sensitivity of the HHM System to its key parameters, such as the aggressiveness factor, to guide future development decisions.
authors.affiliation: Animas Corporation, Wayne, PA, USA dfinan@its.jnj.com.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Finan
authors.affiliation: Animas Corporation, Wayne, PA, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McCann
authors.affiliation: Animas Corporation, Wayne, PA, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Rhein
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, Charlottesville, VA, USA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Breton
authors.affiliation: University of Virginia, Charlottesville, VA, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Patek
authors.affiliation: Animas Corporation, Wayne, PA, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Anhalt
authors.affiliation: University of Virginia, 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: University of Virginia, Center for Diabetes Technology, Charlottesville, VA, USA.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: University of California, Santa Barbara, Santa Barbara, CA, USA Sansum Diabetes Research Institute, Santa Barbara, CA, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Zisser
authors.affiliation: Animas Corporation, Wayne, PA, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Venugopalan
mesh_terms: D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy; D005240:Feasibility Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000628:therapy; D007003:Hypoglycemia / Q000097:blood* / Q000628:therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007332:Insulin Infusion Systems / Q000009:adverse effects / Q000706:statistics & numerical data*; D008297:Male; D061214:Patient Safety
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: aggressiveness factor; algorithm; artificial pancreas; closed loop; tuning parameter