Multinational study of subcutaneous model-predictive closed-loop control in type 1 diabetes mellitus: summary of the results

J Diabetes Sci Technol. 2010 Nov 1;4(6):1374-81. doi: 10.1177/193229681000400611.

Abstract

Background: In 2008-2009, the first multinational study was completed comparing closed-loop control (artificial pancreas) to state-of-the-art open-loop therapy in adults with type 1 diabetes mellitus (T1DM).

Methods: The design of the control algorithm was done entirely in silico, i.e., using computer simulation experiments with N=300 synthetic "subjects" with T1DM instead of traditional animal trials. The clinical experiments recruited 20 adults with T1DM at the Universities of Virginia (11); Padova, Italy (6); and Montpellier, France (3). Open-loop and closed-loop admission was scheduled 3-4 weeks apart, continued for 22 h (14.5 h of which were in closed loop), and used a continuous glucose monitor and an insulin pump. The only difference between the two sessions was that insulin dosing was performed by the patient under a physician's supervision during open loop, whereas insulin dosing was performed by a control algorithm during closed loop.

Results: In silico design resulted in rapid (less than 6 months compared to years of animal trials) and cost-effective system development, testing, and regulatory approvals in the United States, Italy, and France. In the clinic, compared to open-loop, closed-loop control reduced nocturnal hypoglycemia (blood glucose below 3.9 mmol/liter) from 23 to 5 episodes (p<.01) and increased the amount of time spent overnight within the target range (3.9 to 7.8 mmol/liter) from 64% to 78% (p=.03).

Conclusions: In silico experiments can be used as viable alternatives to animal trials for the preclinical testing of insulin treatment strategies. Compared to open-loop treatment under identical conditions, closed-loop control improves the overnight regulation of diabetes.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Algorithms
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Child
  • Computer Simulation
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Dosage Calculations
  • Female
  • France
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Insulin Infusion Systems*
  • Italy
  • Male
  • Middle Aged
  • Models, Biological
  • Monitoring, Physiologic
  • Pancreas, Artificial*
  • Pilot Projects
  • Time Factors
  • Treatment Outcome
  • Virginia
  • Young Adult

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human