Continuous glucose monitoring considerations for the development of a closed-loop artificial pancreas system

J Diabetes Sci Technol. 2011 Nov 1;5(6):1327-36. doi: 10.1177/193229681100500603.

Abstract

Background: Commercialization of a closed-loop artificial pancreas system that employs continuous subcutaneous insulin infusion and interstitial fluid glucose sensing has been encumbered by state-of-the-art technology. Continuous glucose monitoring (CGM) devices with improved accuracy could significantly advance development efforts. However, the current accuracy of CGM devices might be adequate for closed-loop control.

Methods: The influence that known CGM limitations have on closed-loop control was investigated by integrating sources of sensor inaccuracy with the University of Virginia Padova Diabetes simulator. Non-glucose interference, physiological time lag and sensor error measurements, selected from 83 Enlite™ glucose sensor recordings with the Guardian® REAL-Time system, were used to modulate simulated plasma glucose signals. The effect of sensor accuracy on closed-loop controller performance was evaluated in silico, and contrasted with closed-loop clinical studies during the nocturnal control period.

Results: Based on n = 2472 reference points, a mean sensor error of 14% with physiological time lags of 3.28 ± 4.62 min (max 13.2 min) was calculated for simulation. Sensor bias reduced time in target for both simulation and clinical experiments. In simulation, additive error increased time <70 mg/dl and >180 mg/dl by 0.2% and 5.6%, respectively. In-clinic, the greatest low blood glucose index values (max = 5.9) corresponded to sensor performance.

Conclusion: Sensors have sufficient accuracy for closed-loop control, however, algorithms are necessary to effectively calibrate and detect erroneous calibrations and failing sensors. Clinical closed-loop data suggest that control with a higher target of 140 mg/dl during the nocturnal period could significantly reduce the risk for hypoglycemia.

MeSH terms

  • Algorithms*
  • Blood Glucose / analysis*
  • Humans
  • Monitoring, Physiologic / methods*
  • Pancreas, Artificial*

Substances

  • Blood Glucose