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


CONCLUSIONS
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.
Medtronic MiniMed, Northridge, California 91325, USA. barry.keenan@ medtronic.com
D Barry
DB
Keenan
Benyamin
B
Grosman
Harry W
HW
Clark
Anirban
A
Roy
Stuart A
SA
Weinzimer
Rajiv V
RV
Shah
John J
JJ
Mastrototaro
D000465:Algorithms; D001786:Blood Glucose / Q000032:analysis*; D006801:Humans; D008991:Monitoring, Physiologic / Q000379:methods*; D019397:Pancreas, Artificial
D001786:Blood Glucose