On-line calibration of glucose sensors from the measured current by a time-varying calibration function and Bayesian priors

Goal: Minimally invasive continuous glucose monitoring (CGM) sensors measure in the subcutis a current signal, which is converted into interstitial glucose (IG) concentration by a calibration process periodically updated using fingerstick blood glucose (BG) references. Though important in diabetes management, CGM sensors still suffer from accuracy problems. Here, we propose a new online calibration method improving accuracy of CGM glucose profiles with respect to manufacturer calibration. Method: The proposed method fits CGM current signal against the BG references collected twice a day for calibration purposes, by a time-varying calibration function whose parameters are identified in a Bayesian framework using a priori second-order statistical knowledge. The distortion introduced by BG-to-IG kinetics is compensated before parameter identification via nonparametric deconvolution. Results: The method was tested on a database where 108 CGM signals were collected for 7 days by the Dexcom G4 Platinum sensor. Results show the new method drives to a statistically significant accuracy improvement as measured by three commonly used metrics: mean absolute relative difference reduced from 12.73% to 11.47%; percentage of accurate glucose estimates increased from 82.00% to 89.19%; and percentage of values falling in the 'A' zone of the Clark error grid increased from 82.22% to 88.86%. Conclusion: The new calibration method significantly improves CGM glucose profiles accuracy with respect to manufacturer calibration. Significance: The proposed algorithm provides a real-time improvement of CGM accuracy, which can be crucial in several CGM-based applications, including the artificial pancreas, thus providing a potential great impact in the diabetes technology research community.