A GLUCOSE MONITORING-SYSTEM FOR ON LINE ESTIMATION IN MAN OF BLOOD-GLUCOSE CONCENTRATION USING A MINIATURIZED GLUCOSE SENSOR IMPLANTED IN THE SUBCUTANEOUS TISSUE AND A WEARABLE CONTROL UNIT

We have developed a miniaturized glucose sensor which has been shown p reviously to function adequately when implanted in the subcutaneous ti ssue of rats and dogs. Following a glucose load, the sensor output inc reases, making it possible to calculate a sensitivity coefficient to g lucose in vivo, and an extrapolated background current in the absence of glucose. These parameters are used for estimating at any time the a pparent subcutaneous glucose concentration from the current. In the pr evious studies, this calibration was performed a posteriori, on the ba sis of the retrospective analysis of the changes in blood glucose and in the current generated by the sensor. However, for clinical applicat ion of the system, an on line estimation of glucose concentration woul d be necessary. Thus, this study was undertaken in order to assess the possibility of calibrating the sensor in real time, using a novel cal ibration procedure and a monitoring unit which was specifically design ed for this purpose. This electronic device is able to measure, to fil ter and to store the current. During an oral glucose challenge, when a stable current is reached, it is possible to feed the unit with two d ifferent values of blood glucose and their corresponding times. The un it calculates the in vivo parameters, transforms every single value of current into an estimation of the glucose concentration, and then dis plays this estimation. In this study, 11 sensors were investigated of which two did not respond to glucose. In the other nine trials, the vo lunteers were asked to record every 30 s what appeared on the display during the secondary decrease in blood glucose. The results were analy sed by comparing these readings (approximately 220 measurements per tr ial) to the changes in plasma glucose, measured every 15 min. The Erro r Grid Analysis indicated that 84.1 +/- 3.6 % of the measurements were in zone A (accurate) and 15 +/- 3.6 % were in zone B (acceptable). Co nsidering each individual trial, the differences between the displayed value and the concomitant plasma glucose concentration ranged between -1.7 and 0.69 mmol/l. These excellent results were due to the absence of any significant lag between the changes in plasma glucose concentr ation and the changes in the result on the display. We conclude that t his glucose monitoring system, based on subcutaneous sensing of glucos e, is able to provide a direct on line estimation of blood glucose con centration.