Udo Hoss

Continuous Glucose Monitoring in the Subcutaneous Tissue over a 14-Day Sensor Wear Period

Background: Glucose monitoring systems using subcutaneously inserted sensors are currently labeled for up to 7 days of wear. In this study, we evaluated the feasibility of a 14-day wear duration using a modified version of the sensor found in the Freestyle Navigator™ continuous glucose monitoring system. Methods: Sixty-two subjects with diabetes were enrolled in the study. One sensor per subject was inserted on the arm for a wear time of 14 days. Two different calibration algorithms were applied retrospectively, one that uses periodic sensor recalibrations and one without recalibrations. Sensor in vivo stability was determined by least square regression analysis using capillary blood glucose. Mean absolute relative difference (MARD) and mean relative difference were calculated. Consensus error grid analysis was performed by day and over the 14-day wear period to evaluate accuracy of both systems. The sensor insertion sites were inspected after sensor removal for skin reactions. Results: Sensor data from 55 subjects were used for the analysis. The accuracy metrics for the system with recalibration were calculated to MARD = 13.9% and 84.0% in zone A (error grid analysis). The system without recalibration performed significantly better, resulting in MARD of 12.2% and 88.0% in zone A (p < .0001). The maximum change of in vivo sensor sensitivity over the 14-day wear period was 2% per day. Two subjects reported pain during the first 5 days of sensor wear, and 1 subject reported itching at the sensor site. No further skin reactions were noticed. Conclusions: The study shows that a 14-day sensor wear period is achievable. Moreover, sensors using “wired enzyme” technology showed excellent in vivo stability, with no significant sensitivity loss over the 14-day wear period.

Feasibility of Factory Calibration for Subcutaneous Glucose Sensors in Subjects With Diabetes.

Background: Continuous glucose monitoring using subcutaneously inserted sensors currently requires blood glucose tests for sensor calibration. Alternatively, sensors precalibrated during the manufacturing process may eliminate the need for fingerstick calibrations. In this study we evaluated the feasibility of sensor factory calibration in subjects with diabetes. Methods: A total of 33 subjects with diabetes were asked to wear 4 sensors in parallel, 2 on the arm and 2 on the abdomen. Sensors from a lot with low in vitro sensitivity coefficient of variation were used in the study. Based on frequent capillary blood glucose measurements, the average glucose sensitivity of each sensor was determined over a 5-day wear time. The in vivo sensitivities were analyzed for inter- and intrasubject variation. Mean absolute relative difference (MARD) calculation and consensus error grid analysis (EGA) were performed using a single calibration factor for all sensors, to simulate factory calibration and compared against conventional finger-stick calibration. Results: The sensitivity coefficient of variation between sensors increased from 2.9% in vitro to 6.0% in vivo. No difference in sensor response between subjects (P = .069) as well as between insertion sites (arm and abdomen) was detected (P = .104). Applying one calibration factor to all sensors in the study resulted in an MARD of 13.4%, and 83.5% of the values fell in consensus EGA zone A. Multiple fingerstick calibration resulted in an MARD of 12.7% and 84.1% in zone A. Conclusions: Feasibility of factory calibration was demonstrated in subjects with diabetes using sensors based on “wired enzyme” technology, resulting in accuracy metrics similar to sensors calibrated with capillary blood glucose.

A Novel Method for Continuous Online Glucose Monitoring in Humans: The Comparative Microdialysis Technique

The aim of this study was to prove the feasibility of continuous subcutaneous glucose monitoring in humans using the comparative microdialysis technique (CMT). The performance of the CMT was determined by comparing tissue glucose values with venous or capillary blood glucose values in healthy volunteers and type 1 diabetic subjects. The CMT is a microdialysis-based system for continuous online glucose monitoring in humans. This technique does not require calibration by the patient. Physiological saline with glucose (5.5 mM) is pumped in a stop-flow mode through a microdialysis probe inserted into the abdominal s.c. tissue. Tissue glucose concentration is calculated by comparing the dialysate and perfusate glucose concentrations. The time delay due to the measurement process is 9 min. We tested the CMT on six healthy volunteers and six type 1 diabetic patients for 24 h in our clinical setting. Comparisons were made to HemoCue analyzer (Angelholm, Sweden) capillary blood glucose measurements (healthy volunteers) and to venous blood glucose concentration determined with a Hitachi analyzer (diabetic patients). The mean absolute relative error of the CMT glucose values from the blood glucose values was 17.8+/-15.5% (n = 167) for the healthy volunteers and 11.0+/-10.8% (n = 425) for the diabetic patients. The mean difference was 0.42+/-1.06 mM (healthy volunteers) and -0.17+/-1.22 mM (diabetic patients). Error grid analysis for the values obtained in diabetic patients demonstrated that 99% of CMT glucose values were within clinically acceptable regions (regions A and B of the Clarke Error Grid). The study results show that the CMT is an accurate technique for continuous online glucose monitoring.

Continuous glucose monitoring in subcutaneous tissue using factory-calibrated sensors: a pilot study.

BACKGROUND Commercial continuous subcutaneous glucose monitors require in vivo calibration using capillary blood glucose tests. Feasibility of factory calibration, i.e., sensor batch characterization in vitro with no further need for in vivo calibration, requires a predictable and stable in vivo sensor sensitivity and limited inter- and intra-subject variation of the ratio of interstitial to blood glucose concentration. METHODS Twelve volunteers wore two FreeStyle Navigator (Abbott Diabetes Care, Alameda, CA) continuous glucose monitoring systems for 5 days in parallel for two consecutive sensor wears (four sensors per subject, 48 sensors total). Sensors from a prototype sensor lot with a low variability in glucose sensitivity were used for the study. Median sensor sensitivity values based on capillary blood glucose were calculated per sensor and compared for inter- and intra-subject variation. Mean absolute relative difference (MARD) calculation and error grid analysis were performed using a single calibration factor for all sensors to simulate factory calibration and compared to standard fingerstick calibration. RESULTS Sensor sensitivity variation in vitro was 4.6%, which increased to 8.3% in vivo (P < 0.0001). Analysis of variance revealed no significant inter-subject differences in sensor sensitivity (P = 0.134). Applying a single universal calibration factor retrospectively to all sensors resulted in a MARD of 10.4% and 88.1% of values in Clarke Error Grid Zone A, compared to a MARD of 10.9% and 86% of values in Error Grid Zone A for fingerstick calibration. CONCLUSIONS Factory calibration of sensors for continuous subcutaneous glucose monitoring is feasible with similar accuracy to standard fingerstick calibration. Additional data are required to confirm this result in subjects with diabetes.