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.

Comparison of the clinical information provided by the FreeStyle Navigator continuous interstitial glucose monitor versus traditional blood glucose readings.

BACKGROUND: The purpose of the analysis was to compare the clinical utility of data from traditional self-monitoring of blood glucose (SMBG) to that of continuous glucose monitoring (CGM). METHODS: A clinical study of the clinical accuracy of the FreeStyle Navigator CGM System (Abbott Diabetes Care, Alameda, CA), which includes SMBG capabilities, was conducted by comparison to the YSI blood glucose analyzer (YSI Inc., Yellow Springs, OH) using 58 subjects with type 1 diabetes. The Continuous Glucose-Error Grid Analysis (CG-EGA) was used as the analytical tool. RESULTS: Using CG-EGA, the "clinically accurate," "benign errors," and "clinical errors" were 86.8%, 8.7%, and 4.5% for SMBG and 92.7%, 3.7%, and 3.6% for CGM, respectively. If blood glucose is viewed as a process in time, SMBG would provide accurate information about this process 86.8% of the time, whereas CGM would provide accurate information about this process 92.7% of the time (P < 0.0001). In the hypoglycemic range, however, SMBG is more accurate as the "clinically accurate," "benign errors," and "clinical errors" were 83.5%, 6.4%, and 10.1% for SMBG and 57.1%, 8.4%, and 34.5% (P < 0.0001) for CGM, respectively. CONCLUSIONS: While SMBG produces more accurate instantaneous glucose values than CGM, control of blood glucose involves a system in flux, and CGM provides more detailed insight into the dynamics of that system. In the normal and elevated glucose ranges, the additional information about the direction and rate of glucose change provided by the FreeStyle Navigator CGM System increases the ability to make correct clinical decisions when compared to episodic SMBG tests.

Alarm characterization for continuous glucose monitors used as adjuncts to self-monitoring of blood glucose.

BACKGROUND: Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG). Alarm evaluation in the Clinical and Laboratory Standards Institute (CLSI) guideline for CGM does not specifically address devices that employ both CGM and SMBG. In this report, an alarm evaluation method is proposed for these devices. METHOD: The proposed method builds on the CLSI method using data from an in-clinic study of subjects with type 1 diabetes. CGM was used to detect glycemic events, and SMBG was used to determine treatment. To optimize detection of a single glucose level, such as 70 mg/dl, a range of alarm threshold settings was evaluated. The alarm characterization provides a choice of alarm settings that trade off detection and false alarms. Detection of a range of high glucose levels was similarly evaluated. RESULTS: Using low glucose alarms, detection of 70 mg/dl within 30 minutes increased from 64 to 97% as alarm settings increased from 70 to 100 mg/dl, and alarms that did not require treatment (SMBG >85 mg/dl) increased from 18 to 52%. Using high glucose alarms, detection of 180 mg/dl within 30 minutes increased from 87 to 96% as alarm settings decreased from 180 to 165 mg/dl, and alarms that did not require treatment (SMBG <180 mg/dl) increased from 24 to 42%. CONCLUSION: The proposed alarm evaluation method provides information for choosing appropriate alarm thresholds and reflects the clinical utility of CGM alarms.

Alarm characterization for a continuous glucose monitor that replaces traditional blood glucose monitoring.

BACKGROUND: Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG); all CGM alarms require SMBG confirmation before treatment. In this report, an analysis method is proposed to determine the CGM threshold alarm accuracy required to eliminate SMBG confirmation. METHOD: The proposed method builds on the Clinical and Laboratory Standards Institute (CLSI) guideline for evaluating CGM threshold alarms using data from an in-clinic study of subjects with type 1 diabetes. The CLSI method proposes a maximum time limit of +/-30 minutes for the detection of hypo- and hyperglycemic events but does not include limits for glucose measurement accuracy. The International Standards Organization (ISO) standard for SMBG glucose measurement accuracy (ISO 15197) is +/-15 mg/dl for glucose <75 mg/dl and +/-20% for glucose > or = 75 mg/dl. This standard was combined with the CLSI method to more completely characterize the accuracy of CGM alarms. RESULTS: Incorporating the ISO 15197 accuracy margins, FreeStyle Navigator CGM system alarms detected 70 mg/dl hypoglycemia within 30 minutes at a rate of 70.3%, with a false alarm rate of 11.4%. The device detected high glucose in the range of 140-300 mg/dl within 30 minutes at an average rate of 99.2%, with a false alarm rate of 2.1%. CONCLUSION: Self-monitoring of blood glucose confirmation is necessary for detecting and treating hypoglycemia with the FreeStyle Navigator CGM system, but at high glucose levels, SMBG confirmation adds little incremental value to CGM alarms.

The chemistry of commercial continuous glucose monitors.

The analytical methodologies of the continuous glucose monitors (CGMs) commercialized to date are described. The devices include two noninvasive products: the GlucoWatch (Cygnus, Redwood City, CA) G2 Biographer uses iontophoresis to obtain a sample and electrochemistry for glucose detection, and PENDRA (Pendragon Medical Ltd., Zurich, Switzerland) utilizes impedance spectroscopy. Three minimally invasive systems employ subcutaneous amperometric sensors-Guardian REAL-Time (Medtronic MiniMed, Sylmar, CA), DexCom STS-7 (DexCom, San Diego, CA), and FreeStyle Navigator (Abbott Diabetes Care, Alameda, CA). The GlucoDay (A. Menarini I.F.R. S.r.l., Florence, Italy) collects a sample with a minimally invasive microdialysis fiber and measures the glucose electrochemically.

Detection of hypoglycemia with continuous interstitial and traditional blood glucose monitoring using the FreeStyle Navigator Continuous Glucose Monitoring System.

BACKGROUND: The objective of the analysis was to compare detection of hypoglycemic episodes (glucose <70 mg/dL lasting >15 min) with the FreeStyle Navigator Continuous Glucose Monitoring System (FSN-CGM) (Abbott Diabetes Care, Alameda, CA) alarms to detection with traditional finger stick testing at an average frequency of eight tests per day. METHODS: The performance of FSN-CGM alarms was evaluated in a clinic setting using 58 subjects with type 1 diabetes mellitus (T1DM) monitoring interstitial glucose concentration over a 5-day period compared to reference YSI measurements (instrument manufactured by YSI, Yellow Springs, OH) at 15-min intervals. Finger stick glucose testing was evaluated in the home environment with 91 subjects with TIDM monitoring with the blood glucose meter integrated into the FreeStyle Navigator (FSN-BG) over a 20-day period. The reference was FSN-CGM with results masked from the subjects. Blood glucose values <=85 mg/dL were considered the optimal treatment level to avoid or reverse hypoglycemia. RESULTS: With a threshold alarm setting of 85 mg/dL, 90.6% of hypoglycemic episodes were detected within +/- 30 min by FSN-CGM in the clinic study. When the alarm was activated, YSI glucose was <= 85 mg/dL 77.2% of the time. In the home environment, the average FSN-BG testing frequency was 7.9 tests per day. Hypoglycemia was verified within +/- 30 min by FSN-BG measurements <= 85 mg/dL at a rate of 27.5%. CONCLUSIONS: Even with a high rate of FSN-BG testing, hypoglycemia detected by FSN-CGM was verified by patients with T1DM very infrequently. A high rate of hypoglycemia detection with a moderate rate of unnecessary alarms can be attained using FSN-CGM.

Accuracy of the 5-day FreeStyle Navigator Continuous Glucose Monitoring System: comparison with frequent laboratory reference measurements.

OBJECTIVE: The purpose of this study was to compare the accuracy of measurements of glucose in interstitial fluid made with the FreeStyle Navigator Continuous Glucose Monitoring System with Yellow Springs Instrument laboratory reference measurements of venous blood glucose. RESEARCH DESIGN AND METHODS: Fifty-eight subjects with type 1 diabetes, aged 18-64 years, were enrolled in a multicenter, prospective, single-arm study. Each subject wore two sensors simultaneously, which were calibrated with capillary fingerstick measurements at 10, 12, 24, and 72 h after insertion. Measurements from the FreeStyle Navigator system were collected at 1-min intervals and compared with venous measurements taken once every 15 min for 50 h over the 5-day period of sensor wear in an in-patient clinical research center. Periods of high rates of change of glucose were induced by insulin and glucose challenges. RESULTS: Comparison of the FreeStyle Navigator measurements with the laboratory reference method (n = 20,362) gave mean and median absolute relative differences (ARDs) of 12.8 and 9.3%, respectively. The percentage in the clinically accurate Clarke error grid A zone was 81.7% and that in the in the benign error B zone was 16.7%. During low rates of change (< +/-1 mg x dl(-1) x min(-1)), the percentage in the A zone was higher (84.9%) and the mean and median ARDs were lower (11.7 and 8.5%, respectively). CONCLUSIONS: Measurements with the FreeStyle Navigator system were found to be consistent and accurate compared with venous measurements made using a laboratory reference method over 5 days of sensor wear (82.5% in the A zone on day 1 and 80.9% on day 5).