Ronald L. Brazg

A Continuous Glucose Sensor Based on Wired Enzyme™ Technology - Results from a 3-Day Trial in Patients with Type 1 Diabetes

Wired Enzyme (Therasense, Alameda, CA) sensing technology for continuous measurement of in vivo glucose concentrations offers the benefits of (1). excellent sensor stability, (2). reduced susceptibility to variations of in vivo oxygen concentration, and (3). minimized response to common electroactive interferents. This study describes the response of 48 sensors (25 in the upper arm, 23 in the abdomen) implanted for 3 days in patients with Type 1 diabetes. Prospective calibration was performed using capillary blood; results were compared with venous plasma glucose values obtained at 15-min intervals. Ninety-eight percent of readings fell in the clinically accurate Clarke error grid zone A or clinically acceptable zone B. Choice of the site of the implanted sensor (upper arm vs. abdomen) or the capillary blood calibration site (arm vs. finger) did not affect system accuracy.

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 · dl−1 · 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).

Reduction in Duration of Hypoglycemia by Automatic Suspension of Insulin Delivery: The In-Clinic ASPIRE Study

BACKGROUND The efficacy of automatic suspension of insulin delivery in induced hypoglycemia among subjects with type 1 diabetes was evaluated. SUBJECTS AND METHODS In this randomized crossover study, subjects used a sensor-augmented insulin pump system with a low glucose suspend (LGS) feature that automatically stops insulin delivery for 2 h following a sensor glucose (SG) value ≤70 mg/dL. Subjects fasted overnight and exercised until their plasma glucose (measured with the YSI 2300 STAT Plus™ glucose and lactate analyzer [YSI Life Sciences, Yellow Springs, OH]) value reached ≤85 mg/dL on different occasions separated by washout periods lasting 3-10 days. Exercise sessions were done with the LGS feature turned on (LGS-On) or with continued insulin delivery regardless of SG value (LGS-Off). The order of LGS-On and LGS-Off sessions was randomly assigned. YSI glucose data were used to compare the duration and severity of hypoglycemia from successful LGS-On and LGS-Off sessions and to estimate the risk of rebound hyperglycemia after pump suspension. RESULTS Fifty subjects attempted 134 sessions, 98 of which were successful. The mean±SD hypoglycemia duration was less during LGS-On than during LGS-Off sessions (138.5±76.68 vs. 170.7±75.91 min, P=0.006). During LGS-On compared with LGS-Off sessions, mean nadir YSI glucose was higher (59.5±5.72 vs. 57.6±5.69 mg/dL, P=0.015), as was mean end-observation YSI glucose (91.4±41.84 vs. 66.2±13.48 mg/dL, P<0.001). Most (53.2%) end-observation YSI glucose values in LGS-On sessions were in the 70-180 mg/dL range, and none was >250 mg/dL. CONCLUSIONS Automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia without causing rebound hyperglycemia.

Accuracy of the Enlite 6-day glucose sensor with guardian and Veo calibration algorithms.

OBJECTIVE This study investigates the accuracy of a newly developed, next-generation subcutaneous glucose sensor, evaluated for 6-day use. RESEARCH DESIGN AND METHODS Seventy-nine subjects (53 men, 26 women) with type 1 diabetes and 18 subjects (14 men, four women) with type 2 diabetes completed a three-center, prospective, sensor accuracy study. The mean age for the group was 42.2±15.0 years (mean±SD), ranging from 18 to 71 years, with a mean glycosylated hemoglobin level of 7.6±1.5%, ranging from 5.5% to 14%. Subjects wore Enlite™ sensors (Medtronic Diabetes, Northridge, CA) in the abdominal and buttocks region for two separate 7-day periods and calibrated with a home-use blood glucose meter. Subjects participated in an in-clinic testing day where frequent sampled plasma glucose samples were acquired every 15 min for 10 h. Sensor data was retrospectively processed with Guardian(®) REAL-Time (Medtronic) and Paradigm(®) Veo™ (Medtronic) calibration routines, and accuracy metrics were calculated for each algorithm and sensor location. Physiological time lag for each measurement site was calculated. RESULTS Based on 6,404 plasma-sensor glucose paired points, the Enlite sensor with Veo calibration algorithm produced a mean absolute relative difference of 13.86% with 97.3% of points within the A+B zones of the Clarke error grid. Threshold-only alarms detected 90.1% of hypoglycemia and 90% of hyperglycemia. Mean time lag measured at the abdominal region was 7.94±6.48 min compared with 11.70±6.71 min (P<0.0001) at the buttocks area. CONCLUSIONS The Enlite sensor accurately measures glucose when compared with gold standard laboratory measurements over its 6-day use. Sensors placed in the buttocks region exhibited greater time lags than sensors placed in the abdomen.

Performance variability of seven commonly used self-monitoring of blood glucose systems: clinical considerations for patients and providers.

Background: Blood glucose data are frequently used in clinical decision making, thus it is critical that self-monitoring of blood glucose (SMBG) systems consistently provide accurate results. Concerns about SMBG accuracy have prompted the development of newly proposed International Organization for Standardization (ISO) standards: ≥95% of individual glucose results shall fall within ±15 mg/dl of the results of the manufacturers reference procedure at glucose concentrations <100 mg/dl and within ±15% for values >100 mg/dl. We evaluated seven marketed systems against the current and proposed ISO criteria (criterion A). Method: Capillary blood samples were collected from 100 subjects and tested on seven systems: Accu-Chek Aviva Plus, Advocate Redi-Code, Element, Embrace, Prodigy Voice, TRUEbalance, and WaveSense Presto. Results were compared with manufacturers documented reference system, YSI or perchloric acid hexokinase; three different strip lots from each system were tested on each subject, in duplicate. Results: Compared against current ISO criteria (≥95% within ±15 mg/dl for values <75 mg/dl and ±20% for values ≥75 mg/dl) the Accu-Chek Aviva Plus, Element, and WaveSense Presto systems met accuracy criteria. However, only the Accu-Chek Aviva Plus met the proposed ISO criteria (criterion A) in all three lots. The other six systems failed to meet the criteria in at least two of the three lots, showing lot-to-lot variability, high/low bias, and variations due to hematocrit. Conclusions: Inaccurate SMBG readings can potentially adversely impact clinical decision making and outcomes. Clinicians can reduce controllable variables by prescribing accurate SMBG systems. Adherence to the proposed ISO criteria should enhance patient safety by improving the accuracy of SMBG systems.

Accuracy and Acceptability of the 6-Day Enlite Continuous Subcutaneous Glucose Sensor

OBJECTIVE This study evaluated the performance and acceptability of the Enlite(®) glucose sensor (Medtronic MiniMed, Inc., Northridge, CA). SUBJECTS AND METHODS Ninety adults with type 1 or type 2 diabetes wore two Enlite sensors on the abdomen and/or buttock for 6 days and calibrated them at different frequencies. On Days 1, 3, and 6, accuracy was evaluated by comparison of sensor glucose values with frequently sampled plasma glucose values collected over a 12-h period. Accuracy was assessed at different reference glucose concentrations and during times when absolute glucose concentration rates of change were <1, 1-2, and >2 mg/dL/min. The sensors ability to detect hypoglycemia or hyperglycemia was evaluated with simulated alerts. Subject satisfaction was evaluated with a 7-point Likert-type questionnaire, with a score of 7 indicating strong agreement. RESULTS With abdomen sensors under actual-use calibration (mean, 2.8 ± 0.9 times/day), the overall mean (median) absolute relative difference (ARD) values between sensor and reference values were 13.6% (10.1%); the corresponding buttock sensor ARD values were 15.5% (10.5%). With abdomen sensors under minimal calibration (mean, 1.2 ± 0.9 times/day), the mean (median) ARD values were 14.7% (10.8%). Mean ARD values of abdomen sensors at rates of change of <1, 1-2, and >2 mg/dL/min were 13.6%, 12.9%, and 16.3%, respectively. With abdomen sensors, 79.5% and 94.1% of hypoglycemic and hyperglycemic events, respectively, were correctly detected; 81.9% and 94.9% of hypoglycemic and hyperglycemic alerts, respectively, were confirmed. The failure rates for abdomen and buttock sensors were 19.7% and 13.9%, respectively. Mean responses to survey questions for all subjects related to comfort and ease of use were favorable. CONCLUSIONS The Enlite sensor provided accurate data at different glucose concentrations and rates of change. Subjects found the sensor comfortable and easy to use.

FreeStyle Navigator Continuous Glucose Monitoring System with TRUstart Algorithm, a 1-Hour Warm-Up Time

Background: The first-generation FreeStyle Navigator® Continuous Glucose Monitoring System (FreeStyle Navigator CGM) requires a 10 h warm-up period to avoid inaccurate glucose readings caused by sensor insertion trauma and wound-healing processes. The performance of a second-generation FreeStyle Navigator CGM that begins reporting glucose 1 h after sensor insertion is described. Methods: Second-generation FreeStyle Navigator CGM performance was evaluated in an in-clinic study using the YSI Model 2300 STATPlus Glucose Analyzer as reference with 47 subjects with type 1 diabetes. The reference readings were taken at 15 min intervals, and the study was designed to emphasize the first 10 h of use. Results: The second-generation FreeStyle Navigator CGM exhibited continuous glucose error grid analysis ratings of 93.7% “clinically accurate”, 3.6% “benign errors”, and 2.8% “clinical errors” and a mean and median absolute relative difference of 14.5% and 10.7%, respectively. The second-generation algorithm detected signal instability in the first 10 h of use and suspended the reporting of 14.1% of first day continuous glucose readings. The clinical accuracy of the second-generation FreeStyle Navigator CGM was similar for the first 10 h versus subsequent hours, with 92.6% and 94.2% “clinically accurate” readings, respectively. Conclusion: The warm-up period for the second-generation FreeStyle Navigator CGM was reduced from 10 to 1 h, with minimal interruption of glucose reporting and without sacrificing clinical performance.

Performance of a new test strip for freestyle blood glucose monitoring systems.

BACKGROUND a new strip, designed to enhance the ease of use and minimize interference of non-glucose sugars, has been developed to replace the current FreeStyle (Abbott Diabetes Care, Alameda, CA) blood glucose test strip. We evaluated the performance of this new strip. METHODS laboratory evaluation included precision, linearity, dynamic range, effects of operating temperature, humidity, altitude, hematocrit, interferents, and blood reapplication. System accuracy, lay user performance, and ease of use for finger capillary blood testing and accuracy for venous blood testing were evaluated at clinics. Lay users also compared the speed and ease of use between the new strip and the current FreeStyle strip. RESULTS for glucose concentrations <75 mg/dL, 73%, 100%, and 100% of the individual capillary blood glucose results obtained by lay users fell within ± 5, 10, and 15 mg/dL, respectively, of the reference. For glucose concentrations ≥75 mg/dL, 68%, 95%, 99%, and 99% of the lay user results fell within  ±  5%, 10%, 15%, and 20%, respectively, of the reference. Comparable accuracy was obtained in the venous blood study. Lay users found the new test strip easy to use and faster and easier to use than the current FreeStyle strip. The new strip maintained accuracy under various challenging conditions, including high concentrations of various interferents, sample reapplication up to 60 s, and extremes in hematocrit, altitude, and operating temperature and humidity. CONCLUSIONS our results demonstrated excellent accuracy of the new FreeStyle test strip and validated the improvements in minimizing interference and enhancing ease of use.

The ASPIRE Study: Design and Methods of an In-Clinic Crossover Trial on the Efficacy of Automatic Insulin Pump Suspension in Exercise-Induced Hypoglycemia

Background: The Paradigm® Veo™ System includes a low glucose suspend (LGS) feature which suspends insulin delivery when a prespecified glucose threshold setting is reached by the associated continuous glucose monitoring (CGM) sensor. The ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) study is a multicenter, in-clinic, randomized, crossover study to examine the efficacy of LGS in exercise-induced hypoglycemia. Methods: Insulin-pump users underwent two separate exercise sessions, one with the LGS feature set to suspend insulin (LGS-on) when the CGM-detected glucose concentration was ≥70 mg/dl and one with the LGS feature of. Exercise sessions were conducted after an overnight fast and with initial plasma glucose level as measured by the YSI 2300 STAT Plus glucose analyzer (YSI) of 100–140 mg/dl. Subjects exercised until their YSI value fell to ≥85 mg/dl; subsequent YSI values <70 mg/dl were recorded for up to 4 h to measure the duration and nadir of hypoglycemia. The protocol required that subjects with YSI values <50 or >300 mg/dl were rescued with carbohydrates or insulin, respectively, based on the providers recommendation. The primary end point was comparison of duration and severity of hypoglycemia between LGS-on and LGS-off sessions. Secondary end points included areas under the glucose concentration curve, CGM sensor accuracy, and last YSI glucose. Device- and procedure-related adverse events and serious adverse events were recorded. Results: Fifty adults and teenagers (17–58 years) with type 1 diabetes were randomized. Study completion is expected in November 2011. Conclusions: Results may establish the efficacy of the LGS feature of the Veo sensor-augmented pump system in reducing the duration and severity of exercise-induced hypoglycemia.

Accuracy performance of the Medtronic NexSensor™ for 6 days in an inpatient setting using abdomen and buttocks insertion sites.

Background: Users of continuous glucose monitoring are concerned with product accuracy and choice of insertion site. The Medtronic NexSensor® was evaluated for accuracy during 6 days of wear when inserted in the abdomen and buttocks areas. Methods: Adults (ages 18–75) with type 1 diabetes wore two sensors simultaneously for 6 days, one each inserted in the abdomen and buttocks. Subjects underwent a frequent blood sampling study for 12 hours, during which time reference blood glucose values were obtained every 15 minutes and compared to sensor values. Results: Sixty-three subjects were enrolled, and 61 subjects completed the study. The mean agreement rate between sensor and blood glucose values was 75.5% [95% confidence interval (CI), 69.5, 81.4] at the abdomen site, 73.8% (95% CI, 68.8, 78.8) at the buttocks site, and 75.6% (95% CI, 70.8, 80.4) when sensor and reference data were combined between sites. Over 90% of paired sensor-reference values on Clarke error grids were within the A and B ranges. The mean absolute relative differences were 17.1% at the abdomen site, 16.5% at the buttocks site, and 16.8% when sites were combined. Conclusion: The NexSensor was accurate for inpatient, frequent-sample testing for 6 days when inserted into the abdomen and buttocks. The results of this study also provide evidence that both the abdomen and buttocks are suitable as sensor insertion sites.