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 ref-erence method (n ϭ 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 (ϽϮ1 mg ⅐ dl Ϫ1 ⅐ min Ϫ1 ), 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).

The accuracy of continuous interstitial fluid (ISF) glucose sensing is an essential component of current and emerging open- and closed-loop systems for type 1 diabetes. An important determinant of sensor accuracy is the physiological time lag of glucose transport from the vascular to the interstitial space. We performed the first direct measurement of this phenomenon to our knowledge in eight healthy subjects under an overnight fasted condition. Microdialysis catheters were inserted into the abdominal subcutaneous space. After intravenous bolus administrations of glucose tracers, timed samples of plasma and ISF were collected sequentially and analyzed for tracer enrichments. After accounting for catheter dead space and assay noise, the mean time lag of tracer appearance in the interstitial space was 5.3–6.2 min. We conclude that in the overnight fasted state in healthy adults, the physiological delay of glucose transport from the vascular to the interstitial space is 5–6 min. Physiological delay between blood glucose and ISF glucose, therefore, should not be an obstacle to sensor accuracy in overnight or fasting-state closed-loop systems of insulin delivery or open-loop therapy assessment for type 1 diabetes.

Recent advances in insulins, insulin pumps, continuous glucose-monitoring systems, and control algorithms have resulted in an acceleration of progress in the development of artificial pancreas devices. This review discusses progress in the development of external systems that are based on subcutaneous drug delivery and subcutaneous continuous glucose monitoring. There are two major system-level approaches to achieving closed-loop control of blood glucose in diabetic individuals. The unihormonal approach uses insulin to reduce blood glucose and relies on complex safety mitigation algorithms to reduce the risk of hypoglycemia. The bihormonal approach uses both insulin to lower blood glucose and glucagon to raise blood glucose, and also relies on complex algorithms to provide for safety of the user. There are several major strategies for the design of control algorithms and supervision control for application to the artificial pancreas: proportional-integral-derivative, model predictive control, fuzzy logic, and safety supervision designs. Advances in artificial pancreas research in the first decade of this century were based on the ongoing computer revolution and miniaturization of electronic technology. The advent of modern smartphones has created the ability to utilize smartphone technology as the engineering centerpiece of an artificial pancreas. With these advances, an artificial or bionic pancreas is within reach.

The premise of effective closed-loop insulin therapy for type 1 diabetes (T1D) relies on the accuracy of continuous interstitial fluid glucose sensing that represents the crucial afferent arm of such a system. An important determinant of sensor accuracy is the physiological time lag of glucose transport from the vascular to the interstitial space. The purpose of current studies was to determine the physiological time lag of glucose transport from the vascular to the abdominal subcutaneous interstitial space in T1D. Four microdialysis catheters were inserted into the abdominal subcutaneous space in 6 T1D subjects under overnight fasted conditions. Plasma glucose was maintained at 113.7 ± 6.3 mg/dl using a continuous intravenous insulin infusion. After sequential intravenous bolus administrations of glucose isotopes, timed plasma and interstitial fluid samples were collected chronologically and analyzed for tracer enrichments. We observed a median (range) time lag of tracer appearance (time to detection) into the interstitial space after intravenous bolus of 6.8 (4.8-9.8) minutes, with all participants having detectable values by 9.8 minutes. We conclude that in the overnight fasted state in T1D adults, the delay of glucose appearance from the vascular to the interstitial space is less than 10 minutes, thereby implying that this minimal physiological time lag should not be a major impediment to the development of an effective closed-loop control system for T1D.

Background: Use of continuous glucose monitoring (CGM) systems can improve glycemic control, but widespread adoption of CGM utilization has been limited, in part because of real and perceived problems with accuracy and reliability. This study compared accuracy and performance metrics for a new-generation CGM system with those of a previous-generation device. Subjects and Methods: Subjects were enrolled in a 7-day, open-label, multicenter pivotal study. Sensor readings were compared with venous YSI measurements (blood glucose analyzer from YSI Inc., Yellow Springs, OH) every 15 min (-5 min) during in-clinic visits. The aggregate and individual sensor accuracy and reliability of a new CGM system, the Dexcom Ò (San Diego, CA) G4Ô PLATINUM (DG4P), were compared with those of the previous CGM system, the Dexcom SEVEN Ò PLUS (DSP). Results: Both study design and subject characteristics were similar. The aggregate mean absolute relative difference (MARD) for DG4P was 13% compared with 16% for DSP (P < 0.0001), and 82% of DG4P readings were within -20 mg/dL (for YSI £ 80 mg/dL) or 20% of YSI values (for YSI > 80 mg/dL) compared with 76% for DSP (P < 0.001). Ninety percent of the DG4P sensors had an individual MARD £ 20% compared with only 76% of DSP sensors (P = 0.015). Half of DG4P sensors had a MARD less than 12.5% compared with 14% for the DSP sensors (P = 0.028). The mean absolute difference for biochemical hypoglycemia (YSI < 70 mg/dL) for DG4P was 11 mg/dL compared with 16 mg/dL for DSP (P < 0.001). Conclusions: The performance of DG4P was significantly improved compared with that of DSP, which may increase routine clinical use of CGM and improve patient outcomes.