Delays in Minimally Invasive Continuous Glucose Monitoring Devices: A Review of Current Technology

Abstract

Through the use of enzymatic sensors—inserted subcutaneously in the abdomen or ex vivo by means of microdialysis fluid extraction—real-time minimally invasive continuous glucose monitoring (CGM) devices estimate blood glucose by measuring a patient's interstitial fluid (ISF) glucose concentration. Signals acquired from the interstitial space are subsequently calibrated with capillary blood glucose samples, a method that has raised certain questions regarding the effects of physiological time lags and of the duration of processing delays built into these devices. The time delay between a blood glucose reading and the value displayed by a continuous glucose monitor consists of the sum of the time lag between ISF and plasma glucose, in addition to the inherent electrochemical sensor delay due to the reaction process and any front-end signal-processing delays required to produce smooth traces. Presented is a review of commercially available, minimally invasive continuous glucose monitors with manufacturer-reported device delays. The data acquisition process for the Medtronic MiniMed (Northridge, CA) continuous glucose monitoring system—CGMS® Gold—and the Guardian® RT monitor is described with associated delays incurred for each processing step. Filter responses for each algorithm are examined using in vitro hypoglycemic and hyperglycemic clamps, as well as with an analysis of fast glucose excursions from a typical meal response. Results demonstrate that the digital filters used by each algorithm do not cause adverse effects to fast physiologic glucose excursions, although nonphysiologic signal characteristics can produce greater delays.

Evaluation of the Performance of a Novel System for Continuous Glucose Monitoring

“…20,21 Such time delays are caused by two factors: (1) a physiological delay between changes in BG and interstitial glucose and (2) device-dependent delays in measurement. 20,22 In this evaluation, the MARD and the PARD were remarkably better during induced glucose fluctuations compared with available CGM systems. 6,16 This suggests a decreased device-dependent time delay, as the physiological delay is assumed to be constant/comparable among CGM systems.…”

Discrepancies Between Blood Glucose and Interstitial Glucose—Technological Artifacts or Physiology: Implications for Selection of the Appropriate Therapeutic Target

“…The reported time lag between glucose changes in both compartments is about 5 to 25 minutes. 4,6,[8][9][10] This range of time lag can be explained by the fact that the gradient in glucose increase in blood differs depending on the type and amount of carbohydrates in a given meal; that is, the increase in glycemia is steeper with a high glucose load and rapidly absorbable carbohydrates. Differences in prandial glucose profiles between blood and ISF most likely also depend on the glucose utilization rate in the given compartment: If the glycogen storage capacity in the liver is different in a given patient on different days, this might have an impact on how rapidly glucose is taken up by this organ and subsequently how rapidly ISF glucose levels decline.…”

“…6 The calibration of the ISF signal to BG by means of capillary BG measurements may have an impact on the maximal glucose levels recorded.…”

Accuracy of Subcutaneous Continuous Glucose Monitoring in Critically Ill Adults: Improved Sensor Performance with Enhanced Calibrations

“…19 Further improvements in accuracy may be achievable through the intravenous sampling route eliminating or significantly reducing the lag time of 6-15 min reported with subcutaneous sensors. 13,[20][21][22] Preliminary studies using the intravenous microdialysis technique have shown high accuracy (mean absolute relative deviation, 5.6%; data points in Clarke error grid Zone A, 97%). 23 Advantages of subcutaneous glucose monitoring compared with intravenous measurements include reduced invasiveness obviating the need for dedicated venous placement and a risk of contamination from dextrose or other medications that may interfere with glucose measurements.…”