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.

Figure 1.

A two-compartment model of the plasma–ISF glucose relationship.

Figure 2.

A theoretical ISF glucose response to a plasma glucose step function.

Figure 3.

In vitro reproduction of a hypoglycemic glucose profile processed by the CGMS.

Figure 4.

In vitro reproduction of a hypoglycemic glucose profile processed by the Guardian RT.

Figure 5.

Typical fast meal response when processed by the CGMS.

Figure 6.

Typical fast meal response when processed by the Guardian RT.