Fibrotic Encapsulation Is the Dominant Source of Continuous Glucose Monitor Delays

Abstract

Continuous glucose monitor (CGM) readings are delayed relative to blood glucose, and this delay is usually attributed to the latency of interstitial glucose levels. However, CGM-independent data suggest rapid equilibration of interstitial glucose. This study sought to determine the loci of CGM delays. Electrical current was measured directly from CGM electrodes to define sensor kinetics in the absence of smoothing algorithms. CGMs were implanted in mice, and sensor versus blood glucose responses were measured after an intravenous glucose challenge. Dispersion of a fluorescent glucose analog (2-NBDG) into the CGM microenvironment was observed in vivo using intravital microscopy. Tissue deposited on the sensor and nonimplanted subcutaneous adipose tissue was then collected for histological analysis. The time to half-maximum CGM response in vitro was 35 ± 2 s. In vivo, CGMs took 24 ± 7 min to reach maximum current versus 2 ± 1 min to maximum blood glucose ( P = 0.0017). 2-NBDG took 21 ± 7 min to reach maximum fluorescence at the sensor versus 6 ± 6 min in adipose tissue ( P = 0.0011). Collagen content was closely correlated with 2-NBDG latency ( R = 0.96, P = 0.0004). Diffusion of glucose into the tissue deposited on a CGM is substantially delayed relative to interstitial fluid. A CGM that resists fibrous encapsulation would better approximate real-time deviations in blood glucose.

Monitoring with In Vivo Electrochemical Sensors: Navigating the Complexities of Blood and Tissue Reactivity

“…Studies of beyond a week confirm such capsular development and its effect on glucose exchanges, in one example leading to a 24 min. response lag following intravenous glucose [114]. The result was also consistent with the arrival time of injected fluorescent glucose analogue.…”

Continuous glucose monitoring for diabetes: potential pitfalls for the general physician

“…Interstitial glucose readings can lag behind capillary blood glucose readings by as much as 20 minutes. 4 Our case also suggests that local site inflammation can affect the accuracy of interstitial glucose readings. The FreeStyle Libre manufacturer advises that if readings on the Libre do not match the user's symptoms or expectations, to use a fingerpick blood glucose monitor to make treatment decisions.…”

“…Additionally, inflammation in tissue adjacent to a CGM device can potentially delay and reduce the diffusion of glucose to the sensor and hence its ability to accurately read glucose level in the interstitial fluid. 4 Measurement of interstitial glucose to monitor diabetes, while convenient and comfortable, is not perfect and blood glucose monitoring is still required in certain circumstances. Interstitial glucose readings can lag behind capillary blood glucose readings by as much as 20 minutes.…”

Impaction of a continuous glucose monitoring sensor

“…After 3 days of insertion into the subcutaneous layer, the sensor wire undergoes a fibrotic process that provides fibrotic encapsulation, which isolates it from the normal tissue [ 5 ]. We initially guessed that tracing the area of inflammation would make it easier to find the wire.…”