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Publication
Fibrotic Encapsulation Is the Dominant Source of Continuous Glucose Monitor
Delays.
Authors McClatchey PM, McClain ES, Williams IM, Malabanan CM, James FD, Lord PC, Gregory
JM, Cliffel DE, Wasserman DH
Submitted By Submitted Externally on 1/14/2020
Status Published
Journal Diabetes
Year 2019
Date Published 10/1/2019
Volume : Pages 68 : 1892 - 1901
PubMed Reference 31399432
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.




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