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Diabetes. 2019 Aug 9. pii: db190229. doi: 10.2337/db19-0229. [Epub ahead of print]

Fibrotic Encapsulation is the Dominant Source of Continuous Glucose Monitor Delays.

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville TN Penn.McClatchey@Vanderbilt.edu.
2
Department of Chemistry, Vanderbilt University, Nashville TN.
3
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville TN.
4
Mouse Metabolic Phenotyping Center, Vanderbilt University, Nashville TN.
5
PhysioLogic Devices Inc, Alpine, CA.
6
Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville TN.

Abstract

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 seeks 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 following an intravenous glucose challenge. Dispersion of a fluorescent glucose analogue (2-NBDG) into the CGM micro-environment was observed in vivo using intravital microscopy. Tissue deposited on the sensor and non-implanted subcutaneous adipose tissue were then collected for histological analysis. The time to half-maximum CGM response in vitro was 35±2 seconds. In vivo, CGMs took 24±7 minutes to reach maximum current versus 2±1 minutes to maximum blood glucose (p=0.0017). 2-NBDG took 21±7 minutes to reach maximum fluorescence at the sensor, vs 6±6 minutes 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.

PMID:
31399432
DOI:
10.2337/db19-0229

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