Abstract
Objective: Continuous glucose monitor (CGM) measured glucose lags blood glucose by several minutes, and this delay is usually attributed to the latency of interstitial fluid. However, independent findings suggest that interstitial glucose dispersion is near-immediate. This study seeks to determine the physiological locus of CGM latency. Methods: Current was measured at 1 Hz in Dexcom G4 CGMs using a CHI 1440 potentiostat. CGMs were exposed to varying glucose levels in vitro to define sensor kinetics. Next, CGMs were implanted in mice, and sensor vs. blood glucose responses were measured following an intravenous glucose challenge. Finally, dispersion of a fluorescent glucose analogue (2-NBDG) into the CGM micro-environment was observed in vivo using intravital microscopy. Tissue deposited on sensors and non-CGM implanted subcutaneous fat were then collected for histological analysis. Results: The CGM time constant in vitro was 51±3 seconds. In vivo, CGMs took 24±7 minutes to reach a local maximum in maximum current following intravenous injection of glucose. 2-NBDG took 21±7 minutes to reach maximum fluorescence near the sensor, vs. 6±6 minutes in subcutaneous fat (p=0.0011). Collagen was increased in sensor deposits relative to non-CGM implanted subcutaneous fat (p=0.0018), and collagen content was correlated with 2-NBDG latency (R=0.96, p=0.0004). Conclusions: Interstitial glucose responds to changes in blood glucose within seconds, whereas the glucose levels seen by a CGM are delayed by several minutes due to fibrous encapsulation. A CGM that avoids encapsulation could approximate real-time blood glucose measurements. Additionally, these data raise the possibility that fibrosis underlies insulin resistance by creating a biophysical impediment to the interstitial dispersion of glucose. Disclosure P.M. McClatchey: None. E.S. McClain: None. I.M. Williams: None. J.M. Gregory: Consultant; Self; InClinica. D. Cliffel: None. D. Wasserman: None. Funding National Institutes of Health (DK059637, DK054902, DK050277, T32DK101003, F32DK120104); American Heart Association
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