Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation Impact on Sensor Accuracy

Diabetes Technol Ther. 2018 Apr;20(4):296-302. doi: 10.1089/dia.2017.0321. Epub 2018 Feb 22.

Abstract

Background: Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance.

Methods: Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%.

Results: Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm2; P < 0.05).

Conclusion: The accumulation of macrophages at the sensor-tissue interface is related with decrease in accuracy of the glucose measure.

Keywords: Foreign body response; Glucose sensors; Macrophages; Sensor accuracy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biosensing Techniques
  • Blood Glucose / metabolism*
  • Blood Glucose Self-Monitoring / instrumentation*
  • Female
  • Foreign-Body Reaction / etiology
  • Foreign-Body Reaction / metabolism*
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism
  • Insulin Infusion Systems / adverse effects
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Obesity / metabolism
  • Subcutaneous Tissue / metabolism*

Substances

  • Blood Glucose