Venous, Arterialized-Venous, or Capillary Glucose Reference Measurements for the Accuracy Assessment of a Continuous Glucose Monitoring System

Background: Different reference methods are used for the accuracy assessment of continuous glucose monitoring (CGM) systems. The effect of using venous, arterialized-venous, or capillary reference measurements on CGM accuracy is unclear. Methods: We evaluated 21 individuals with type 1 diabetes using a capillary calibrated CGM system. Venous or arterialized-venous reference glucose samples were taken every 15min at two separate visits and assessed per YSI 2300 STAT Plus. Arterialization was achieved by heated-hand technique. Capillary samples were collected hourly during the venous reference visit. The investigation sequence (venous or arterialized-venous) was randomized. Effectiveness of arterialization was measured by comparing free venous oxygen pressure (PO2) of both visit days. Primary endpoint was the median absolute relative difference (ARD). Results: Median ARD using arterialized-venous reference samples was not different from venous samples (point estimated difference 0.52%, P=0.181). When comparing the three reference methods, median ARD was also not different over the full glycemic range (venous 9.0% [n=681], arterialized-venous 8.3% [n=684], and capillary 8.1% [n=205], P=0.216), nor over the separate glucose ranges. Arterialization was successful (PO2 venous 5.4kPa vs. arterialized-venous 8.9kPa, P<0.001). Arterialized-venous glucose was significantly higher than venous glucose and numerically higher than capillary glucose (arterialized-venous 142mg/dL vs. venous 129mg/dL [P<0.001] and vs. capillary 134mg/dL [P=0.231]). Inconvenience related to arterialization included transient mild edema and redness of the hand in 4 out of 21 (19%) patients. Conclusions: The use of venous, arterialized-venous, or capillary reference measurements did not significantly impact CGM accuracy. Venous reference seems preferable due to its ease of operation.