A Novel Approach to Mitigating the Physiological Lag Between Blood and Interstitial Fluid Glucose Measurements

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Abstract
Background: Lag between blood and interstitial fluid (ISF) glucose levels can contribute significantly to accuracy error in current and anticipated continuous glucose monitoring systems. Mitigating this physiological lag can be an important and useful means for improving the accuracy, and hence the clinical utility, of continuous glucose monitors. Methods: In a test of 22 subjects with diabetes in which a glucose excursion was induced through oral ingestion of a glucose load, glucose levels in finger blood and forearm dermal ISF were monitored over a 5–6-h period. ISF was sampled from two types of sites: sites at which local blood perfusion was elevated through modulated pressure application (test ISF), and control sites at which no perfusion elevation technique was employed (control ISF). Results: Average lag times (mean ± SD values) between the two ISF samples and finger capillary blood glucose were determined to be 38.3 ± 11.5 and 2.5 ± 6.6 min, respectively, for the control and test ISF samples. Modulated pressure application mitigated the ISF physiological error by an average of 95% in this test. Conclusions: The methodology presented here of using a pressure modulation technique to create an elevation in blood flow holds promise for significantly mitigating one of the most significant components of accuracy error for continuous monitoring systems.