Noninvasive Glucose Monitoring by Reverse Iontophoresis in Vivo: Application of the Internal Standard Concept

Abstract

Abstract Background: The GlucoWatch® Biographer uses reverse iontophoresis to extract glucose across the skin to monitor glycemia in diabetes. The invasive daily calibration with a conventional “fingerstick” has been perceived as a disadvantage. We used an “internal standard” to render the approach completely noninvasive. Methods: The simultaneous extraction of glucose and sodium by reverse iontophoresis was performed on human volunteers over 5 h, and blood glucose was measured in the conventional manner at each collection interval. These data were used for each volunteer to calculate an extraction constant (K), which equals the ratio of the extracted fluxes (JGlucose/JNa+) normalized by the corresponding ratio of the concentrations in the blood ([Glucose]/[Na+]). The values of K were compared between and within volunteers. Results: The iontophoretically extracted glucose flux reflected the glucose concentration profiles in the blood, and sodium extraction remained essentially constant, consistent with the fact that its systemic concentration does not vary significantly. A constant value of K was established for two thirds of the study population. However, the efficiency of glucose extraction varied seasonally, whereas the reverse iontophoresis of Na+ did not; i.e., variation in K became apparent. Conclusions: Use of the sodium ion as an internal standard could refine the determination of glycemia by reverse iontophoresis without requiring calibration with a blood sample.