CGM detects abnormalities in glycemic control in a manner heretofore impossible to obtain. However, our studies revealed sufficient incongruence between simultaneous laboratory blood glucose levels and interstitial fluid glucose (after calibrations) to question the fundamental assumption that interstitial fluid glucose and blood glucose could be made identical by resorting to algorithms based on concurrent blood glucose levels alone.

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.

Alternative methods for self-monitoring of blood glucose have been pursued by many researchers, largely in response to evidence gathered in several long-term studies of patients with diabetes mellitus. These studies suggest that long-term complications of the disease may be mitigated if the disease is intensively managed, a component of which is increased monitoring. Many of the alternative methods utilize interstitial fluid (ISF) as the diagnostic fluid, rather than finger blood. A time lag in the distribution of glucose from blood to the interstitium has been observed by many, with estimates of lag time varying from none to 45 min. Dermal ISF was sampled from diabetic subjects in two tests and compared to finger blood glucose. In the first test, data were collected over time in a manner that allowed a cross-correlation analysis to predict an average lag time. Information from this test was then used as input to a data collection format for a method comparison test of 691 patients with diabetes in which ISF data were collected immediately after the finger blood reference and 15 min after the reference. An average lag time of about 25 min was determined from the cross-correlation analysis, with the correlation error reduced by three-fourths within a 15-min lag time. In the method comparison test, the correlation coefficient between finger blood glucose and ISF glucose improved from 0.923 to 0.951, and the percentage of data in the A zone of the Clarke Error Grid rose from 80.2% to 90.6% for the ISF glucose data collected at no lag and 15-min lag, respectively. Dermal ISF glucose measurement might be a reasonable alternative to blood glucose measurement for patients routinely monitoring ambient glycemia, although more testing in the sensitive hypoglycemic range is needed to clarify what might happen in cases of rapidly changing glucose.

Background: Minimally invasive interstitial fluid (ISF) sampling and glucose measurement technologies were integrated into a hand-held device for diabetic glucose monitoring investigations. Methods: Conventional electrochemical test strip technology (Bayer Glucometer Elite®) was adapted to measure glucose in small (0.5–2.0 μL) samples of ISF. Test strip glucose measurements were performed on a commercial potentiostat and were compared to various reference glucose methodologies (YSI 2300 analyzer, microhexokinase procedure, Bayer Glucometer Elite). Characterizations of the integrated ISF sampling-glucose test strip design included accuracy and precision in various sample media (saline, ISF surrogates, diabetic ISF samples), sample volume dependence, test strip sterilization studies (electron beam, γ irradiation), and diabetic ISF sampling and glucose measurements. Results: Glucose measurements were free from significant media effects. Sample volume variations (0.6–3.2 μL) revealed only modest dependence of glucose measurement bias on sample volume (−1.5% per microliter). Sterilization treatments had only a minor impact on glucose response and test strip aging and no significant impact on interferent responses of the glucose test strips. Diabetic subject testing under minimum fasting conditions of at least 2 h with integrated ISF sampling and glucose measurement gave low ISF glucose measurement imprecision (CV, 4%) and mean glucose results that were indistinguishable from reference (microhexokinase) ISF glucose measurements and from capillary blood glucose measurements (Glucometer Elite). Conclusions: Conventional single-use, electrochemical glucose test strip and ISF collection technologies can be readily integrated to provide real-time ISF sampling and glucose measurements for diabetic monitoring applications.

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