A model for transport of glucose in adipose tissue to a microdialysis probe.

A model is presented, describing diffusion of solutes (as glucose) through adipose tissue. The model is based on the well-known extraction equation for diffusion across capillary walls or across the membrane of microdialysis probes, but adapted for use in adipose tissue. Arguments are presented for a simple scheme in which the mean capillary concentration of a solute (i.e., glucose) is substituted for the interstitial fluid solute concentration in the extraction equation, as the driving force for diffusion of glucose from capillary to cell or from capillary to a microdialysis probe. The model is discussed by evaluating the results of previous studies by our group and others on the equilibrium concentration of glucose in a microdialysis probe, as well as the effect of insertion on recovery of glucose by the probe and the time it takes for glucose in adipose tissue to diffuse to the probe. The results of these studies are in good agreement with the predictions derived from the model: The equilibrium concentration of glucose in the microdialysis probe is equal to the capillary glucose concentration. Insertion effects can be explained by a lower glucose concentration around the probe because of inflammation (12-18 h) and by a slow increase in the number of functioning capillaries around the probe due to wound healing (4-6 days). Transport time of glucose from capillaries to a microdialysis probe is not more than a few seconds. Reported delay times in the literature are probably caused by an uneven distribution of blood glucose after a glucose challenge.

Continuous glucose monitoring: reliable measurements for up to 4 days with the SCGM1 system.

Continuous glucose monitoring allows patients with diabetes to check their metabolic status throughout the day, including rarely monitored time periods, such as postprandial and nocturnal periods. The performance of a prototype of the novel SCGM1 System (Roche Diagnostics GmbH, Mannheim, Germany) employing the microdialysis technique was evaluated. Forty-two patients with type 1 diabetes participated in the study [29 males/13 females, age 34 +/- 9 years, duration of diabetes 16 +/- 11 years, glycated hemoglobin 7.7 +/- 1.2% (mean +/- SD)]. Forty-seven experiments were performed at four different investigational sites. A microdialysis catheter was inserted into the subcutaneous tissue of the patient's abdominal wall. Glucose was extracted from the interstitial fluid, and glucose levels were determined and stored by the SCGM1 System continuously for the duration of the experiment. Capillary blood glucose was measured frequently (at least 10 times per day) and used for linear retrospective calibration. The patients were instructed to maintain their normal diet and insulin therapy. Thirty experiments (mean duration 103 +/- 18 h) were analyzed in detail. The mean deviation of the calibrated glucose sensor values from the capillary blood glucose values (expressed as percent predicted error sum of squares) was <12.5% in 25 and <20% for all of the 30 experiments analyzed. The percent median absolute difference between the calibrated values and the reference values was <10% in 28 experiments, with a median of 5.8% for all 30 experiments. The error grid analysis of all 30 experiments showed that 99.5% of all 1,195 pairs' values were in zones A and B with only 0.2% in zone C and 0.3% in zone D. Thus the microdialysis technique employed by the SCGM1 System allows precise and accurate continuous glucose monitoring over prolonged periods of time. It appears also that effective monitoring of acute metabolic deteriorations is possible.

Effects of microdialysis catheter insertion into the subcutaneous adipose tissue assessed by the SCGM1 system.

To monitor glucose in patients with diabetes continuously a microdialysis-based glucose sensor system (SCGM1 System, Roche Diagnostics GmbH, Mannheim, Germany) is under clinical development. This system allows monitoring of glucose levels in the subcutaneous interstitial fluid of patients with diabetes for a maximum duration of up to 120 h. The aim of the study was to determine the effect of microdialysis catheter insertion on the stability of the SCGM1 System glucose sensor signal. At four study sites, 47 experiments with the prototype of the novel SCGM1 System were performed in 42 patients with type 1 diabetes; two additional experiments were performed in two healthy volunteers. The microdialysis catheter was inserted in the subcutaneous adipose tissue of the patients in order to measure the glucose concentration in the interstitial fluid continuously. The catheter was perfused with a pump rate of 0.3 microL/min. For method comparison capillary blood glucose measurements were performed as reference values. In addition, the skinfold thickness was measured. Out of the total of 49 experiments 34 were usable. The average monitoring time in these experiments was 106.0 +/- 14.3 h (mean +/- SD). However, for this study the data from the first study day were evaluated in more detail. The analysis showed that during the first 12 h after catheter insertion the sensor signal increased 20% in comparison with the capillary blood glucose values (normalized calibration factor). This leads to a lower normalized calibration factor compared with the following study days. It remains stable in the time thereafter. The skinfold thickness showed no significant effect on the sensor signal. The observed increase in sensor signal in the first hours after insertion of the microdialysis catheter was probably due to a local trauma, which can induce an inflammation reaction. Thereafter, the signal registered by the SCGM1 System was stable and free of drift to the end of the experiment.