Determination of time delay between blood and interstitial adipose tissue glucose concentration change by microdialysis in healthy volunteers.

For the development and use of subcutaneous glucose sensors it is important to know the time lag between changes in blood glucose and subcutaneous interstitial glucose concentration. To determine the time lag we inserted a microdialysis probe into the abdominal subcutaneous adipose tissue of healthy volunteers (n = 19) and performed oral glucose tolerance tests (n = 39) over a 7-day period. After correction for the microdialysis system time lag, we compared the change in dialysate glucose concentration with the capillary blood glucose concentration. We found no significant delay time between a change in capillary blood glucose concentration and subcutaneous interstitial fluid glucose concentration using the Mann-Whitney test. The substantial interindividual variation of glucose recovery and the changing recovery in time makes it difficult to draw unambiguous conclusions about the exact physiological time lag. Based on the present experimental findings and theoretical calculations of glucose transport in adipose tissue, the physiological lag time is short and negligible compared to the system delay time of a glucose sensor.

Microdialysis measurement of glucose in subcutaneous adipose tissue up to three weeks in type 1 diabetic patients.

BACKGROUND: Microdialysis of subcutaneous adipose tissue may provide an opportunity to monitor glucose continuously, when the device is connected to an extracorporal glucose sensor. We assessed whether our microdialysis probes are capable of measuring adipose tissue glucose over a prolonged period in Type 1 diabetic patients. Furthermore, the relationship between abdominal skinfold thickness and glucose recovery and the effect of spontaneous glucose excursions on its recovery were evaluated. METHODS: Microdialysis probes were pairwise inserted subcutaneously into the abdominal fat and remained in situ for 3 weeks in eight Type 1 diabetic patients. At days 1, 3, 4, 8, 11, 16, and 18 of probe retention, glucose, as measured by microdialysis, was compared to capillary blood glucose concentrations during a 4 h period. The recovery of glucose obtained by microdialysis was expressed as a percentage of the capillary blood glucose concentration. RESULTS: Eleven of the 16 inserted probes (69%) were evaluable during the complete study. Recovery of glucose was lower at day 1 and 3 (51+/-23% and 56+/-18%, respectively, mean+/-S.D.) compared to values found afterwards (67+/-19%, 72+/-13%, 76+/-14%, 71+/-16%, and 76+/-18%, for day 4, 8, 11, 16, and 18, respectively, for all P<0.05 vs. day 1 and 3). Skinfold thickness was inversely related to the overall 3 week glucose recovery (r=-0.76; P<0.03). Recovery was similar over a wide range of capillary blood glucose concentrations. CONCLUSIONS: Prolonged in vivo retention of microdialysis probes improves the recovery and lowers the variability of adipose tissue-sampled glucose in Type 1 diabetic patients. These findings show that microdialysis-based glucose measurements offer an opportunity for prolonged glucose monitoring.

Effects of glucose and insulin levels on adipose tissue glucose measurement by microdialysis probes retained for three weeks in Type 1 diabetic patients.

BACKGROUND: To evaluate the effects of acute hyperglycaemia and hyperinsulinaemia on adipose tissue glucose measurements by microdialysis probes inserted for a 3-week period. METHODS: Microdialysis probes were implanted pairwise in abdominal adipose tissue in seven Type 1 diabetic patients and remained in situ during the complete study. Stepped hyperglycaemic hyperinsulinaemic clamps were performed at weekly intervals at which the probes were prepared for microdialysis. Adipose tissue glucose by microdialysis was compared to venous and capillary blood glucose concentrations. RESULTS: The mean time after which the acute rise in blood glucose was first detected was 11.3 min, which corresponds to the system delay of the microdialysis probe. The increase of the glucose concentration in dialysate was completed during the following 16 min. Hyperglycaemia and hyperinsulinaemia did not influence recovery compared to venous blood glucose concentrations, while recovery values compared to capillary blood glucose levels increased slightly under hyperinsulinaemic conditions (P<0.01). CONCLUSIONS: In Type 1 diabetic patients, recovery of glucose in adipose tissue compared to venous and capillary blood does not decrease during acute hyperglycaemia and hyperinsulinaemia. Although there is still a relevant time-delay to monitor a rise in blood glucose, these results show that microdialysis may offer an opportunity for future glucose monitoring over a prolonged time-period.

Microdialysis of glucose in subcutaneous adipose tissue up to 3 weeks in healthy volunteers.

OBJECTIVE: To measure possible changes in dialysate glucose concentrations over time, to validate the diffusional model for glucose transport from tissue to the probe, and to evaluate the actual glucose concentration in adipose tissue. RESEARCH DESIGN AND METHODS: Glucose concentrations in the subcutaneous adipose tissue of five healthy subjects (age 25 +/- 2.7 years, BMI 23.2 +/- 2.3 kg/m2 [mean +/- SD]) were measured by the microdialysis technique and compared with blood glucose. We applied microdialysis probes with hollow fibers of various membrane length (10-35 mm), used eight perfusion flow rates (0.5-20 microl/min), and perfused four glucose solutions (0.0, 2.8, 8.3, 11.1 mmol/l). RESULTS: After implantation, a substantial decrease in glucose recovery to the lowest value of 26 +/- 10% of the final plateau value was noted during the first few hours (n = 4). Recovery increased and stabilized after 5-9 days at 84.0 +/- 7.4% of capillary blood glucose when a flow rate of 0.5 microl/min was applied. According to the zero net-flux method, the glucose concentration in equilibrium, Cequi, with the surrounding tissue can be obtained. This concentration also decreases; however, 1 h after recovery, Cequi increases again over 1 or 2 days to a stable value that is not significantly different from the measured capillary blood glucose (P < 0.05). Using various perfusion flow rates and probes (membrane length 10-35 mm), it is shown that diffusion is the rate-limiting process for glucose transport through tissue. CONCLUSIONS: Insertion of the microdialysis probes causes damage to the adipose cells and the vascular bed around the probe. Glucose recovery decreases because of a lower blood supply. In 5-9 days, glucose recovery increases; apparently, this time is needed to repair the microstructure of tissue around the probe. After stabilization of the recovery, no loss of probe permeability, which is due to biocompatibility problems, was seen. The change during the 2 days in equilibrium concentration is probably caused by an inflammation reaction that consumes glucose around the probe. The individual increase in recovery during the 1st days after probe insertion until a stable plateau value is reached (flow rate >0 microl/min) is complicated for short-term clinical glucose measurements in adipose tissue. After stabilization, the mean equilibrium concentration of all subjects was equal to the mean capillary blood glucose concentration. Therefore, we conclude that capillary blood glucose concentration probably is the driving force for diffusion through the capillary wall into the probe and is not some interstitial concentration.