Microdialysis of Glucose in Subcutaneous Adipose Tissue up to 3 Weeks in Healthy Volunteers

Abstract

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 μl/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 μ/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 μ/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.