OBJECTIVE- To compare the subcutaneous glucose sensor measurements wit
h two reference methods. Previous studies provide conflicting findings
about the real glucose concentrations in subcutaneous tissue. Some su
ggest substantially lower concentration, whereas others measure propor
tionally higher glucose concentrations compared with the blood compart
ment. Before these results can be taken seriously as an expression of
die real glucose concentration in the extracellular space, the measure
ments must be validated by an independent method. RESEARCH DESIGN AND
METHODS- We applied a microdialysis-based enzyme sensor to measure glu
cose concentration in subcutaneous tissue. We also developed two refer
ence methods: subcutaneous filtrate collection and an equilibration me
thod using ultrafiltration membranes to support the earlier findings.
We provided an anatomical model to explain the results. RESULTS - The
mean overall intercellular filtrate glucose concentration, sampled wit
h the filtrate collector and taken after a 6-h stabilization time, inc
luding die values during the glucose clamp period, was 46 +/- 9%. The
mean subcutaneous glucose concentration measured with the glucose sens
or, calibrated in vitro, was 44 +/- 8% of the mean venous blood glucos
e concentration. Mean overall intercellular equilibrate glucose concen
tration, i.e., the mean glucose concentration in the subcutaneous extr
acellular space, taken after a 4-h stabilization time, was 46 +/- 15%
of the mean venous blood glucose concentration. CONCLUSIONS - The clos
e agreement between the mean values of subcutaneous glucose concentrat
ions, obtained with three independent methods-filtration, equilibratio
n, and dialysis (sensor)-shows die real glucose concentration in subcu
taneous interstitial fluid is approximately 50% the blood glucose valu
e in normal humans. Our results clarify some of the conflicting eviden
ce presented in previous studies.