Purpose: To demonstrate that ''reverse iontophoresis'' can be used to
noninvasively obtain information about systemic glucose levels in vivo
in humans. Methods. The passage of current across the skin in vivo dr
ives ions into the tissue, from the electrode chambers positioned on t
he skin surface, and simultaneously pulls ions from the body in the op
posite direction. Because of the net negative charge on the skin, unde
r normal conditions, the membrane is permselective to cations, and a p
otential gradient also results, therefore, in electroosmotic convectio
n of Solvent in the direction of counterion flow (i.e., from anode to
cathode). Thus, it is also possible to enhance the transport of polar,
yet uncharged, species using iontophoresis: In an earlier study, the
in vitro extraction of glucose, by ''reverse iontophoresis'' was estab
lished, and extension of the approach to an in vivo model was indicate
d. The idea has therefore been further explored in vivo in humans. Res
ults. Using small, simple, prototypical electrode chambers, attached t
o the ventral forearm surface, direct current iontophoresis at 0.25 mA
/cm(2) for periods of up to 1 hour, and a sensitive analytical procedu
re to measure the quantities of glucose extracted, it has been shown t
hat iontophoretic sampling of glucose is feasible. However, the shorte
r periods (15 minutes or less) of extraction considered yield results
which are ''contaminated'' (it is believed) by glucose that is a produ
ct of lipid metabolism within the skin. While this material is expecte
d to complicate the initial calibration of the approach, the problem i
s effectively resolved within one hour, by which time the glucose arri
ving in the electrode chambers on the skin surface is expected to dire
ctly reflect the subcutaneous tissue concentration. Conclusions. Based
upon these initial observations, further investigation can now be dir
ected towards optimization of electroosmotic flow and sampling time, i
mproved reproducibility and the development of a practical assay metho
dology.