Non-invasive glucose measurement technologies: an update from 1999 to the dawn of the new millennium.

There are three main issues in non-invasive (NI) glucose measurements: namely, specificity, compartmentalization of glucose values, and calibration. There has been progress in the use of near-infrared and mid-infrared spectroscopy. Recently new glucose measurement methods have been developed, exploiting the effect of glucose on erythrocyte scattering, new photoacoustic phenomenon, optical coherence tomography, thermo-optical studies on human skin, Raman spectroscopy studies, fluorescence measurements, and use of photonic crystals. In addition to optical methods, in vivo electrical impedance results have been reported. Some of these methods measure intrinsic properties of glucose; others deal with its effect on tissue or blood properties. Recent studies on skin from individuals with diabetes and its response to stimuli, skin thermo-optical response, peripheral blood flow, and red blood cell rheology in diabetes shed new light on physical and physiological changes resulting from the disease that can affect NI glucose measurements. There have been advances in understanding compartmentalization of glucose values by targeting certain regions of human tissue. Calibration of NI measurements and devices is still an open question. More studies are needed to understand the specific glucose signals and signals that are due to the effect of glucose on blood and tissue properties. These studies should be performed under normal physiological conditions and in the presence of other co-morbidities.