Noise contribution to the correlation between temperature-induced localized reflectance of diabetic skin and blood glucose.

We used the effect of temperature on the localized reflectance of human skin to assess the role of noise sources on the correlation between temperature-induced fractional change in optical density of human skin (DeltaOD(T)) and blood glucose concentration [BG]. Two temperature-controlled optical probes at 30 degrees C contacted the skin, one was then cooled by -10 degrees C; the other was heated by +10 degrees C. DeltaOD(T) upon cooling or heating was correlated with capillary [BG] of diabetic volunteers over a period of three days. Calibration models in the first two days were used to predict [BG] in the third day. We examined the conditions where the correlation coefficient (R2) for predicting [BG] in a third day ranked higher than R2 values resulting from fitting permutations of randomized [BG] to the same DeltaOD(T) values. It was possible to establish a four-term linear regression correlation between DeltaOD(T) upon cooling and [BG] with a correlation coefficient higher than that of an established noise threshold in diabetic patients that were mostly females with less than 20 years of diabetes duration. The ability to predict [BG] values with a correlation coefficient above biological and body-interface noise varied between the cases of cooling and heating.

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.

Near-infrared thermo-optical response of the localized reflectance of intact diabetic and nondiabetic human skin.

We observed a difference in the thermal response of localized reflectance signal of human skin between type 2 diabetics and nondiabetics. We investigated the use of this thermo-optical behavior as the basis for a noninvasive method for the determination of the diabetic status of a subject. We used a two-site temperature differential method, which is predicated upon the measurement of localized reflectance from two areas on the surface of the skin. Each of these areas is subjected to a different thermal perturbation. The response of localized reflectance to temperature perturbation was measured and used in a classification algorithm. We used a discriminant function to classify subjects as diabetic or nondiabetic. In a prediction set of twenty-four noninvasive tests collected from six diabetic and six nondiabetic subjects, the sensitivity ranged between 73 and 100%, and the specificity ranged between 75 and 100%, depending on the thermal conditions and the probe-skin contact time. The difference in the thermo-optical response of the skin of the two groups is explained in terms of a difference in the response of cutaneous microcirculation, which is manifested as a difference in the near-infrared light absorption. Another factor is the difference in the temperature response of the scattering coefficient between the two groups, which may be caused by cutaneous structural differences induced by nonenzymatic glycation of skin protein fibers, and possibly by the difference in blood cell aggregation.

Monitoring blood glucose changes in cutaneous tissue by temperature-modulated localized reflectance measurements.

BACKGROUND: Most proposed noninvasive methods for glucose measurements do not consider the physiologic response of the body to changes in glucose concentration. Rather than consider the body as an inert matrix for the purpose of glucose measurement, we exploited the possibility that noninvasive measurements of glucose can be approached by investigating their effects on the skin's thermo-optical response. METHODS: Glucose concentrations in humans were correlated with temperature-modulated localized reflectance signals at wavelengths between 590 and 935 nm, which do not correspond to any near-infrared glucose absorption wavelengths. Optical signal was collected while skin temperature was modulated between 22 and 38 degrees C over 2 h to generate a periodic set of cutaneous vasoconstricting and vasodilating events, as well as a periodic change in skin light scattering. The method was tested in a series of modified meal tolerance tests involving carbohydrate-rich meals and no-meal or high-protein/no-carbohydrate meals. RESULTS: The optical data correlated with glucose values. Changes in glucose concentrations resulting from a carbohydrate-rich meal were predicted with a model based on a carbohydrate-meal calibration run. For diabetic individuals, glucose concentrations were predicted with a standard error of prediction <1.5 mmol/L and a prediction correlation coefficient 0.73 in 80% of the cases. There were run-to-run differences in predicted glucose concentrations. Non-carbohydrate meals showed a high degree of scatter when predicted by a carbohydrate meal calibration model. CONCLUSIONS: Blood glucose concentrations alter thermally modulated optical signals, presumably through physiologic and physical effects. Temperature changes drive cutaneous vascular and refractive index responses in a way that mimics the effect of changes in glucose concentration. Run-to-run differences are attributable to site-to-site structural differences.

Temperature modulation of the visible and near infrared absorption and scattering coefficients of human skin.

We determine temperature effect on the absorption and reduced scattering coefficients (mu(a) and mu(s)(')) of human forearm skin. Optical and thermal simulation data suggest that mu( a) and mu(s)(') are determined within a temperature-controlled depth of approximately 2 mm. Cutaneous mu(s)(') change linearly with temperature. Change in mu(a) was complex and irreversible above body normal temperatures. Light penetration depth (delta) in skin increased on cooling, with considerable person-to-person variations. We attribute the effect of temperature on mu(s)(') to change in refractive index mismatch, and its effect on mu(a) to perfusion changes. The reversible temperature effect on mu (s)(' ) was maintained during more than 90 min. contact between skin and the measuring probe, where temperature was modulated between 38 and 22 degrees C for multiple cycles While temperature modulated mu(s)(' ) instantaneously and reversibly, mu(a) exhibited slower response time and consistent drift. There was a statistically significant upward drift in mu(a) and a mostly downward drift in mu( s)(') over the contact period. The drift in temperature-induced fractional change in mu(s)(') was less statistically significant than the drift in mu(s)('). Deltamu( s)(') values determined under temperature modulation conditions may have less nonspecific drift than mu(s)(') which may have significance for noninvasive determination of analytes in human tissue.