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.

[1]  P A Oberg,et al.  Spatial and temporal variations in human skin blood flow. , 1983, International journal of microcirculation, clinical and experimental.

[2]  Mamoru Tamura,et al.  Noninvasive blood glucose monitoring by novel optical-fiber probe , 2002, SPIE BiOS.

[3]  E Gratton,et al.  Possible correlation between blood glucose concentration and the reduced scattering coefficient of tissues in the near infrared. , 1994, Optics letters.

[4]  I M Braverman,et al.  The Cutaneous Microcirculation: Ultrastructure and Microanatomical Organization , 1997, Microcirculation.

[5]  Airat K. Amerov,et al.  Method and device for noninvasive blood glucose measurement , 1999, Photonics West - Biomedical Optics.

[6]  O. Khalil,et al.  Spectroscopic and clinical aspects of noninvasive glucose measurements. , 1999, Clinical chemistry.

[7]  I. Gabriely,et al.  Transcutaneous glucose measurement using near-infrared spectroscopy during hypoglycemia. , 1999, Diabetes care.

[8]  M Essenpreis,et al.  The influence of glucose concentration upon the transport of light in tissue-simulating phantoms. , 1995, Physics in medicine and biology.

[9]  M Essenpreis,et al.  Effect of temperature on the optical properties of ex vivo human dermis and subdermis. , 1998, Physics in medicine and biology.

[10]  T. B. Blank,et al.  Noninvasive prediction of glucose by near-infrared diffuse reflectance spectroscopy. , 1999, Clinical chemistry.

[11]  H M Heise,et al.  Transcutaneous glucose measurements using near-infrared spectroscopy: validation of statistical calibration models. , 2000, Diabetes care.

[12]  Jody T. Bruulsema,et al.  Correlation between blood glucose concentration in diabetics and noninvasively measured tissue optical scattering coefficient. , 1997, Optics letters.

[13]  Thomas B. Blank,et al.  Clinical results from a noninvasive blood glucose monitor , 2002, SPIE BiOS.

[14]  C. Fischbacher,et al.  Enhancing calibration models for non-invasive near-infrared spectroscopical blood glucose determination , 1997 .

[15]  M A Arnold,et al.  Evaluation of measurement sites for noninvasive blood glucose sensing with near-infrared transmission spectroscopy. , 1999, Clinical chemistry.

[16]  H. G. Rylander,et al.  Use of an agent to reduce scattering in skin , 1999, Lasers in surgery and medicine.

[17]  I M Braverman,et al.  Correlation of laser Doppler wave patterns with underlying microvascular anatomy. , 1990, The Journal of investigative dermatology.

[18]  T. Forst,et al.  Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals , 2009, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[19]  Shu-Jen Yeh,et al.  Temperature dependence of optical properties of in-vivo human skin , 2001, SPIE BiOS.

[20]  N. Wiernsperger Defects in microvascular haemodynamics during prediabetes: contributor or epiphenomenon? , 2000, Diabetologia.

[21]  A Knüttel,et al.  Spatially confined and temporally resolved refractive index and scattering evaluation in human skin performed with optical coherence tomography. , 2000, Journal of biomedical optics.

[22]  M. Cope,et al.  Influence of glucose concentration on light scattering in tissue-simulating phantoms. , 1994, Optics letters.

[23]  David M. Haaland,et al.  Post-Prandial Blood Glucose Determination by Quantitative Mid-Infrared Spectroscopy , 1992 .

[24]  H. Heise,et al.  Noninvasive Blood Glucose Assay by Near-Infrared Diffuse Reflectance Spectroscopy of the Human Inner Lip , 1993 .

[25]  M A Arnold,et al.  Noninvasive blood glucose measurements by near-infrared transmission spectroscopy across human tongues. , 2000, Diabetes technology & therapeutics.

[26]  Michael S. Patterson,et al.  Optical properties of phantoms and tissue measured in vivo from 0.9 to 1.3 um using spatially resolved diffuse reflectance , 1997, Photonics West - Biomedical Optics.

[27]  E. V. Thomas,et al.  Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation. , 1992, Clinical chemistry.

[28]  J. Tooke,et al.  Effect of changes in local skin temperature on postural vasoconstriction in man. , 1988, Clinical science.

[29]  T. Kuehl,et al.  Jelly beans as an alternative to a fifty-gram glucose beverage for gestational diabetes screening. , 1999, American journal of obstetrics and gynecology.

[30]  H. M. Heise,et al.  Clinical Chemistry and near Infrared Spectroscopy: Technology for Non-Invasive Glucose Monitoring , 1998 .

[31]  V. Tuchin Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis , 2000 .

[32]  O. Khalil,et al.  Noninvasive determination of hemoglobin and hematocrit using a temperature-controlled localized reflectance tissue photometer. , 2000, Analytical biochemistry.

[33]  P. Marquet,et al.  In vivo local determination of tissue optical properties: applications to human brain. , 1999, Applied optics.

[34]  R J McNichols,et al.  Optical glucose sensing in biological fluids: an overview. , 2000, Journal of biomedical optics.

[35]  Gilwon Yoon,et al.  Determination of glucose concentration in a scattering medium based on selected wavelengths by use of an overtone absorption band. , 2002, Applied optics.

[36]  F. D. de Mul,et al.  Temperature modulation of the visible and near infrared absorption and scattering coefficients of human skin. , 2003, Journal of biomedical optics.

[37]  L. Heinemann,et al.  Non-invasive continuous glucose monitoring in Type I diabetic patients with optical glucose sensors , 1998, Diabetologia.

[38]  H. Yki-Järvinen,et al.  Insulin-induced vasodilatation: physiology or pharmacology? , 1998, Diabetologia.