Noninvasive Monitoring of Glucose Using Near-Infrared Reflection Spectroscopy of Skin-Constraints and Effective Novel Strategy in Multivariate Calibration.

H Michael Heise,Ralf Marbach,Sven Delbeck

doi:10.3390/bios11030064

H Michael Heise, Ralf Marbach + Show 1 more

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https://doi.org/10.3390/bios11030064

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Abstract

For many years, successful noninvasive blood glucose monitoring assays have been announced, among which near-infrared (NIR) spectroscopy of skin is a promising analytical method. Owing to the tiny absorption bands of the glucose buried among a dominating variable spectral background, multivariate calibration is required to achieve applicability for blood glucose self-monitoring. The most useful spectral range with important analyte fingerprint signatures is the NIR spectral interval containing combination and overtone vibration band regions. A strategy called science-based calibration (SBC) has been developed that relies on a priori information of the glucose signal (“response spectrum”) and the spectral noise, i.e., estimates of the variance of a sample population with negligible glucose dynamics. For the SBC method using transcutaneous reflection skin spectra, the response spectrum requires scaling due to the wavelength-dependent photon penetration depth, as obtained by Monte Carlo simulations of photon migration based on estimates of optical tissue constants. Results for tissue glucose concentrations are presented using lip NIR-spectra of a type-1 diabetic subject recorded under modified oral glucose tolerance test (OGTT) conditions. The results from the SBC method are extremely promising, as statistical calibrations show limitations under the conditions of ill-posed equation systems as experienced for tissue measurements. The temporal profile differences between the glucose concentration in blood and skin tissue were discussed in detail but needed to be further evaluated.

Highlights

The advantages of tight glycemic control in people with diabetes mellitus have often been documented since the diabetes control and complications trial (DCCT) studies were completed [1,2,3]. Those studies proved that intensive insulin therapy in such patients could dramatically delay many serious complications caused by an increase of glycation of body proteins due to above-average blood glucose concentration, which can be connected to problems from micro- and macrovascular diseases leading, e.g., to retino, nephro, and neuropathy
The validation of calibration models for a noninvasive and transcutaneous blood glucose assay based on NIR spectrometry of skin illustrates a rather critical aspect
The accuracy was tested on time-sequenced NIR-spectra collected over two oral glucose tolerance test (OGTT) days with better performance on the second day, which allowed conclusions about the behavior of the glucose concentration–time profiles in the blood and in the measured skin volume

Summary

Introduction

The advantages of tight glycemic control in people with diabetes mellitus have often been documented since the diabetes control and complications trial (DCCT) studies were completed [1,2,3] Those studies proved that intensive insulin therapy in such patients could dramatically delay many serious complications caused by an increase of glycation of body proteins due to above-average blood glucose concentration, which can be connected to problems from micro- and macrovascular diseases leading, e.g., to retino-, nephro-, and neuropathy. When undergoing intensive insulin therapy, current surveillance still requires people with diabetes to use lancets to prick their fingertips for blood sampling several times a day They can use continuous glucose monitoring (CGM) devices that have recently been brought to the market. Minimalinvasive continuous glucose sensing systems have been suggested for glycemic control in people with diabetes mellitus and critically ill patients [15]

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