JP3580607B2 - Blood glucose measurement device using corneal natural fluorescence - Google Patents

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an apparatus for non-invasively measuring a blood glucose level.
[0002]
[Prior art]
Since the measurement of the blood glucose level is an important index for diagnosing the condition of diabetes and managing it after disease, various measuring methods have been conventionally developed. At present, mainly the enzymatic method, various methods including the o-toluidine-boric acid (o-TB) method have been used. However, all of these methods require blood sampling each time, causing pain to the patient, and also require time and labor for the examination.
[0003]
The present inventors irradiate the eye with excitation light of a selected wavelength between the visible and near-infrared regions, measure the natural fluorescence from the vitreous body and the lens, and determine the significant difference between diabetic patients and normal persons. (See Shinkai, 38 (10): 1059-1064, (1984)). The measurement of fluorescence from the eyeball is generally performed after intravenous injection of fluorescein-Na, but the natural fluorescence is fluorescence measured without intravenous injection of fluorescein-Na.
[0004]
[Problems to be solved by the invention]
However, the correlation between the natural fluorescence from various places of the eyeball and the blood sugar level has not been obtained so far.
An object of the present invention is to make it possible to non-invasively measure a blood glucose level using natural fluorescence from an eyeball.
[0005]
[Means for Solving the Problems]
The present inventor has found that among natural fluorescence from the eyeballs, the fluctuation value of the corneal natural fluorescence has a correlation with the fluctuation value of the blood glucose level, and has led to the present invention. That is, as shown in FIG. 1, the present invention focuses an excitation light having a wavelength selected from the visible to the near-infrared region on the cornea, and detects natural fluorescence from the cornea due to the excitation light. 2 and
The relationship between the blood glucose fluctuation value and the corneal natural fluorescence fluctuation value is held, and the blood glucose measurement value for each patient is set as the blood glucose reference value, and the detected corneal natural fluorescence detection value at that time is stored as the corneal natural fluorescence reference value. The corneal spontaneous fluorescence fluctuation value is obtained as a difference between the subsequent corneal spontaneous fluorescence detection value by the optical system 2 and the corneal spontaneous fluorescence reference value. A calculation unit 4 for obtaining an absolute blood sugar level at each time point by comparing the blood sugar level with the measured value, so that the blood sugar level can be measured non-invasively.
[0006]
The corneal spontaneous fluorescence value and the blood glucose level were measured twice at different times of the same day on 16 patients with proliferative diabetic retinopathy (PDR) in non-insulin-dependent diabetes mellitus, and the blood glucose fluctuation values shown in FIG. And the relationship between the corneal spontaneous fluorescence fluctuation value was obtained. These data show the results of correlation coefficient r = 0.648, p <0.01 (p is the risk rate), indicating a significant positive correlation. The correlation as shown in FIG.
On the other hand, no significant correlation was observed between the blood glucose fluctuation value and the lens natural fluorescence fluctuation value measured at the same time, as shown in FIG.
[0007]
Since it is not the absolute value of the blood glucose level but the fluctuation value that is obtained from the corneal natural fluorescence, in order to obtain the absolute value, the blood glucose level measured value by the conventional blood sampling and the corneal natural fluorescence detection value at that time are obtained for each patient. Is measured and stored as a reference value, a corneal spontaneous fluorescence fluctuation value is obtained as a difference between the subsequent corneal spontaneous fluorescence detection value and the reference value, and a corresponding blood glucose fluctuation value is obtained. By comparing with, the absolute blood glucose level at each time point can be obtained. Since the measurement for obtaining the blood sugar level reference value is performed by blood sampling, the blood sampling is not non-invasive, but since subsequent blood sampling is not required, it can be said that the blood sampling is substantially non-invasive. “Non-invasive” in the present invention thus means substantially non-invasive.
[0008]
【Example】
An example of an optical system for measuring a corneal natural fluorescence value will be described with reference to FIGS. FIG. 4 shows an optical system that irradiates the cornea with excitation light having a selected wavelength in the visible to near-infrared region and detects natural fluorescence from the cornea due to the excitation light. In order to selectively detect the fluorescence from the cornea, the anterior ocular segment fluorescence measurement adapter shown in FIG. 5 is attached to the optical system shown in FIG. Fluorescence can be measured.
[0009]
A fixed lens 12 and a scanning lens 14 are arranged along the optical axis 10, and an eyeball 16, which is a subject, is on an extension of the optical axis 10 on the scanning lens 14 side so that the eye axis coincides with the optical axis 10. Be placed. An adapter 20 shown in FIG. 4 is arranged between the lens 18 provided on the optical axis 10 and the eyeball 16.
[0010]
In order to irradiate the eye 16 with the excitation light, a tungsten lamp is provided as the excitation light source 22, a filter 24 that extracts predetermined wavelength light from the continuous wavelength light from the light source 22 as the excitation light, and the excitation light is a small system light flux. Excitation light 28 narrowed down to a predetermined wavelength through the slit 26 is reflected by the mirror 30 and enters the lenses 12 and 14. The excitation light 28 condensed by the lenses 12 and 14 is condensed from the lens 18 via the adapter 20 to a position at a predetermined depth of the eyeball. By moving the scanning lens 14 along the optical axis, the depth position where the excitation light 28 is condensed moves along the eye axis. Here, in particular, the excitation light 28 is focused on the cornea.
[0011]
A photomultiplier tube (PMT) 36 is disposed on an extension of the fixed lens 12 on the optical axis 16 via the detector slit 32 and the barrier filter 34 in order to detect the fluorescence generated from the eye 16 by the irradiation of the excitation light. Have been.
An eye axis fixing target light source 38 for generating light for a target is provided on the optical axis 10 so that the eye axis of the patient's eyeball 16 coincides with the optical axis 10, and the light is beam-formed through a slit 40. And is incident on the optical axis 10 by the beam splitter 41.
[0012]
In order for an operator to confirm the position of the patient's eye, a patient alignment port 46 is disposed on an optical axis orthogonal to the optical axis 10 via a split screen 42 and a lens 44, and an optical axis for the patient alignment port 46 is provided. A mirror 48 is detachably mounted at the intersection of the optical axis 10 and the optical axis 10. The patient's eye 16 can be seen from the patient alignment port 46 when the mirror 48 is positioned across the optical axis 10.
[0013]
In order to correct the detection value based on the intensity of the light source, a calibration glass surface 50 integrally provided with the mirror 48 is provided. When the mirror 48 is disposed at a position crossing the optical axis 10, The glass surface 50 is also disposed on the optical axis 10 so that the excitation light from the light source 22 is reflected by the glass surface 50 and enters the detector 36, and the intensity of the light source is detected.
[0014]
【The invention's effect】
In the present invention, if the relationship between the blood glucose level and the corneal natural fluorescence value by the blood sampling method is measured only once for each patient, then the blood glucose level can be obtained noninvasively only by measuring the corneal natural fluorescence value. . Therefore, it becomes possible to easily and quickly determine and monitor the condition of a diabetic patient.
[Brief description of the drawings]
FIG. 1 is a block diagram illustrating the present invention.
FIG. 2 is a diagram showing a correlation between a blood glucose fluctuation value and a corneal natural fluorescence fluctuation value in the present invention.
FIG. 3 is a diagram showing a correlation between a blood glucose fluctuation value and a lens natural fluorescence fluctuation value as a comparative example.
FIG. 4 is a schematic configuration diagram showing an optical system used in one embodiment.
FIG. 5 is a schematic configuration diagram showing an adapter in the optical system of the embodiment.
[Explanation of symbols]
2 Optical system 4 Operation unit

Claims (1)

An optical system that focuses excitation light of a selected wavelength between the visible and near-infrared regions on the cornea and detects natural fluorescence from the cornea due to the excitation light,
The relationship between the blood glucose fluctuation value and the corneal natural fluorescence fluctuation value is held, and the blood glucose measurement value for each patient is set as the blood glucose reference value, and the detected corneal natural fluorescence detection value at that time is stored as the corneal natural fluorescence reference value. The corneal spontaneous fluorescence fluctuation value is determined as the difference between the subsequent corneal spontaneous fluorescence detection value by the optical system and the corneal spontaneous fluorescence reference value, and the corresponding blood sugar fluctuation value is determined from the relationship, and the blood sugar level is calculated. A non-invasive blood glucose measurement device, comprising: a calculation unit that obtains an absolute blood glucose level at each time point by comparing with a reference value .

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