WO2016074282A1 - 一种糖尿病及其并发症的无创检测系统和方法 - Google Patents

一种糖尿病及其并发症的无创检测系统和方法 Download PDF

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Publication number
WO2016074282A1
WO2016074282A1 PCT/CN2014/092325 CN2014092325W WO2016074282A1 WO 2016074282 A1 WO2016074282 A1 WO 2016074282A1 CN 2014092325 W CN2014092325 W CN 2014092325W WO 2016074282 A1 WO2016074282 A1 WO 2016074282A1
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Prior art keywords
urine
module
test strip
layer
creatinine
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English (en)
French (fr)
Inventor
张贯京
陈兴明
葛新科
王海荣
张少鹏
方静芳
程金兢
梁艳妮
周荣
徐之艳
周亮
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Shenzhen Qianhai AnyCheck Information Technology Co Ltd
E Techno Information Technologies Co Ltd
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Shenzhen Qianhai AnyCheck Information Technology Co Ltd
E Techno Information Technologies Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration

Definitions

  • the invention relates to the technical field of medical instruments, in particular to a non-invasive detection system and method for diabetes and its complications.
  • diabetes is primarily diagnosed by monitoring fasting or postprandial blood glucose.
  • current medical and home blood glucose measurements are mainly based on invasive methods, which are not conducive to the screening of diabetes in a large number of people, so that most people still have diabetes, and until the discovery, various complications have emerged.
  • diabetic patients need to frequently measure and control blood glucose concentrations in order to avoid diabetic complications.
  • Frequent blood collection for blood glucose concentration measurement brings huge economic burden and medical expenses to diabetic patients, on the other hand, it brings great physical and psychological pain to diabetic patients and increases the risk of infectious diseases.
  • Non-invasive urine test strips commonly used in the market due to limited measurement accuracy, often have false negatives, false positives, and cannot be widely promoted. In order to cope with the above situation, there is an urgent need for a non-invasive detection system for diabetes and its complications (diabetic nephropathy).
  • the urine glucose test paper is mainly measured qualitatively, and the measurement accuracy is low. It is difficult to be popular and practical in the early screening of diabetes and subsequent blood glucose detection. Therefore, an instrument or method with high sensitivity and accurate quantitative determination of urine sugar is needed;
  • the urine composition changes relatively large, and the concentration of urine sugar is easily affected by the concentration of urine in the kidney and the dilution of urine, resulting in random urine sugar test inaccurate and prone to false negatives;
  • the patient's renal function damage may affect the change of renal sugar threshold, which may lead to inaccurate urine glucose test results, false negative or false positive;
  • the concentration of urine sugar is susceptible to external influences.
  • the current monitoring of urine glucose concentration is mainly the use of morning urine.
  • the test results reflect the average value of urine sugar within a period of time and cannot reflect the level of real-time blood sugar.
  • diabetic nephropathy is one of the major complications of diabetes and is the leading cause of death in diabetic patients. Therefore, a detection system and method are needed to simultaneously monitor blood glucose (urine sugar) and renal function in diabetic patients, but the current blood glucose meter Or urine glucose test strips can not achieve simultaneous monitoring of diabetes and its complications;
  • nephropathy microalbumin/inosine
  • the currently used diagnostic method for nephropathy cannot be predicted in the early stage of diabetic nephropathy, which is not conducive to the monitoring and intervention of diabetic nephropathy.
  • the invention provides a non-invasive detection system and method for diabetes and its complications, which can quantitatively detect various markers of diabetes and its complications in urine, improve detection accuracy and sensitivity, and reduce urine sugar concentration by external factors. Interference, true reflection of urine sugar concentration, simultaneous monitoring of diabetes and its complications.
  • the invention provides a non-invasive detection system for diabetes and its complications, comprising:
  • a spectral emission module for emitting an incident spectrum of a predetermined wavelength
  • a detection module for reacting urine glucose, urinary creatinine and/or urinary cysteine protease inhibitor C in a urine sample with a test strip and receiving an incident spectrum
  • a spectrum receiving module configured to receive a spectral or fluorescent signal that has passed through the test strip and is attenuated, and converted into an analog electrical signal
  • a signal conversion module connected to the spectrum receiving module to convert the analog electrical signal into a digital signal
  • the data processing module is connected with the signal conversion module, and calculates the concentration values of urine sugar, urine creatinine, urinary cystatin C, and urine/creatinine ratio and/or urine in the urine sample according to the digital signal. Cystatin C/urinary creatinine ratio;
  • An output module coupled to the data processing module, for outputting concentration values and/or ratios.
  • the urine sample is obtained from the urine of the subject at 0.5 to 2.5 hours after the meal, and the urine taken at 2 to 4.5 hours after the meal.
  • the test strip for detecting urine sugar is a dry chemical test strip comprising a urine diffusion layer, a filter layer, a hydrophilic layer and a reagent layer disposed in order from top to bottom, wherein the reagent layer has Glucose oxidase, peroxidase, potassium iodide and polyvinylpyrrolidone.
  • the test strip for detecting urine sugar further comprises an upper baffle and a bottom support, and a urine diffusion layer, a filter layer, a hydrophilic layer and a reagent layer are interposed between the upper baffle and the bottom support as an intermediate layer.
  • the test strip for detecting urinary creatinine is a dry chemical test strip comprising a urine diffusion layer, a filter layer, a hydrophilic layer and a reagent layer disposed in order from top to bottom, wherein the reagent layer has Copper sulfate, sodium citrate, orange yellow, polyvinylpyrrolidone and tetramethylbenzidine.
  • the test strip for detecting urinary creatinine further comprises an upper baffle and a bottom support, and a urine diffusion layer, a filter layer, a hydrophilic layer and a reagent layer are interposed between the upper baffle and the bottom support as an intermediate layer.
  • the test strip for detecting urinary cysteine protease inhibitor C is a dry chemical test strip comprising a sample mat sequentially lapped, a nitrocellulose membrane and an absorbent pad, wherein the nitrocellulose membrane There are detection lines and quality control lines.
  • the detection line is coated with anti-cysteine protease inhibitor C antibody
  • the quality control line is coated with IgG antibody.
  • the test strip for detecting urinary cystatin C further comprises an upper baffle and a bottom support, and the sample pad, the nitrocellulose membrane and the absorbent pad are placed between the upper baffle and the bottom support as the middle Floor.
  • the spectral emission module includes a spectral transmitting circuit and a transmitting power supply circuit; and the spectral receiving module includes a spectral receiving circuit and a receiving power circuit.
  • the data processing module includes a microprocessor (MCU) and its peripheral circuits.
  • MCU microprocessor
  • the output module includes a human-computer interaction module and a data communication module; a human-computer interaction module is configured to implement human-computer interaction, display output concentration values and/or ratios; and a data communication module for implementing remote information Communication function to transfer concentration values and/or ratios to remote data storage and analysis platforms.
  • the present invention provides a non-diagnostic method for non-invasive detection of diabetes and its complications, comprising:
  • the detecting module drops urine into the reaction hole of the test strip, and the test strip reacts with urine sugar, urine creatinine and urinary cystatin C in urine;
  • the spectral emission module emits an incident spectrum of a predetermined wavelength to the reacted test strip
  • the spectral receiving module receives the spectral or fluorescent signal that has passed through the test strip and is attenuated, and is converted into an analog electrical signal;
  • the signal conversion module converts the analog electrical signal into a digital signal
  • the data processing module calculates the concentration of urine glucose, urinary creatinine, urinary cystatin C, and urine glucose/creatinine ratio and/or urinary cysteine protease inhibitor in the urine sample based on the digital signal. C/urinary creatinine ratio;
  • the output module outputs concentration values and/or ratios.
  • the method before the detecting module adds urine to the reaction strip of the test strip, the method further comprises: obtaining the urine of the subject after evacuating from 0.5 to 2.5 hours after the meal and taking it from 2 to 4.5 hours after the meal. Urine.
  • the invention Compared with the existing diabetes detection technology, the invention has the following advantages: the invention is quantitative measurement, the accuracy and sensitivity are higher than the existing urine glucose test paper; the introduction of urine creatinine as a reference, the urine sugar / urine creatinine ratio is accurate Reflecting the concentration of random urine sugar in urine, can eliminate the influence of external interference factors on urine sugar concentration; Introduce renal function evaluation index urinary cysteine protease inhibitor C, used to rule out the result of urine glucose test due to kidney damage False positive or false negative, and the evaluation of renal function by urinary cystatin C, can monitor the complications of diabetic nephropathy at an early stage, and achieve simultaneous monitoring of diabetes and its complications.
  • FIG. 1 is a structural schematic view showing a non-invasive detection system for diabetes and its complications according to an embodiment of the present invention
  • FIG. 2 is a structural schematic view showing a non-invasive detection system for diabetes and its complications according to another embodiment of the present invention
  • FIG. 3 is a flow chart of a non-diagnostic non-diagnostic method for detecting non-invasive diabetes and its complications according to an embodiment of the present invention
  • FIG. 4 is a schematic view showing the structure of a test strip for urine sugar and urine creatinine in a non-invasive detection system for diabetes and its complications according to an embodiment of the present invention
  • Fig. 5 is a schematic view showing the structure of a test strip for urinary cystatin C in a non-invasive detection system for diabetes and its complications according to an embodiment of the present invention.
  • Embodiment 1 is a diagrammatic representation of Embodiment 1:
  • a non-invasive detection system for diabetes and its complications in an embodiment of the present invention includes: a spectral emission module 10 for emitting an incident spectrum of a predetermined wavelength; and a detection module 20 for passing a test strip and urine
  • the urine sugar, urine creatinine and/or urinary cystatin C in the sample reacts and receives the incident spectrum;
  • the spectral receiving module 30 receives the spectral or fluorescent signal that has passed through the test strip and is attenuated and converted into An analog electrical signal;
  • the signal conversion module 40 is connected to the spectrum receiving module 30 to convert the electrical signal into a digital signal;
  • the data processing module 50 is connected to the signal conversion module 40, and calculates urine sugar and urine in the urine sample according to the digital signal.
  • Concentration values of creatinine, urinary cystatin C, and urinary glucose/creatinine ratio and/or urinary cystatin C/urinary creatinine ratio are Concentration values of creatinine, urinary cystatin C, and urinary glucose/creatinine ratio and/or urinary cystatin C/urinary creatinine ratio; output module 60, coupled to data processing module 50, Used to output concentration values and/or ratios.
  • the non-invasive detection system for diabetes and its complications of this example introduces urinary creatinine as a reference.
  • the basis of the explanation is as follows:
  • glucose can pass freely through the glomerulus, that is, the glucose concentration in the original urine is consistent with the glucose concentration in the blood.
  • glucose is heavy by the renal tubular epithelial cells. absorb.
  • the renal sugar threshold (8.96) Mmmol/L -10.08mmol / L)
  • renal tubular epithelial cells to the limit of glucose absorption, glucose can not be completely reabsorbed back into the blood, there will be diabetes.
  • the concentration of urine sugar is susceptible to changes in urine volume, resulting in a randomized urine glucose concentration test.
  • the urinary creatinine content secreted by each person to the urine per unit time is certain.
  • the change of urine creatinine concentration in urine is directly affected by the external environment (such as excessive water intake).
  • the concentration of urinary creatinine decreases.
  • the concentration of urinary creatinine increases.
  • the urine sugar / urine creatinine ratio it is possible to eliminate the interference of the concentration of the urine solution due to factors such as excessive water intake, and accurately reflect the relative level of one of the solute of the urine solution - urine sugar.
  • urine sugar / urine creatinine (per unit time urine sugar content / urine volume) / (per unit time urine creatinine content / urine volume), because the individual urine creatinine content per unit time is constant, so through the urine sugar / urine Creatinine can rule out the effect of urine volume on urine sugar and accurately reflect the urine urine sugar content.
  • the non-invasive detection system for diabetes and its complications of the present embodiment introduces a renal function evaluation index (specifically, a renal tubular function index) urinary cystatin C (Cystatin) C), used to rule out false positive or false negative results in urine glucose test results due to kidney damage.
  • a renal function evaluation index specifically, a renal tubular function index
  • Cystatin C evaluation of the user's renal function can be used for early detection of the occurrence of complications of diabetic nephropathy.
  • Cystatin C is tissue-free and is produced at a constant rate in human cells. Cystatin C levels in the blood reflect glomerular filtration rate.
  • Cystatin in the blood C can pass through the glomerular basement membrane at a constant rate, and Cystatin C entering the urinary urine is completely reabsorbed at the renal tubules of healthy people.
  • the renal tubules When the renal tubules are damaged, there will be Cystatin in the urine. C exists.
  • a large number of studies have pointed out that when the kidney is damaged, the renal tubules will also be damaged at the same time, affecting the renal tubular reabsorption function. At the same time, these studies point out Cystatin in urine.
  • C can be used as an early biomarker for kidney disease, including diabetic nephropathy.
  • Embodiment 2 is a diagrammatic representation of Embodiment 1:
  • the non-invasive detection system for diabetes and its complications in another embodiment of the present invention includes: a spectral emission module 10, a detection module 20, and a spectrum.
  • the spectral emission module 10 includes a spectral transmitting circuit 11 and a transmitting power supply circuit 12 for transmitting light waves of a specific wavelength to the reacted test strip in real time; and the detecting module 20 detects the test strip by detecting the test strip.
  • the strip consists of a thin sheet of sensitive chemical composition containing urinary sugar, urine creatinine and urine Cystatin.
  • the signal receiving module 30 includes a spectrum receiving circuit 31 and a receiving power circuit 32 for receiving a spectral signal of a certain wavelength range. When the spectral signal illuminates the reacted test strip, the illumination spectrum may attenuate to some extent or fluoresce. Calculating the optical loss rate or fluorescence intensity, and converting the reflected spectrum or fluorescent signal into an electrical signal; the signal conversion module 40 is connected to the spectrum receiving module 30 to treat urine urine, urine creatinine, and urine Cystatin in the urine.
  • the C concentration related electrical signal is converted into a digital signal that the microprocessor can recognize and receive;
  • the data processing module 50 is coupled to the signal conversion module 40, including a microprocessor (MCU) 51 and its peripheral circuitry 52, which will receive the urine.
  • MCU microprocessor
  • Sugar, urine creatinine, urine Cystatin C information is analyzed and calculated, and finally the urine sample, urine creatinine, urinary Cystatin C concentration value and urine sugar/urinary creatinine and urine Cystatin are obtained.
  • the output module 60 is connected to the data processing module 50, and includes a human-computer interaction module 61 and a data communication module 62.
  • the human-computer interaction module 61 may further include an MCU, an LCM display circuit, and a keyboard input circuit.
  • the output concentration value and ratio are displayed, that is, urine sugar, urine creatinine, and urine Cystatin in urine.
  • Concentration value of C, as well as urine sugar / urine creatinine, urine Cystatin The C/urinary creatinine ratio measurement data result; the data communication module 62 further includes an MCU and a data communication circuit for implementing a telematics function, and transmitting the concentration value and the ratio to the remote data storage and analysis platform.
  • modules or circuits in the present invention are not limited to a specific circuit diagram configuration, because a module or a circuit for realizing respective functions can be selected by those skilled in the art according to the current technology.
  • a flow chart of a method for detecting urine biomarkers in the non-invasive detection system for diabetes and its complications according to the first embodiment and the second embodiment of the present invention is shown in FIG. 3, and includes the following steps: S1.
  • the detection module is responsive to the test strip.
  • Urea, test strip reacts with urine sugar, urine creatinine and urinary cysteine protease inhibitor C in urine;
  • Spectral emission module emits incident wavelength of predetermined wavelength to the test strip after reaction;
  • the spectral receiving module receives the spectral or fluorescent signal that has passed through the test strip and is attenuated, and converts it into an analog electrical signal; S4.
  • the signal conversion module converts the analog electrical signal into a digital signal; S5.
  • the data processing module calculates the concentration of urine glucose, urinary creatinine, urinary cystatin C, and urine glucose/creatinine ratio and/or urinary cystatin C/ in the urine sample.
  • Urinary creatinine ratio S6.
  • the output module outputs the concentration value and/or the ratio.
  • the dry chemical test strip for detecting urine sugar and urine creatinine comprises, in order from top to bottom, an upper baffle (not shown), an intermediate layer and a bottom support (not shown).
  • the intermediate layer is provided with a urine diffusion layer, a filtration layer, a hydrophilic layer and a reagent layer in this order from top to bottom, wherein the reagent layer may be fused on the hydrophilic layer.
  • the urine sample is uniformly diffused in the urine diffusion layer of the porous polyester fiber material, passing through the filter layer (glass).
  • the fiber membrane filters out the impurities, reacts with the reagents in the reagent layer, generates a change in the absorbance value by changing the color of the test paper, detects the light loss, and obtains the content of the corresponding target substance in the urine.
  • Method for detecting urine creatinine test paper preparing a reagent layer of urine creatinine test paper by using copper sulfate, sodium citrate, orange yellow, polyvinylpyrrolidone and tetramethylbenzidine, and the specific preparation method is as follows: firstly immersing the reagent layer into liquid A (1000 ml) 2mol/L in solution Tris buffer, copper sulfate 0.4g-2g, sodium citrate 2-5g, orange 2mg0-200mg, fixed to volume with pure water, then taken out and dried at 70-100 ° C for 15-30min, then the reagent after drying The layer was immersed in liquid B (polyvinylpyrrolidone 10-20 g, tetramethylbenzidine 3-5 g, made up to volume with chloroform), and dried at 70-100 ° C for 5-15 min.
  • liquid A 1000 ml) 2mol/L
  • Tris buffer copper sulfate 0.4g-2g, sodium citrate 2-5g, orange 2
  • creatinine and copper sulfate form a complex which can react with the colorants orange yellow and tetramethylbenzidine to develop color.
  • the creatinine concentration ranged from 0.6mmol/L to 28mmol/L, and the test paper showed four distinct color gradations from light yellow to dark green, namely light yellow-light green-grass green-dark green.
  • the reflected light is spectrally analyzed by a sensor (using a wavelength range of 580-650 nm) to detect light loss, and the concentration of creatinine in the urine is obtained.
  • the concentration of urinary creatinine is correlated with the color depth of the test strip after the reaction, that is, the correlation with the spectral intensity after attenuation by the test strip, and thus correlates with the converted analog electrical signal and digital signal.
  • the standard curve relationship between urine creatinine concentration and digital signal can be established by a series of gradient concentrations of standard urine creatinine and the corresponding digital signal intensity.
  • the concentration of urine creatinine in the tested sample can be calculated according to the standard curve.
  • Urine sugar test strip test method urinary glucose test paper is prepared by using glucose oxidase (GOD), peroxidase, potassium iodide and polyvinylpyrrolidone. Specifically, weigh 1200 U of peroxidase, 1200 U of glucose oxidase, 100 mg of potassium iodide, 100 mg of polyvinylpyrrolidone, and make up to 100 ml. The reagent layer was immersed in the solution and dried for 30 min.
  • GOD glucose oxidase
  • peroxidase peroxidase
  • potassium iodide potassium iodide
  • polyvinylpyrrolidone polyvinylpyrrolidone
  • the urine sugar reacts with the glucose oxidase on the test paper, residual gluconic acid and hydrogen peroxide; and hydrogen peroxide releases hydrogen radical [O:], oxygen under the catalysis of hydrogen peroxide and catalase.
  • the free radical reacts with the substrate potassium iodide, and the free iodine produced forms a brown complex with the polyvinylpyrrolidone.
  • Spectral analysis of the reflected light by the sensor (using a wavelength range of 550-750 nm) detects the light loss and obtains the urine sugar concentration in the urine.
  • the concentration of urine sugar is correlated with the color depth of the test strip after the reaction, that is, the correlation with the spectral intensity after attenuation by the test strip, and thus correlates with the converted analog electrical signal and the digital signal.
  • the concentration of urine sugar in the tested sample can be calculated according to the standard curve.
  • the dry immunofluorescence test strip of C includes an upper baffle (not shown), an intermediate layer, and a bottom support (not shown). Among them, the middle layer is adhered to the sample pad (C in FIG. 5), the nitrocellulose membrane, and the water absorption pad from the left to the right, as shown in FIG. 5, and the detection line (C1) and the quality are provided on the nitrocellulose membrane.
  • Control line (C2) the specific antibody coated by the detection line is anti-Cystatin
  • the monoclonal antibody of C, the specific antibody coated by the quality control line is a rabbit IgG antibody. Individually packaged platinum porphyrin labeled antibodies are anti-microalbumin monoclonal antibodies and anti-rabbit IgG antibodies. Calculate Cystatin in urine samples by detecting the fluorescence intensity of the platinum and porphyrin on the nitrocellulose membrane The concentration of C.
  • Urine Cystatin C test strip test method urine Cystatin
  • the nitrocellulose membrane of the C test strip has a detection line and a quality control line in the detection area near the spotting hole.
  • the test line is coated with anti-Cystatin
  • the antibody of C is coated with rabbit IgG antibody on the quality control line.
  • the platinum porphyrin labeling solution contains platinum porphyrin labeled anti-Cystatain C antibody and platinum porphyrin labeled anti-rabbit IgG antibody.
  • the urine sample and the platinum porphyrin labeling solution are uniformly mixed in a certain ratio to make the platinum porphyrin-labeled antibody and the target protein in the urine (Cystatin).
  • the urinary Cystatin in the sample can be calculated.
  • concentration of C Those skilled in the art can calculate the value of the urine Cystatin C concentration by the prior art through the understanding of the embodiments of the present invention, and details are not described herein.
  • urine sugar / urine creatinine According to urine sugar, urine creatinine, urine Cystatin C, urine sugar / urine creatinine and urine Cystatin C / urinary creatinine measurement to make a judgment: 1) If the urine sugar value or urine sugar / urine creatinine value is beyond the normal range (the normal range of urine sugar is 0-20mg / dL; urine sugar / urine creatinine normal range The upper limit is between 50 and 100 mg/g), but no urine Cystatin is detected. C, it is judged that the subject has diabetes, but no complications have occurred.
  • This kind of application can be used for large-scale screening of diabetic patients in the crowd, because the renal sugar threshold is certain, so when using this method to measure a certain amount of glucose in the urine, it means that the subject has or will have a certain degree Risk of diabetes; 2) If you have diabetes, if you have Cystatin If the C value is outside the normal range ( ⁇ 0.15mg/dL), the patient is prone to diabetic nephropathy; 3) For diabetic patients with normal renal function, a reaction test paper containing urine sugar and urine creatinine may be used (see A in Figure 4). B) Measurement, urine sugar, urine sugar / urine creatinine parameters can reflect the patient's blood sugar level to a certain extent, to a certain extent can reduce the pain of the patient's fingers.
  • the monitoring recommendation method of the non-invasive detection system for diabetes and its complications of the present invention is that for large-scale screening of diabetic patients, preferably, the subject empties urine at 0.5h-2.5h after a meal, 2h after meal- 4.5h taking urine to measure urine sugar, urine creatinine, urine Cystatin C. For example, urine is emptied at 1.5h after a meal, and urine is collected 3h after a meal. The concentration of urine sugar in the collected urine reflects the average concentration of urine within 1.5h-3h after meal, which reflects the blood after meal.
  • Blood glucose (real-time) concentration for diabetic patients with predictive complications (diabetic nephropathy), preferably, the subject takes morning urine in the urine, measuring urine sugar, urinary inosine, and urine Cystatin C; For patients who have diabetes but no complications, the subject can take morning urine, postprandial urine, random urine test urine sugar, urine creatinine, and replace the measurement to a certain extent. blood sugar.
  • Table 1 shows the case of 10 samples detected using the system and method of the present invention.
  • No. 1-8 in the table is diabetic patients (glycated hemoglobin and postprandial blood glucose), and 9 and 10 are normal controls.
  • patient No. 6 has mild diabetic nephropathy (eGFR) 87).
  • eGFR diabetic nephropathy
  • Tested by this method found that the tester of the 6th urine Cystatin C value is greater than the normal range, suggesting that diabetic nephropathy is not suitable for predicting blood glucose concentration with urine glucose/creatinine value; other patients have no kidney disease; by urine sugar/creatinine value, 1-5 and 7, 8 are affected
  • the urine sugar/urinary creatinine was higher than the normal range, suggesting different degrees of diabetes.

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Abstract

一种糖尿病及其并发症的无创检测系统和方法，该系统包括：光谱发射模块(10)，用于发射预定波长的入射光谱；检测模块(20)，用于通过试纸条与尿液样品中的尿糖、尿肌酐和/或尿半胱氨酸蛋白酶抑制剂C反应并接收入射光谱；光谱接收模块(30)，用于接收通过试纸条并衰减后的光谱或荧光信号，并转换为模拟电信号；信号转换模块(40)，与光谱接收模块(30)连接，将模拟电信号转换成数字信号；数据处理模块(50)，与信号转换模块(40)连接，根据数字信号计算出尿液样品中的生物标志物的量值；输出模块(60)，与数据处理模块(50)连接，用于输出量值。该系统定量检测糖尿病及其并发症的多种标志物，提高检测准确性和灵敏度，减少干扰，真实反映尿糖浓度，同步监测糖尿病及其并发症。

Description

一种糖尿病及其并发症的无创检测系统和方法
技术领域
本发明涉及医疗器械技术领域，尤其涉及一种糖尿病及其并发症的无创检测系统和方法。
背景技术
随着国民经济的快速发展，人民生活水平的提高，我国的肥胖人群也逐步增加；除肥胖人口的快速增加，老龄人口的增长也促进了糖尿病患者人群的增长。据统计，目前我国糖尿病患者已达1.2亿人，未来10年内我国的糖尿病患者人数将会突破2亿。同时，若糖尿病患者血糖控制不稳，会导致各种并发症，如糖尿病心血管疾病、糖尿病眼病、糖尿病肾病、糖尿病神经性疾病等。其中，糖尿病肾病是糖尿病最严重和最重要的慢性微血管并发症之一。据统计，30%～40%的2型糖尿病人将发展为糖尿病肾病，20%～40%的1型糖尿病患者在15～30年后也将发展为糖尿病肾病，会给我国带来越来越多的社会和经济负担。
目前，糖尿病主要是通过监测空腹或餐后血糖而进行初期诊断。然而，当前医用和家用血糖测量主要是基于有创方式进行，不利于对大范围人群进行糖尿病筛查，致使大多数人患了糖尿病仍然浑然不觉，等到发现时已出现各种并发症。同时，糖尿病患者为了避免糖尿病并发症，需要频繁地测量和控制血糖浓度。频繁的采血进行血液葡萄糖浓度的测量，一方面给糖尿病患者带来了巨大的经济负担和医疗费用，另一方面也给糖尿病患者带来了巨大的身体和心理痛苦和增加感染疾病的风险。而市场上普遍采用的无创尿糖试纸，由于测量精度受限，常常出现假阴性、假阳性，不能大规模推广。为了应对上述形势，迫切需要一种糖尿病及其并发症（糖尿病肾病）无创检测系统。
目前利用无创尿糖技术筛查及监测尿糖水平的产品已有使用，主要是尿糖试纸，但由于该类产品均采用定性检测尿糖，测量精度有限或出现假阳性或假阴性，不能大规模使用。主要问题集中在以下几点：
第一，尿糖试纸主要采用定性方式测量，测量精确度较低，在糖尿病早期筛查及后续血糖检测中难以普及实用，因此需要一种灵敏度较高，能准确定量尿糖的仪器或方法；
第二，尿液成分变化相对较大，尿糖浓度易受肾脏尿浓缩和尿稀释的影响，导致随机尿糖测试不准，易出现假阴性；
第三，患者肾功能损伤（肾小管或肾小球功能受损）会影响肾糖阈发生改变，进而导致尿糖检测结果不准，出现假阴性或假阳性；
第四，尿糖浓度易受外界影响，当前临床上尿糖浓度的监测主要是采用晨尿，检测结果反应的是一段时间内尿糖的平均值，不能反映实时血糖的水平；
第五，糖尿病肾病是糖尿病主要的并发症之一，是导致糖尿病患者死亡的主要原因，因此需要一种检测系统和方法同步监测糖尿病患者血糖（尿糖）及其肾功能，但当前的血糖仪或尿糖试纸还不能实现同步监测糖尿病及其并发症；
第六，目前常用的肾病诊断方法（微量白蛋白/肌苷）不能在糖尿病肾病初期进行预测，不利于糖尿病肾病的监测和干预。
发明内容
本发明提供一种糖尿病及其并发症的无创检测系统和方法，能够定量检测尿液中的糖尿病及其并发症的多种标志物，提高检测准确性和灵敏度，减少尿糖浓度受外界因素的干扰，真实反映尿糖浓度，同步监测糖尿病及其并发症。
根据本发明的第一方面，本发明提供一种糖尿病及其并发症的无创检测系统，包括:
光谱发射模块，用于发射预定波长的入射光谱；
检测模块，用于通过试纸条与尿液样品中的尿糖、尿肌酐和/或尿半胱氨酸蛋白酶抑制剂C反应并接收入射光谱；
光谱接收模块，用于接收通过试纸条并衰减后的光谱或荧光信号，并转换为模拟电信号；
信号转换模块，与光谱接收模块连接，将模拟电信号转换成数字信号；
数据处理模块，与信号转换模块连接，根据数字信号计算出尿液样品中的尿糖、尿肌酐、尿半胱氨酸蛋白酶抑制剂C的浓度值，以及尿糖/尿肌酐比值和/或尿半胱氨酸蛋白酶抑制剂C/尿肌酐比值；
输出模块，与数据处理模块连接，用于输出浓度值和/或比值。
作为本发明的优选方案，尿液样品来自受试者在餐后0.5~2.5h排空尿液，且在餐后2~4.5h所取的尿液。
作为本发明的优选方案，检测尿糖的试纸条为干式化学试纸条，包括从上至下依次设置的尿液扩散层、过滤层、亲水层和试剂层，其中试剂层上有葡萄糖氧化酶、过氧化物酶、碘化钾和聚乙烯吡络烷酮。
更优选地，检测尿糖的试纸条还包括上层挡板和底层支架，尿液扩散层、过滤层、亲水层和试剂层置于上层挡板和底层支架之间，作为中间层。
作为本发明的优选方案，检测尿肌酐的试纸条为干式化学试纸条，包括从上至下依次设置的尿液扩散层、过滤层、亲水层和试剂层，其中试剂层上有硫酸铜、柠檬酸钠、橙黄、聚乙烯吡咯烷酮和四甲基联苯胺。
更优选地，检测尿肌酐的试纸条还包括上层挡板和底层支架，尿液扩散层、过滤层、亲水层和试剂层置于上层挡板和底层支架之间，作为中间层。
作为本发明的优选方案，检测尿半胱氨酸蛋白酶抑制剂C的试纸条为干式化学试纸条，包括依次搭接的样品垫、硝酸纤维素膜和吸水垫，其中硝酸纤维素膜上有检测线和质控线，检测线上包被有抗半胱氨酸蛋白酶抑制剂C的抗体，质控线上包被有IgG抗体。
更优选地，检测尿半胱氨酸蛋白酶抑制剂C的试纸条还包括上层挡板和底层支架，样品垫、硝酸纤维素膜和吸水垫置于上层挡板和底层支架之间，作为中间层。
作为本发明的优选方案，光谱发射模块包括光谱发射电路和发射电源电路；光谱接收模块包括光谱接收电路和接收电源电路。
作为本发明的优选方案，数据处理模块包括微处理器（MCU）及其外围电路。
作为本发明的优选方案，输出模块包括人机交互模块和数据通讯模块；人机交互模块，用于实现人机交互，显示输出的浓度值和/或比值；数据通讯模块，用于实现远程信息通讯功能，将浓度值和/或比值传输至远程数据存储、分析平台。
根据本发明的第二方面，本发明提供一种非诊断性的糖尿病及其并发症的无创检测方法，包括：
检测模块向试纸条反应孔滴加尿液，试纸条与尿液中的尿糖、尿肌酐和尿半胱氨酸蛋白酶抑制剂C反应；
光谱发射模块向反应后的试纸条发射预定波长的入射光谱；
光谱接收模块接收通过试纸条并衰减后的光谱或荧光信号，并转换为模拟电信号；
信号转换模块将模拟电信号转换成数字信号；
数据处理模块根据数字信号计算出尿液样品中的尿糖、尿肌酐、尿半胱氨酸蛋白酶抑制剂C的浓度值，以及尿糖/尿肌酐比值和/或尿半胱氨酸蛋白酶抑制剂C/尿肌酐比值；
输出模块输出浓度值和/或比值。
作为本发明的优选方案，在检测模块向试纸条反应孔滴加尿液前还包括：获取受试者在餐后0.5~2.5h排空尿液且在餐后2~4.5h所取的尿液。
与现有糖尿病检测技术相比，本发明具有以下优势：本发明是定量测量，准确性和灵敏度相较现有尿糖试纸更高；引入尿肌酐作为参比，通过尿糖/尿肌酐比值准确反映尿液中随机尿糖的浓度，能排除外界干扰因素对尿糖浓度的影响；引入肾功能评价指标尿半胱氨酸蛋白酶抑制剂C，用于排除由于肾脏损伤，导致尿糖测试结果出现假阳性或假阴性，并且通过尿半胱氨酸蛋白酶抑制剂C评价肾功能，可以在早期监控糖尿病肾病并发症，实现糖尿病及其并发症的同步监测。
附图说明
图1为本发明一个实施例中的糖尿病及其并发症的无创检测系统的结构模式图；
图2为本发明另一个实施例中的糖尿病及其并发症的无创检测系统的结构模式图；
图3为本发明一个实施例中的非诊断性的糖尿病及其并发症的无创检测方法的流程图；
图4为本发明一个实施例中的糖尿病及其并发症的无创检测系统中尿糖和尿肌酐的检测试纸条结构示意图；
图5为本发明一个实施例中的糖尿病及其并发症的无创检测系统中尿半胱氨酸蛋白酶抑制剂C的检测试纸条结构示意图。
具体实施方式
下面通过具体实施例结合附图对本发明作进一步详细说明。
实施例一：
请参考图1，本发明一个实施例中的糖尿病及其并发症的无创检测系统包括：光谱发射模块10，用于发射预定波长的入射光谱；检测模块20，用于通过试纸条与尿液样品中的尿糖、尿肌酐和/或尿半胱氨酸蛋白酶抑制剂C反应并接收入射光谱；光谱接收模块30，用于接收通过试纸条并衰减后的光谱或荧光信号，并转换为模拟电信号；信号转换模块40，与光谱接收模块30连接，将电信号转换成数字信号；数据处理模块50，与信号转换模块40连接，根据数字信号计算出尿液样品中的尿糖、尿肌酐、尿半胱氨酸蛋白酶抑制剂C的浓度值，以及尿糖/尿肌酐比值和/或尿半胱氨酸蛋白酶抑制剂C/尿肌酐比值；输出模块60，与数据处理模块50连接，用于输出浓度值和/或比值。
本实施例的糖尿病及其并发症的无创检测系统引入尿肌酐作为参比。其依据说明如下：肾脏在过滤血液杂质时，葡萄糖可以自由通过肾小球，也就是说原尿中葡萄糖浓度和血液中葡萄糖浓度一致，在肾小管重吸收过程中，葡萄糖被肾小管上皮细胞重吸收。当血糖浓度超过肾糖阈（8.96 mmol/L -10.08mmol/L），肾小管上皮细胞对葡萄糖的吸收达到极限，葡萄糖不能被完全重吸收回血液，便出现糖尿。然而，尿糖浓度易受尿液量变化的影响，导致随机尿糖浓度测试不准。每个人在单位时间内分泌至尿中的尿肌酐含量是一定的，尿液中尿肌酐的浓度变化直接受外界环境的影响（如水分摄取过多等），当排出的水分多,尿肌酐浓度降低；当排出的水分较少，尿肌酐浓度升高。通过尿糖/尿肌酐比值，可以排除因为水分摄取过多等因素对尿溶液浓度的干扰，准确反应尿溶液溶质之一-尿糖的相对水平。其中，尿糖/尿肌酐=（单位时间尿糖含量/尿液量）/（单位时间尿肌酐含量/尿液量），因为单位时间内个体尿肌酐含量是恒定的，所以通过尿糖/尿肌酐可以排除尿液量对尿糖的影响，准确反映尿液实时尿糖含量。
本实施例的糖尿病及其并发症的无创检测系统引入肾功能评价指标（具体是肾小管功能指标）尿半胱氨酸蛋白酶抑制剂C（Cystatin C），用于排除由于肾脏损伤，导致尿糖测试结果出现假阳性或假阴性。同时，通过Cystatin C评价使用者的肾功能，可以用于早期检测糖尿病肾病并发症的发生。其依据说明如下：Cystatin C无组织特异性，在人体细胞内以恒定速度产生。血液中Cystatin C水平能反映肾小球滤过率。血液中Cystatin C能以恒定的速度通过肾小球基底膜，进入原尿中的Cystatin C在健康人肾小管处被完全重吸收。当肾小管发生损伤，尿液中就会有Cystatin C存在。大量的研究指出，当肾脏发生损伤，肾小管也会同时受损，影响肾小管重吸收功能。同时这些研究指出尿液中Cystatin C可作为肾病（包括糖尿病肾病）早期生物标志物。
实施例二：
请参考图2，在实施例一中监测系统的组成及其功能的基础上，本发明另一个实施例中的糖尿病及其并发症的无创检测系统包括：光谱发射模块10、检测模块20、光谱接收模块30、信号转换模块40、数据处理模块50和输出模块60。更详细地，光谱发射模块10包括光谱发射电路11和发射电源电路12，用于实时向发生反应后的试纸条发射特定波长的光波；检测模块20，通过检测试纸条进行检测，检测试纸条由敏感化学成分的薄片组成，薄片上含有能与尿糖、尿肌酐和尿Cystatin C发生特异的反应酶、底物或抗体，用于与尿液样品中的尿糖、尿肌酐和尿半胱氨酸蛋白酶抑制剂C反应并经入射光谱的照射后发出衰减后的光谱或荧光信号；光谱接收模块30，包括光谱接收电路31和接收电源电路32，用于接收一定波长范围的光谱信号，当光谱信号照射发生反应的试纸条后，照射光谱会发生一定程度衰减或发出荧光，计算光损失率或荧光强度，并将反射光谱或荧光信号转换为电信号；信号转换模块40，与光谱接收模块30连接，将尿液中尿糖、尿肌酐、尿Cystatin C浓度相关的电信号转换成微处理器能够识别和接收的数字信号；数据处理模块50，与信号转换模块40连接，包括微处理器（MCU）51及其外围电路52，将接收到的尿糖、尿肌酐、尿Cystatin C信息进行分析、计算，最后得到所测尿液样本中尿糖、尿肌酐、尿Cystatin C的浓度值以及尿糖/尿肌酐、尿Cystatin C/尿肌酐比值；输出模块60，与数据处理模块50连接，包括人机交互模块61和数据通讯模块62，其中，人机交互模块61进一步可以包括MCU、LCM显示器电路及键盘输入电路，用于实现人机交互，显示输出的浓度值和比值，即尿液中尿糖、尿肌酐、尿Cystatin C的浓度值，以及尿糖/尿肌酐、尿Cystatin C/尿肌酐比值测量数据结果；数据通讯模块62进一步可以包括MCU和数据通讯电路，用于实现远程信息通讯功能，将浓度值和比值传输至远程数据存储、分析平台。
需要说明的是，本发明中的模块或电路并不局限于特定电路图构造，因为用于实现各自功能的模块或电路，本领域的技术人员可以根据目前的技术进行选择。
本发明实施例一和实施例二的糖尿病及其并发症的无创检测系统检测尿液生物标志物的方法流程图如图3所示，包括以下步骤：S1.检测模块向试纸条反应孔滴加尿液，试纸条与尿液中的尿糖、尿肌酐和尿半胱氨酸蛋白酶抑制剂C反应；S2.光谱发射模块向反应后的试纸条发射预定波长的入射光谱；S3.光谱接收模块接收通过所述试纸条并衰减后的光谱或荧光信号，并转换为模拟电信号；S4.信号转换模块将所述模拟电信号转换成数字信号；S5.数据处理模块根据所述数字信号计算出所述尿液样品中的尿糖、尿肌酐、尿半胱氨酸蛋白酶抑制剂C的浓度值，以及尿糖/尿肌酐比值和/或尿半胱氨酸蛋白酶抑制剂C/尿肌酐比值；S6.输出模块输出所述浓度值和/或所述比值。
应当理解的是，本发明的糖尿病及其并发症的无创检测方法的应用范围并不局限于本发明中的具体构造的系统。
本发明实施例一和实施例二的糖尿病及其并发症的无创检测系统中的干式生化试纸条如图4和图5所示。
1）检测尿糖和尿肌酐的干式化学试纸条从上至下依次包括上层挡板（未示出）、中间层和底层支架（未示出）。中间层从上至下依次设有尿液扩散层、过滤层、亲水层和试剂层，其中试剂层可以融合在亲水层上。当向上层挡板两个相互独立的孔（图4中A和B）中分别加入尿液样本后，尿液样本在多孔聚酯纤维材料的尿液扩散层中均匀扩散，通过过滤层（玻璃纤维膜）滤掉杂质，与试剂层中的试剂发生反应，通过试纸颜色变化产生吸光值变化，检测光损失，得到尿液中相应目标物质的含量。
尿肌酐检测试纸检测方法：利用硫酸铜、柠檬酸钠、橙黄、聚乙烯吡咯烷酮和四甲基联苯胺制备尿肌酐检测试纸的试剂层，具体制备方法如下：先将试剂层充分浸入A液（1000ml溶液中含2mol/L Tris缓冲液，硫酸铜0.4g-2g，柠檬酸钠2-5g，橙黄2mg0-200mg，用纯水定容）后，取出并于70-100℃下干燥15-30min，然后将干燥后的试剂层浸入B液（聚乙烯吡咯烷酮10-20g，四甲基联苯胺3-5g，用氯仿定容），于70-100℃条件下干燥5-15min。当将尿液加入试纸反应孔中后，肌酐和硫酸铜生成络合物，该络合物可以与显色物橙黄和四甲基联苯胺发生反应显色。肌酐浓度在0.6mmol/L〜28mmol/L范围内，试纸呈现从浅黄到深绿的四级明显色阶，即淡黄-浅绿-草绿-深绿。通过传感器对反射光进行光谱分析（采用波长范围580-650nm），检测光损失，得到尿液中肌酐的浓度。具体地，尿肌酐的浓度与反应后试纸条的颜色深浅呈相关性，即与通过试纸条并衰减后的光谱强度呈相关性，进而与转换后的模拟电信号和数字信号呈相关性，通过一系列梯度浓度的标准品尿肌酐与对应的数字信号强度可以建立尿肌酐浓度与数字信号的标准曲线关系，根据标准曲线可以计算出测试的样本中尿肌酐的浓度。本领域技术人员通过本发明实施例的理解，能够通过现有技术计算出尿肌酐浓度值，在此不赘述。
尿糖检测试纸检测方法：利用葡萄糖氧化酶（GOD）、过氧化物酶、碘化钾、聚乙烯吡络烷酮配制尿葡糖糖试纸。具体来说，称取过氧化物酶1200U，葡萄糖氧化酶1200U，碘化钾100mg，聚乙烯吡络烷酮100mg，定容至100ml，将试剂层在溶液中浸泡，干燥30min。当将尿液加入试纸反应孔中后，尿糖与试纸上的葡萄糖氧化酶发生反应，残生葡萄糖酸和双氧水；双氧水再过氧化氢酶的催化下，释放出氧自由基[O：]，氧自由基与底物碘化钾发生显色反应，产生的游离碘与聚乙烯吡络烷酮形成棕色络合物。通过传感器对反射光进行光谱分析（采用波长范围550-750nm），检测光损失，得到尿液中尿糖浓度。具体地，尿糖的浓度与反应后试纸条的颜色深浅呈相关性，即与通过试纸条并衰减后的光谱强度呈相关性，进而与转换后的模拟电信号和数字信号呈相关性，通过一系列梯度浓度的标准品尿糖与对应的数字信号强度可以建立尿糖浓度与数字信号的标准曲线关系，根据标准曲线可以计算出测试的样本中尿糖的浓度。本领域技术人员通过本发明实施例的理解，能够通过现有技术计算出尿糖浓度值，在此不赘述。
2）检测尿Cystatin C的干式免疫荧光试纸条包括上层挡板（未示出）、中间层和底层支架（未示出）。其中，中间层从左到右依次粘有样品垫（图5中C）、硝酸纤维素膜、吸水垫三层，如图5所示，硝酸纤维素膜上设有检测线（C1）和质控线（C2），检测线包被的特异抗体为抗Cystatin C的单克隆抗体，质控线包被的特异抗体为兔IgG抗体。单独包装的铂卟啉标记抗体为抗微量白蛋白单克隆抗体和抗兔IgG抗体。通过检测硝酸纤维素膜上检测线和质控线铂卟啉荧光强度，计算出尿液样本中Cystatin C的浓度。
尿Cystatin C检测试纸检测方法：尿Cystatin C检测试纸条的硝酸纤维素膜在靠近点样孔的检测区域分别有检测线和质控线。检测线上包被有抗Cystatin C的抗体，质控线上包被有兔IgG抗体。同时，铂卟啉标记液中包含铂卟啉标记抗Cystatain C抗体和铂卟啉标记抗兔IgG抗体。检测时，将尿液样本和铂卟啉标记液以一定比例混合均匀，使铂卟啉标记抗体与尿液中目标蛋白（Cystatin C）充分结合，然后将混合液加入点样孔，3分钟后，将干式免疫荧光试纸条插入仪器，传感器发出光波（范围是400-420nm），读取检测线和质控线的荧光强度，根据荧光强度得出尿液中Cystatin C的浓度。具体地，尿Cystatin C的浓度与反应后试纸条上检测线的荧光强度呈相关性，进而与转换后的模拟电信号和数字信号呈相关性，通过一系列梯度浓度的标准品尿Cystatin C与对应的数字信号强度可以建立尿Cystatin C浓度与数字信号的标准曲线关系，根据标准曲线可以计算出测试的样本中尿Cystatin C的浓度。本领域技术人员通过本发明实施例的理解，能够通过现有技术计算出尿Cystatin C浓度值，在此不赘述。
根据尿糖、尿肌酐、尿Cystatin C、尿糖/尿肌酐和尿Cystatin C/尿肌酐的测量值作出判断：1）若尿液中尿糖值或尿糖/尿肌酐值超出正常范围（尿糖的正常范围为0-20mg/dL；尿糖/尿肌酐正常范围的上限值介于50-100mg/g），但未检测到尿Cystatin C，则判断受试者已患糖尿病，但未有并发症出现。此种应用可用于在人群中进行大规模初筛糖尿病患者，因为肾糖阈是一定的，所以当利用本方法测量出尿中有一定量葡萄糖时，说明受测人在一定程度上有或者将有患糖尿病的危险；2）对于已患糖尿病患者，若尿Cystatin C值超出正常范围（<0.15mg/dL），则说明患者易患糖尿病肾病；3）对于肾脏功能正常的糖尿病患者，可使用包含检测尿糖、尿肌酐的反应试纸（如图4中A、B）测量，尿糖、尿糖/尿肌酐参数可以在一定程度上反映患者血糖水平，在一定程度上可以减少患者扎手指的痛苦。
本发明的糖尿病及其并发症的无创检测系统的监测推荐方法为，对于人群大规模筛查糖尿病患者，优选地，受试者在餐后0.5h-2.5h排空尿液，餐后2h-4.5h取次尿测量尿糖、尿肌酐、尿Cystatin C。例如，在餐后1.5h排空尿液，餐后3h采集尿液，所采集的尿液中的尿糖浓度反应了餐后1.5h-3h内尿液的平均浓度，更能反映餐后血液血糖（实时）浓度；对于糖尿病患者预测并发症（糖尿病肾病）发生，优选地，受试者取晨尿中段尿液，测量尿糖、尿肌苷、尿Cystatin C；对于已患糖尿病，但未出现并发症的患者，受试者可以在血糖相对稳定的情况下，取晨尿、餐后尿、随机尿检测尿糖、尿肌酐，在一定程度上代替测量血糖。
表1示出了使用本发明的系统和方法检测的10个样本的情况。
编号 年龄 性别 BMI 餐后 (2h) 血糖<11.1( 正常 ) 糖化血红蛋白 (%)<6.5( 正常 ) eGFR(mg/min/1.73m2)>100( 正常 )
1 56 男 24.5 13.5 7.4 125
2 48 男 28 18.6 8.5 120
3 67 女 22 21 8.9 118
4 65 男 25 19.5 8.2 122
5 44 女 31 15 8.1 110
6 52 女 22.5 14.8 7.6 87
7 48 男 24 17 7.8 115
8 50 男 23 15.5 7.5 110
9 49 女 26 8.6 5.5 123
10 62 男 27.6 9 6.2 117
编号 年龄 性别 尿糖 0-20mg/dl(正常) 尿糖 / 尿肌酐<50-100mg/g (正常) 尿 CystatinC 0-0.15mg/L(正常)
1 56 男 44 225 0.1
2 48 男 56 286 0.04
3 67 女 58 193 0.06
4 65 男 41 391 0.08
5 44 女 50 152 0.12
6 52 女 37 480 1.05
7 48 男 55 355 0.06
8 50 男 61 173 0.11
9 49 女 11 68 0
10 62 男 13 73 0.02
注：表中1-8号为糖尿病患者（糖化血红蛋白及餐后血糖），9及10号为正常对照。其中，6号患者具有轻度糖尿病肾病（eGFR 87）。通过该方法检测，发现6号测试者尿Cystatin C值大于正常范围，暗示患有糖尿病肾病，不适用于用尿糖/尿肌酐值预测血糖浓度；其余患者无肾脏疾病；通过尿糖/尿肌酐值看，1-5及7、8号受试者尿糖/尿肌酐高于正常范围，暗示有不同程度糖尿病。
以上内容是结合具体的实施方式对本发明所作的进一步详细说明，不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干简单推演或替换。

Claims (13)

  1. 一种糖尿病及其并发症的无创检测系统，其特征在于，所述系统包括:
    光谱发射模块，用于发射预定波长的入射光谱；
    检测模块，用于通过试纸条与尿液样品中的尿糖、尿肌酐和/或尿半胱氨酸蛋白酶抑制剂C反应并接收所述入射光谱；
    光谱接收模块，用于接收通过所述试纸条并衰减后的光谱或荧光信号，并转换为模拟电信号；
    信号转换模块，与所述光谱接收模块连接，将所述模拟电信号转换成数字信号；
    数据处理模块，与所述信号转换模块连接，根据所述数字信号计算出所述尿液样品中的尿糖、尿肌酐、尿半胱氨酸蛋白酶抑制剂C的浓度值，以及尿糖/尿肌酐比值和/或尿半胱氨酸蛋白酶抑制剂C/尿肌酐比值；
    输出模块，与所述数据处理模块连接，用于输出所述浓度值和/或所述比值。
  2. 根据权利要求1所述的系统，其特征在于，所述尿液样品来自受试者在餐后0.5~2.5h排空尿液，且在餐后2~4.5h所取的尿液。
  3. 根据权利要求1所述的系统，其特征在于，所述检测尿糖的试纸条为干式化学试纸条，包括从上至下依次设置的尿液扩散层、过滤层、亲水层和试剂层，其中所述试剂层上有葡萄糖氧化酶、过氧化物酶、碘化钾和聚乙烯吡络烷酮。
  4. 根据权利要求3所述的系统，其特征在于，所述试纸条还包括上层挡板和底层支架，所述尿液扩散层、过滤层、亲水层和试剂层置于所述上层挡板和底层支架之间，作为中间层。
  5. 根据权利要求1所述的系统，其特征在于，所述检测尿肌酐的试纸条为干式化学试纸条，包括从上至下依次设置的尿液扩散层、过滤层、亲水层和试剂层，其中所述试剂层上有硫酸铜、柠檬酸钠、橙黄、聚乙烯吡咯烷酮和四甲基联苯胺。
  6. 根据权利要求5所述的系统，其特征在于，所述试纸条还包括上层挡板和底层支架，所述尿液扩散层、过滤层、亲水层和试剂层置于所述上层挡板和底层支架之间，作为中间层。
  7. 根 据权利要求1所述的系统，其特征在于，所述检测尿半胱氨酸蛋白酶抑制剂C的试纸条为干式化学试纸条，包括依次搭接的样品垫、硝酸纤维素膜和吸水垫，其中所述硝酸纤维素膜上有检测线和质控线，所述检测线上包被有抗半胱氨酸蛋白酶抑制剂C的抗体，所述质控线上包被有IgG抗体。
  8. 根据权利要求7所述的系统，其特征在于，所述试纸条还包括上层挡板和底层支架，所述样品垫、硝酸纤维素膜和吸水垫置于所述上层挡板和底层支架之间，作为中间层。
  9. 根据权利要求1所述的系统，其特征在于，所述光谱发射模块包括光谱发射电路和发射电源电路；所述光谱接收模块包括光谱接收电路和接收电源电路。
  10. 根据权利要求1所述的系统，其特征在于，所述数据处理模块包括MCU及其外围电路。
  11. 根据权利要求1所述的系统，其特征在于，所述输出模块包括人机交互模块和数据通讯模块；所述人机交互模块，用于实现人机交互，显示输出的所述浓度值和/或所述比值；所述数据通讯模块，用于实现远程信息通讯功能，将所述浓度值和/或所述比值传输至远程数据存储、分析平台。
  12. 一种非诊断性的糖尿病及其并发症的无创检测方法，其特征在于，所述方法包括：
    检测模块向试纸条反应孔滴加尿液，试纸条与尿液中的尿糖、尿肌酐和尿半胱氨酸蛋白酶抑制剂C反应；
    光谱发射模块向反应后的试纸条发射预定波长的入射光谱；
    光谱接收模块接收通过所述试纸条并衰减后的光谱或荧光信号，并转换为模拟电信号；
    信号转换模块将所述模拟电信号转换成数字信号；
    数据处理模块根据所述数字信号计算出所述尿液样品中的尿糖、尿肌酐、尿半胱氨酸蛋白酶抑制剂C的浓度值，以及尿糖/尿肌酐比值和/或尿半胱氨酸蛋白酶抑制剂C/尿肌酐比值；
    输出模块输出所述浓度值和/或所述比值。
  13. 根据权利要求12所述的方法，其特征在于，在所述检测模块向试纸条反应孔滴加尿液前还包括：
    获取受试者在餐后0.5~2.5h排空尿液且在餐后2~4.5h所取的尿液。
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