Kit and system for diagnosing diabetes

Abstract

The invention relates to a kit and a system for diagnosing diabetes. The kit includes several cells to contain several concentrations of an HDAR2 receptor activator or an HDAR3 receptor activator or an ester aqueous solution thereof. The kit provided by the invention can be used for effectively diagnosing diabetes mellitus by evaluating the sensitivity degree of a subject to the HDAR2 receptor activator or the HDAR3 receptor activator or the ester thereof. The system disclosed by the invention can be used for quickly obtaining a detection result through several simple steps of operation in a short time, realizes multi-scene real-time detection in wards, physical examination centers, homes and the like, and is an objective, quick and effective biological detection means for diabetes risk early warning.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical detection technology. In particular, the present application relates to a kit and a system for diagnosing diabetes. BACKGROUND

[0002] Diabetes is a metabolic disease with high incidence in the population, characterized by high blood sugar.

[0003] Currently, the clinical diagnosis of diabetes relies on fasting blood glucose and glucose tolerance test. Fasting blood glucose detection is easily disturbed by other diseases such as chronic renal insufficiency, hemolysis, jaundice, and some drugs such as glucocorticoids, oral contraceptives, etc. Glucose tolerance test is easily affected by non-strict fasting, drugs, etc. In order to ensure the stability of the results of glucose tolerance test, the venous blood of the subject is usually collected continuously, and the operation is complex.

[0004] Therefore, it is desirable to develop a simple, stable and less disturbed method for the auxiliary diagnosis of diabetes. SUMMARY

[0005] An object of the present application is to provide a method for diagnosing diabetes, which is simple, stable and less disturbed, and can be used for the auxiliary diagnosis of diabetes.

[0006] Another object of the present application is to provide a kit for diagnosing diabetes, which can be used in the above-mentioned diagnostic method.

[0007] Another object of the present application is to provide a system for diagnosing diabetes, which can be used to implement the above-mentioned diagnostic method.

[0008] The present application is based on the following findings of the inventors: HCAR2 receptor activators and HCAR3 receptor activators and esters thereof can be used for the detection of diabetes.

[0009] Therefore, according to a first aspect, the present application provides the use of an active substance selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof and combinations thereof in the manufacture of a kit for diagnosing diabetes.

[0010] According to a second aspect, the present application provides a system for diagnosing diabetes, characterized in that it comprises:

[0011] a kit comprising an active substance selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof and combinations thereof;

[0012] a reactor;

[0013] an imaging device for obtaining images; and

[0014] An image processing device for information acquisition and optionally processing of images.

[0015] According to a third aspect, the present application provides a method for diagnosing diabetes, characterized in that it comprises the following steps:

[0016] contacting the skin of the subject with an active selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof, and combinations thereof;

[0017] acquiring an image of the skin of the subject;

[0018] acquiring information from the image; and

[0019] processing the acquired information and comparing the result of the processing with predetermined information.

[0020] The kit of the present application can be used to effectively diagnose and evaluate diabetes by assessing the sensitivity of the subject to HCAR2 receptor activators or HCAR3 receptor activators or esters thereof.

[0021] The system and method of the present application can be used to quickly obtain a detection result in a short time through a simple few-step operation, realize real-time detection in multiple scenarios such as a ward, a physical examination center, and a home, and is an objective, fast, and effective biological detection means for early warning of diabetes, which is not easily interfered by other diseases, drugs, and the like. BRIEF DESCRIPTION OF DRAWINGS

[0022] The present application will be described and explained in more detail in connection with the following drawings in which:

[0023] Figure 1 A reactor with several wells is schematically shown, wherein 1 is the reactor and 11 is the well.

[0024] Figure 2 A reactor composed of several patches is schematically shown, wherein 2 is the reactor and 21 is the patch.

[0025] Figure 3 The comparison of the degree of skin niacin response values of the diabetes patients and the healthy control population in Example 1 is shown. DETAILED DESCRIPTION

[0026] Some specific embodiments of the present application are described for illustrative purposes and not by way of limitation.

[0027] Kit for diagnosing diabetes

[0028] According to a first aspect, the present application provides the use of an active selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof, and combinations thereof in the preparation of a kit for diagnosing diabetes.

[0029] HCAR2 receptor refers to hydroxycarboxylic acid receptor 2, also known as GPR109A.

[0030] HCAR3 receptor refers to hydroxycarboxylic acid receptor 3, also known as GPR109B.

[0031] In the present application, for the sake of simplicity, the HCAR2 receptor activator or HCAR3 receptor activator or ester thereof is also sometimes referred to as active compound.

[0032] Preferably, the active substance is selected from the group consisting of nicotinic acid, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0033] Nicotinic acid, methyl nicotinate and ethyl nicotinate have the following structures, respectively:

[0034]

[0035] Preferably, the active substance in the kit is in the form of an aqueous solution.

[0036] Preferably, the kit comprises an aqueous solution of the active substance at a concentration of 0.1 mM or more. More preferably, the concentration of the active substance in the aqueous solution is 0.15 mM or more, or 0.5 mM or more, or 1 mM or more, or 3 mM or more, or 10 mM or more, or 20 mM or more.

[0037] Preferably, the concentration of the active substance in the aqueous solution is not more than 1000 mM.

[0038] The kit comprises several chambers to accommodate several concentrations of aqueous solutions of the active substance.

[0039] In the present specification and claims, several can encompass one or more.

[0040] In the case of more than one chamber, the concentrations of the aqueous solutions of the active substance contained therein can be the same or different.

[0041] In some embodiments, the kit comprises at least 2 different concentrations of aqueous solutions of the active substance, the maximum concentration being at least 20 mM, with the concentrations decreasing by a factor of 2-10.

[0042] In some embodiments, the kit comprises at least 2 different concentrations of aqueous solutions of the active substance, the maximum concentration being 100 mM or less, with the concentrations decreasing by a factor of 2-10.

[0043] In some embodiments, the kit comprises at least 6 different concentrations of aqueous solutions of the active substance, the maximum concentration being 60 mM, with the concentrations decreasing by a factor of 3.

[0044] The diagnosis comprises:

[0045] contacting the active substance to the skin of the subject;

[0046] capturing an image of the skin of the subject;

[0047] information acquisition from the image and processing of the information acquired from the image and comparing the results of the processing with predetermined information.

[0048] The subject is a human.

[0049] In the present application, the reaction degree value refers to the degree of reaction of the skin when it is in contact with the active compound, the determination of which is described in detail hereinafter.

[0050] Further details regarding the diagnosis are described in detail hereinafter.

[0051] System for diagnosing diabetes

[0052] According to a second aspect, the present application provides a system for diagnosing diabetes, characterized in that it comprises:

[0053] a kit comprising an active substance selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof and combinations thereof;

[0054] a reactor;

[0055] an imaging device for obtaining an image; and

[0056] an image processing device for information acquisition from the image and optionally processing of the information acquired from the image.

[0057] Preferably, the active substance is selected from the group consisting of niacin, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0058] In some embodiments, the reactor can have several holes to place the active substance.

[0059] The holes can have any shape, preferably circular holes, square holes, rectangular holes, or combinations thereof.

[0060] The holes can have the same or different areas.

[0061] Figure 1 A reactor with several holes is schematically shown, wherein 1 is the reactor and 11 is the hole.

[0062] In the case of using a reactor with several holes, the reactor is brought into contact with the skin of the subject and then several amounts of the active substance are applied to the holes.

[0063] In some embodiments, the reactor simply consists of several patches capable of containing the active substance.

[0064] The patches can have any shape, preferably a circular hole, a square hole, a rectangular hole, or a combination thereof.

[0065] The patches can have the same or different areas.

[0066] Figure 2 A reactor composed of several patches is schematically shown, wherein 2 is the reactor and 21 is the patch.

[0067] In the case of a reactor composed of several patches, the patches are brought into contact with the skin of the subject.

[0068] Preferably, the imaging device comprises:

[0069] a box constituting a closed space, the box being provided with an entrance for the forearm of the subject to extend into; and

[0070] an image acquisition assembly for imaging the skin of the forearm of the subject extending into the box and acquiring the resulting image.

[0071] Preferably, the image acquisition assembly is further capable of receiving a timed shooting signal. The timed shooting signal is used to trigger the image acquisition assembly to image the skin of the forearm of the subject at a plurality of predetermined time points.

[0072] Preferably, the image processing device comprises:

[0073] an image information acquisition assembly for acquiring information from the image; and

[0074] an optional information processing assembly for calculating the information acquired from the image.

[0075] The information includes at least one of the redness characteristic values of the red and swollen area, such as the area of the skin redness and swelling, and the chroma.

[0076] For example, the image can be acquired as described in patent application CN202110707754.0.

[0077] The processing can be quantifying the red and swollen area using algorithm software or calculation formula.

[0078] For example, the information can be processed as described in patent application CN202110707754.0.

[0079] Optionally, the system further comprises auxiliary tools, such as ranging tools, timers, etc.

[0080] In some embodiments, the system further comprises a ranging tool to determine the distance between the active substance contact areas.

[0081] In some embodiments, the system further comprises a timer to control the active substance contact time and / or the interval and total time of image acquisition.

[0082] Method for diagnosing diabetes

[0083] According to a third aspect, the present application provides a method for diagnosing diabetes, characterized in that it comprises the steps of:

[0084] contacting the skin of the subject with an active substance selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof and combinations thereof;

[0085] acquiring an image of the skin of the subject;

[0086] information acquisition from the image; and

[0087] processing the acquired information and comparing the result of the processing with pre-set information.

[0088] The subject is a human.

[0089] The inventors have found that the method of the present application is particularly effective for the diagnosis of diabetes.

[0090] The active substance is selected from the group consisting of nicotinic acid, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0091] The active substance is in the form of an aqueous solution.

[0092] One or more different concentrations of the active substance aqueous solution can be used to contact the skin of the subject.

[0093] Preferably, several different concentrations of the active substance aqueous solution are used to contact the skin of the subject.

[0094] For example, at least 2 different concentrations of the active substance aqueous solution are used to contact the skin of the subject, the maximum concentration being at least 20 mM, for example 0.50-100 mM, the concentrations decreasing by a factor of 2 in each case.

[0095] For example, at least 2 different concentrations of the active substance aqueous solution are used to contact the skin of the subject, the maximum concentration being 100 mM, the concentrations decreasing by a factor of 10 in each case.

[0096] For example, at least 6 different concentrations of the active substance aqueous solution are used to contact the skin of the subject, the maximum concentration being 60 mM, the concentrations decreasing by a factor of 3 in each case.

[0097] The active substance can be brought into contact with the skin of the subject by placing it in a reactor and contacting the reactor with the skin of the subject.

[0098] The active substance can also be brought into contact with the skin by means of a patch comprising the active substance.

[0099] Preferably, the active substance is allowed to contact the skin of the subject for 0.5-2 minutes. More preferably, the active substance is allowed to contact the skin of the subject for at least 1 minute.

[0100] Preferably, the skin refers to the skin of the forearm of the subject.

[0101] Without being bound by any theory, the inventors believe that after the active substance penetrates into the skin, it or its decomposition product, nicotinic acid, activates the HCAR2 or HCAR3 receptors on the skin cells, which in turn causes a transient redness reaction of the local skin. The inventors found that this reaction is widely impaired in diabetic patients, showing a weaker redness than in healthy people.

[0102] The image acquisition of the skin of the subject can be performed by an imaging device.

[0103] The image acquisition of the skin of the subject can be performed by an imaging device.

[0104] Preferably, the image acquisition of the skin of the subject is performed immediately after the end of the contact of the skin with the active substance.

[0105] Preferably, the image acquisition of the skin of the subject is performed by an imaging device for at least 30 seconds, for example from 30 seconds to 20 minutes. The image acquisition frequency can be several images per minute, for example 1 image / minute or 6 images / minute (i.e. 1 image / 10 seconds).

[0106] The image acquisition is performed perpendicular to the skin in contact with the active compound.

[0107] The information acquisition from the images can be performed by an image processing device.

[0108] The information acquisition from the images comprises the acquisition of the characteristics of the skin reaction of the subject from the images, i.e. the redness characteristics of the redness area, including at least one of the area of the skin redness, the chroma, and giving a corresponding quantification index.

[0109] The quantification index is a reaction degree value of the active substance, which can be obtained, for example, by superimposing the redness area.

[0110] For example, in some embodiments, the reaction degree value is obtained by:

[0111] (1) the software positions the reaction area and the skin base color with the first photo as the base map;

[0112] (2) starting from the second photo, the software identifies the redness area on each photo according to the color change of each photo relative to the base map, and quantifies the area of each redness area;

[0113] (3) the area values of the redness areas on each photo are added to obtain the reaction degree value.

[0114] Processing the collected information can include substituting the quantitative indicators of the collected information (i.e. the active substance reaction degree value) into the binary logistic regression algorithm of Formula 1 to obtain the diabetes risk value P of the subject, and making a diabetes diagnosis according to the calculation result:

[0115]

[0116] Wherein k is the active ingredient reaction degree value of the subject.

[0117] The greater the P value, the higher the risk degree.

[0118] When the P value is greater than 0.35, the subject is diagnosed as a diabetes patient.

[0119] In some embodiments, the method according to the present application comprises the following steps:

[0120] Several patches containing aqueous solutions of active substances with different concentrations are attached flat to the inner side of the subject's forearm;

[0121] After a certain reaction time, the patches are removed and the subject's arm is placed in an imaging device for image acquisition;

[0122] The skin reaction characteristics of the subject are extracted from the image acquisition, including at least one of the skin redness area and the color under each concentration of stimulation, and the corresponding quantitative indicators are given;

[0123] The quantitative indicators of the collected information are substituted into the binary logistic regression algorithm of Formula 1 above to obtain the diabetes risk value P of the subject, and a diabetes diagnosis is made according to the calculation result.

[0124] In some embodiments, the method according to the present application comprises the following steps:

[0125] At least two patches containing aqueous solutions of active substances (methyl nicotinate) with different concentrations (the maximum concentration is 50-100 mM, and the concentration decreases by 2-10 times successively) are attached flat to the inner side of the subject's forearm;

[0126] After a certain reaction time (e.g. 0.5-2 minutes, e.g. 1 minute), the patches are removed and the subject's arm is placed in an imaging device for image acquisition at a frequency of 1 photo / 10 seconds for a certain time (e.g. 10 minutes);

[0127] An image recognition software based on machine learning is used to extract and analyze the skin reaction characteristics of the subject, including at least one of the skin redness area and the color under each concentration of stimulation;

[0128] The quantified skin reaction index given by the software is substituted into the binary logistic regression algorithm of formula 1 above to obtain the diabetes risk value P of the subject, and the diabetes is diagnosed according to the calculation result.

[0129] For example, the skin reaction characteristics of the subject can be extracted and analyzed as described in patent application CN202110707754.0.

[0130] For example, in some embodiments, the skin is contacted with an aqueous solution of the active compound at 6 different concentrations (the maximum concentration is 50-100M, and the concentration decreases by 3 times in turn) for 0.5-2 minutes, for example 1 minute, and photographs are taken at a frequency of 1 photograph per 10 seconds after stopping the contact for 0-10 minutes, the characteristic information of the subject, i.e. the skin redness area and color, is collected, the characteristic information is processed to obtain the active ingredient reaction degree value k of the subject, which is substituted into the binary logistic regression algorithm of formula 1 to obtain the diabetes risk value P of the subject:

[0131]

[0132] When the P value is greater than 0.35, the subject is diagnosed as a diabetes patient.

[0133] By the method of the present application, the detection rate of diabetes reaches more than 80%.

[0134] The method according to the present application is a non-invasive detection method, which has very high sensitivity for diabetes, and therefore has good application prospects in auxiliary diagnosis.

[0135] The method according to the present application is different from the conventional hospital detection, and can well realize real-time disease monitoring of the subject at home, and is an effective monitoring means that can simultaneously realize hospital detection and independent completion by the terminal patient.

[0136] The present application at least provides the following embodiments:

[0137] Embodiment 1: Use of an active substance selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof and combinations thereof in the preparation of a kit for diagnosing diabetes.

[0138] Embodiment 2: The use according to embodiment 1, characterized in that the active substance is selected from the group consisting of nicotinic acid, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0139] Embodiment 3: The use according to embodiment 1 or 2, characterized in that the active substance is in the form of an aqueous solution.

[0140] Embodiment 4: The use according to any one of embodiments 1 to 3, characterized in that the kit comprises a plurality of chambers to accommodate aqueous solutions of the active substance at a plurality of concentrations.

[0141] Embodiment 5. The use according to any one of embodiments 1 to 4, characterized in that the kit comprises an aqueous solution of the active substance in a concentration of 0.1 mM or more, 0.15 mM or more, 0.5 mM or more, 1 mM or more, 3 mM or more, 10 mM or more, or 20 mM or more.

[0142] Embodiment 6. The use according to any one of embodiments 1 to 5, characterized in that the kit comprises an aqueous solution of the active substance in a concentration of 1000 mM or less.

[0143] Embodiment 7. The use according to embodiment 4, characterized in that the kit comprises at least two aqueous solutions of the active substance in different concentrations, the maximum concentration being at least 20 mM, the concentrations decreasing by a factor of 2 to 10.

[0144] Embodiment 8. The use according to embodiment 4, characterized in that the kit comprises at least two aqueous solutions of the active substance in different concentrations, the maximum concentration being 100 mM or less, the concentrations decreasing by a factor of 2 to 10.

[0145] Embodiment 9. The use according to embodiment 4, characterized in that the kit comprises at least six aqueous solutions of the active substance in different concentrations, the maximum concentration being 60 mM, the concentrations decreasing by a factor of 3.

[0146] Embodiment 10. The use according to any one of embodiments 1 to 9, characterized in that the diagnosis comprises:

[0147] contacting the active substance with the skin of the subject;

[0148] capturing an image of the skin of the subject;

[0149] information acquisition from the image and processing of the information acquired from the image and comparing the results of the processing with predetermined information.

[0150] Embodiment 11. A system for diagnosing diabetes, characterized in that it comprises:

[0151] a kit comprising an active substance selected from the group consisting of an HCAR2 receptor activator, an HCAR3 receptor activator, esters thereof, and combinations thereof;

[0152] a reactor;

[0153] an imaging device for obtaining an image; and

[0154] an image processing device for information acquisition from the image and optionally processing of the image.

[0155] Embodiment 12. The system of claim 11, wherein the active substance is selected from the group consisting of niacin, methyl niacin, ethyl niacin, and combinations thereof.

[0156] Embodiment 13. The system of embodiment 11 or 12, wherein the reactor has a plurality of holes for placing the active substance, the holes having any shape, preferably circular holes, square holes, rectangular holes, or combinations thereof.

[0157] Embodiment 14. The system of embodiment 11 or 12, wherein the reactor is composed of a plurality of patches capable of containing the active substance, the patches having any shape, preferably circular holes, square holes, rectangular holes, or combinations thereof.

[0158] Embodiment 15. The system of any one of embodiments 11 to 14, wherein the imaging device comprises:

[0159] a box constituting a closed space, the box being provided with an entrance for a human forearm to enter; and

[0160] an image acquisition assembly for imaging the skin of the human forearm entering the box and acquiring the resulting image.

[0161] Embodiment 16. The system of claim 15, wherein the image acquisition assembly is capable of receiving a timed shooting signal.

[0162] Embodiment 17. The system of any one of claims 11 to 16, wherein the image processing device comprises:

[0163] an image information acquisition assembly for acquiring information from the image; and

[0164] an optional information processing assembly for calculating the information acquired from the image.

[0165] Embodiment 18. The system of any one of embodiments 11 to 17, wherein the information comprises at least one selected from the group consisting of skin redness area, color intensity.

[0166] Embodiment 19. A method for diagnosing diabetes, comprising the steps of:

[0167] contacting the skin of a subject with an active substance selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof, and combinations thereof;

[0168] acquiring an image of the skin of the subject;

[0169] acquiring information from the image; and

[0170] The collected information is processed and the processing result is compared with preset information.

[0171] Embodiment 20. The method according to embodiment 19, characterized in that the active substance is selected from the group consisting of nicotinic acid, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0172] Embodiment 21. The method according to embodiment 19 or 20, characterized in that the active substance is in the form of an aqueous solution.

[0173] Embodiment 22. The method according to any one of embodiments 19 to 21, characterized in that the skin of the subject is contacted with one or more different concentrations of the active substance in aqueous solution.

[0174] Embodiment 23. The method according to embodiment 22, characterized in that the skin of the subject is contacted with at least two different concentrations of the active substance in aqueous solution, the maximum concentration being at least 20 mM, the concentrations decreasing by a factor of 2-10 in sequence.

[0175] Embodiment 24. The method according to embodiment 22, characterized in that the skin of the subject is contacted with at least two different concentrations of the active substance in aqueous solution, the maximum concentration being 100 mM or less, the concentrations decreasing by a factor of 2-10 in sequence.

[0176] Embodiment 25. The method according to embodiment 22, characterized in that the skin of the subject is contacted with at least six different concentrations of the active substance in aqueous solution, the maximum concentration being 60 mM, the concentrations decreasing by a factor of 3 in sequence.

[0177] Embodiment 26. The method according to any one of embodiments 19 to 25, characterized in that the skin of the subject is contacted with the active substance for 0.5-2 minutes.

[0178] Embodiment 27. The method according to any one of embodiments 19 to 26, characterized in that, after the end of the contact of the skin with the active substance, the skin is subjected to image acquisition by an imaging device for at least 2 minutes, preferably at least 3 minutes, for example 5 to 20 minutes.

[0179] Embodiment 28. The method according to any one of embodiments 19 to 27, characterized in that the information acquisition from the image comprises the acquisition of a feature value of the skin reaction of the subject from the image, namely the redness of the area of the skin reaction, including at least one of the area of the skin reaction and the chroma, and the provision of a corresponding quantification index.

[0180] Embodiment 29. The method according to embodiment 28, characterized in that the quantification index is a degree of reaction value of the active substance, which is obtained by:

[0181] (1) The software takes the first photo as the base map, locates the reaction area and the skin base color;

[0182] (2) Starting from the second photo, the software identifies the redness area on each photo according to the color change of each photo relative to the base map, and quantifies the area of each redness area;

[0183] (3) Add the area values of the redness areas on each photo to get the reaction degree value.

[0184] Embodiment 30, the method according to any one of embodiments 19 to 29, characterized in that processing the collected information can include substituting the quantitative indicators of the collected information into a binary logistic regression algorithm of formula 1 to obtain a diabetes risk value P of the subject, and making a diagnosis of diabetes according to the calculation result:

[0185]

[0186] Wherein k is the active ingredient reaction degree value of the subject.

[0187] Embodiment 31, the method according to embodiment 30, characterized in that when the P value is greater than 0.4, the subject is diagnosed as a diabetes patient.

[0188] The descriptions of various features in the present application can be combined with each other without contradiction, and all fall within the scope of the present application.

[0189] In the present application, "comprising" and "including" cover the case of also containing or including other elements not explicitly mentioned and the case of consisting of the mentioned elements.

[0190] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. When terms in the specification are defined in the present application, they are defined in accordance with the definitions described herein.

[0191] Unless otherwise indicated, all numerical values of the amount of components expressed in the specification and claims are understood to be modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that can vary depending upon the desired properties sought to be obtained by the present application.

[0192] Examples

[0193] The concept and the technical effects of the present application will be further described in conjunction with the embodiments and the technical effects generated, so that those skilled in the art can fully understand the purposes, features and effects of the present application. Those skilled in the art will understand that the embodiments herein are only for illustrative purposes, and the scope of the present application is not limited thereto.

[0194] Example 1:

[0195] Sample collection

[0196] Fifty-three patients with diabetes mellitus (patient group) and seventy-nine healthy persons (healthy control group (HC)) who were definitely diagnosed by a clinician were recruited as subjects.

[0197] Methyl nicotinate reaction

[0198] Six points in a designated area on one arm of the above-mentioned subjects were designated as active substance reaction points, and 60 mM, 20 mM, 6.67 mM, 2.22 mM, 0.74 mM, and 0.25 mM aqueous solutions of methyl nicotinate were applied to the reaction points by patches, and the patches were removed after 1 minute.

[0199] Skin image acquisition

[0200] After the patches were removed, the subjects were asked to place their arms in an imaging device, and immediately after the start of the imaging, one image was taken every 10 seconds for 10 minutes, and a total of 60 images were taken for each subject, and each image had six reaction areas.

[0201] Image processing of acquired photographs

[0202] The redness area was quantified by a processing device (e.g., algorithm software), and the sum of all quantified values within the observation time was calculated as the reaction degree value of the subject to nicotinic acid.

[0203] Specifically, the software used the first image as a base image, and located the reaction area and the skin base color. Starting from the second image, the software identified the redness area on each image based on the color change of each image relative to the base image, and quantified the area of each redness area. The area values of the redness area on each image were added to obtain the reaction degree value.

[0204] Figure 3 The nicotinic acid reaction degree values of the diabetes mellitus group and the healthy control group after stimulation with different concentrations of methyl nicotinate are shown.

[0205] From Figure 3 It can be seen that the methyl nicotinate reaction of the diabetes mellitus group was significantly impaired (p<0.001).

[0206] Methyl nicotinate reaction evaluation

[0207] The degree of skin nicotinic acid reaction redness value is substituted into the binary logistic regression algorithm of Formula 1 to obtain the diabetes risk value P of the subject:

[0208]

[0209] wherein k represents the degree of active ingredient reaction of the subject.

[0210] When P is greater than 0.35, the subject is diagnosed as a diabetes patient.

[0211] In this embodiment, the diagnosis efficiency for patients is 81%, and the diagnosis efficiency for healthy people is 72%.

[0212] The above only describes exemplary embodiments or examples of the present application, and is not intended to limit the present application. The present application can be variously changed and modified by those skilled in the art. Any modification, equivalent replacement, improvement, etc. within the spirit and principle of the present application is included in the scope of the claims of the present application.

Claims

1. Use of an active substance selected from the group consisting of HCAR2 receptor activators, HCAR3 receptor activators, esters thereof and combinations thereof for the manufacture of a kit for the diagnosis of diabetes.

2. Use according to claim 1, characterized in that, The active substance is selected from the group consisting of nicotinic acid, methyl nicotinate, ethyl nicotinate and combinations thereof.

3. Use according to claim 1 or 2, characterized in that, The active substance is in the form of an aqueous solution.

4. Use according to any one of claims 1 to 3, characterized in that, The kit comprises several chambers to contain several concentrations of the active substance aqueous solution.

5. Use according to any one of claims 1 to 4, characterized in that, The kit comprises an active substance aqueous solution at a concentration of 0.1 mM or more, 0.15 mM or more, 0.5 mM or more, 1 mM or more, 3 mM or more, 10 mM or more or 20 mM or more.

6. Use according to any one of claims 1 to 5, characterized in that, The kit comprises an active substance aqueous solution at a concentration of not more than 1000 mM.

7. Use according to claim 4, characterized in that, The kit comprises at least two different concentrations of the active substance aqueous solution, the maximum concentration being at least 20 mM, the concentrations decreasing by a factor of 2 to 10.

8. Use according to claim 4, characterized in that, The kit comprises at least two different concentrations of the active substance aqueous solution, the maximum concentration being 100 mM or less, the concentrations decreasing by a factor of 2 to 10.

9. Use according to claim 4, characterized in that, The kit comprises at least six different concentrations of the active substance aqueous solution, the maximum concentration being 60, the concentrations decreasing by a factor of 3.

10. Use according to any one of claims 1 to 9, characterized in that, The diagnosis comprises: contacting the active substance with the skin of the subject; capturing an image of the skin of the subject; capturing information from the image and processing the information captured from the image and comparing the results of the processing with predetermined information.

Images