Health state evaluation system, health state evaluation program, health state evaluation method, dietary evaluation system, dietary evaluation program and dietary evaluation method

Abstract

To increase the accuracy of discovering a high risk group of lifestyle-related diseases.SOLUTION: The inventors of the present application have first noted relations among lifestyle-related diseases, metabolic syndrome, and a concentration of LPS in blood. After deep consideration based on the relations, the inventors of the present application have found out that there are a correlation between an index of the adult disease and the concentration of LPS in blood and a correlation between the metabolic syndrome and the concentration of LPS in blood. When the present invention is defined from this point of view, processing executed by a computer according to a health state evaluation program is at least determination. What is determined by the computer is a health state of a subject, and what is referenced at that time is the concentration of LPS in blood in the subject.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to a health condition evaluation system, a health condition evaluation program, and a health condition evaluation method, as well as a dietary habit evaluation system, a dietary habit evaluation program, and a dietary habit evaluation method. [Background technology]

[0002] Improvement of metabolic syndrome is essential for preventing lifestyle-related diseases. Lifestyle-related diseases are a general term for diseases caused by lifestyle habits. Examples include cancer, cardiovascular disease, COPD (chronic obstructive pulmonary disease), diabetes, hypertension, dyslipidemia, fatty liver, arteriosclerosis, etc. Metabolic syndrome is a pathological condition of visceral fat obesity, which is accompanied by two or more of hyperglycemia, dyslipidemia, and hypertension. In other words, metabolic syndrome is defined as a high-risk group for lifestyle-related diseases (particularly cardiovascular disease).

[0003] The situation in Japan is serious. According to a report in Non-Patent Document 1, approximately 25% of people undergoing specific health checkups in Japan are either at risk of developing metabolic syndrome or at risk of developing it. Specific health checkups are primarily responsible for the early detection of metabolic syndrome. Specific health checkups examine waist circumference, blood sugar, lipids, and blood pressure (hereinafter, these are referred to as "test indicators" and their values ​​as "test values").

[0004] Specific health guidance is primarily responsible for improving metabolic syndrome. Specific health guidance is given to subjects whose test values ​​are outside the range of prescribed standards. In other words, subjects who are neither at risk of metabolic syndrome nor at risk of developing it (hereinafter referred to as "persons not at risk of metabolic syndrome, etc.") are not eligible for guidance.

[0005] However, those who are overlooked in specific health examinations and specific health guidance are those who are not affected by metabolic syndrome and are at high risk of lifestyle-related diseases. According to a report in Non-Patent Document 2, the proportion of Japanese men in their 20s who are affected by metabolic syndrome or at risk of developing it is about 10%, and about 40% in their 30s. As such an increase in the proportion suggests, even those who are not affected by metabolic syndrome are not necessarily at high risk of developing lifestyle-related diseases. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Status of implementation of specific health examinations and specific health guidance for fiscal year 2015 (Ministry of Health, Labour and Welfare) [Non-Patent Document 2] FY2017 National Health and Nutrition Survey Report (Ministry of Health, Labour and Welfare) Summary of the Invention [Problem to be solved by the invention]

[0007] The problem to be solved by the present invention is to improve the accuracy of detecting individuals at high risk of lifestyle-related diseases. [Means for solving the problem]

[0008] <First viewpoint> The present inventors first focused on the relationship between lifestyle-related diseases, metabolic syndrome, and blood lipopolysaccharide (LPS) concentration (hereinafter referred to as "blood LPS concentration") (Diabetes Care, 34: 1809-1815 (2011)). Based on this relationship, the present inventors conducted extensive research and discovered a correlation between indicators of lifestyle-related diseases and blood LPS concentration, as well as a correlation between metabolic syndrome and blood LPS concentration. From this viewpoint, the present invention is defined as follows.

[0009] <Health Status Evaluation System> The health status evaluation system is composed of at least a measuring device, an output device, and a processing device. The measuring device measures the LPS concentration in the blood of the person being measured. The output device outputs the health status of the person being measured. At least the output device is connected to the processing device. The processing device processes the LPS concentration in the blood, and thereby obtains the health status of the person being measured.

[0010] <Health status evaluation program> The processing executed by the computer by the health status evaluation program is at least judgment. What is judged by the computer is the health status of the person being measured, and what is referred to at that time is the LPS concentration in the blood of the person being measured. <Health status evaluation method> A health status evaluation method (excluding medical procedures, however) is comprised of at least measurement, judgment, and presentation. In other words, what is measured by a person or a device or instrument is the LPS concentration in the blood of the person being measured. What is judged by a person or a device or instrument is the health status of the person being measured, and what is referred to at that time is the LPS concentration in the blood. What is presented by a person or a device or instrument is the health status.

[0011] <Second viewpoint> The inventors of the present application next focused on the relationship between dietary habits and blood LPS concentration. That is, when dietary habits deteriorate (e.g., excessive intake of oil, etc.), LPS from intestinal bacteria invades the blood. When LPS in the blood increases, inflammation occurs chronically in the body. Chronic inflammation worsens the health state. From this viewpoint, the present invention is defined as follows.

[0012] <Dietary Life Evaluation System> The dietary life evaluation system is composed of at least a measuring device, an output device, and a processing device. The measuring device measures the LPS concentration in the blood of the person being measured. The output device outputs the dietary life status of the person being measured. At least the output device is connected to the processing device. The processing device processes the LPS concentration in the blood, and thereby obtains the dietary life status.

[0013] <Dietary Life Evaluation Program> The process executed by the computer in accordance with the dietary life evaluation program is at least a judgment. The computer judges the dietary life status of the subject, and the LPS concentration in the blood of the subject is referred to in the judgment.

[0014] <Dietary assessment method> At least, measurement, judgment, and presentation constitute the dietary assessment method. That is, what is measured by a person or a device or instrument is the blood LPS concentration of the person being measured. What is judged by a person or a device is the dietary condition of the person being measured, and what is referred to at that time is the blood LPS concentration. What is presented by a person or a device or instrument is the dietary condition. Effect of the Invention

[0015] The present invention makes it possible to improve the accuracy of detecting people at high risk of lifestyle-related diseases, because the health condition of the person being measured can be grasped more accurately than ever before, even if the person is not a person with metabolic syndrome or a person at risk of developing it. [Brief description of the drawings]

[0016] [Figure 1] This is the configuration of the health status evaluation system. [Diagram 2] 13 shows the flow of a determination process. [Diagram 3] This is the procedure for diagnosing LPS. [Figure 4]1 is an output screen for the health condition of a person who is considered to have metabolic syndrome. [Diagram 5] This is an output screen of the health condition, in which the subject is not affected by metabolic syndrome or the like, and the LPS diagnostic value is normal. [Figure 6] This is an output screen of the health condition, in which the subject is not affected by metabolic syndrome or the like, and the LPS diagnostic value is abnormal. [Figure 7] This is the flow of the health status evaluation method. [Figure 8] This is a health status assessment chart. [Figure 9] 13 shows the flow of a determination process. [Figure 10] This is the procedure for diagnosing LPS. [Figure 11] 1 shows an output screen of an eating habits evaluation, in which (a) a case where a disordered eating habit is not suspected, and (b) a case where a disordered eating habit is suspected. [Figure 12] This is the flow of the dietary assessment method. [Figure 13] This is a dietary assessment chart. [Figure 14] 1 shows the distribution of LPS concentrations in the blood of subjects. [Figure 15] The relationship between blood LPS concentration and each test value. [Figure 16] 1 shows the evaluation results of plasma LPS concentrations in healthy subjects and NAFLD patients, (a) comparison of plasma LPS concentrations (healthy subjects vs. NAFLD patients), and (b) ROC curve. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] <Present embodiment> The present invention is embodied in the following embodiment. The definitions of terms used herein are as follows.

[0018] <Blood LPS concentration> Blood LPS concentration refers to the concentration (unit: EU / mL) of lipopolysaccharide (LPS) contained in blood. "Blood LPS concentration" includes plasma LPS concentration and serum LPS concentration. Plasma LPS concentration refers to the concentration (unit: EU / mL) of LPS contained in plasma. Serum LPS concentration refers to the concentration (unit: EU / mL) of LPS contained in serum. In this embodiment, the plasma LPS concentration is used (hereinafter, sometimes simply referred to as "blood LPS concentration"). This is because the plasma LPS concentration is approximately equal to the blood LPS concentration (i.e., "blood LPS concentration" ≒ "plasma LPS concentration").

[0019] <Health condition (broad definition)>Health condition (broad definition) refers to the functional or organic state of the body. Examples of the functional state of the body include the state of glucose metabolism, the state of lipid metabolism, the state of liver function, and the state of blood pressure regulation. Examples of the organic state of the body include arterial hardness (state of the arteries) and liver fat content (state of liver fat).

[0020] <Health condition (narrow sense)>Health condition (narrow sense) refers to whether or not one has a lifestyle-related disease, whether or not one has metabolic syndrome, or both. Here, "whether or not" refers to whether or not one falls under the category.

[0021] <Health condition (narrowest sense)>Health condition (narrowest sense) refers to at least one of the following: lipid metabolism, liver function, blood pressure regulation, and arterial hardness (arterial condition). These conditions are correlated with the blood LPS concentration. There is no restriction on how the condition is expressed. Following the expressions used in specific medical examinations, examples of such expressions are "no abnormalities," "mild abnormalities," "needs follow-up observation," and "needs medical treatment."

[0022] <Lifestyle-related diseases> Lifestyle-related diseases are a general term for diseases caused by lifestyle habits. Examples include cancer, cardiovascular disease, COPD (chronic obstructive pulmonary disease), diabetes, high blood pressure, dyslipidemia, fatty liver, arteriosclerosis, etc.

[0023] <Metabolic syndrome>Metabolic syndrome (visceral fat syndrome) is a pathological condition of visceral fat obesity, which is accompanied by two or more of hyperglycemia, dyslipidemia, and hypertension. In other words, metabolic syndrome is defined as a high-risk group for lifestyle-related diseases (particularly cardiovascular disease). A person with metabolic syndrome is a human whose condition is metabolic syndrome.

[0024] The diagnostic indicators for metabolic syndrome are waist circumference, blood sugar, blood pressure, and lipids. The requirements for a person to have atherosclerotic syndrome are (1) and (2A), (2B), and (2C): (1) Waist circumference of 85 cm or more for men and 90 cm or more for women (2A) Fasting blood glucose of 110 mg / dL or more (2B) Triglycerides of 150 mg / dL or more and / or HDL cholesterol of less than 40 mg / dL (2C) Systolic blood pressure of 130 mmHg or more and / or diastolic blood pressure of 85 mmHg or more

[0025] <People at risk of developing metabolic syndrome and people at risk of developing metabolic syndrome> People at risk of developing metabolic syndrome are obese and in a state just before the onset of metabolic syndrome. People at risk of developing metabolic syndrome are people whose attributes are at risk of developing metabolic syndrome. People at risk of developing metabolic syndrome are required to meet the requirements for being at risk of developing metabolic syndrome if they meet (1) and also meet one of (2A), (2B), or (2C).

[0026] (1) Waist circumference of 85 cm or more for men and 90 cm or more for women; (2A) Fasting blood glucose of 110 mg / dL or more; (2B) Triglycerides of 150 mg / dL or more and / or HDL cholesterol of less than 40 mg / dL; (2C) Systolic blood pressure of 130 mmHg or more and / or diastolic blood pressure of 85 mmHg or more.

[0027] <Group not affected by metabolic syndrome, etc. and individuals not affected by metabolic syndrome, etc.> The group not affected by metabolic syndrome, etc. refers to a state in which the individual is not in the metabolic syndrome or pre-metabolic syndrome group. Individuals not affected by metabolic syndrome, etc. refer to people whose attributes are in the group not affected by metabolic syndrome, etc. Individuals not affected by metabolic syndrome, etc. meet all of the following (1) to (5): (1) Waist circumference: less than 85 cm for men and less than 90 cm for women (2) Fasting blood glucose: less than 110 mg / dL (3) Triglycerides: less than 150 mg / dL (4) HDL cholesterol: 40 mg / dL or higher (5) Blood pressure: Systolic blood pressure less than 130 mmHg and diastolic blood pressure less than 85 mmHg

[0028] <Dietary status>Dietary status refers to the state of daily meals. Examples include the amount of oil intake, sugar intake, salt intake, and alcohol intake. These factors are related to lifestyle-related diseases, metabolic syndrome, and both. Furthermore, blood LPS concentration is correlated with each of these factors. In other words, if the amount of oil intake, sugar intake, or alcohol intake is excessive, the blood LPS concentration increases.

[0029] <Health Status Evaluation System> Figure 1 shows the configuration of a health status evaluation system. Health status evaluation system 10 is made up of a measuring device 20, an output device 30, a processing device 40, an input device 50, and an external storage device 60. Some or all of these devices may be connected by wire or wirelessly. These devices may be independent of each other, or may be integrated in part or in whole. When output device 30, processing device 40, and input device 50 are integrated, such integration is realized by a personal computer, tablet terminal, or the like. Details of each device are as follows.

[0030] <Measuring device> The measuring device 20 measures the LPS concentration in the blood of the subject. That is, the measuring device 20 first analyzes the blood or plasma of the subject, and outputs the LPS concentration in the blood of the subject. The blood and plasma are pre-processed. The details of the pre-processing will be described later. The blood LPS concentration may be output to any destination, but is preferably the processing device 30. The measuring device 20 can be realized by various devices, but is not particularly limited thereto, and examples include a spectrometer, a spectrophotometer, and a microplate reader. In this embodiment, a microplate reader (Microplate Reader ELx808 manufactured by Biotech Co., Ltd.) is used.

[0031] <Output device> The output device 30 outputs the LPS concentration in the blood of the subject and the health condition of the subject. The manner in which this information is output is not important, and specifically, it may be image output, audio output, paper output, a combination of these, etc. Examples of the output device 30 include a display, a speaker, a printer, etc.

[0032] <Processing Device> The processing device 40 is connected to an output device 30, an input device 50, and an external storage device 60. The processing device 40 processes the LPS concentration in the blood of the subject, and as a result, the health condition of the subject is obtained. In this embodiment, the source of the LPS concentration in the blood of the subject is the measuring device 20. The blood LPS concentration is directly inputted by the input device 50. The processing device 40 is made up of the basic elements of a computer, specifically, an input / output unit, a communication unit, a program storage unit, a temporary storage unit, and a processing unit. These components are connected to each other by a bus. The following is an explanation of these components.

[0033] <Input / Output Unit> Various data are exchanged in the input / output unit. The output device 40, the input device 50, and the external storage device 60 are connected to the input / output unit. The measuring device 20 can be connected to the input / output unit. In this case, the measuring device 20 is provided with an input / output function.

[0034] <Communication Unit> The communication unit transmits and receives various data. The communication unit is connected to a network. Examples of the communication unit include a dial-up connection module, a Wi-Fi module, a Bluetooth (registered trademark) module, etc.

[0035] <Program Storage Unit> Various programs are stored in the program storage unit. The program storage unit is embodied by a non-volatile storage device (e.g., ROM, etc.) and a non-volatile storage device (e.g., HDD, SSD, etc.). Basic programs (including data required for them) are stored in the non-volatile storage device. Examples of basic programs include a basic input / output system (BIOS), an operation system (OS) setting program, and a network setting program. An operation system (OS) and application programs are stored in the non-volatile storage device. Examples of operation systems (OS) include Windows (registered trademark), Linux (registered trademark), and Android (registered trademark). An example of an application program is a health condition evaluation program, which will be described later.

[0036] <Temporary Storage Unit> The various programs and various data are temporarily stored in the temporary storage unit. The various programs are as described above. The various data indicate input values, output values, etc. An example of the temporary storage unit is a volatile storage device (e.g., RAM, etc.).

[0037] <Processing Unit> The processing unit executes various programs and processes various data. By executing various programs, input values ​​are processed to become output values. The processing unit is embodied by a central processing unit (so-called CPU).

[0038] <Input Device> Various data are input through the input device 50. Examples of the input device 50 include a touch panel, operation keys, buttons, a keyboard, and a mouse.

[0039] <External Storage Device> Various data and programs are stored in the external storage device 60. Examples of external storage devices include magnetic storage devices (HDD, etc.), optical storage devices (CD, DVD, BD, etc., including their drives), and semiconductor storage devices (USB memory, SD card memory, SSD, etc.).

[0040] <Health Condition Evaluation Program> The health condition evaluation program causes the processing device 30 to execute a judgment process. That is, the processing device 30 judges the health condition of the person being measured. In doing so, the processing device 30 refers to the LPS concentration in the blood of the person being measured. Figure 2 shows the flow of the judgment process. The judgment process is made up of a metabolic syndrome diagnosis (S10), an LPS diagnosis (S20), and a health condition output (S30).

[0041] <Metabolic syndrome diagnosis (S10)> A metabolic syndrome diagnosis gives a corresponding / non-corresponding value. This corresponding / non-corresponding value indicates at least whether the person diagnosed does not have metabolic syndrome, etc. The corresponding / non-corresponding value is stored in the temporary storage unit. In this embodiment, a corresponding / non-corresponding value of "1" indicates that the person diagnosed does not have metabolic syndrome, etc. On the other hand, a corresponding / non-corresponding value of "0" indicates that the subject is not a non-corresponding person to metabolic syndrome, etc. (i.e., a person with metabolic syndrome or a person at risk of having metabolic syndrome).

[0042] The test indicator value for metabolic syndrome and the metabolic syndrome applicable requirements are referenced when obtaining the applicable or non-applicable value. In other words, the applicable requirements are compared with the test indicator value. These definitions are as described above. The test indicator value is stored in a temporary memory unit. The test indicator value is input automatically or manually. The means for automatically inputting the test indicator value is a communication device. The means for manually inputting the test indicator value is an input device.

[0043] <LPS Diagnosis (S20)>If the flag value is "1", the LPS diagnosis is executed. What is obtained from the LPS diagnosis is the LPS diagnosis value. The details of the LPS diagnosis are as follows. What is shown in Figure 3 is the flow of the LPS diagnosis. The LPS concentration is read (S31), and a return value is returned (S32~S36). If the LPS concentration "Y" is less than the reference value "a" (Y < a), the return value "A" is returned (S32). What the return value "A" means is that no deterioration of the health state is inferred. More specifically, it means that neither deterioration of lipid metabolism ability, deterioration of liver function, deterioration of blood pressure regulation ability, nor deterioration of arterial stiffness (deterioration of arteries) is inferred.

[0044] If the LPS concentration "Y" is greater than or equal to the reference value "a" and less than "b" (a ≤ Y < b), the return value "B" is returned (S33). What the return value "B" means is that a deterioration of the health state is inferred (deterioration degree 1% - 20%). Specifically, any one of deterioration of lipid metabolism ability, deterioration of liver function, deterioration of blood pressure regulation ability, and deterioration of arterial stiffness (deterioration of arteries) is inferred (deterioration degree 1% - 20%).

[0045] If the LPS concentration "Y" is greater than or equal to the reference value "b" and less than "c" (b ≤ Y < c), the return value "C" is returned (S34). What the return value "C" means is that a deterioration of the health state is inferred (deterioration degree 21% - 50%). Specifically, any one of deterioration of lipid metabolism ability, deterioration of liver function, deterioration of blood pressure regulation ability, and deterioration of arterial stiffness (deterioration of arteries) is inferred (deterioration degree 21% - 50%).

[0046] If the LPS concentration "Y" is greater than or equal to the reference value "c" and less than or equal to "d" (c ≤ Y ≤ d), the return value "D" is returned (S35). What the return value "D" means is that a deterioration of the health state is inferred (deterioration degree 51% - 70%). Specifically, any one of deterioration of lipid metabolism ability, deterioration of liver function, deterioration of blood pressure regulation ability, and deterioration of arterial stiffness (deterioration of arteries) is inferred (deterioration degree 51% - 70%).

[0047] If the LPS concentration "Y" is greater than the reference value "d" (Y>d), a return value "E" is returned (S36). The return value "E" means that a deterioration in health condition is suspected (degree of deterioration 71% or more). Specifically, deterioration in lipid metabolism, deterioration in liver function, deterioration in blood pressure regulation, or arterial hardness (deterioration of the arteries) is suspected (degree of deterioration 71% or more). In the above, the thresholds "a", "b", "c", and "d" depend on the race and place of residence. In the case of Japanese people, the thresholds "a", "b", "c", and "d" are respectively "0.001", "0.004", "0.007", and "0.010".

[0048] <Health Status Output (S30)> The health status is output when the suitability value is "0" or after the LPS diagnosis is completed. There are three main ways to output the health status. The details are as follows. Figure 4 shows a health status output screen for a subject who is at risk of having metabolic syndrome. This screen is output when the suitability value is "0". In other words, the subject is at risk of having metabolic syndrome, and the overall assessment result is "requires guidance".

[0049] FIG. 5 shows an output screen of health status when the subject is not affected by metabolic syndrome, etc., and the LPS diagnostic value is normal. This screen is output when the LPS diagnostic value (return value) is "A." In other words, the subject is not affected by metabolic syndrome, etc., and is not suspected of having a worsening health condition. The overall judgment result is "no abnormalities" (or "normal").

[0050] FIG. 6 shows an output screen of health status when the subject is not affected by metabolic syndrome and the LPS diagnostic value is abnormal. This screen is output when the LPS diagnostic value (return value) is any of "B", "C", "D" and "E". In other words, the subject is not affected by metabolic syndrome and the health condition is suspected to be deteriorating. The overall judgment result is "normal" (or "no abnormality"), but a note (for example, an asterisk "*") is added to it. The element that changes the output mode of the note is the return value. When the note "*" is used, if the return value is "B", one "*" is added. If the return value is "E", four "*" are added.

[0051] <Health Status Evaluation Method> Figure 7 shows the flow of the health status evaluation method. The health status evaluation method is composed of measurement (P1), judgment (P2), and presentation (P3). Specifically, it is as follows.

[0052] <Measurement (P1)> The purpose of the measurement is to ascertain the LPS concentration in the blood of the subject. That is, what is measured by a person or by a device or instrument is the LPS concentration in the blood of the subject. In other words, the measurement of the LPS concentration in the blood may be automatic, manual, or semi-automatic. The measurement principle is not important, and an example is the LAL endpoint assay (colorimetric method). The method adopted in this embodiment is the LAL endpoint assay. In this case, the measurement procedure of the LPS concentration in the blood is as follows.

[0053] The specimen is the blood of the subject. The storage temperature of this blood is -80°C to 35°C, preferably -10°C to 10°C. The blood fraction is not particularly limited, but is preferably plasma. What the fraction does not exclude is serum. The plasma is pretreated. Specifically, the plasma is first diluted. The dilution solvent is a liquid not containing LPS (e.g., distilled water, physiological saline, phosphate buffered saline, etc.), and the dilution rate is 10 times. Next, the diluted plasma is heated. The heating temperature is 70°C, and the heating time is 10 minutes. The LAL reagent is reacted with the plasma treated in this way. This reagent is commercially available. Examples of commercially available kits include Endotoxin-Single Test Wako (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and Limulus amebocyte lysate assay kit (QCL-1000, Lonza). The pretreated plasma is analyzed by a measuring device, which will be described later. The plasma is analyzed to obtain the LPS concentration in the subject's blood.

[0054] <Determination (P2)> The purpose of the determination is to derive the health condition of the subject. The health condition of the subject is determined by a person or device, and the blood LPS concentration is referenced at that time. Determination (P2) is preferably performed when the subject does not fall under the category of metabolic syndrome, etc. In other cases, determination (P2) is omitted.

[0055] FIG. 8 shows a health condition judgment table. This health condition judgment table shows the relationship between LPS concentration and health condition judgment value. The LPS concentration in the blood of the subject is applied to this health condition judgment table, and the result is the health condition judgment value of the subject. The thresholds "a", "b", "c", and "d" depend on the race and place of residence.

[0056] <Presentation (P3)> The purpose of presentation is to make the subject aware of the health condition. The blood LPS concentration and health condition are presented by a person, device, or instrument to the subject. There is no restriction on the method for presenting the measured blood LPS concentration and health condition, but specifically, it is electromagnetic (electronically or magnetically). There is no restriction on the manner in which the blood LPS concentration and health condition are presented, but specifically, it is visually. There is no restriction on the means for presenting the blood LPS concentration and health condition, but examples include paper and a screen.

[0057] <Effects of the health condition evaluation system, the health condition evaluation program, and the health condition evaluation method> These embodiments improve the accuracy of detecting high-risk groups for lifestyle-related diseases, because the LPS concentration of a subject can be further grasped even if the subject does not fall under the category of metabolic syndrome or the like.

[0058] <Modification> If other indices (blood glucose level, triglyceride level, etc.) are referred to in the above-mentioned determination process or determination in addition to the LPS concentration, the accuracy of detecting high-risk groups for lifestyle-related diseases will be further improved.

[0059] <Dietary Life Evaluation System / Dietary Life Evaluation Program> The dietary life evaluation system is composed of a measuring device, an output device, a processing device, an input device, and an external storage device. The detailed description of these hardware components will be referenced from the descriptions of the measuring device 20, the output device 30, the processing device 40, the input device 50, and the external storage device 60. The dietary life evaluation system is characterized by the dietary life evaluation program.

[0060] <Dietary habit evaluation program> The health condition evaluation program causes the processing device to execute a judgment process. That is, what is judged by the processing device is the dietary habit state of the person being measured. At that time, what is referred to by the processing device is the blood LPS concentration of the person being measured. Figure 9 shows the flow of the judgment process. The judgment process consists of an LPS diagnosis (S40) and a dietary habit output (S50).

[0061] <LPS Diagnosis (S40)>After startup, the LPS diagnosis is executed. What is obtained from the LPS diagnosis is the LPS diagnosis value. The details of the LPS diagnosis are as follows. What is shown in FIG. 10 is the flow of the LPS diagnosis. The LPS concentration is read (S41), and a return value is returned (S42 - S43). If the LPS concentration "Z" is less than the reference value "e" (Z < e), the return value "F" is returned (S42). Here, the threshold value "e" depends on race and place of residence. What the return value "F" means is that no disruption of eating habits is inferred. Specifically, neither excessive intake of oil, excessive intake of sugar, excessive intake of salt, nor excessive intake of alcohol is inferred.

[0062] If the LPS concentration "Z" is greater than or equal to the reference value "e", the return value "G" is returned (S43). What the return value "G" means is that a lifestyle disease is inferred. Specifically, either excessive intake of oil, excessive intake of sugar, excessive intake of salt, or excessive intake of alcohol is inferred.

[0063] <Diet Evaluation Output (S50)>The diet evaluation is output after the LPS diagnosis is completed. The output modes of the diet evaluation are roughly divided into two. The details are as follows. What is shown in FIG. 11 is the output screen of the diet evaluation, which is (a) when no disruption of eating habits is inferred and (b) when a disruption of eating habits is inferred. The screen is composed of the LPS concentration 71 of the subject, the diet evaluation 72, and the guidance content (advice) 73. When no disruption of eating habits is inferred, what is indicated in the diet evaluation is that the eating habits are not disrupted 72a. Also, what is included in the guidance content is that the current eating habits should be continued 73a. On the other hand, when a disruption of eating habits is inferred, what is indicated in the diet evaluation is that the eating habits are disrupted 72b. Also, what is included in the guidance content is that the current eating habits should be improved 73b.

[0064] <Diet Evaluation Method>What is shown in FIG. 12 is the flow of the diet evaluation method. The diet evaluation method is composed of measurement (P11), determination (P12), and presentation and / or guidance (P13). Specifically, it is as follows.

[0065] <Measurement (P11)> The purpose of the measurement is to grasp the LPS concentration in the blood of the subject. For a detailed explanation, please refer to the explanation of Measurement (P1).

[0066] <Judgment (P12)> The purpose of the judgment is to derive the diet of the subject. The subject's diet is judged by a person or device, and the blood LPS concentration is referred to. Figure 14 shows a diet judgment table. The diet judgment table shows the relationship between LPS concentration and diet judgment value. The subject's blood LPS concentration is applied to the diet judgment table, and the diet judgment value of the subject is obtained. The threshold value "e" depends on the race and place of residence. The diet judgment value indicates "disordered diet is suspected" or "disordered diet is not suspected". The diet judgment value allows multiple stages of the degree of "disordered diet". In that case, the diet judgment value adopts a more detailed expression, such as "it is suspected that the diet is somewhat disordered" or "it is suspected that the diet is significantly disordered".

[0067] <Presentation and / or Guidance (P13)> The purpose of presentation is to make the subject aware of the dietary assessment. The blood LPS concentration and dietary assessment are presented by a person, device, or instrument to the subject. There is no restriction on the method for presenting the measured blood LPS concentration and dietary assessment, but specifically, it is electromagnetic (electronically or magnetically). There is no restriction on the manner in which the blood LPS concentration and dietary assessment are presented, but specifically, it is visually. There is no restriction on the means for presenting the blood LPS concentration and dietary assessment, but examples include paper and a screen.

[0068] Along with or instead of the presentation, guidance is given by a person, device, or instrument. Guidance is given when the dietary assessment value is "eating disorders are suspected." The purpose of the guidance is to improve the diet. If the intake of oil, sugar, or alcohol is excessive, the blood LPS concentration increases. Therefore, the guidance is to limit the intake of these substances. Preferably, the implementation of the guidance is continuous, not temporary.

[0069] <Effects of the dietary habit evaluation system, dietary habit evaluation program, and dietary habit evaluation method> These embodiments contribute to the prevention of lifestyle-related diseases, because the cause of lifestyle-related diseases is an unbalanced diet, and the unbalanced diet can be detected at an early stage.

[0070] <Modifications> If other indices (blood glucose level, neutral fat level, etc.) are referred to in the above-mentioned determination process or determination in addition to the LPS concentration, prevention of lifestyle-related diseases will be even more effective.

[0071] <Test results on which the present embodiment is based> The present embodiment is based on the correlation between indicators of lifestyle-related diseases and blood LPS concentration, and the correlation between metabolic syndrome and blood LPS concentration. These correlations are derived from the following test results.

[0072] <Test 1> The purpose of Test 1 is to determine whether there is a correlation between blood LPS concentration and health status. The procedure for this test is as follows.

[0073] <Selection of subjects> Thirty-one adult men and women were selected as subjects. The selection criteria were: (1) informed consent; and (2) they do not meet any of the diagnostic criteria for metabolic syndrome in a health check or medical examination within the past three months. In other words, selection condition (2) must meet all of the following criteria: a) Waist circumference: less than 85 cm for men and less than 90 cm for women b) Fasting blood glucose: less than 110 mg / dL c) Triglyceride: less than 150 mg / dL d) HDL cholesterol: 40 mg / dL or higher e1) Systolic blood pressure: less than 130 mmHg e2) Diastolic blood pressure: less than 85 mmHg

[0074] <Data collection> Data on the subjects was collected. Specifically, it was the results of the subjects' health checkups or medical examinations that were conducted within the past three months of the subjects' participation in this study. These results included BMI, waist circumference, systolic blood pressure, diastolic blood pressure, and blood biochemistry test values ​​(ALT, AST, γ-GTP, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, HbA1c). In the following, pulse pressure refers to the difference between systolic blood pressure and diastolic blood pressure.

[0075] <Collection of blood and plasma> Blood was collected from the subjects. Using this blood, the subjects' blood LPS concentration, blood glucose level, insulin concentration, and HOMA-IR (homeostasis model assessment of insulin resistance) were measured or calculated. The specific procedures are as follows.

[0076] Procedure 1: 5 mL of fasting blood was collected from the subject. The subject fasted from 9 p.m. on the day before blood collection until the time of blood collection. Procedure 2: The collected blood was centrifuged to obtain heparinized plasma. Procedure 3: The heparinized plasma was stirred. The stirring time was approximately 1 minute, and a test tube mixer was used for the stirring.

[0077] Step 4: After a portion of the stirred plasma was collected, the collected plasma was diluted. The dilution conditions were as follows: the dilution solvent was Otsuka distilled water, the dilution ratio (amount of dilution solvent relative to the amount of plasma) was 10 times, and the dilution environment was ice. Step 5: The diluted plasma was heated. The conditions were as follows: the heating temperature was 70°C, and the heating time was 10 minutes.

[0078] Step 6: The heated plasma was cooled in ice to bring the temperature of the plasma to about room temperature (around 25°C). Step 7: The plasma at room temperature was stirred. The conditions were that the stirring time was about 30 seconds and the stirring device was a test tube mixer.

[0079] Step 8: Plate 1 was prepared. Specifically, a 96-well plate was prepared. (1) Two of the 96 wells of plate 1 were used for the plasma (one specimen) of one subject (2 wells / specimen). In other words, plasma was injected into a total of 62 wells (31 subjects x 2 wells). The amount of plasma injected per well was 50 μL / well. In addition, 50 μL of Limulus reagent (Endospecy (registered trademark) ES-50M set, manufactured by Seikagaku Corporation) was also poured into each well (50 μL / well). (2) Distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) was poured into two of the remaining 34 wells. In addition, 50 μL of Limulus reagent (Endospecy (registered trademark) ES-50M set, manufactured by Seikagaku Corporation) was also poured into each well (50 μL / well). (3) To prepare a calibration curve, seven kinds of standard LPS aqueous solutions were prepared using an endotoxin standard (manufactured by Seikagaku Corporation). The concentrations of the seven kinds of standard LPS aqueous solutions were 0.0001EU / mL, 0.0004EU / mL, 0.0016EU / mL, 0.0063EU / mL, 0.025EU / mL, 0.10EU / mL, and 2.0EU / mL, respectively. Two of the remaining 32 wells were used for one kind of standard LPS aqueous solution (2 wells / calibration curve LPS aqueous solution). In other words, a total of 14 wells (7 kinds x 2 wells) were injected with the standard LPS aqueous solution. In addition, 50 μL of Limulus reagent (Endospecy (registered trademark) ES-50M set, manufactured by Seikagaku Corporation) was also poured into each well (50 μL / well).

[0080] Step 9: Plate 1 was incubated. The conditions were an incubation temperature of 37°C and an incubation time of 1 hour. Step 10: Plate 2 was created. The purpose was to cancel the effect of the color of the plasma on the absorbance measurement. Specifically, a 96-well plate was prepared. (1) Plasma was injected into a total of 62 wells (31 people x 2 wells). The amount of plasma injected per well was 50 μL / well. Each well was further filled with 50 μL of distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) (50 μL / well). (2) Distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) was injected into 2 of the remaining 34 wells. Each well was further filled with 50 μL of distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) (50 μL / well). Step 11: Plate 2 was incubated. The conditions were an incubation temperature of 37°C and an incubation time of 1 hour.

[0081] <Measurement of absorbance> After incubation, the absorbance at 405 nm (control wavelength 492 nm) was measured. Here, the control wavelength refers to a wavelength for correcting the influence of factors interfering with absorbance (for example, scratches or distortion of the plate, etc.), specifically, the control wavelength refers to the wavelength designated by the manufacturer of the Limulus reagent (in this embodiment, Seikagaku Corporation). The relationship between the absorbances is as follows. Here, the average value of two wells was used for the absorbance of each sample. (Formula) Absorbance A = Absorbance B - {Absorbance C + (Absorbance D1 - Absorbance D2)} Absorbance A: Reaction of LPS in plasma and Limulus reagent Absorbance B: Plasma and Limulus reagent (plate 1) Absorbance C: Distilled water and Limulus reagent (plate 1) Absorbance D1: Plasma and distilled water (plate 2) Absorbance D2: Distilled water (plate 2)

[0082] <Procedure for creating a calibration curve>The procedure for creating a calibration curve is as follows. By measuring the absorbance at 405 nm (reference wavelength 492 nm) of the reaction product of the standard LPS aqueous solution and the Limulus reagent (see (3) in Step 8), the relationship between the LPS concentration and the absorbance (calibration curve) was obtained. The suitability of this calibration curve was confirmed. Specifically, the criterion for determining the suitability is whether the absorbance A of all the subjects is within the range of the absorbance of each reaction product.

[0083] <Calculation of LPS concentration in blood (plasma)>The LPS concentration in the blood (plasma) of each subject was calculated. The absorbance A of each subject was applied to the calibration curve, and the LPS concentration (EU / mL) in the plasma of each subject was obtained thereby.

[0084] <Measurement of blood glucose level>The blood glucose level was measured. The measuring instrument used was FreeStyle Libre (Abbott).

[0085] <Measurement of insulin concentration>The insulin concentration was measured. The measuring instrument used was an existing kit (Mercodia Insulin ELISA, manufactured by Mercodia).

[0086] <Calculation of HOMA-IR>The calculation formula for HOMA-IR is as follows. (Formula) HOMA-IR = [fasting insulin concentration (μU / mL) × fasting blood glucose level (mg / dl)] ÷ 405

[0087] <Profiles of the subjects>Table 1 shows the profiles of the subjects in this study. Among the indicators, those with an asterisk "*" represent the values as the mean ± standard deviation. It was confirmed for all subjects that they did not meet any of the diagnostic criteria for metabolic syndrome.

[0088]

Table 1

[0089] <Distribution of LPS concentrations in subjects> Figure 14 shows the distribution of LPS concentrations in the blood of the subjects. The median LPS concentration in the blood of the subjects was 0.0038 EU / mL. The range of LPS concentrations in the blood of the subjects was 0 to 0.0117 EU / mL. LPS was detected in 22 subjects, which is 71% of the total subjects.

[0090] <Simple regression analysis> The relationship between the subjects' blood LPS concentration and each test value was analyzed (simple regression analysis). The test values ​​in question were BMI, waist circumference, systolic blood pressure, diastolic blood pressure, pulse pressure, AST, ALT, γ-GTP, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, fasting blood glucose, HbA1c, insulin, and HOMA-IR.

[0091] Figure 15 shows the relationship between blood LPS concentration and each test value. "ρ" in the figure indicates the correlation coefficient. That is, significant positive correlations (Spearman's rank sum correlation coefficient: P<0.05) were observed between (1) blood LPS concentration and systolic blood pressure, (2) blood LPS concentration and diastolic blood pressure, (3) blood LPS concentration and pulse pressure, (4) blood LPS concentration and γ-GTP, and (5) blood LPS concentration and triglyceride. Hereinafter, systolic blood pressure, diastolic blood pressure, pulse pressure, γ-GTP, and triglyceride are collectively referred to as simply correlated test values.

[0092] These results suggest that (1) there is a correlation between elevated blood LPS concentrations and impaired blood pressure regulation, (2) there is a correlation between elevated blood LPS concentrations and impaired arteriosclerosis, (3) there is a correlation between elevated blood LPS concentrations and impaired liver function, and (4) there is a correlation between elevated blood LPS concentrations and impaired lipid metabolism.

[0093] <Multiple regression analysis> The relationship between each single correlation test value and blood LPS concentration, age, sex, and BMI was analyzed (multiple regression analysis). In other words, the objective variable was each single correlation test value, and the explanatory variables were blood LPS concentration, age, sex, and BMI. The Shapiro-Wilk test confirmed that LPS concentration (P = 0.005), age (P = 0.001), BMI (P = 0.03), and γ-GTP (P = 0.004) were not normally distributed. Therefore, these values ​​were log-transformed and multiple regression analysis was performed. As sex is a binary value, multiple regression analysis was performed without log-transformation.

[0094] Table 2 shows the results of multiple regression analysis (P values). Even after adjustment for age, sex, and BMI, a significant positive correlation (P<0.05) was observed between blood LPS concentration and triglyceride. Furthermore, a correlation trend (P<0.1) was observed between blood LPS concentration and systolic blood pressure, between blood LPS concentration and pulse pressure, and between blood LPS concentration and γ-GTP. These results suggest that blood LPS concentration is independent of age, sex, and BMI.

[0095] [Table 2]

[0096] <Distribution range of test values> Table 3 shows the distribution range of single correlation test values ​​for subjects with and without detectable LPS in the blood. These results show that the distribution range of all single correlation test values ​​is the same, regardless of whether LPS is detected in the blood. In other words, it is the blood LPS concentration that is difficult to estimate from the high or low single correlation test values. Conversely, these results suggest that a deterioration in health status (especially blood pressure regulation, arteriosclerosis, liver function, and lipid metabolism) can be detected by blood LPS concentration, even if it cannot be detected by existing test indicators.

[0097] [Table 3]

[0098] <Test 2> Blood LPS concentration in healthy subjects and patients with nonalcoholic fatty liver disease The blood LPS concentration of subjects with nonalcoholic fatty liver disease (hereinafter referred to as "NAFLD patients") was evaluated. Here, nonalcoholic fatty liver disease refers to fatty liver disease whose cause is clearly other than alcoholic liver disease. The blood LPS concentration of the subjects was measured. The measurement method was the same as in Study 1. The subjects consisted of 31 healthy subjects and 31 NAFLD patients.

[0099] <Parameters for each group> Table 4 shows the profile of the subjects in Study 2. Indicators marked with an asterisk "*" are the mean ± standard deviation. Student's t-test or Mann-Whitney U-test was performed for each item, and the p-value obtained was the result. When comparing healthy subjects and NAFLD patients, the age of NAFLD patients was significantly higher. No difference in male / female ratio was observed between the groups. When comparing healthy subjects and NAFLD patients, significant (p<0.05) deterioration was confirmed in the test values ​​of NAFLD patients related to obesity, blood pressure, liver function, lipid metabolism, and glucose metabolism.

[0100] [Table 4]

[0101] <Results> Figure 16 shows the evaluation results of plasma LPS concentrations in healthy subjects versus NAFLD patients. Figure 16(a) shows the comparison results of plasma LPS concentrations (healthy subjects versus NAFLD patients). The horizontal lines in the box plot indicate, from the bottom, the minimum, first quartile, median, third quartile, and maximum value. The dots above the maximum value indicate outliers. The median plasma LPS concentration in healthy subjects is 0.0038 EU / mL (0-0.0117 EU / mL). The median in NAFLD patients is 0.0169 EU / mL (0.0009-0.3003 EU / mL). Comparing the two, the plasma LPS concentration in NAFLD patients is significantly (p<0.05) higher than that of healthy subjects.

[0102] Figure 16(b) shows the receiver operating characteristic (ROC) curve. The diagnostic ability of plasma LPS concentration for NAFLD is the area under the ROC curve (AUC) = 0.87. If the plasma LPS concentration is 0.010EU / mL, the cutoff value (dotted line) is optimal. In this case, the positive predictive value (sensitivity) is 71.0% and the negative predictive value (specificity) is 96.8%. These results suggest that the boundary for worsening health status is a plasma LPS concentration of 0.010EU / mL. In other words, the standard value for determining health status is a plasma LPS concentration of 0.010EU / mL.

[0103] <Effects of this embodiment> The effect of this embodiment is to improve the accuracy of detecting high-risk groups for lifestyle-related diseases, because the health conditions of people other than those with metabolic syndrome and those at risk of developing the same can be grasped more accurately than ever before. [Industrial Applicability]

[0104] One area in which the present invention is useful is in the health services industry. [Explanation of symbols]

[0105] 10 Health condition evaluation system 20 Measuring device 30 Output device 40 Processing device

Claims

1. The dietary evaluation system comprises at least the following: a measuring device, which measures the blood LPS concentration of the person being measured; an output device, which outputs an evaluation of the dietary lifestyle of the person being measured; and a processing device, which is connected to at least the output device, and which processes the blood LPS concentration and thereby obtains the dietary status.

2. A dietary evaluation program, in which the processes executed by a computer are at least the following processes: Determination: What is determined here is the dietary status of the subject, and the reference in this regard is the blood LPS concentration of the subject.

3. A dietary evaluation method comprising at least the following steps: Measurement: what is measured here is the blood LPS concentration of the subject; Determination: what is determined here is the dietary condition of the subject, and the blood LPS concentration is used as reference at that time; and Presentation: what is presented here is the dietary condition.

Images