Health status assessment system, health status assessment program and health status assessment method, as well as dietary lifestyle assessment system, dietary lifestyle assessment program and dietary lifestyle assessment 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 status evaluation system, a health status evaluation program, and a health status evaluation method, as well as a dietary habit evaluation system, a dietary habit evaluation program, and a dietary habit evaluation method.

Background Art

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

[0003] The situation in Japan is serious. According to the report of Non-Patent Document 1, about 25% of the examinees of specific health checkups in Japan are those who meet the criteria for metabolic syndrome or those in the preparatory group. Specific health checkups are mainly responsible for the early detection of metabolic syndrome. What is examined in specific health checkups is abdominal circumference, as well as blood glucose, lipids, and blood pressure (hereinafter, these are referred to as "examination indicators", and their values are also referred to as "examination values").

[0004] Specific health guidance is mainly responsible for improving metabolic syndrome. Those who are guided in specific health guidance are those among the examinees whose examination values are outside the range of a predetermined standard. In other words, if the examinee is not any of those who meet the criteria for metabolic syndrome and those in the preparatory group (hereinafter referred to as "non-metabolic syndrome and the like non-corresponding persons"), the examinee is not the object of guidance. [[ID=2,22]]

[0005] However, those who are overlooked in specific health checkups and health guidance are individuals who do not meet the criteria for metabolic syndrome, etc., but who are at high risk of lifestyle-related diseases. According to Non-Patent Literature 2, the proportion of Japanese men in their 20s who meet the criteria for metabolic syndrome or are at risk of it is approximately 10%, and in their 30s, it is approximately 40%. As this increase in proportion suggests, even those who do not meet the criteria for metabolic syndrome, etc., are not necessarily at low risk of lifestyle-related diseases. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Status of Implementation of Specific Health Checkups and Specific Health Guidance in FY2015 (Ministry of Health, Labour and Welfare) [Non-Patent Document 2] Report on the 2017 National Health and Nutrition Survey (Ministry of Health, Labour and Welfare) [Overview of the project] [Problems that the invention aims to solve]

[0007] The problem that this invention aims to solve is to improve the accuracy of identifying individuals at high risk of lifestyle-related diseases. [Means for solving the problem]

[0008] <First Perspective> The inventors of this invention 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 inventors of this invention diligently investigated and discovered the correlation between indicators of lifestyle-related diseases and blood LPS concentration, as well as the correlation between metabolic syndrome and blood LPS concentration. From this perspective, the present invention can be defined as follows.

[0009] <Health Status Assessment System> The health status assessment system consists of at least a measuring device, an output device, and a processing device. The measuring device measures the blood LPS concentration 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 blood LPS concentration, and the result obtained is the health status of the person being measured.

[0010] <Health Status Assessment Program> The process performed by the computer using the health status assessment program is, at a minimum, a determination. The computer determines the health status of the person being measured, and the subject's blood LPS concentration is referenced in this determination. <Health Status Assessment Method> The health status assessment method (excluding medical procedures) consists of, at a minimum, measurement, determination, and presentation. That is, the subject's blood LPS concentration is measured by a person or device or instrument. The person or device or instrument determines the health status of the person being measured, and the subject's blood LPS concentration is referenced in this determination. The person or device or instrument presents the health status.

[0011] <Second Perspective> The inventors of this invention then focused on the relationship between dietary habits and blood LPS concentration. That is, when dietary habits deteriorate (for example, excessive intake of oil), LPS from intestinal bacteria enters the bloodstream. When LPS in the blood increases, chronic inflammation occurs in the body. Chronic inflammation worsens the state of health. From this perspective, the present invention can be defined as follows.

[0012] <Dietary Habits Assessment System> The dietary habits assessment system consists of at least a measuring device, an output device, and a processing device. The measuring device measures the blood LPS concentration of the person being measured. The output device outputs the dietary status of the person being measured. At least the output device is connected to the processing device. The processing device processes the blood LPS concentration, and the result obtained is the dietary status.

[0013] <Dietary Habits Assessment Program> The process performed by the computer using the dietary habits assessment program is, at a minimum, judgment. The computer determines the dietary status of the person being measured, and the subject's blood LPS concentration is referenced in this process.

[0014] <Dietary Habits Assessment Method> The dietary habits assessment method consists of at least measurement, judgment, and presentation. Specifically, what is measured by a person or device or instrument is the blood LPS concentration of the person being measured. What is judged by a person or device is the dietary status of the person being measured, and the blood LPS concentration is used as a reference in this judgment. What is presented by a person or device or instrument is the dietary status. [Effects of the Invention]

[0015] The present invention enables an improvement in the accuracy of identifying individuals at high risk of lifestyle-related diseases. This is because, even if the person being measured is not a person with metabolic syndrome or a person at risk of developing it, the health status of that person can be assessed more accurately than before. [Brief explanation of the drawing]

[0016] [Figure 1] This is the configuration of the health status assessment system. [Figure 2] This is the flow of the judgment process. [Figure 3] This is the procedure for diagnosing LPS (Low-Plant Syndrome). [Figure 4]An output screen of a health condition, where the subject is a person with metabolic syndrome. [Figure 5] An output screen of a health condition, where the subject is not a person with metabolic syndrome or the like, and the LPS diagnostic value is normal. [Figure 6] An output screen of a health condition, where the subject is not a person with metabolic syndrome or the like, and the LPS diagnostic value is abnormal. [Figure 7] The flow of a health condition evaluation method. [Figure 8] A health condition judgment table. [Figure 9] The flow of a judgment process. [Figure 10] The flow of an LPS diagnosis. [Figure 11] An output screen of a dietary life evaluation, including (a) when no disorder in the dietary life is inferred, and (b) when a disorder in the dietary life is inferred. [Figure 12] The flow of a dietary life evaluation method. [Figure 13] A dietary life judgment table. [Figure 14] The distribution of the blood LPS concentration of a subject. [Figure 15] The relationship between the blood LPS concentration and each test value. [[ID=3A]] [Figure 16] The evaluation results of the plasma LPS concentration of healthy subjects versus NAFLD patients, including (a) the comparison results of the plasma LPS concentration (healthy subjects versus NAFLD patients), and (b) the ROC curve.

Embodiments for Carrying Out the Invention

[0017] <This Embodiment> The present invention is embodied in the following embodiments. The definitions of the terms used here are as follows.

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

[0019] <Health Status (Broad Sense)> Health status (broad sense) refers to the functional or structural state of the body. Examples of the functional state of the body include the state of glucose metabolism, lipid metabolism, liver function, and blood pressure regulation. Examples of the structural state of the body include arterial stiffness (condition of the arteries) and liver fat mass (condition of liver fat).

[0020] <Health Status (Narrow Sense)> Health status (narrow sense) refers to whether or not a person has a lifestyle-related disease, whether or not they have metabolic syndrome, or both. Here, "whether or not" means whether or not they meet the criteria.

[0021] <Health Status (Narrowest Sense)> Health status (narrowest sense) refers to at least one of the following: lipid metabolism ability, liver function, blood pressure regulation ability, and arterial stiffness (arterial condition). Blood LPS concentration correlates with these states. The manner in which the state is expressed is not restricted. Following the expression used in specific health checkups, examples of expressions include "no abnormality," "mild abnormality," "requires follow-up observation," and "requires medical treatment."

[0022] <Lifestyle-related diseases> Lifestyle-related diseases are a general term for diseases whose cause is related to lifestyle. Examples include cancer, cardiovascular diseases, COPD (chronic obstructive pulmonary disease), diabetes, hypertension, dyslipidemia, fatty liver, and arteriosclerosis.

[0023] <Metabolic Syndrome> Metabolic syndrome (visceral fat syndrome) is a condition characterized by visceral fat obesity, accompanied by two or more of the following: hyperglycemia, dyslipidemia, and hypertension. In other words, metabolic syndrome is defined as a high-risk group for lifestyle-related diseases (especially cardiovascular diseases). A person diagnosed with metabolic syndrome is a human being whose condition is classified as metabolic syndrome.

[0024] The diagnostic indicators for metabolic syndrome are waist circumference, as well as blood glucose, blood pressure, and lipids. In the case of Japanese people, The requirements for a person to be diagnosed with bolic syndrome are that (1) is met, and at least two of the following conditions are met: (2A), (2B), and (2C). (1) For men, waist circumference is 85 cm or more, and for women, it is 90 cm or more. (2A) Fasting blood glucose is 110 mg / dL or higher. (2B) Triglycerides are 150 mg / dL or higher, and / or HDL cholesterol is less than 40 mg / dL. (2C) Systolic blood pressure is 130 mmHg or higher, and / or diastolic blood pressure is 85 mmHg or higher.

[0025] <Metabolic Syndrome Pre-Growth Group and Individuals at Risk of Metabolic Syndrome> A person at risk of metabolic syndrome is obese, and their condition is just before developing metabolic syndrome. An individual at risk of metabolic syndrome is a human being whose characteristics fall within the range of a person at risk of metabolic syndrome. The requirements that an individual at risk of metabolic syndrome must meet are that (1) is met, and only one of (2A), (2B), or (2C) is met.

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

[0027] <Group Not Subject to Metabolic Syndrome, etc. and Individuals Not Subject to Metabolic Syndrome, etc.> The group not subject to metabolic syndrome, etc. refers to a state in which the individual is neither diagnosed with metabolic syndrome nor is at risk of developing metabolic syndrome. Individuals not subject to metabolic syndrome, etc. refer to a person whose attributes fall within the group not subject to metabolic syndrome, etc. Individuals not subject to metabolic syndrome, etc. must satisfy all of the following conditions (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 Habits> Dietary habits refer to the state of daily meals. Examples include the intake of fats, sugars, salts, and alcohol. These factors are related to lifestyle-related diseases, metabolic syndrome, and both. Furthermore, blood LPS concentration correlates with each of these factors. In other words, if the intake of fats, sugars, or alcohol is excessive, blood LPS concentration will rise.

[0029] <Health Status Assessment System> Figure 1 shows the configuration of the health status assessment system. The health status assessment system 10 consists 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 are connected by wired or wireless connections. These devices are independent of each other, or some or all of them are integrated. When the output device 30, processing device 40, and input device 50 are integrated, such integration is realized by a personal computer or tablet terminal, etc. Details of each device are as follows.

[0030] <Measuring Device> The measuring device 20 measures the blood LPS concentration of the subject. That is, the measuring device 20 first analyzes the subject's blood or plasma, and the output is the subject's blood LPS concentration. The blood and plasma are pre-treated. Details of the pre-treatment will be described later. The output destination of the blood LPS concentration is not specified, but preferably the processing device 30. The measuring device 20 can be implemented in various ways and is not particularly limited, but examples include a spectrometer, spectrophotometer, microplate reader, etc. In this embodiment, a microplate reader (Microplate Reader ELx808 manufactured by Biotech) is used.

[0031] <Output Device> The output device 30 outputs the subject's blood LPS concentration and the subject's health status. The manner in which this information is output is not limited and may include image output, audio output, paper output, or a combination thereof. Examples of the output device 30 include a display, speaker, printer, etc.

[0032] <Processing Device> The output device 30, input device 50, and external storage device 60 are connected to the processing device 40. The processing device 40 processes the blood LPS concentration of the subject, and as a result, the subject's health status is obtained. In this embodiment, the source of the subject's blood LPS concentration is the measuring device 20. The input device 50 is directly input to the blood LPS concentration. The processing device 40 is composed of basic computer elements, 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 via a bus. A description of these components is as follows.

[0033] <Input / Output Section> Various types of data are exchanged in the input / output section. The output device 40, input device 50, and external storage device 60 are connected to the input / output section. The measuring device 20 can be connected to the input / output section. In this case, the measuring device 20 is equipped with input / output functions.

[0034] <Communication Section> The communication section transmits and receives various types of data. The communication section is connected to a network. Examples of communication sections include dial-up connection modules, Wi-Fi modules, Bluetooth® modules, etc.

[0035] <Program Memory Unit> The program memory unit stores various programs. The program memory unit is implemented using non-volatile memory devices (e.g., ROM) and non-volatile memory devices (e.g., HDDs and SSDs). The non-volatile memory device stores basic programs (including the data necessary for them). Examples of basic programs include the Basic Input / Output System (BIOS), operating system (OS) configuration programs, and network configuration programs. The non-volatile memory device stores operating system (OS) and application programs. Examples of operating systems (OS) include Windows®, Linux®, and Android®. An example of an application program is the health status assessment program, which will be discussed later.

[0036] <Temporary Storage Unit> The temporary storage unit temporarily stores various programs and various data. The various programs are as described above. The various data represent input values, output values, etc. An example of a temporary storage unit is a volatile memory device (for example, RAM).

[0037] The processing unit executes various programs and processes various data. The execution of these programs processes the input values, resulting in output values. The central processing unit (the so-called CPU) embodies the processing unit.

[0038] <Input Device> Various types of data are input into the input device 50. Examples of input devices 50 include touch panels, operation keys, buttons, keyboards, and mice.

[0039] <External Storage Devices> The external storage device 60 stores various types of data and programs. Examples of external storage devices include magnetic storage devices (such as HDDs), optical storage devices (such as CDs, DVDs, and BDs, including their drive units), and semiconductor storage devices (such as USB memory, SD card memory, and SSDs).

[0040] <Health Status Assessment Program> The health status assessment program is what the processing unit 30 performs in determining the health status. In other words, the processing unit 30 determines the health status of the person being measured. At that time, the processing unit 30 refers to the blood LPS concentration of the person being measured. Figure 2 shows the flow of the determination process. The determination process consists of metabolic syndrome diagnosis (S10), LPS diagnosis (S20), and health status output (S30).

[0041] <Metabolic Syndrome Diagnosis (S10)> The metabolic syndrome diagnosis yields a "yes / no" value. This value indicates, at a minimum, whether the person being diagnosed is not a person with metabolic syndrome, etc. The "yes / no" value is stored in a temporary storage unit. In this embodiment, a "yes / no" value of "1" indicates that the person being diagnosed is not a person with metabolic syndrome, etc. On the other hand, a "yes / no" value of "0" indicates that the subject is not a person who is not a person with metabolic syndrome, etc. (i.e., they are a person with metabolic syndrome or a person at risk of having it).

[0042] When obtaining the eligibility value, the values ​​of the metabolic syndrome test indicators and the eligibility requirements are referenced. In other words, the eligibility requirements are compared with the values ​​of the test indicators. These definitions are as described above. The values ​​of the test indicators are stored in a temporary storage unit. The methods for inputting the values ​​of the test indicators are automatic or manual. The means for automatically inputting the values ​​of the test indicators is a communication device. The means for manually inputting the values ​​of the test indicators 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. Figure 3 shows 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 (arterial deterioration) 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 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 (arterial deterioration) 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 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 (arterial deterioration) 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 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 (arterial deterioration) is inferred (deterioration degree:​​​If the LPS concentration "Y" is greater than the reference value "d" (Y>d), the return value "E" is returned (S36). The return value "E" means that a deterioration in health status is inferred (deterioration degree of 71% or more). Specifically, it is inferred that one of the following is inferred (deterioration degree of 71% or more): deterioration of lipid metabolism, deterioration of liver function, deterioration of blood pressure regulation, or arterial stiffness (deterioration of arteries). In the above, the thresholds "a", "b", "c", and "d" depend on race and place of residence. In the case of Japanese people, the thresholds "a", "b", "c", and "d" are, respectively, These values ​​are 0.001, 0.004, 0.007, and 0.010.

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

[0049] Figure 5 shows the output screen for health status, where the subject is not classified as having metabolic syndrome, etc., and their LPS diagnostic value is normal. This screen is displayed when the LPS diagnostic value (return value) is "A". In other words, the subject is not classified as having metabolic syndrome, etc., and there is no indication of deterioration in their health status. The overall assessment result is "No abnormalities" (or "Normal").

[0050] Figure 6 shows the output screen for health status, for individuals who do not have metabolic syndrome, etc., and whose LPS diagnostic value is abnormal. This screen is displayed when the LPS diagnostic value (return value) is one of "B", "C", "D", or "E". In other words, the subject does not have metabolic syndrome, etc., and a deterioration in their health status is presumed. The overall judgment result is "normal" (or "no abnormality"), but a note (e.g., an asterisk "*") is attached. The element that changes the output of the note is the return value. If the note "*" is adopted, one "*" is attached if the return value is "B". If the return value is "E", four "*"s are attached.

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

[0052] <Measurement (P1)> The purpose of the measurement is to determine the blood LPS concentration of the subject. In other words, the blood LPS concentration of the subject is measured by a person, device, or instrument. To put it another way, the method of measuring the blood LPS concentration can be automatic, manual, or semi-automatic. The measurement principle is not specified, but an example is the LAL endpoint assay (colorimetric method). The LAL endpoint assay is used in this embodiment. In this case, the procedure for measuring the blood LPS concentration is as follows.

[0053] The sample is the blood of the person being tested. The storage temperature of this blood is -80°C to 35°C, preferably -10°C to 10°C. The fraction of the blood is not particularly limited, but preferably plasma. The fraction that is not excluded is serum. The plasma is pre-treated. Specifically, first the plasma is diluted. The dilution solvent is an LPS-free liquid (e.g., distilled water, physiological saline, phosphate-buffered saline, etc.), and the dilution ratio 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 used to react with the treated plasma. 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 pre-treated plasma is analyzed using a measuring device described later. The result of this plasma analysis is the blood LPS concentration of the subject.

[0054] <Determination (P2)> The purpose of the determination is to derive the health status of the person being measured. The health status of the person being measured is determined by a person or device, and the blood LPS concentration is referenced in this process. Preferably, determination (P2) is performed when the person being measured does not have metabolic syndrome, etc. Otherwise, determination (P2) is omitted.

[0055] Figure 8 shows a health status assessment table. This health status assessment table shows the relationship between LPS concentration and health status assessment values. The subject's blood LPS concentration is applied to this health status assessment table, and the result is the subject's health status assessment value. The thresholds "a," "b," "c," and "d" depend on race and place of residence.

[0056] <Presentation (P3)> The purpose of presentation is to make the subject aware of their health status. The blood LPS concentration and health status are presented by a person, device, or instrument, and the recipient of the presentation is the subject. The method of presenting the measured blood LPS concentration and health status is not limited, but specifically it is electromagnetic (electronic or magnetic). Furthermore, the manner in which the blood LPS concentration and health status are presented is not limited, but specifically it is a visual manner. The means of presenting the blood LPS concentration and health status are not limited, but examples include paper or a screen.

[0057] <Effects of Health Status Assessment System, Health Status Assessment Program, and Health Status Assessment Method> The effect of these embodiments is an improvement in the accuracy of detecting high-risk groups for lifestyle-related diseases. This is because even if the person being measured does not have metabolic syndrome, etc., their LPS concentration can be further determined.

[0058] <Modification> If, in addition to LPS concentration, other indicators (such as blood glucose levels or triglyceride levels) are referenced in the aforementioned judgment process or judgment, the accuracy of identifying high-risk groups for lifestyle-related diseases will be further improved.

[0059] <Dietary Habits Assessment System / Dietary Habits Assessment Program> The dietary habits assessment system consists of a measuring device, an output device, a processing device, an input device, and an external storage device. The detailed descriptions of these hardware components refer to 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. A key feature of the dietary habits assessment system is the dietary habits assessment program.

[0060] <Dietary Habits Assessment Program> The processing unit performs a judgment process when the health status assessment program is used. In other words, the processing unit determines the dietary habits of the person being measured. At that time, the processing unit refers to the blood LPS concentration of the person being measured. Figure 9 shows the flow of the judgment process. The judgment process consists of LPS diagnosis (S40) and 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. Figure 10 shows 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 it is not inferred that the eating habits are disordered. Specifically, it is not inferred that there is excessive intake of oil, sugar, salt, or alcohol.

[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 it is inferred that there is a lifestyle disease. Specifically, it is inferred that there is excessive intake of oil, sugar, salt, or alcohol.

[0063] <Eating Habits Evaluation Output (S50)>The eating habits evaluation is output after the LPS diagnosis is completed. The output modes of the eating habits evaluation are roughly divided into two. The details are as follows. Figure 11 shows the output screen of the eating habits evaluation, which is (a) when it is not inferred that the eating habits are disordered, and (b) when it is inferred that the eating habits are disordered. The screen is composed of the LPS concentration 71 of the measured person, the eating habits evaluation 72, and the guidance content (advice) 73. When it is not inferred that the eating habits are disordered, what is shown in the eating habits evaluation is that the eating habits are not disordered 72a. Also, what is included in the guidance content is that the current eating habits should be continued 73a. On the other hand, when it is inferred that the eating habits are disordered, what is shown in the eating habits evaluation is that the eating habits are disordered 72b. Also, what is included in the guidance content is that the current eating habits should be improved 73b.

[0064] <Eating Habits Evaluation Method>Figure 12 shows the flow of the eating habits evaluation method. The eating habits evaluation method is composed of measurement (P11), determination (P12), presentation and / or guidance (P13). Specifically, it is as follows.

[0065] <Measurement (P11)> The purpose of the measurement is to determine the blood LPS concentration of the subject. The detailed explanation will refer to the explanation in Measurement (P1).

[0066] <Judgment (P12)> The purpose of the judgment is to derive the dietary habits of the person being measured. The person being measured is judged by a person or device, and the blood LPS concentration is referenced in this process. Figure 14 shows the dietary habits judgment table. The dietary habits judgment table shows the relationship between LPS concentration and the dietary habits judgment value. The blood LPS concentration of the person being measured is applied to the dietary habits judgment table, and the result obtained is the dietary habits judgment value of the person being measured. The threshold "e" depends on race and place of residence. The dietary habits judgment value indicates either "a disordered diet is inferred" or "a disordered diet is not inferred". The dietary habits judgment value allows for a multi-level classification of the degree of "disordered diet". In that case, the dietary habits judgment value adopts a more detailed expression, for example, "a somewhat disordered diet is inferred" or "a considerably disordered diet is inferred".

[0067] <Presentation and / or Guidance (P13)> The purpose of presentation is to make the subject aware of their dietary assessment. The blood LPS concentration and dietary assessment are presented by a person, device, or instrument, and the recipient of the presentation is the subject. The method of presenting the measured blood LPS concentration and dietary assessment is not limited, but specifically it is electromagnetic (electronic or magnetic). Furthermore, the manner in which the blood LPS concentration and dietary assessment are presented is not limited, but specifically it is a visual manner. The means of presenting the blood LPS concentration and dietary assessment are not limited, but examples include paper or a screen.

[0068] The guidance provided by a person, device, or instrument in conjunction with, or in place of, the presentation. Guidance is provided when the dietary assessment value indicates "a disorder in dietary habits is suspected." The purpose of the guidance is to improve dietary habits. Excessive intake of fat, sugar, or alcohol raises blood LPS levels. Therefore, the guidance should be to reduce the intake of these substances. Preferably, the guidance should be provided on a continuous basis, not just a one-time event.

[0069] <Effects of the Dietary Habits Assessment System, Dietary Habits Assessment Program, and Dietary Habits Assessment Method> The effect of these embodiments is the prevention of lifestyle-related diseases. This is because the cause of lifestyle-related diseases is disordered eating habits, and such disorder can be identified at an early stage.

[0070] <Modified Version> If, in addition to LPS concentration, other indicators (such as blood glucose levels or triglyceride levels) are referenced in the aforementioned judgment process or judgment, the prevention of lifestyle-related diseases will be even more effective.

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

[0072] <Test 1> Test 1 aims 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> 31 adult men and women were selected as subjects. The selection criteria were: (1) Informed consent (1) The applicant must have obtained a score, and (2) have not met any of the metabolic syndrome diagnostic criteria in a health checkup or medical examination within the past three months. Selection criterion (2) can be rephrased as the applicant must meet all of the following criteria: a) Waist circumference: less than 85 cm for men, less than 90 cm for women b) Fasting blood glucose: less than 110 mg / dL c) Triglycerides: 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 from the subjects was collected. Specifically, this included the results of health checkups or medical examinations conducted by the subjects within the past three months prior to joining 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 samples were collected from the subjects. Using these blood samples, the following parameters were measured or calculated: the subjects' blood LPS concentration, blood glucose level, insulin concentration, and HOMA-IR (homeostasis model assessment of insulin resistance). The specific procedure is as follows:

[0076] Procedure 1: 5 mL of fasting blood was collected from the subject. The subject fasted from 9 PM the day before blood collection until the time of collection. Procedure 2: Heparinized plasma was obtained by centrifugation of the collected blood. Procedure 3: The heparinized plasma was mixed. The mixing time was approximately 1 minute, and a test tube mixer was used for mixing.

[0077] Step 4: After separating a portion of the stirred plasma, the separated 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: 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 its temperature to approximately room temperature (around 25°C). Step 7: The room-temperature plasma was stirred. The stirring time was approximately 30 seconds, and a test tube mixer was used as the stirring device.

[0079] Procedure 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 (1 sample) of one subject (2 wells / sample). In other words, plasma was injected into a total of 62 wells (31 subjects x 2 wells). The amount of plasma injected into each well was 50 μL / well. In addition, 50 μL of Limulus reagent (Endospecie® ES-50M set, manufactured by Seikagaku Corporation) was added to each well (50 μL / well). (2) Distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) was injected into two of the remaining 34 wells. In addition, 50 μL of Limulus reagent (Endospecie® ES-50M set, manufactured by Seikagaku Corporation) was added to each well (50 μL / well). (3) To create a calibration curve, seven standard LPS aqueous solutions were prepared using endotoxin standards (manufactured by Seikagaku Corporation). The concentrations of the seven standard LPS aqueous solutions were 0.0001 EU / mL, 0.0004 EU / mL, 0.0016 EU / mL, 0.0063 EU / mL, 0.025 EU / mL, and 0.10 EU / mL and 2.0 EU / mL, respectively. Two of the remaining 32 wells were used for one standard LPS aqueous solution (2 wells / LPS aqueous solution for calibration curve). In other words, a total of 14 wells (7 types × 2 wells) were injected with standard LPS aqueous solutions. In addition, 50 μL of Limulus reagent (Endospecy® ES-50M set, manufactured by Seikagaku Corporation) was added to 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 prepared. The purpose was to cancel out the influence of plasma color in absorbance measurements. 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. In addition, 50 μL of distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) was added to each well (50 μL / well). (2) Distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) was injected into 2 of the remaining 34 wells. In addition, 50 μL of distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) was added to each well (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 (reference wavelength 492 nm) was measured. Here, the reference wavelength is a wavelength used to correct for the effects of absorbance interfering factors (e.g., scratches or distortions on the plate), and specifically refers to the wavelength specified by the manufacturer of the Limulus reagent (in this embodiment, Seikagaku Corporation). The relationship between each absorbance is as follows: Here, the absorbance of each sample used is the average value of two wells. (Equation) Absorbance A = Absorbance B - {Absorbance C + (Absorbance D1 - Absorbance D2)} Absorbance A: Reaction of LPS and Limulus reagent in plasma 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 standard LPS aqueous solution and the reactant of 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 subjects is within the range of the absorbance of each reactant.

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

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

[0085] <Measurement of insulin concentration> The insulin concentration was measured. The measuring instrument 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] <Subject profile> Table 1 shows the profiles of the subjects in this study. For the indicators marked with an asterisk "*", the values are the mean ± standard deviation. It was confirmed for all subjects that they do not meet any metabolic syndrome diagnostic criteria.

[0088]

Table 1

[0089] <Distribution of LPS concentration in subjects> Figure 14 shows the distribution of LPS concentration in the blood of the subjects. The median blood LPS concentration in the subjects was 0.0038 EU / mL. The concentration range of LPS concentration in the subjects was from 0 to 0.0117 EU / mL. LPS was detected in 22 subjects, representing 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 ​​included 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 various test values. The "ρ" in the figure represents the correlation coefficient. Specifically, 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 triglycerides. Hereinafter, systolic blood pressure, diastolic blood pressure, pulse pressure, γ-GTP, and triglycerides will be collectively referred to as simple correlation test values.

[0092] These results suggest that (1) elevated blood LPS levels are associated with impaired blood pressure regulation, (2) elevated blood LPS levels are associated with impaired arteriosclerosis, (3) elevated blood LPS levels are associated with impaired liver function, and (4) elevated blood LPS levels are associated with impaired lipid metabolism.

[0093] <Multiple Regression Analysis> The relationship between each simple correlation test value and blood LPS concentration, age, sex, and BMI was analyzed (multiple regression analysis). Specifically, the dependent variable was each simple correlation test value, and the independent 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. Sex is a binary value, so it was not log-transformed and multiple regression analysis was performed.

[0094] Table 2 shows the results (P-values) of the multiple regression analysis. After adjusting for age, sex, and BMI, a significant positive correlation (P<0.05) was observed between blood LPS concentration and triglycerides. Furthermore, a trend of correlation (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] Table 3 shows the distribution range of simple correlation test values ​​for subjects with detected and undetected blood LPS. These results indicate that the distribution range of simple correlation test values ​​is similar regardless of whether blood LPS is detected or not. In other words, blood LPS concentration is difficult to estimate from the level of simple correlation test values. Conversely, these results suggest that deterioration of health status (especially blood pressure regulation, arteriosclerosis, liver function, and lipid metabolism) can be detected by blood LPS concentration, even if it is not detected by existing test indicators.

[0097] [Table 3]

[0098] <Study 2> Blood LPS concentration in healthy individuals and patients with nonalcoholic fatty liver disease The blood LPS concentration of subjects (hereinafter referred to as "NAFLD patients") was evaluated. Here, non-alcoholic fatty liver disease refers to fatty liver disease in which the 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 individuals and 31 NAFLD patients.

[0099] <Parameters for Each Group> Table 4 shows the profiles of the subjects in Study 2. For indicators marked with an asterisk "*", the values ​​are mean ± standard deviation. Student's t-test or Mann-Whitney U test was performed on each item, and the p-values ​​obtained were those obtained. Comparing healthy individuals and NAFLD patients, NAFLD patients were significantly older. No significant difference was observed between groups in the male-female ratio. Comparing healthy individuals and NAFLD patients, significant deterioration (p<0.05) was observed in NAFLD patients' laboratory values ​​related to obesity, blood pressure, liver function, lipid metabolism, and glucose metabolism.

[0100] [Table 4]

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

[0102] Figure 16(b) shows the Receiver Operating Characteristic (ROC) curve. The diagnostic accuracy of plasma LPS concentration for NAFLD is an area under the curve (AUC) of 0.87. The optimal cutoff value (dotted line) is when the plasma LPS concentration is 0.010 EU / mL. 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 threshold for deterioration of health status is a plasma LPS concentration of 0.010 EU / mL. In other words, the criterion value for determining health status is a plasma LPS concentration of 0.010 EU / mL.

[0103] <Effects of this embodiment> The effect of this embodiment is an improvement in the accuracy of detecting high-risk groups for lifestyle-related diseases. This is because the health status of individuals other than those with metabolic syndrome and those at risk of developing it can be assessed more accurately than before. [Industrial applicability]

[0104] The field in which this invention is useful is the healthcare services business. [Explanation of Symbols]

[0105] 10 Health status assessment system 20 Measurement device 30 Output device 40 Processing device

Claims

1. The lifestyle improvement support system comprises at least the following: Measuring device: This device measures the LPS concentration in the subject's blood. Output device: The output from this device is lifestyle improvement information for the subject of measurement, aimed at preventing lifestyle-related diseases. Processing device: Connected to it is at least the output device, and This process processes the LPS concentration in the blood. If the processing device infers a deterioration in health based on the blood LPS concentration, it causes the output device to output lifestyle improvement information, including a recommendation to reduce at least one of the intake of oil, sugar, and alcohol.

2. A lifestyle improvement support program, wherein the processing performed by the computer thereunder is at least the following: Acquisition: What is acquired here is the blood LPS concentration of the subject. Judgment: The judgment here is whether or not there is an inference of deterioration in health status based on the blood LPS concentration. Output: The output here is lifestyle improvement information for the subject of measurement, aimed at preventing lifestyle-related diseases. In the output, if a deterioration in the health condition is inferred, lifestyle improvement information for preventing lifestyle-related diseases is output, including a recommendation to reduce at least one of the intake of oil, sugar, and alcohol.

3. A method for supporting the improvement of lifestyle habits, comprising at least the following steps: Measurement: What is measured here is the blood LPS concentration of the subject. Judgment: The judgment here is whether or not there is an inference of deterioration in health status based on the blood LPS concentration. Presentation: The information presented here is lifestyle improvement information for the prevention of lifestyle-related diseases for the subject being measured. In the aforementioned presentation, if a deterioration in the health condition is suspected, lifestyle improvement information for preventing lifestyle-related diseases is presented, including the recommendation to reduce at least one of the intake of oil, sugar, and alcohol.

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