HEALTH STATE EVALUATION SYSTEM, HEALTH STATE EVALUATION PROGRAM, AND HEALTH STATE EVALUATION METHOD, AND DIETARY LIVING EVALUATION SYSTEM, HEALTH LIVING EVALUATION PROGRAM, AND DIETARY LIVING EVALUATION METHOD

Abstract

To increase the accuracy of discovering a high risk group of adult disease.SOLUTION: The inventors of the present application has first noted the relations between adult disease, the metabolic syndrome, and the concentration of LPS in blood, and has found out, after deep consideration based on the relations, that there are a correlation between the 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 that a computer executes according to the health state evaluation program is at least determination. The determination target of the computer is the health state of a subject and the determination is based on 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, dietary assessment system, dietary assessment program, and dietary assessment method do. [Background technology]

[0002] Improving metabolic syndrome is essential to preventing lifestyle-related diseases. Disease is a general term for illnesses that are caused by lifestyle habits. For example, , cancer, cardiovascular disease, COPD (chronic obstructive pulmonary disease), diabetes, high blood pressure, dyslipidemia, These include fatty liver and arteriosclerosis. Metabolic syndrome is a pathology of visceral fat obesity. It means that two or more of hyperglycemia, dyslipidemia, and hypertension are present. The metabolic syndrome is defined as a combination of lifestyle-related diseases (especially cardiovascular disease) This is a high-risk group.

[0003] The situation in Japan is serious. According to a report in Non-Patent Document 1, Approximately 25% of people undergoing regular health checkups are at risk of developing metabolic syndrome or at risk of developing it. It is. Early detection of metabolic syndrome is mainly carried out through specific health checkups. The items examined in the regular health checkup are waist circumference, blood sugar, lipids, and blood pressure (hereinafter, these are referred to as "examinations"). These are also called "test indicators" and their values ​​"test values."

[0004] The main role in improving metabolic syndrome is through specific health guidance. Health guidance is given to those among the test subjects whose test results are outside the range of the specified standards. In other words, the subjects were neither those with metabolic syndrome nor those at risk of developing it (see below). In the following cases, the subjects are referred to as "non-metabolic syndrome" and are not subject to guidance. It's outside.

[0005] However, what is overlooked in specific health checkups and specific health guidance is the metabolic syndrome. Those who are not eligible for the WHO-related disability insurance and are at high risk of lifestyle-related diseases. According to the report, 100 Japanese men in their 20s are at risk of metabolic syndrome or at risk of developing it. The proportion of people who fall under this category is about 10%, and for those in their 30s, it is about 40%. As suggested by the report, even those who are not affected by metabolic syndrome are at risk of lifestyle-related diseases. The danger isn't necessarily low. [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 detect high-risk individuals who are at high risk for lifestyle-related diseases. This is an improvement in degree. [Means for solving the problem]

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

[0009] <Health status evaluation system> A health status evaluation system is composed of at least a measuring device. The measuring device measures the blood concentration of the subject. The LPS concentration is the concentration of the LPS in the blood. The output device outputs the health condition of the subject. At least the output device is connected to the processing device. The LPS concentration in the blood is what is measured, and the result is the health of the person being measured. This is the state.

[0010] <Health Status Evaluation Program> A computer executes a health status evaluation program. The process is at least a judgment. The computer judges the health of the person being measured. The LPS concentration in the blood of the subject is the reference state. <Health status evaluation method> Health status evaluation method (excluding medical procedures) consists of: At a minimum, they are measurement, determination, and presentation, i.e., by a person or by a device or instrument. The LPS concentration in the blood of the subject is measured. What is judged is the health condition of the person being measured, and the blood L The PS concentration is the health condition of the person or device or instrument. .

[0011] <Second viewpoint> The next thing the inventors focused on was the relationship between dietary status and blood LPS concentration. In other words, when your diet deteriorates (e.g., you eat too much oil), the LP of intestinal bacteria increases. S enters the bloodstream. When the amount of LPS in the blood increases, it becomes a chronic condition in the body. The cause of chronic inflammation is inflammation. It is a health condition that deteriorates with chronic inflammation. is defined as follows:

[0012] <Dietary assessment system> The dietary assessment system is composed of at least a measuring device, The output device and the processing device are used to measure the subject's blood LP. The output device outputs the dietary condition of the subject. At least the output device is connected to the processing device. The LPS concentration in the blood is the result of the dietary condition. .

[0013] <Dietary assessment program> Processing performed by the computer using the dietary assessment program The computer determines the eating habits of the person being measured. The LPS concentration in the blood of the subject is used as a reference.

[0014] <Dietary assessment method> The dietary assessment method consists of at least measurement, judgment, and That is, what is measured by a person or a device or instrument is the blood The LPS concentration is determined by a person or device based on the subject's dietary condition. The reference in this case is the blood LPS concentration. What is presented is the dietary state in question. Effect of the Invention

[0015] What the present invention makes possible is an improvement in the accuracy of detecting individuals at high risk for lifestyle-related diseases. Even if the person being measured is not a person with metabolic syndrome or a person at risk of having it, This is because the health condition of the person being measured can be grasped more accurately than before. [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] <Embodiments> The present invention is embodied in the following embodiments. The phrases are defined as follows:

[0018] <Blood LPS concentration> Blood LPS concentration is the concentration of lipopolysaccharide (LP) in the blood. The "blood LPS concentration" refers to the concentration of LPS in plasma (unit: EU / mL). The plasma LPS concentration is the amount of LPS in plasma. The concentration of LPS in serum is measured in EU / mL. (Unit: EU / mL). In this embodiment, the LPS concentration in plasma is used ( Hereafter, it may be simply referred to as "blood LPS concentration." Because the blood LPS concentration is roughly equivalent to The important thing is the LPS concentration in plasma (i.e., "blood LPS concentration" ≒ "plasma LPS concentration"). "PS concentration").

[0019] <Health condition (broad definition)>Health condition (broad definition) refers to the functional or organic state of the body. Examples of functional status of the body include the state of glucose metabolism, the state of lipid metabolism, and the state of liver function. The organic condition of the body is exemplified by arterial hardness (the condition of the arteries) and state of liver fat, liver fat content (state of liver fat), etc.

[0020] <Health status (narrow sense)>Health status (narrow sense) refers to whether or not you have lifestyle-related diseases, metabolic syndrome, etc. "Applicability" refers to whether or not a product falls under the category of "rohm" or both. .

[0021] <Health status (narrowest sense)>Health status (narrowest sense) refers to the state of lipid metabolism, liver function, This refers to at least one of the following: blood pressure regulation ability, and arterial hardness (arterial condition). The condition is correlated with the blood LPS concentration. The form in which the condition is expressed is not important. Following the expressions used in medical examinations, examples of such expressions are "no abnormalities," "slight abnormalities," "needs follow-up observation," and "Medical treatment required."

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

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

[0024] Diagnostic indicators for metabolic syndrome are waist circumference, as well as blood glucose, blood pressure and lipids. For Japanese people, the requirements for metabolic syndrome are met by those who meet the criteria in (1) and and two or more of (2A), (2B) and (2C) are permitted. (1) Waist circumference must be 85 cm or more for men and 90 cm or more for women. (2A) Fasting blood glucose level is 110 mg / dL or higher (2B) Triglycerides are 150 mg / dL or more and / or HDL cholesterol is 100 mg / dL or more. LDL is less than 40 mg / dL (2C) Systolic blood pressure is 130 mmHg or more and / or diastolic blood pressure is 85 mmHg or more. mHg or more

[0025] <Those at risk of metabolic syndrome and those at risk of metabolic syndrome> Meta The pre-obesity group is a group of people who are obese and at the stage of metabolic syndrome. The term "pre-metabolic syndrome" refers to a condition in which a person is at risk of developing metabolic syndrome. The term refers to those who are at risk of developing metabolic syndrome. The requirements for potential ROHM applicants are that (1) is met, and also that (2A), (2B), and Only one of (2C) is permitted.

[0026] (1) For men, waist circumference must be 85 cm or more, and for women, waist circumference must be 90 cm or more. Something (2A) Fasting blood glucose level is 110 mg / dL or higher (2B) Triglycerides are 150 mg / dL or more and / or HDL cholesterol is 100 mg / dL or more. LDL is less than 40 mg / dL (2C) Systolic blood pressure is 130 mmHg or more and / or diastolic blood pressure is 85 mmHg or more. mHg or more

[0027] <Group not affected by metabolic syndrome, etc. and those not affected by metabolic syndrome, etc.> The non-metabolic syndrome group is a condition that does not include metabolic syndrome and This means that you are not in the metabolic syndrome pre-group. A non-applicable person is a human being whose attributes are not applicable to metabolic syndrome, etc. Those who are not subject to metabolic syndrome, etc., meet the following criteria (1) to (5): ) all the way up to (1) Waist circumference: For men, less than 85 cm; for women, less than 90 cm (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 130mmHg and diastolic blood pressure less than 85mmHg Less than

[0028] <Dietary status>Dietary status refers to the state of daily meals. For example, the amount of oil intake , sugar intake, salt intake, alcohol intake, etc. These factors are related The causes of lifestyle-related diseases, metabolic syndrome, and both are also included. The factor correlates with the blood LPS concentration. That is, the amount of oil intake, the amount of sugar intake, Excessive alcohol intake increases blood LPS levels.

[0029] <Health Status Evaluation System> Figure 1 shows the configuration of the health status evaluation system. The condition evaluation system 10 includes a measurement device 20, an output device 30, a processing device 40, an input device 41, and an output device 30. The external storage device 50 and the external storage device 60 are connected to a The system may be wired or wireless. These devices may be independent of each other or may be part or entirely integrated. When the output device 30, the processing device 40, and the input device 50 are integrated, Such integration is embodied in personal computers and tablet terminals. The 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 blood or plasma of the subject is first analyzed by the measuring device 20. The LPS concentration in the blood of the subject is output. The details of the pretreatment will be described later. The blood LPS concentration may be output to any device. Preferably, the processing device 30. The measurement device 20 may be realized in a variety of ways, including but not limited to the following: Examples of such devices include, but are not limited to, spectrometers, spectrophotometers, microplate readers, etc. The microplate reader used in this embodiment is a microplate reader (Biotec Microplate). The ELx808 is a standard 10-pin 12V 1000mA ...

[0031] <Output device> The output device 30 outputs the LPS concentration in the blood of the subject and the health status of the subject. The manner in which this information is output is not important. Specifically, image output, sound output, etc. The output device 30 may be a voice output, a paper output, or a combination thereof. Speakers, printers, etc.

[0032] <Processing Device> The processing device 40 is connected to an output device 30, an input device 50 and an external storage device. The LPS concentration in the blood of the subject is processed by the processing device 40. As a result, the health condition of the subject is obtained. The source of the LPS concentration is the measurement device 20. Alternatively, the blood LPS concentration can be directly input. The input device 50 is the one that operates the input. 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. The components are connected to the bus. The description of these components is as follows:

[0033] <Input / Output Unit> The input / output unit exchanges various data. are an output device 40, an input device 50, and an external storage device 60. The measuring device 20 is equipped with an input / output function. It is.

[0034] <Communication section> The communication section transmits and receives various data. Examples of communication units include a dial-up connection module, a Wi-Fi Wi-Fi) module, Bluetooth (registered trademark) “Bluetooth”, module Ru et al.

[0035] <Program Storage Unit> Various programs are stored in the program storage unit. The program storage unit is realized by a non-volatile memory device (e.g., ROM, etc.) and a non-volatile A storage device (e.g., HDD, SSD, etc.). The non-volatile storage device stores: A basic program (including the data required for it). Examples of basic programs are: Basic Input / Output System (BIOS), Operating System ( OS) setting program, network setting program, etc. Stored in non-volatile memory device The operating system (OS) and application programs are included. An example of an operating system (OS) is Windows (registered trademark) “Windows ws”, Linux (registered trademark), Android (registered trademark) ) “Android” and others. Examples of application programs are It is a health status assessment program.

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

[0037] <Processing section> The processing section executes various programs and processes: Various data. When various programs are executed, the input values ​​are processed and 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. These include touch panels, operation keys, buttons, keyboards, mice, etc.

[0039] <External Storage Device> The external storage device 60 stores various data and programs. Examples of external storage devices include magnetic storage devices (HDDs, etc.), optical storage devices (CDs, , DVD, BD, etc. Including their drive devices.), semiconductor memory devices (USB memory, SD card memory, SSD, etc.).

[0040] <Health Condition Evaluation Program> The processing device 30 executes the health condition evaluation program. This is a determination process. That is, what is determined by the processing device 30 is the health status of the person to be measured. At that time, what is referred to by the processing device 30 is the blood LPS concentration of the person to be measured. What is shown in FIG. 2 is the flow of the determination process. What constitutes the determination process is the metabolic syndrome diagnosis (S10), the LPS diagnosis (S20), and the health status output (S30).

[0041] <Metabolic syndrome diagnosis (S10)> What is obtained in the metabolic syndrome diagnosis is the non - value. What this non - value indicates is at least whether the person to be diagnosed is a non - candidate for metabolic syndrome or not. What stores this non - value is the temporary storage unit. In this embodiment, what is indicated by the non - value "1" is that the person to be diagnosed is a non - candidate for metabolic syndrome or the like. On the other hand, what is indicated by the non - value "0" is that the subject is not a non - candidate for metabolic syndrome or the like (that is, the subject is a candidate for metabolic syndrome or a candidate for its preliminary group).

[0042] What is referred to when obtaining the non - value are the values of the inspection indicators for metabolic syndrome and the criteria for metabolic syndrome eligibility. That is, what is compared with the value of the inspection indicator is the eligibility criterion. These definitions are as described above. What stores the value of the inspection indicator is the temporary storage unit. The mode of inputting the value of the inspection indicator is automatic or manual. The means for automatically inputting the value of the inspection indicator is the communication device. The means for manually inputting the value of the inspection indicator is the input device.

[0043] <LPS diagnosis (S20)> If the non - value is "1", the LPS diagnosis is executed. LPS ​​​​​​​​​​​​​What can be obtained through diagnosis is the LPS diagnostic 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 condition is inferred. More specifically, it means that no deterioration of lipid metabolism ability, liver function, blood pressure regulation ability, and 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 a deterioration of the health condition is inferred (deterioration degree 1% - 20%). Specifically, any one of the deterioration of lipid metabolism ability, liver function deterioration, blood pressure regulation ability deterioration, and 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 a deterioration of the health condition is inferred (deterioration degree 21% - 50%). Specifically, any one of the deterioration of lipid metabolism ability, liver function deterioration, blood pressure regulation ability deterioration, and arterial stiffness (arterial deterioration) is inferred (deterioration degree 2 1% - 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 condition is inferred Specifically, the deterioration of lipid metabolism and liver function Deterioration of the arteries, deterioration of blood pressure regulation, or arterial hardening (deterioration of the arteries) is suspected (degree of deterioration 5 1%~70%).

[0047] 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 the health condition is suspected to be deteriorating (degree of deterioration 71 % or more). Specifically, the deterioration of lipid metabolism, liver function, and blood pressure regulation. or arterial hardening (deterioration of the arteries) is suspected (deterioration of the arteries by 71% or more). In the above, the thresholds "a", "b", "c", and "d" depend on the race and For 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 corresponding value is "0" or This is 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, with the target being metabolic syndrome. This screen is displayed when the relevant value is "0". That is, the subjects were those who were classified as having metabolic syndrome, and the overall assessment results were as follows: "Guidance required."

[0049] Figure 5 shows the health status output screen, with the target being metabolic syndrome. The person is not eligible for the above and the LPS diagnostic value is normal. This screen is displayed. The LPS diagnostic value (return value) is "A". Those who are not subject to the pulmonary embolism syndrome and whose health condition is not deteriorated. The overall result is "no abnormalities" (or "normal").

[0050] Figure 6 shows the health status output screen, with the target being metabolic syndrome. The person is not eligible for the above and the LPS diagnostic value is abnormal. This screen is displayed. The LPS diagnostic value (return value) is either "B", "C", "D" or "E". In other words, the subjects were those who did not fall under the category of metabolic syndrome, etc., and The overall result is "normal" (or "abnormal") None), but only a note (e.g., an asterisk "*") is added. The element that changes the output behavior of the note is the return value. When the note "*" is used, the return value If the return value is "B", one "*" is added. If the return value is "E", four "*"s are added. " is added.

[0051] <Health Status Evaluation Method> Figure 7 shows the flow of the health status evaluation method. Health Status Evaluation The method consists of measurement (P1), judgment (P2), and presentation (P3). The following are the

[0052] <Measurement (P1)> The purpose of the measurement is to grasp 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 person being measured. In other words, the measurement of the blood LPS concentration may be performed automatically, manually, or semi-automatically. The measurement principle is not important. For example, it is the LAL endpoint assay (colorimetric method). In this embodiment, the LAL endpoint assay is used. The procedure for measuring blood LPS concentration is as follows.

[0053] The sample is the subject's blood. The storage temperature of this blood is preferably -80°C to 35°C. The temperature is preferably −10° C. to 10° C. The blood fraction is not particularly limited, but is preferably is plasma. What the fraction does not exclude is serum. The plasma is pretreated. Specifically, the plasma is first diluted with a dilution solvent. , an LPS-free liquid (e.g., distilled water, saline, phosphate-buffered saline, etc.), The dilution ratio is 10 times. Then, the diluted plasma is heated. The heating temperature is 70 degrees and the heating time is 10 minutes. The reagent that reacts with the plasma is the LAL reagent. This reagent is commercially available. For example, Endotoxin-Single Test Wako (FUJIFILM Wako Pure Chemical Industries, Ltd.) Company) and Limulus amebocyte lysate assay kit (QC L-1000, Lonza), etc. The pretreated plasma is analyzed by a measuring device, which will be described later. What is measured is the LPS concentration in the subject's blood.

[0054] <Judgment (P2)> The purpose of judgment is to derive the health condition of the person being measured. The device determines the health condition of the person being measured, and the reference for this is Preferably, the determination (P2) is performed when the subject is If the patient does not fall under the category of those with pulmonary syndrome, etc., the decision is made as follows (P2). is omitted.

[0055] FIG. 8 shows a health condition judgment table. The health condition judgment table shows LPS The relationship between concentration and health condition judgment value. The result is the blood LPS concentration of the person being measured, and the result is a value that determines the health status of the person being measured. The thresholds "a", "b", "c", and "d" depend on race and place of residence.

[0056] <Presentation (P3)> The purpose of the presentation is to make the person being measured aware of their health condition. The device or instrument provides the LPS concentration in the blood and the health status. The recipient of the information is the person being measured. The method of identification is not limited, but specifically, it is electromagnetic (electronic or magnetic). The manner in which the LPS concentration and the health status are displayed is not limited, but specifically, it is preferably displayed visually. The means for displaying the blood LPS concentration and the health condition is not limited, and examples thereof include paper and Screens, etc.

[0057] <Effects of health status evaluation system, health status evaluation program and health status evaluation method> These embodiments contribute to improving the accuracy of detecting high-risk groups for lifestyle-related diseases. If so, even if the person being measured does not have metabolic syndrome, the LPS concentration of that person can be measured. This is because it becomes more clear.

[0058] <Modification> In addition to the LPS concentration, other indicators ( If the data were to be used for blood glucose levels or triglyceride levels, the accuracy of detecting high-risk groups for lifestyle-related diseases would be further improved. do.

[0059] <Diet Evaluation System / Diet Evaluation Program> The diet evaluation system is composed of a measuring device, an output device, a processing device, an input device, and an external storage device. The details of these hardware components to be referred to in the detailed description are 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 feature of the diet evaluation system is the diet evaluation program.

[0060] <Diet Evaluation Program> What the processing device executes by the health status evaluation program is a determination process. That is, what is determined by the processing device is the diet status of the subject. At that time, what the processing device refers to is the blood LPS concentration of the subject. What is shown in FIG. 9 is the flow of the determination process. What constitutes the determination process is the LPS diagnosis (S4 0), and the diet output (S50).

[0061] <LPS Diagnosis (S40)> After activation, the LPS diagnosis is executed. What is obtained by 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, what the threshold value "e" depends on is the race and place of residence. What the return value "F" means is that no disorder in the diet is inferred. Specifically, excessive intake of oil, excessive intake of sugar, excessive intake of salt, and excessive intake of alcohol are not inferred.

[0062] If the LPS concentration "Z" is greater than or equal to the reference value "e", the return value "G" is returned (S43). The return value "G" means that lifestyle-related diseases are suspected. It is suspected that the cause is excessive intake of food, sugar, salt, or alcohol. do.

[0063] <Dietary evaluation output (S50)> The dietary evaluation is output after the LPS diagnosis is completed. The output format of the dietary assessment is roughly divided into two types. The details are as follows. It is. FIG. 11 shows the output screen of the dietary assessment. (a) If no disordered eating habits are suspected, (b) when her eating habits were poor, and (b) when her eating habits were poor. The LPS concentration of the subject 71, dietary evaluation 72, and guidance content (advice) 73. If no disordered lifestyle is suspected, the dietary assessment will show that the dietary habits are not disordered. 2a. The guidance also includes 73a, which states that the current diet should be continued. On the other hand, if a disordered diet is suspected, the dietary assessment will show that the disordered diet The guidance also includes the following: 73b. It is.

[0064] <Dietary assessment method> Figure 12 shows the flow of the dietary assessment method. It consists of measurement (P11), judgment (P12), and presentation and / or instruction (P13). Specifically, it is as follows:

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

[0066] <Judgment (P12)> The purpose of the judgment is to derive the dietary habits of the person being measured. The dietary habits of the person being measured are judged by the device, and the reference for this is the This is the blood LPS concentration. FIG. 14 shows a dietary assessment table. The dietary assessment table shows the LPS concentration. The relationship between the degree of oxidative stress and the dietary assessment value is as follows: The result is the blood LPS concentration, and the result is the dietary assessment value of the person being measured. "e" depends on race and place of residence. "Irregular eating habits are suspected." or "Irregular eating habits are not suspected." The fixed value allows for multiple stages of the degree of "eating disorder." The judgment score is more detailed, for example, "My eating habits are somewhat irregular." "It is inferred that his eating habits are quite irregular," etc.

[0067] <Presentation and / or Guidance (P13)> The purpose of the presentation is to make the subject aware of the dietary assessment. The blood LPS concentration and The dietary assessment is presented to the subject. Measured blood LPS concentration The method of presenting the dietary assessment is not limited, but specifically, it can be electromagnetic (electronic or magnetic) The blood LPS concentration and dietary assessment may be presented in any form, but Specifically, the method for presenting the blood LPS concentration and the dietary assessment is visual. Examples include paper and a screen.

[0068] Any act performed by a person, device or instrument in conjunction with or in place of such presentation. Guidance is given when the dietary assessment value is "indicating that the disorder of the dietary habits is serious" The purpose of the guidance is to improve eating habits. Excessive intake of either fish or alcohol increases blood LPS levels. Therefore, the guidance is to limit the intake of these substances. It is not temporary, but ongoing.

[0069] <Effects of dietary assessment systems, dietary assessment programs, and dietary assessment methods> The purpose of this program is to prevent lifestyle-related diseases. This is because it is a disruption of daily life, and this disruption can be detected early.

[0070] <Modification> In addition to the LPS concentration, other indicators ( If the blood sugar levels, triglyceride levels, etc. are monitored, 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 indicators of lifestyle-related diseases. and blood LPS concentration, and the relationship 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) Infrastructural (2) Informed consent was obtained, and (3) the subject has undergone a medical examination or medical examination within the past three months. The selection criteria were: In other words, item (2) is someone who meets all of the following criteria: a) Waist circumference: For men, it must be less than 85 cm; for women, it must be less than 90 cm 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 130mmHg e2) Diastolic blood pressure: less than 85mmHg

[0074] <Data collection> Data on subjects was collected. Specifically, the subjects' health checkups or medical questionnaires were The results are from a medical check-up, and the subjects' visits were within the past 3 months of participating in this study. These results include BMI, waist circumference, systolic blood pressure, diastolic blood pressure, and blood chemistry values. (ALT, AST, γ-GTP, triglycerides, total cholesterol, HDL cholesterol, In the following, pulse pressure refers to the ratio of systolic blood pressure to diastolic blood pressure. It is the difference between the diastolic blood pressure.

[0075] <Collection of blood and plasma> Blood was collected from the subjects. The calculations were performed on the subjects' blood LPS concentration, blood glucose level, insulin concentration, and HOMA- IR(homeostasis model assessment of insulin) The specific steps are as follows:

[0076] Procedure 1: 5 mL of fasting blood was collected from the subject. The period is from 9 p.m. on the day before blood collection until the time of blood collection. Step 2: The collected blood was centrifuged to obtain heparinized plasma. Step 3: The heparin plasma was stirred. The stirring time was about 1 minute. The device used was a test tube mixer.

[0077] Step 4: After taking a portion of the stirred plasma, the taken plasma was diluted. The dilution solvent was Otsuka distilled water, and the dilution ratio (amount of dilution solvent relative to the amount of plasma) was 10 The dilution temperature was 25° C. and the dilution environment was ice. Step 5: The diluted plasma was heated. The heating conditions were: heating temperature 70°C and heating The heating time is 10 minutes.

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

[0079] Step 8: Plate 1 was prepared. Specifically, a 96-well plate was prepared. (1) Subject Two of the 96 wells on plate 1 were used for the plasma of one subject (one sample) (2 wells / In other words, plasma was injected into a total of 62 wells (31 patients x 2 wells). The injection volume per well was 50 μL. In addition, the following was added to each well: , Limulus Reagent (Endospecy (registered trademark) ES-50M set, Seikagaku Corporation (2) Distilled water (Otsuka Pharmaceutical Co., Ltd.) was injected (50 μL / well). The remaining 34 holes were filled with 2 holes. In addition, the rim 5 x 100 ml of elution reagent (Endospecy (registered trademark) ES-50M set, manufactured by Seikagaku Corporation) (3) To prepare a calibration curve, an endotoxin standard ( Seven types of standard LPS aqueous solutions were prepared using 100% ethanol (manufactured by Seikagaku Corporation). The concentrations of the standard LPS aqueous solutions were 0.0001EU / mL and 0.0004EU / m L, 0.0016EU / mL, 0.0063EU / mL, 0.025EU / mL, and The standard LPS solution used was 0.10EU / mL and 2.0EU / mL. , and 2 wells out of the remaining 32 wells (2 wells / LPS aqueous solution for calibration curve). In other words, the standard LPS aqueous solution A total of 14 wells (7 types x 2 wells) were filled with the solution. Further, Limulus reagent (Endospecy (registered trademark) ES-50M set, Biochemical Engineering (manufactured by Epson Corporation) 50 μL (50 μL / well).

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

[0081] <Measurement of absorbance> After incubation, measure the absorbance at 405 nm (reference wavelength 492 nm). Here, the control wavelength is a wavelength that is free of any absorption interference factors (e.g., scratches on the plate, etc.). Specifically, the Limulus reagent manufacturing company The relationship between the absorbances is as follows: The absorbance of each sample was calculated by the average value of two wells. . (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. The absorbance of the Limulus reagent reaction product (see step 8 (3)) at 405 nm (reference wavelength 49 2 nm) to obtain the relationship between LPS concentration and absorbance (standard curve). Specifically, the criteria for determining suitability were whether the absorbance A of all subjects was within the range of Whether or not the absorbance of the reactant falls within the range.

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

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

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

[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] <Profile of the subjects>Table 1 shows the profile of the subjects in this test. Among the indicators marked with an asterisk "*", the values are mean ± standard deviation. For all subjects, it was confirmed that they did not meet any metabolic syndrome diagnostic criteria.

[0088]

Table 1

[0089] <LPS concentration distribution of the subjects>Figure 14 shows the blood LPS concentration distribution of the subjects. The median blood LPS concentration of the subjects was 0.0038 EU / mL. The concentration range of the blood LPS concentration of the subjects was from 0 to 0.0117 EU / mL. Among the subjects, the number of those in whom LPS was detected was 22, which was 71% of all the subjects.

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

[0091] Figure 15 shows the relationship between blood LPS concentration and each test value. is the correlation coefficient. That is, a significant positive correlation (Spearman's rank sum correlation coefficient: P<0.05) was observed between (1) the blood LPS concentration and the systolic blood pressure, (2) (3) between blood LPS concentration and pulse pressure; (4) between blood LPS concentration and pulse pressure. (5) between blood LPS concentration and neutral fats. Below, systolic blood pressure, diastolic blood pressure, pulse pressure, γ-GTP and triglyceride are collectively referred to as single correlation test values. He said.

[0092] These results suggest that (1) the increase in blood LPS concentration and the deterioration of blood pressure regulation are (2) an increase in blood LPS concentration is associated with a worsening of arteriosclerosis; and (3) (4) the association between elevated blood LPS levels and impaired liver function; These findings are associated with increased cholesterol and impaired lipid metabolism.

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

[0094] Table 2 shows the results of multiple regression analysis (P value). Even after adjustment, a significant positive correlation (P<0.05) was observed for blood LPS concentration and triglyceride A correlation tendency (P<0.1) was observed between the blood LPS concentration and the systolic Between 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 dependent on age, sex, and BMI. It is about being independent.

[0095] [Table 2]

[0096] <Distribution range of test values> Table 3 shows the distribution range of test values ​​for subjects with and without LPS in the blood. The range of the single correlation test values ​​for each examiner. These results show that blood LP Regardless of whether S is detected or not, the distribution range of each single correlation test value is the same. In other words, it is the blood LPS concentration that is difficult to estimate from the high and low values ​​of the single correlation test. The results suggest that even if the disease is not detected by existing test indicators, it may be detected by blood LPS concentration. What is possible is a deterioration in health (especially blood pressure regulation, arteriosclerosis, liver function, and lipid metabolism). do.

[0097] [Table 3]

[0098] <Test 2> Blood LPS concentration in healthy subjects and nonalcoholic fatty liver disease holic fatty liver disease) patients (hereinafter referred to as "NAFLD patients") The blood LPS concentration in patients with nonalcoholic fatty liver disease was evaluated. This 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 Test 1. The study consisted of 31 healthy subjects and 31 patients with NAFLD.

[0099] <Parameters of each group> Table 4 shows the profile of the subjects in Study 2. The values ​​marked with an asterisk (*) are the mean ± standard deviation. The tests used were Student's t-test or Mann-Whitney U test. The p-value was obtained by comparing healthy subjects and NAFLD patients. The age of D patients was significantly higher. There was no difference in the gender ratio between the groups. When comparing AFLD patients, a significant (p<0.05) deterioration was confirmed in NAFLD patients. The patient's test values ​​are related to obesity, blood pressure, liver function, lipid metabolism, and glucose metabolism.

[0100] [Table 4]

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

[0102] Figure 16(b) shows the Receiver Operating Character The diagnostic ability of plasma LPS concentration for NAFLD is R The area under the OC curve (AUC) was 0.87. If the plasma LPS concentration is 0.010 EU / 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. These results suggest that the boundary between poor health and plasma LP is The standard value for determining a healthy state is a plasma S concentration of 0.010 EU / mL. The medium LPS concentration was 0.010EU / mL.

[0103] <Effects of this embodiment> The effects of this embodiment are the discovery of high-risk groups for lifestyle-related diseases. This is because the accuracy of the study is improved. This is because it allows for a more accurate understanding of a patient's health status 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 Status Rating System 20 Measuring Equipment 30 Output Device 40 Processing equipment

Claims

1. A health status assessment system comprising, at a minimum, the following: Measuring device: This measures the LPS concentration in the subject's blood. An output device that outputs the health status of the person being measured, and a processing device connected to said output device, and The LPS concentration in the blood is then processed, and the result is the health condition of the subject. The blood LPS concentration is processed after the metabolic syndrome positive / negative value is processed.

2. A health status evaluation program, which causes a computer to execute the following processes: Judgment: What is judged here is the health condition of the person being measured, and the reference for this is, The LPS concentration in the blood of the subject is The blood LPS concentration is referred to after the values ​​indicating whether or not a patient has a lifestyle-related disease and whether or not a patient has metabolic syndrome are referred to.

3. The program of claim 2, The health condition is at least one of the lipid metabolism status, the liver function status, the blood pressure regulation status, and the arterial hardness.

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