JP7604181B2 - 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 - Google Patents

Description

The present invention relates to a health condition evaluation system, a health condition evaluation program, and a health condition evaluation method, as well as a dietary habit evaluation system, a dietary habit evaluation program, and a dietary habit evaluation method.

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

The situation in Japan is serious. According to a report in Non-Patent Document 1, about 25% of people undergoing specific health checkups in Japan are at risk of metabolic syndrome or at risk of developing it.
Early detection of metabolic syndrome is primarily carried out through specific health checkups. The items examined during specific health checkups are waist circumference, blood sugar, lipids, and blood pressure (hereinafter, these are referred to as "test indicators" and their values as "test values").

The main focus of improving metabolic syndrome is specific health guidance, which is given to individuals whose test results are outside the prescribed standard range.
In other words, if the subject is neither a person with metabolic syndrome nor a person at risk of having metabolic syndrome (hereinafter referred to as a "person not with metabolic syndrome, etc."), the subject is not subject to the guidance.

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

Status of implementation of specific health examinations and specific health guidance for fiscal year 2015 (Ministry of Health, Labour and Welfare) FY2017 National Health and Nutrition Survey Report (Ministry of Health, Labour and Welfare)

The problem to be solved by the present invention is to improve the accuracy of detecting individuals at high risk of lifestyle-related diseases.

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

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

<Health Condition Evaluation Program> The process executed by the computer in accordance with the health condition evaluation program is at least a judgment process. The computer judges the health condition of the subject, and references the LPS concentration in the subject's blood.
<Health status evaluation method> Health status evaluation method (excluding medical procedures) consists of:
At least, the measurement, determination, and presentation are performed. That is, what is measured by a person, device, or instrument is the blood LPS concentration of the subject. What is determined by a person, device, or instrument is the health condition of the subject, and what is referred to at that time is the blood LPS concentration.
It is the PS concentration. It is the health state that is presented by the person or the device or instrument.

<Second viewpoint> The next thing the inventors focused on was the relationship between dietary status and blood LPS concentration. That is, when dietary status deteriorates (e.g., excessive intake of oil, etc.), the LPS concentration of intestinal bacteria increases.
S enters the blood. When LPS in the blood increases, inflammation occurs chronically in the body. Chronic inflammation worsens health conditions. From this perspective, the present invention is defined as follows.

<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 blood LP of the subject.
The output device outputs the LPS concentration in the blood. The dietary condition of the subject is output. At least the output device is connected to the processing device. The processing device processes the LPS concentration in the blood, and the dietary condition is obtained.

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

<Dietary assessment method> The dietary assessment method comprises at least measurement, judgment, and
That is, what is measured by a person or a device or instrument is the blood LPS concentration of the person being measured. What is determined by a person or a device is the dietary condition of the person being measured, and what is referred to at that time is the blood LPS concentration. What is presented by a person or a device or instrument is the dietary condition.

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

This is the configuration of the health status evaluation system. 13 shows the flow of a determination process. This is the procedure for diagnosing LPS. 1 is an output screen for the health condition of a person who is considered to have metabolic syndrome. 13 is an output screen of a health condition, in which the subject is not affected by metabolic syndrome or the like, and the LPS diagnostic value is normal. 13 is an output screen of a health condition, in which the subject is not affected by metabolic syndrome or the like and the LPS diagnostic value is abnormal. This is the flow of the health status evaluation method. This is a health status assessment chart. 13 shows the flow of a determination process. This is the procedure for diagnosing LPS. 13 is an output screen of an eating habit evaluation, (a) when a disordered eating habit is not suspected, and (b) when a disordered eating habit is suspected. This is the flow of the dietary assessment method. This is a dietary assessment chart. 1 shows the distribution of LPS concentrations in the blood of subjects. The relationship between blood LPS concentration and each test value. 1 shows the evaluation results of plasma LPS concentrations in healthy subjects versus NAFLD patients, (a) comparison results of plasma LPS concentrations (healthy subjects versus NAFLD patients), and (b) ROC curve.

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

<Blood LPS concentration> Blood LPS concentration is the concentration of lipopolysaccharide (LPS) contained in blood.
The "blood LPS concentration" refers to the concentration of LPS in plasma (unit: EU/mL).
The plasma LPS concentration refers to the concentration of LPS contained in plasma (unit: EU/mL). The serum LPS concentration refers to the concentration of LPS contained in serum (unit: EU/mL). In this embodiment, the plasma LPS concentration is used (
Hereinafter, it may be simply referred to as "blood LPS concentration." This is because the blood LPS concentration is approximately equal to the plasma LPS concentration (i.e., "blood LPS concentration" ≒ "plasma LPS concentration").
PS concentration").

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

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

<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: the state of blood pressure regulation ability, and arterial hardness (condition of the arteries). These states are correlated with the blood LPS concentration. There is no restriction on how the state is expressed. Following the expressions used in the specific medical examination, examples of the expressions are "no abnormality", "mild abnormality", "needs follow-up observation", and "needs medical treatment".

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

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

Diagnostic indicators for metabolic syndrome are waist circumference, as well as blood glucose, blood pressure and lipids.
In the case of Japanese people, the requirement that a person has metabolic syndrome is met if (1) is present and two or more of (2A), (2B), and (2C) are also present.
(1) Waist circumference of 85 cm or more for men and 90 cm or more for women; (2A) Fasting blood glucose of 110 mg/dL or more; (2B) Triglyceride of 150 mg/dL or more and/or HDL cholesterol of less than 40 mg/dL; (2C) Systolic blood pressure of 130 mmHg or more and/or diastolic blood pressure of 85 mmHg or more;
mmHg or more

<Metabolic syndrome pre-group and individuals with metabolic syndrome pre-group> The metabolic syndrome pre-group refers to an obese state that is at a stage just before metabolic syndrome. An individual with metabolic syndrome pre-group refers to a human whose attributes are those with metabolic syndrome pre-group. An individual with metabolic syndrome pre-group must meet the requirements (1) and one of (2A), (2B), and (2C).

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

<Group not applicable to metabolic syndrome, etc. and individuals not applicable to metabolic syndrome, etc.> The group not applicable to metabolic syndrome, etc. refers to a state in which the individual is not metabolic syndrome or a group at risk of metabolic syndrome. Individuals not applicable to metabolic syndrome, etc. refer to people whose attributes are in the group not applicable to metabolic syndrome, etc. Those not applicable to metabolic syndrome, etc. meet the following criteria (1) to (5):
) all the way up to
(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 more; (5) Blood pressure: systolic blood pressure less than 130 mmHg and diastolic blood pressure 85 mmHg or more.
Less than

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

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

<Measuring device> The measurement device 20 measures the LPS concentration in the blood of the subject. In other words, the measurement device 20 first analyzes the blood or plasma of the subject, and the result is the LPS concentration in the blood of the subject. The blood and plasma are pre-processed. Details of this pre-processing will be described later. There is no restriction on where the blood LPS concentration can be output,
Preferably, it is the processing device 30. The measuring device 20 can be realized in a variety of ways and is not particularly limited, but examples thereof include a spectrometer, a spectrophotometer, a microplate reader, etc. In this embodiment, a microplate reader (Microplate Reader ELx808 manufactured by Biotec Co., Ltd.) is used.

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

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

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

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

<Program Storage Unit> Various programs are stored in the program storage unit. The program storage unit is embodied in a non-volatile storage device (e.g., ROM, etc.) and a non-volatile storage device (e.g., HDD, SSD, etc.). The following are stored in the non-volatile storage device:
A basic program (including the data required for it). Examples of basic programs are:
Basic Input/Output System (BIOS), Operating System (
These include an operating system (OS) setting program, a network setting program, etc. The non-volatile storage device stores an operating system (OS) and application programs.
An example of an operating system (OS) is Windows (registered trademark)
WS”, Linux (registered trademark), and Android (registered trademark). An example of an application program is a health condition evaluation program, which will be described later.

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

<Processing section> The processing section executes various programs and processes:
The input values are various data. By executing various programs, the input values are processed and become output values. The processing unit is embodied by a central processing unit (so-called CPU).

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

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

<Health Condition Evaluation Program> The health condition evaluation program causes the processing device 30 to execute a judgment process. That is, the processing device 30 judges the health condition of the subject. In this case, the processing device 30 refers to the LPS concentration in the blood of the subject.
2 shows the flow of the judgment process. The judgment process comprises a metabolic syndrome diagnosis (S10), an LPS diagnosis (S20), and a health condition output (S30).

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

The values to be referenced when obtaining the non-negative value are the values of the test indicators for metabolic syndrome and the metabolic syndrome-related requirements. In other words, the values to be compared with the test indicators are:
The relevant requirement is as described above. The value of the inspection index is stored in a temporary storage unit. The mode of inputting the value of the inspection index is automatic or manual. The means for automatically inputting the value of the inspection index is a communication device. The means for manually inputting the value of the inspection index is an input device.

<LPS Diagnosis (S20)> If the value is "1", the LPS diagnosis is performed.
The diagnosis provides an LPS diagnostic value. The details of the LPS diagnosis are as follows:
3 shows the flow of LPS diagnosis. The LPS concentration is read out (S31), and a return value is returned (S32 to S36).
If the LPS concentration "Y" is less than the reference value "a"(Y<a), the return value "A" is returned (
S32) The return value "A" means that no deterioration in health condition is suspected, more specifically, that no deterioration in lipid metabolism, liver function, blood pressure regulation, or arterial hardness (deterioration of the arteries) is suspected.

If the LPS concentration "Y" is equal to or greater than the reference value "a" and less than "b"(a≦Y<b), a return value "B" is returned (S33). The return value "B" means that a deterioration in health condition is suspected (degree of deterioration 1% to 20%). Specifically, any of the following is suspected (degree of deterioration 1% to 20%): deterioration in lipid metabolism, deterioration in liver function, deterioration in blood pressure regulation, and arterial hardness (deterioration of arteries).
~20%).

If the LPS concentration "Y" is equal to or greater than the reference value "b" and less than "c"(b≦Y<c), a return value "C" is returned (S34). The return value "C" means that a deterioration in health is suspected (degree of deterioration 21% to 50%). Specifically, any of the following is suspected (degree of deterioration 21% to 50%): deterioration in lipid metabolism, deterioration in liver function, deterioration in blood pressure regulation, and arterial hardness (deterioration of arteries).
1% to 50%).

If the LPS concentration "Y" is equal to or greater than the reference value "c" and equal to or less than "d" (c≦Y≦d), a return value "D" is returned (S35). The return value "D" means that a deterioration in health is suspected (degree of deterioration 51% to 70%). Specifically, any of the following is suspected (degree of deterioration 51% to 70%): deterioration in lipid metabolism, deterioration in liver function, deterioration in blood pressure regulation, and arterial hardness (deterioration of arteries).
1% to 70%).

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

<Health Condition Output (S30)> The health condition is output when the corresponding value is "0" or after the LPS diagnosis is completed. There are three main ways to output the health condition. The details are as follows:
FIG. 4 shows an output screen of health condition, in which the subject is a person with metabolic syndrome. This screen is output when the corresponding value is "0". In other words, the subject is a person with metabolic syndrome, and the overall judgment result is as follows:
"Guidance required."

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

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

<Health Status Assessment Method> Figure 7 shows the flow of the health status assessment method. The health status assessment method is composed of measurement (P1), judgment (P2), and presentation (P3). More specifically, it is as follows.

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

The specimen is the blood of the subject. The storage temperature of this blood is -80°C to 35°C, preferably -10°C to 10°C. The blood fraction is not particularly limited, but is preferably plasma. The fraction that is not excluded is serum.
The plasma is pretreated. Specifically, the plasma is first diluted with a dilution solvent that does not contain LPS (e.g., distilled water, physiological saline, phosphate buffered saline, etc.).
The dilution rate is 10 times. Next, the diluted plasma is heated. The heating temperature is 70 degrees, and the heating time is 10 minutes. The LAL reagent is reacted with the plasma treated in this manner. 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 (QC
L-1000, Lonza) and the like.
The pretreated plasma is analyzed by a measuring device, which will be described later. The plasma is analyzed to obtain the LPS concentration in the subject's blood.

<Judgment (P2)> The purpose of the judgment is to derive the health condition of the person being measured. The health condition of the person being measured is judged by a person or a device, and the following are referenced at that time:
The blood LPS concentration is preferably determined when the subject is not affected by metabolic syndrome or the like.
is omitted.

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

<Presentation (P3)> The purpose of presentation is to make the subject aware of his/her health condition. The blood LPS concentration and health condition are presented by a person, device, or instrument to the subject. The method of presenting the measured blood LPS concentration and health condition is not important, but specifically, it is electromagnetic (electronic or magnetic). The manner of presenting the blood LPS concentration and health condition is not important, but specifically, it is visual. The means of presenting the blood LPS concentration and health condition are not limited, and examples include paper and a screen.

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

<Modification> In addition to the LPS concentration, other indicators (
If the data collected is accurate to within 100%, the accuracy of identifying those at high risk of lifestyle-related diseases will be further improved.

<Dietary assessment system/Dietary assessment program> The dietary assessment system consists of:
These are a measuring device, an output device, a processing device, an input device, and an external storage device. The detailed description of these hardware components will be referred 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. The dietary habit evaluation system is characterized by the dietary habit evaluation program.

<Dietary assessment program> The health status assessment program causes the processing device to execute the following:
That is, what is determined by the processing device is the eating habits of the person being measured.
At this time, the processing device refers to the LPS concentration in the blood of the subject.
FIG. 9 shows the flow of the judgment process. The judgment process is composed of the LPS diagnosis (S4
0), and dietary output (S50).

<LPS Diagnosis (S40)> After startup, the LPS diagnosis is executed. The LPS diagnosis provides an LPS diagnosis value. The details of the LPS diagnosis are as follows.
FIG. 10 shows the flow of LPS diagnosis. The LPS concentration is read out (S41).
A return value is returned (S42 to S43).
If the LPS concentration "Z" is less than the reference value "e"(Z<e), a return value "F" is returned (
S42). Here, the threshold value "e" depends on the race and place of residence. The return value "F" means that no irregular eating habits are suspected. Specifically, excessive intake of oil,
Neither excessive sugar intake, excessive salt intake, nor excessive alcohol intake was suggested.

If the LPS concentration "Z" is equal to or greater than the reference value "e", a return value "G" is returned (S43).
The return value "G" means that a lifestyle-related disease is suspected. Specifically, any one of the following is suspected: excessive intake of oil, sugar, salt, or alcohol.

<Output of dietary evaluation (S50)> The dietary evaluation is output after the LPS diagnosis is completed. The output mode of the dietary evaluation is roughly divided into two modes. The details are as follows.
11 shows an output screen of the dietary assessment, (a) when no disordered diet is suspected, and (b) when disordered diet is suspected. The screen is composed of the subject's LPS concentration 71, dietary assessment 72, and guidance (advice) 73. When disordered diet is not suspected, the dietary assessment shows that the subject has a normal diet 73.
2a. The guidance includes a message 73a to continue the current diet. On the other hand, if a disordered diet is suspected, the dietary assessment indicates that the diet is disordered 72b. The guidance includes a message 73b to improve the current diet.
It is.

<Dietary Life Assessment Method> Figure 12 shows the flow of the dietary life assessment method. The dietary life assessment method is composed of measurement (P11), judgment (P12), and presentation and/or guidance (P13). Specifically, it is as follows.

<Measurement (P11)> The purpose of the measurement is to ascertain the LPS concentration in the blood of the subject.
The detailed description is based on the description of measurement (P1).

<Determination (P12)> The purpose of the determination is to derive the dietary habits of the subject. What is determined by a person or device is the dietary habits of the subject, and the blood LPS concentration is used as a reference for this determination.
FIG. 14 shows a dietary assessment table. The dietary assessment table shows the relationship between LPS concentration and dietary assessment value. The blood LPS concentration of the subject is applied to the dietary assessment table, and the dietary assessment value of the subject is obtained. The threshold value "e" depends on the race and place of residence. The dietary assessment value indicates "disordered diet is suspected" or "disordered diet is not suspected." The dietary assessment value allows multiple stages of the degree of "disordered diet." In this case, the dietary assessment value adopts a more detailed expression, such as "it is suspected that the dietary lifestyle is somewhat disordered" or "it is suspected that the dietary lifestyle is significantly disordered."

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

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

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

<Modification> In addition to the LPS concentration, other indicators (
If the level of blood sugar or triglyceride is reduced, prevention of lifestyle-related diseases will be even more effective.

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

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

<Selection of subjects> Thirty-one adult men and women were selected as subjects. The selection criteria were (1) that informed consent was obtained, and (2) that none of the metabolic syndrome diagnostic criteria were met in a health check or medical examination within the past three months. In other words, selection criteria (2) were people who met all of the following criteria:
a) Waist circumference: for men, less than 85 cm; for women, 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 more e1) Systolic blood pressure: less than 130 mmHg e2) Diastolic blood pressure: less than 85 mmHg

<Data collection> Data on the subjects was collected. Specifically, the results of the subjects' health checkups or medical examinations were collected from subjects who had undergone medical examinations within the past three months of participating in this study. These results included BMI, waist circumference, systolic blood pressure, diastolic blood pressure, blood biochemistry test values (ALT, AST, γ-GTP, triglycerides, total cholesterol, HDL cholesterol,
In the following, pulse pressure refers to the difference between systolic blood pressure and diastolic blood pressure.

<Collection of blood and plasma> Blood was collected from the subjects. Using this blood, the following were measured or calculated: LPS concentration, blood glucose level, insulin concentration, and HOMA-
IR (homeostasis model assessment of insulin)
The specific procedure is as follows.

Procedure 1: 5 mL of fasting blood was collected from the subject. The subject fasted from 9 p.m. on the day before blood collection until the time of blood collection.
Step 2: The collected blood was centrifuged to obtain heparinized plasma.
Step 3: The heparin plasma was stirred for about 1 minute using a test tube mixer.

Step 4: A portion of the stirred plasma was taken and then diluted. The dilution conditions were as follows: the dilution solvent was Otsuka distilled water, and the dilution ratio (the 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 at a heating temperature of 70° C. for a heating time of 10 minutes.

Step 6: The heated plasma was cooled in ice to bring the temperature of the plasma to about room temperature (25°C).
(around that time).
Step 7: The plasma at room temperature was stirred under the following conditions: stirring time was about 30 seconds;
The mixing device is a test tube mixer.

Step 8: Plate 1 was prepared. Specifically, a 96-well plate was prepared. (1) Two of the 96 wells of Plate 1 were used for the plasma (one sample) of one subject (2 wells/
(1) Samples). In other words, plasma was injected into a total of 62 wells (31 subjects x 2 wells). The amount of plasma injected per well was 50 μL/well. Furthermore, 50 μL of Limulus reagent (Endospecy (registered trademark) ES-50M set, manufactured by Seikagaku Corporation) was also poured into each well (50 μL/well). (2) Distilled water (manufactured by Otsuka Pharmaceutical Co., Ltd.) was injected into two of the remaining 34 wells. Furthermore, 50 μL of Limulus reagent (Endospecy (registered trademark) ES-50M set, manufactured by Seikagaku Corporation) was also poured into each well (50 μL/well).
(3) In order to prepare a calibration curve, an endotoxin standard sample (
Seven types of standard LPS aqueous solutions were prepared using 100% LPS solution (manufactured by Seikagaku Corporation). The concentrations of the seven types of standard LPS aqueous solutions were 0.0001 EU/mL, 0.0004 EU/mL, and 100% LPS solution (manufactured by Seikagaku Corporation).
L, 0.0016 EU/mL, 0.0063 EU/mL, 0.025 EU/mL, and
The concentrations were 0.10 EU/mL and 2.0 EU/mL. Two of the remaining 32 wells were used for one type of standard LPS aqueous solution (2 wells/calibration curve LPS aqueous solution). In other words, a total of 14 wells (7 types x 2 wells) were injected with the standard LPS aqueous solutions. Furthermore, 50 μL of Limulus reagent (Endospecy (registered trademark) ES-50M set, manufactured by Seikagaku Corporation) was also poured into each well (50 μL/well).

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 prepared. The purpose was to cancel the effect of the color of the plasma on the absorbance measurement. Specifically, a 96-well plate was prepared. (1) Plasma was injected into a total of 62 wells (31 subjects x 2 wells). The amount of plasma injected per well was 50 μL/well.
Each well was filled with 50 μL of distilled water (Otsuka Pharmaceutical Co., Ltd.).
(2) Distilled water (Otsuka Pharmaceutical Co., Ltd.) was poured into two of the remaining 34 holes. Each hole was further filled with 50 μL of distilled water (Otsuka Pharmaceutical Co., Ltd.) (50 μL/hole).
Step 11: Plate 2 was incubated under the following conditions: incubation temperature was 37
° C. and the incubation time is 1 hour.

<Measurement of absorbance> After incubation, the absorbance at 405 nm (reference wavelength 492 nm) was measured. Here, the reference wavelength refers to a wavelength used to correct the effects of absorption-interfering factors (e.g. scratches or distortion of the plate, etc.), specifically, the reference wavelength refers to the wavelength designated by the manufacturer of the Limulus reagent (in this embodiment, Seikagaku Corporation). The relationship between the absorbances is as follows: Here, the absorbance of each sample was 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)

<Procedure for preparing a calibration curve> The procedure for preparing a calibration curve is as follows. The absorbance at 405 nm (reference wavelength 49 nm) of the reaction product of the standard LPS aqueous solution and the Limulus reagent (see step 8 (3)) was measured.
The relationship between LPS concentration and absorbance (calibration curve) was obtained by measuring the concentration of LPS at 2 nm. The suitability of this calibration curve was confirmed. Specifically, the criterion for the suitability was whether or not the absorbance A of all subjects was within the range of the absorbance of each reactant.

<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 fitted to the calibration curve, and the plasma LPS concentration (EU/mL) for each subject was obtained.

<Measurement of blood glucose level> Blood glucose level was measured using a measuring device, FreeStyle Libre (Abbott).

<Measurement of insulin concentration>
The insulin concentration was measured. The measuring device was a conventional kit (Mercodia In
(sulin ELISA, manufactured by Mercodia).

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

<Subject Profile> Table 1 shows the profile of the subjects in this study. Indicators marked with an asterisk "*" are the mean ± standard deviation. It was confirmed that all subjects did not meet any of the metabolic syndrome diagnostic criteria.

<Distribution of LPS Concentration in Subjects> FIG. 14 shows the distribution of LPS concentration in the blood of subjects.
The median LPS concentration in the blood of the subjects was 0.0038 EU/mL.
The range of S concentrations was 0 to 0.0117 EU/mL. LPS was detected in 22 subjects, which was 71% of the total subjects.

<Simple regression analysis> The relationship between the subject's blood LPS concentration 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, fasting blood glucose, HbA1c, insulin, and HOMA-IR.

FIG. 15 shows the relationship between blood LPS concentration and each test value. "ρ" in the figure indicates the correlation coefficient. That is, significant positive correlation (Spearman's rank sum correlation coefficient:
P<0.05) was 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, and (4) blood LPS
(4) between blood LPS concentration and triglyceride. Hereinafter, systolic blood pressure, diastolic blood pressure, pulse pressure, γ-GTP, and triglyceride are collectively referred to as single correlation test values.

These results suggest that: (1) an increase in blood LPS concentration is associated with a worsening of blood pressure regulation; (2) an increase in blood LPS concentration is associated with a worsening of arteriosclerosis; and (3)
(4) an increase in blood LPS concentration is associated with a deterioration in liver function, and (5) an increase in blood LPS concentration is associated with a deterioration in lipid metabolism.

<Multiple regression analysis> The relationship between each single correlation test value and the blood LPS concentration, age, sex, and BMI was analyzed (multiple regression analysis). That is, the objective variable was each single correlation test value, and the explanatory variables were the blood LPS concentration, age, sex, and BMI. Shapiro-Wilk
The assay confirmed that LPS concentration (P = 0.005), age (P = 0.001), and BM
The I (P = 0.03) and γ-GTP (P = 0.004) were not normally distributed. Therefore, these values were log-converted and subjected to multiple regression analysis.
Multiple regression analysis was performed without g-transformation.

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

<Distribution range of test values> Table 3 shows the distribution range of the single correlation test values for subjects with and without LPS in the blood.
The distribution range of each single correlation test value is the same regardless of the presence or absence of S. In other words, it is the blood LPS concentration that is difficult to estimate from the high or low single correlation test value. Conversely, these results suggest that deterioration of health conditions (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.

<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 of patients with non-alcoholic fatty liver disease was evaluated. Here, non-alcoholic fatty liver disease refers to fatty liver disease whose cause is clearly other than alcoholic liver disease.
The LPS concentration in the blood of the subjects was measured by the same method as in Test 1. The subjects consisted of 31 healthy subjects and 31 NAFLD patients.

<Parameters of each group> Table 4 shows the profile of the subjects in Study 2. Indices marked with an asterisk "*" are the mean ± standard deviation. Student's t-test or Mann-Whitney U-test was performed for each item, and the p-value was obtained. 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.

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

FIG. 16(b) shows the Receiver Operating Character
The diagnostic ability of plasma LPS concentration for NAFLD is shown in R
The area under the curve (AUC) is 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 poor blood sugar levels is plasma LPS.
In other words, the standard value for determining a healthy state is a plasma LPS concentration of 0.010 EU/mL.

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

An area in which this invention is useful is the health services industry.

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

Claims (3)

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. 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. 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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