WO2010041439A1 - Blood sample analysis method, blood sample analysis apparatus, and program - Google Patents

Blood sample analysis method, blood sample analysis apparatus, and program Download PDF

Info

Publication number
WO2010041439A1
WO2010041439A1 PCT/JP2009/005208 JP2009005208W WO2010041439A1 WO 2010041439 A1 WO2010041439 A1 WO 2010041439A1 JP 2009005208 W JP2009005208 W JP 2009005208W WO 2010041439 A1 WO2010041439 A1 WO 2010041439A1
Authority
WO
WIPO (PCT)
Prior art keywords
blood sample
treatment
value
formula
hemoglobin
Prior art date
Application number
PCT/JP2009/005208
Other languages
French (fr)
Japanese (ja)
Inventor
高妻卓司
古賀正史
Original Assignee
旭化成ファーマ株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 旭化成ファーマ株式会社 filed Critical 旭化成ファーマ株式会社
Priority to JP2010532814A priority Critical patent/JP5323853B2/en
Publication of WO2010041439A1 publication Critical patent/WO2010041439A1/en

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
    • G01N33/721—Haemoglobin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/04—Endocrine or metabolic disorders
    • G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism

Definitions

  • the present invention relates to a blood sample analysis method, a blood sample analysis device, and a program.
  • Diabetes is a disease in which the number of patients is increasing explosively, and countermeasures are urgently needed.
  • complications such as nephropathy, retinopathy, and neuropathy caused by the complications of systemic microvessels that coexist may be related to the patient's quality of life (QOL). )
  • QOL quality of life
  • DECORD studies and boat-shaped studies show that if there is a symptom of postprandial hyperglycemia even before the onset of diabetes, macrovascular disorders such as the heart and brain progress, and postprandial hyperglycemia is corrected. Came to be preached.
  • HbA1c HbA1c, GA, 1,5-anhydrol (1.5-AG), etc. reflecting average blood glucose is measured.
  • HbA1c is said to reflect glycemic control for the past 2-3 months, GA for 2-4 weeks, and 1.5AG for several days.
  • HbA1c was used for patients who have been introduced to new patients due to poor glycemic control, or patients who have poor glycemic control but need surgery. In some cases, it takes two to three months to determine the effect. In addition, even if treatment is started smoothly, exercise therapy, diet therapy, and drug therapy may not be continued after several months. However, if the pattern of future GA or HbA1c transition can be calculated in advance, As a result, it is possible to grasp whether a problem has occurred, and the management on the medical side becomes easier to perform in each stage.
  • Predicting future blood glucose is also useful for diagnosing fulminant type 1 diabetes.
  • fulminant type 1 diabetes one day, the pancreas suddenly stops functioning and blood sugar rises rapidly, resulting in type 1 diabetes.
  • the symptoms are initially similar to those of a cold, with high blood sugar and normal HbA1c.
  • HbA1c normal HbA1c
  • Measurement of the onset of type 1 diabetes is considered very important.
  • the present invention relates to a blood sample analysis method, blood sample analysis apparatus, and program capable of measuring the effects of diabetes treatment and the onset of fulminant type 1 diabetes by calculating changes in mean blood glucose, GA, and HbA1c.
  • the purpose is to provide.
  • the blood sample analysis method includes a mean blood glucose MBG (0), glycoalbumin value (GA (0)), hemoglobin in a blood sample at a reference time before the value of a blood glucose control marker in the blood sample changes.
  • the present invention by calculating changes in average blood glucose, GA, and HbA1c, it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Furthermore, it becomes possible to provide useful information regarding the onset of fulminant type 1 diabetes. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
  • the present invention by calculating the change in glycoalbumin GA, it is possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information that is effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
  • TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA ( ⁇ )) / 2 when treatment for rapidly lowering blood glucose is performed. 26 days constant, You may make it calculate k in said Formula (3) using Formula (14).
  • k ⁇ log2 ⁇ t1 / TGA (1/2) / log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (14)
  • the blood sample analysis method includes a hemoglobin A1c value (A1c (0)) of a blood sample collected before the start of treatment, and a hemoglobin A1c value (A1c ( t1)), and a first step of obtaining a hemoglobin A1c value (A1c ( ⁇ )) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and using the equation (4),
  • a second step of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date, A1c (t2) A1c ( ⁇ ) + (A1c (0) ⁇ A1c ( ⁇ )) ⁇ 10 B (4)
  • hemoglobin A1c by calculating the change in hemoglobin A1c (HbA1c), it is possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information that is effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
  • TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c ( ⁇ )) / 2 when treatment for rapidly lowering blood glucose is performed.
  • the constant is 86 days, and k in the equation (6) may be calculated using the equation (15).
  • k ⁇ log2 ⁇ t1 / TA1c (1/2) / log ((A1c (t1) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ ))) (15)
  • TA1c (1/2) reaches a value (A1c (0) + A1c ( ⁇ )) / 2 of the hemoglobin A1c value of the blood sample when treatment for rapidly lowering blood glucose is performed It is a constant of 19 to 86 days indicating the period until and t1 ⁇ t2.
  • HbA1c hemoglobin A1c
  • the blood sample analysis method includes a glycoalbumin value (GA (0)) of a blood sample collected before the start of treatment, a glycoalbumin value (GA (0) of a blood sample collected after t1 days from the start of treatment. t1)), the glycoalbumin level (GA ( ⁇ )) of the blood sample collected when sufficient time has passed since the treatment start date, the mean blood glucose (MBG (0)) of the blood sample collected before the treatment start ), And a first step of obtaining an average blood glucose (MBG ( ⁇ )) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and using the formula (8), the treatment start date
  • a second step of calculating an average blood glucose (MBG (t2)) of a blood sample collected after t2 days from MBG (t2) MBG ( ⁇ ) + (MBG (0) ⁇ MBG ( ⁇ )) ⁇ 10 C (8)
  • TMBG is the average blood sugar level of the blood sample reaches (MBG (0) + MBG ( ⁇ )) / 2 when treatment is performed to rapidly reduce blood sugar.
  • MBG is an average blood sugar, it is complicated to obtain the average value by collecting blood many times in order to obtain the value. You can also use it to calculate MBG. Since GA requires only one blood collection, MBG can be easily predicted based on calculations.
  • the blood sample analysis method includes a hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, and a hemoglobin A1c value (A1c (A1c (0)) of the blood sample collected t1 days after the treatment start date.
  • TMBG is the average blood sugar of the blood sample reaches (MBG (0) + MBG ( ⁇ )) / 2 when treatment is performed to rapidly reduce blood sugar.
  • MBG is an average blood sugar, it is complicated to obtain an average value by collecting blood many times in order to obtain its value. You can also use it to calculate MBG. Since HbA1c only needs to be collected once, MBG can be easily predicted based on the calculation.
  • the blood sample analysis method includes a hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, and a hemoglobin A1c value (A1c (A1c (0)) of the blood sample collected t2 days after the treatment start date.
  • TGA (1/2) reaches the level of (GA (0) + GA ( ⁇ )) / 2 in the blood sample when blood glucose is rapidly reduced.
  • the blood sample analysis method includes a hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, and a hemoglobin A1c value (A1c (A1c (0)) of the blood sample collected t2 days after the treatment start date. t2)), and hemoglobin A1c values A1c ( ⁇ D1), A1c ( ⁇ D2) of blood samples collected when a sufficient amount of time has elapsed from the treatment start date when the dosage is D1, D2, and D3, respectively.
  • B in the above formula (30) is calculated by formula (32), and B in formula (31) is calculated by formula (33).
  • B ⁇ log2 ⁇ (t2 ⁇ t1) / (TA1c (1/2) ⁇ k ⁇ k2 / k1) (32)
  • B -log2 * (t2-t1) / (TGA (1/2) * k * k2 / k1) (33)
  • K in the equations (32) and (33) is calculated using the equation (34)
  • k ⁇ log2 ⁇ t1 / TGA (1/2) / log ((GA (t1) ⁇ GA ( ⁇ 1)) / (GA (0) ⁇ GA ( ⁇ 1))) (34)
  • TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c ( ⁇ )) / 2 when treatment for rapidly lowering blood glucose is performed.
  • TGA (1/2) reaches the level of (GA (0) + GA ( ⁇ )) / 2 in the blood sample when blood glucose is rapidly reduced. It is characterized by being a constant of 7 to 26 days indicating the period until.
  • This makes it possible to estimate the A1c (t2) or GA (t2) of a blood sample when the dosage is changed, and to provide information that is useful for deciding treatment strategies and increasing patient motivation in advance. Is possible.
  • the present invention can be used not only for changing the drug dosage but also for switching therapy such as exercise therapy, switching drugs, etc., and is useful for patients as well as improving the accuracy of diabetes medical care. Information can be provided.
  • t2 is 3 months or more and A1c (t2) is less than 5.8% (excellent), when it is less than 5.8 to 6.5% (good), when it is less than 6.5 to 7.0% (insufficient), If it is 7.0 to less than 8.0% (bad), if it is 8.0% or more (impossible), GA (t2) is less than 17.0% (excellent), 17.0 to less than 20.0% (good), 20.0 It is desirable to judge that it is less than 21.0% (insufficient), 21.0 to less than 24.0% (bad), and 24.0% or more (impossible). By using such a determination, it is possible not only to improve the accuracy of diabetes medical care but also to provide useful information for patients.
  • t2 when t2 is 3 months or more, t1 is 1 to 5 weeks, and A1c (t2) is less than 5.8% (excellent), when 5.8 to less than 6.5% (good), less than 6.5 to 7.0% (Inadequate), 7.0 to less than 8.0% (Bad), 8.0% or more (Not possible), GA (t2) less than 17.0% (Excellent), 17.0 to less than 20.0% If it is (good), 20.0 to less than 21.0% (insufficient), 21.0 to less than 24.0% (bad), 24.0% or more (impossible), GA (t1) -GA The effect of treatment may be determined using (0).
  • GA (t1) -GA (0), A1c (O), A1c (t2) need only be displayed.
  • GA (t A table in which t1) -GA (0) and A1c (O) are displayed and A1c (t2) is displayed according to the values of GA (t1) -GA (0) and A1c (O) is preferable.
  • A1c (t2) -A1c (0) may be used instead of A1c (t2).
  • GA (t1) -GA (0), A1c (t2) is taken on the X-axis or Y-axis, a graph is shown for each value of A1c (O), and GA (t1) -A graph that can read A1c (t2) if GA (0) and A1c (O) are determined.
  • A1c (t2) -A1c (0) may be used instead of A1c (t2).
  • the dosage at the start of treatment is 0.3 mg
  • the change in GA value after 2 weeks of treatment is 2.5% or more
  • the GA value change after 2 weeks of treatment is 2.0-2.4%
  • the GA value change after 2 weeks of treatment is 1.0-1.9%
  • 2 weeks If it is determined that the dosage will be increased to 0.6 mg later and further increased to 0.9 mg two weeks later, and the change in GA level is less than 1.0% 2 weeks after the start of treatment, switching to another drug is necessary. It is desirable to judge.
  • the dosage at the start of treatment is minimized, and after determining the therapeutic effect after a certain period, the dosage can be increased if the effect is insufficient.
  • the therapeutic drug for diabetes, liraglitide is increased while confirming the effect starting from the lowest dose, but according to the present invention, the initial GA change, i.e., GA (t1) -GA (0)
  • the initial GA change i.e., GA (t1) -GA (0)
  • the effect can be estimated.
  • A1c (t2) is less than 5.8% (excellent), 5.8-6.5% (good), 6.5-7.0% (insufficient), 7.0-8.0% (bad), If it is 8.0% or more (impossible), if GA (t2) is less than 17.0% (excellent), if it is less than 17.0-20.0% (good), if less than 20.0-21.0% (insufficient), if less than 21.0-24.0%
  • a guideline for the dosage can be created.
  • the GA ( ⁇ ) is preferably 11 to 20%.
  • the A1c ( ⁇ ) is preferably 4 to 7%.
  • the MBG ( ⁇ ) is preferably 80 to 180 mg / dl.
  • the blood sample analysis method is a first method for acquiring a glycoalbumin value (GA (t)) of a blood sample after the onset of diabetes t and a hemoglobin A1c value A1c (t) of the blood sample after the onset of diabetes t.
  • the onset of fulminant type 1 diabetes can be determined from the values of GA and HbA1c.
  • the TGA ( ⁇ ) is 35 to 90%
  • the TA1c ( ⁇ ) is 10 to 30%
  • k is 1 to 3.
  • TGA (1/2) may be calculated using the equation (11).
  • TGA (1/2) ⁇ log2 ⁇ t / log ((GA (t) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (11)
  • the TA1c (1/2) may be calculated using the equation (12).
  • TA1c (1/2) ⁇ log2 ⁇ t / log ((A1c (t) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ ))) (12)
  • TMBG (1/2) may be calculated using the equation (13).
  • TMBG (1/2) ⁇ log2 ⁇ t / log ((MBG (t) ⁇ MBG ( ⁇ )) / (MBG (0) ⁇ MBG ( ⁇ ))) (13)
  • the GA (t) / A1c (t) threshold is preferably 3.0 to 3.5. Further, the threshold value of GA (t) / A1c (t) is preferably 3.2.
  • the blood sample analyzer includes a glycoalbumin value (GA (0)) of a blood sample collected on the treatment start date, a glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date
  • the glycoalbumin value of the blood sample is (GA (0) + GA ( ⁇ )) / 2 indicates the period until reaching 7 to 26 days constant (
  • a first computing unit to calculate; GA (t2) GA ( ⁇ ) + (GA (0) ⁇ GA ( ⁇ )) ⁇ 10 A (1)
  • A1c (t2) A1c ( ⁇ ) + (A1c (0) ⁇ A1c ( ⁇ )) ⁇ 10 B (4)
  • An output unit that outputs the GA (t2) and the A1c (t2) to an output device, wherein the first arithmetic unit represents A in the formula (1) as the formula (2) or the formula (3) )
  • A t2 / t1 ⁇ log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (2)
  • A ⁇ log 2 ⁇ t 2 / (TGA (1/2) ⁇ k) (3)
  • the second calculation unit calculates B in the formula (4) using any one
  • the present invention by calculating changes in glycoalbumin GA and hemoglobin A1c (HbA1c), it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
  • the blood sample analyzer inputs a glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after the onset of diabetes and a hemoglobin A1c value (A1c (t1)) of the blood sample.
  • GA (t) glycoalbumin value
  • A1c (t1) hemoglobin A1c value
  • An input unit that receives GA, a calculation unit that calculates GA (t) / A1c (t1) using GA (t) and A1c (t1), and GA (t) / A1c calculated by the calculation unit a determination unit that determines whether or not (t1) is equal to or greater than a predetermined threshold; and when the determination unit determines that GA (t) / A1c (t1) is equal to or greater than the predetermined threshold, An output unit that outputs to the output device a determination result indicating that type 1 diabetes has developed.
  • the onset of fulminant type 1 diabetes can be determined from the values of GA and HbA1c.
  • the threshold is preferably 3.0 to 3.5.
  • the program according to the present invention stores, in a computer, a glycoalbumin value (GA (0)) of a blood sample collected on the treatment start date, a glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date
  • the present invention by calculating changes in glycoalbumin GA and hemoglobin A1c (HbA1c), it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
  • the program according to the present invention inputs, to a computer, a glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after the onset of diabetes and a hemoglobin A1c value (A1c (t1)) of the blood sample.
  • GA (t) glycoalbumin value
  • A1c (t1) hemoglobin A1c value
  • a function of calculating GA (t) / A1c (t1) using GA (t) and A1c (t1), and GA (t) / A1c (t1 calculated by the arithmetic unit ) Is greater than or equal to a predetermined threshold value, and if the determination unit determines that GA (t) / A1c (t1) is equal to or greater than the predetermined threshold value, the patient is fulminant type 1 And a function of outputting a determination result that diabetes is developed to an output device.
  • the onset of fulminant type 1 diabetes can be determined from the values of GA and HbA1c.
  • the present invention it is possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Furthermore, it becomes possible to provide useful information regarding the onset of fulminant type 1 diabetes.
  • the blood glucose level may be any blood glucose level measured in a normal clinical test. Fasting blood glucose, occasional blood glucose, postprandial blood glucose, daily maximum blood glucose, average blood glucose ( Mean Blood Glucose (MBG) or the like can be used, but the daily average blood sugar is preferable.
  • the average blood glucose is the average value of blood glucose measured several times a day, preferably the average of 6 measurements before meal, after meal and 7 before sleep, or continuous blood glucose measurement You may use the average of the blood glucose measured using the apparatus (CGMS) etc.
  • a blood collection method for blood glucose measurement is not limited, but a blood collection tube or a serum blood collection tube in which sodium fluoride or citric acid is enclosed may be used, and blood of a fingertip may be directly measured with an electrode.
  • the blood glucose can be measured using a known method such as an enzymatic method, an HPLC method, or an electrode method.
  • blood sample analysis is based on the measured values of various biomolecules (eg, glycoalbumin, hemoglobin A1c, average blood glucose) contained in the blood sample, and the presence or absence of various diseases and the presence or absence of the effect of disease treatment. Or predicting the degree or the like. Examples of such diseases to be predicted or determined include diabetes (fulminant type 1 diabetes and the like).
  • diabetes treatment is not limited to diabetes treatment with drugs, but also includes treatment with exercise and diet.
  • Drugs used for pharmacotherapy for diabetes are not particularly limited, and examples include insulin and oral diabetes drugs (sulfonylurea drugs, rapid-acting insulin secretagogues, ⁇ -glucosidase inhibitors, biguanides, insulin resistance improvers, etc.) Can be done.
  • Examples of the blood sample analysis include a method for predicting the content of various biomolecules contained in the blood sample and a method for determining whether or not the blood sample is derived from a patient with fulminant type 1 diabetes.
  • glycoalbumin refers to a glycated protein in which a saccharide is bound to albumin, and any method may be used for the measurement.
  • Enzymatic method, immunization method, mass spectrometry, capillary electrophoresis Method, mini-column method, high performance liquid chromatography method (HPLC method) or the like can be used.
  • HPLC method high performance liquid chromatography method
  • serum and plasma are preferable, but other samples may be preferable.
  • hemoglobin A1c refers to hemoglobin in which sugar is bound to the N-terminal valine of hemoglobin ⁇ chain, and any method may be used for the measurement. Enzyme method, immunization method, mass spectrometry Method, capillary electrophoresis, mini-column method, HPLC method or the like can be used. In particular, it is preferable to use the most commonly used immunization method, enzyme method, and HPLC method. As a sample for measuring HbA1c, whole blood, blood cells, and hemolyzed blood are preferable, but other samples may be preferable.
  • 0, t1, and t2 in parentheses given to the right of MBG, GA, and HbA1c indicate the number of days after the start of treatment or after the onset of fulminant type 1 diabetes, and before the start of treatment.
  • the measured values of MBG, GA, and HbA1c before the onset of fulminant type 1 diabetes are MBG (0), GA (0), A1c (0), MBG at the start of treatment or after the onset of fulminant type 1 diabetes
  • the measured values of GA and HbA1c are expressed as MBG (t1), GA (t1), and A1c (t1), respectively, and similarly the measured values after t2 days are expressed as MBG (t2), GA (t2), and A1c (t2).
  • MBG (0), GA (0), A1c (0) should be measured before diabetes treatment when used for the number of days from the start of diabetes treatment. In particular, it may not be the 0th day. When used for the number of days since the onset of fulminant type 1 diabetes, there is generally no measured value on day 0, so it is desirable to substitute a normal value.
  • GA (0) that can be substituted as the normal value on day 0 in the case of fulminant type 1 diabetes is different depending on the individual and treatment, but it is sufficient to set GA corresponding to normal blood glucose or blood glucose close to normal blood glucose, for example 13.7 -20%, preferably 14.0-20%, more preferably 14.5-19.0%.
  • 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, or 17.0% may be simply used, and may be set higher as 18.0, 18.5, 19.0, 19.5, or 20.0% in consideration of age and symptoms.
  • HbA1c (0) varies depending on the individual and treatment, but HbA1c corresponding to normoglycemia or blood glucose close to normoglycemia may be set, for example, 3.0 to 6.0%, preferably 4.0 to It is 5.8%, more preferably 4.0 to 5.5%. Alternatively, 5.0, 5.3, 5.5, or 6.0% that is near the upper limit of the normal range may be used. In addition, considering the age and symptoms, it may be set higher, such as 6.5, 7.0, or 7.5%.
  • the target value MBG (0) for lowering the average blood glucose in fulminant type 1 diabetes may vary depending on the individual or treatment, but an MBG corresponding to normal blood glucose or blood glucose close to normal blood glucose may be set. It is ⁇ 180 mg / dl, preferably 90 to 170 mg / dl, more preferably 100 to 160 mg / dl. Moreover, 80, 90, 100, 110, 120, 130 or 140 mg / dl may be simply used, or 150, 160, 170 or 180 mg / dl may be set higher considering the age and symptoms.
  • MBG, GA, and HbA1c after a sufficient time has elapsed are denoted as MBG ( ⁇ ), GA ( ⁇ ), and HbA1c ( ⁇ ), respectively.
  • MBG ( ⁇ ), GA ( ⁇ ), and HbA1c ( ⁇ ) are denoted as MBG ( ⁇ ), GA ( ⁇ ), and HbA1c ( ⁇ ), respectively.
  • Sufficient time can be several days for MBG, 1 to 4 weeks for GA, and 1 to 3 months or more for HbA1c.
  • a target value that decreases MBG, GA, HbA1c by treatment may be used.
  • a value close to the normal value should be used.
  • the target value GA ( ⁇ ) for lowering the GA differs depending on the individual or treatment, but it is sufficient to set a GA corresponding to blood sugar or blood sugar close to normal blood sugar.
  • it is close to GA ( ⁇ ) of fulminant type 1 diabetes, but it may be a number near the lower limit of the normal value, for example, 11 to 20%, preferably 12 to 19%, more preferably 13 to 18%. Most preferably, 14 to 17% can be selected.
  • a numerical value of 11.0, 12.0, 13.0, 14.0, 15.0, 16.0, or 17.0% may be simply used, or may be set higher as 18.0, 19.0, or 20.0% in consideration of age and symptoms.
  • GA ( ⁇ ) as an abnormally high value in fulminant type 1 diabetes is, for example, 30 to 90%, more preferably 40 to 90%, still more preferably 50 to 90%, and simply 60 , 70, 80 or 90% may be set.
  • HbA1c ( ⁇ ) varies depending on the individual and treatment, but HbA1c corresponding to normoglycemia or blood glucose close to normoglycemia may be set, for example, 4.0 to 7.0%, Preferably it is 4.5 to 6.5%, more preferably 5.0 to 6.0%. Also, 4.0, 4.5, 5.0, 5.5, or 6.0% may be simply used, and may be set higher such as 6.5, 7.0, or 7.5% in consideration of age and symptoms.
  • A1c ( ⁇ ) as an abnormally high value in the case of fulminant type 1 diabetes is, for example, 10 to 30%, more preferably 15 to 30%, still more preferably 20 to 30%. You may set 15, 20, 25 or 30%.
  • the target value for reducing average blood sugar in diabetes treatment, MBG ( ⁇ ) varies depending on the individual and treatment, but MBG corresponding to normal blood sugar or blood sugar close to normal blood sugar may be set, for example, 80 to 180 mg / dl,
  • the dosage is preferably 90 to 170 mg / dl, more preferably 100 to 160 mg / dl.
  • 100, 110, or 120 mg / dl, which is near the upper limit of the normal range, may be used, and may be set higher, such as 130, 140, or 150 mg / dl in consideration of age and symptoms.
  • MBG ( ⁇ ) as an abnormally high value in the case of fulminant type 1 diabetes is, for example, 300 to 1000 mg / dl, more preferably 400 to 1000 mg / dl, still more preferably 500 to 1000 mg / dl, You may simply set 600, 700, 800, 900 or 1000 mg / dl.
  • TMBG (1/2), TGA (1/2), and THbA1c (1/2) indicate that MBG, GA, and HbA1c are (MBG (0) + MBG) when blood glucose is changed rapidly.
  • ( ⁇ )) / 2 (GA (0) + GA ( ⁇ )) / 2
  • (A1c (0) + A1c ( ⁇ )) / 2 are constants indicating periods until reaching.
  • TMBG (1/2), TGA (1/2), and THbA1c (1/2) may be derived using the formulas described below, and approximate numbers estimated from the half-lives of blood glucose, albumin, and hemoglobin are substituted. You may do it.
  • TMBG For numbers that can be substituted into TMBG (1/2), TGA (1/2), and THbA1c (1/2), for example, in the case of TMBG (1/2), when blood sugar is drastically decreased in the treatment of diabetes Since blood glucose usually decreases in 1 to 6 days, it is 1 to 6 days, preferably 1 to 5 days, and more preferably 1 to 4 days. Alternatively, 1, 2, 3, 4, 5 or 6 days may be simply substituted. In the case of fulminant type 1, it is necessary to substitute the number when blood glucose rapidly deteriorates, but the same number as that used for lowering can be used.
  • the present invention is characterized in that MBG, GA, and A1c change as a function when a blood glucose control state changes, and that the calculation and prediction based on the calculation can be easily performed.
  • the function is the average blood glucose level before the change in glycemic control state, t days after change, and the values of glycoalbumin and hemoglobin A1c are MBG (0), MBG (t), MBG ( ⁇ ), When GA (0), GA (t), GA ( ⁇ ), A1c (0), A1c (t), and A1c ( ⁇ ), (GA (t) ⁇ GA ( ⁇ )) / (GA (0 ) -GA ( ⁇ )), logarithm of (A1c (t) -A1c ( ⁇ )) / (A1c (0) -A1c ( ⁇ )) or (MBG (t) -MBG (0)) / (MBG Based on the fact that the logarithm of (0) -MBG ( ⁇ )) is linear with the elapsed time t after the
  • TGA (1/2) be a period until GA reaches (GA (0) + GA ( ⁇ )) / 2 when blood sugar is rapidly lowered.
  • log1 / 2 a ⁇ TGA (1/2) (18)
  • equation (17) into a in equation (18) yields the following equation (11).
  • TGA (1/2) ⁇ log2 ⁇ t / log ((GA (t) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (11)
  • Equation (12) for obtaining TA1c (1/2) and Equation (13) for obtaining TMBG (1/2) are obtained.
  • TA1c (1/2) ⁇ log2 ⁇ t / log ((A1c (t) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ )))
  • TMBG (1/2) ⁇ log2 ⁇ t / log ((MBG (t) ⁇ MBG ( ⁇ )) / (MBG (0) ⁇ MBG ( ⁇ ))) (13)
  • Equation (20) can be described as Equation (21) below.
  • A ⁇ log 2 ⁇ t / (TGA (1/2) ⁇ k) (21)
  • equation (14) is obtained by solving k from equation (21).
  • k ⁇ log2 ⁇ t1 / TGA (1/2) / (log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (14)
  • Equation (15) for obtaining k using A1c and Equation for obtaining k using MBG are obtained.
  • k ⁇ log2 ⁇ t1 / A1c (1/2) / (log ((A1c (t1) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ )))
  • GA (t2) which is the GA value at the future t2 can be expressed as the following formulas 1 and 3 from the formulas 19 and 21.
  • GA (t2) GA ( ⁇ ) + (GA (0) ⁇ GA ( ⁇ )) ⁇ 10 A (1)
  • A -log2 * t2 / (GA (1/2) * k) (3)
  • HbA1c The method for deriving HbA1c is also the same. If GA is replaced with A1c, equations 4, 5 and 6 are derived.
  • A1c (t2) A1c ( ⁇ ) + (A1c (0) ⁇ A1c ( ⁇ )) ⁇ 10 B (4)
  • B t2 / t1 ⁇ log ((A1c (t1) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ ))) (5)
  • B ⁇ log2 ⁇ t2 / (TA1c (1/2) ⁇ k) (6)
  • A1c (t2) can be calculated using Equations 4 and 5.
  • Equation 5 is a function of HbA1c, and as described above, HbA1c changes in value because it reflects blood glucose in the past 2 to 4 weeks. Takes a long time and results are slow to judge. Therefore, A1c (t2) can be calculated in a shorter period of time by calculating using GA or MBG.
  • A1c Formula 4 and Formula 6 are shown below.
  • A1c (t2) A1c ( ⁇ ) + (A1c (0) ⁇ A1c ( ⁇ )) ⁇ 10 B (4)
  • B -log2 * t2 / (TA1c (1/2) * k) (6)
  • k in Equation 6 can be expressed by the following Equation 14 using GA.
  • k ⁇ log2 ⁇ t1 / TGA (1/2) / (log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (14)
  • Equation 14 t2 / t1 ⁇ TGA (1/2) / A1c (1/2) ⁇ log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ )) (7)
  • HbA1c may be indicated using MBG.
  • k may be expressed using MBG, and by using MBG, it becomes possible to predict it more quickly.
  • B t2 / t1 ⁇ MBG (1/2) / TA1c (1/2) ⁇ log ((MBG (t1) ⁇ MBG ( ⁇ )) / (MBG (0) ⁇ MBG ( ⁇ ))) (25)
  • the GA function may be indicated using part of MBG.
  • k may be expressed using MBG, and by using MBG, it becomes possible to predict it more quickly.
  • MBG is an average blood sugar, so it is complicated to obtain the average value by collecting blood many times, but using the above formulas for calculating GA and A1c, MBG is calculated. It can also be calculated. Since GA and HbA1c need only be collected once, MBG is easily required.
  • TGA (1/2), TA1c (1/2), and TMBG (1/2) change blood glucose rapidly, glycoalbumin, hemoglobin A1c, and average blood glucose are (GA (0) + GA ( ⁇ )) / 2, (A1c (0) + A1c ( ⁇ )) / 2, and (MBG (0) + MBG ( ⁇ )) / 2 are constants indicating periods until reaching.
  • TGA (1/2) in Equation 9 is TA1c (1/2), GA (0), GA (t1), and GA ( ⁇ ) are A1c (0), A1c (t1), A1c ( ⁇ ) Can be expressed by the function of HbA1c shown in the following formula 10.
  • C t2 / t1 ⁇ TA1c (1/2) / TMBG (1/2) ⁇ log ((A1c (t1) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ ))) (10)
  • the fulminant type 1 diabetes in the present invention is a fulminant type in type 1 diabetes, which is type 1 diabetes that progresses very rapidly, in which the pancreas stops functioning in a few days.
  • type 1 diabetes blood sugar rapidly deteriorates and HbA1c is usually normal, but it is difficult to distinguish from type 2 diabetes combined with a cold.
  • fulminant type 1 diabetes rapidly deteriorates blood glucose, it can be differentiated from type 2 diabetes when the ratio of GA / A1c is not less than a characteristic value.
  • the characteristic value of GA / A1c can be obtained using the formula of the present invention.
  • GA (t) and A1c (t) are calculated using the calculation formulas 1, 3, 4, 6 of the present invention, and GA (t) / A1c (t) is obtained to set characteristic values. good.
  • GA (0) and A1c (0) are assigned normal values 15.0% and 5.0% of GA and HbA1c
  • GA ( ⁇ ) and HbA1c ( ⁇ ) are GA and HbA1c 90.0%
  • A1c (1) 30-25 x 10
  • GA / HbA1c is set to 3.2 or higher, it will be at least 35 days from the first day after the onset, actually longer Can pick up fulminant type 1 diabetes.
  • GA (1) / HbA1c (1) is 3.15, 3.35, 3.44, 3.54, 3.63, respectively.
  • GA / HbA1c is 3.15, 3.35, 3.44, 3.54, 3.63, respectively.
  • fulminant type 1 diabetes can be detected from the first day after onset if GA (0) is 14.4% or higher.
  • t 2
  • GA (0) 15.0% instead of 14.0, 13.7%
  • GA (2) / A1c (2) 3.20, 3.15.
  • GA / HbA1c is set to 3.2 or higher, for example, GA (0) is 13.7% or higher. Diabetes can be detected.
  • the standard range of GA is 11 to 17%, and since diabetes is strongly suspected from 20% or more, the upper limit can be set to 20%.
  • the normal value GA (0) for fulminant type 1 can be set between 13.7 and 20%. Since GA / A1c increases as GA (0) increases, a number of 17 or more can be set.
  • Type diabetes can be detected.
  • the reference range of A1c is 4.0 to 5.8%, and the lower limit can be set to 4.0%. That is, the normal value A1c (0) in the case of fulminant type 1 can be set between 4.0 and 5.5%. Note that GA / A1c increases as A1c (0) decreases, so a value of 4.0% or less can be set.
  • A1c ( ⁇ ) can be any number as long as it is 10% or more, but clinically it should never exceed HbA1c30%.
  • A1c ( ⁇ ) is GA (t) / A1c (t ) Tends to increase and may be set low, but if it is clinically untreated and hyperglycemia persists, it often exceeds HbA1c10%, so A1c ( ⁇ ) is practically 10-30 % Is preferred.
  • TGA (1/2) in the present invention is a constant indicating a period until GA reaches (GA (0) + GA ( ⁇ )) / 2 when blood glucose is rapidly changed as described above. However, it may be derived using Equation 14, or an approximate number estimated from the half-life of albumin may be substituted.
  • the half-life of albumin is about 2 weeks, so it is 7 to 26 days, preferably 9 to 24 days, most preferably 11 to 17 days, and simply 11 , 12, 13, 14, 15, 16, 17 etc. may be substituted.
  • GA (2) / A1c (2) is 3.30, 3.24, 3.18, 3.15, respectively.
  • TGA (1/2) can detect fulminant type 1 diabetes from the second day after onset regardless of the number of 7-26 days. . Since GA / A1c increases as TGA (1/2) decreases, it is possible to set a number of 7 days or less.
  • TA1c (1/2) in the present invention is a constant indicating a period until HbA1c reaches (A1c (0) + A1c ( ⁇ )) / 2 when blood glucose is rapidly changed as described above. However, it may be derived using Equation 15, or an approximate number estimated from the half-life of albumin may be substituted.
  • the half-life of hemoglobin is about 2 months, so 1 to 3 months, ie 4 to 12 weeks, or 19 to 84 days can be used, preferably 5 to 11 Weeks or 25 to 77 days, most preferably 6 to 10 weeks or 54 to 70 days.
  • Simply 4, 5, 6, 7, 8, 9, 10, 11, 12 weeks, that is, 28, 35, 42, 49, 56, 63, 70, 77, 84 days, etc. may be substituted.
  • the k value in the present invention is a constant indicating a difference in blood glucose change speed in a case where blood glucose is suddenly changed and in actual treatment or fulminant type 1 diabetes, and takes a different value depending on the individual patient and the type of treatment. Generally, it is a number larger than 1. In addition, in the case of fulminant type 1 diabetes, since blood glucose increases rapidly and no treatment is performed, the k value can be easily set. The average k value of patients with type 1 diabetes was approximately 1.8.
  • GA / HbA1c of type 2 diabetes is usually about 2.8 to 3.0, and fulminant type 1 diabetes is higher than that. Therefore, any number may be used as long as it is 3.0 or more, but it is preferably 3.0 to 4.0, more preferably 3.0 to 3.5, still more preferably 3.1 to 3.4, and most preferably 3.1 to 3.3. Also, 3.2 may be used.
  • the arithmetic device may be a calculator that can automatically calculate GA (t2), A1c (t2), MBG (t2), GA / A1c, etc. by substituting blood glucose, GA, and HbA1c, for example.
  • Any device having an arithmetic function such as a personal computer or a mobile phone may be used.
  • it is easy to use if there is a special button for calculating GA (t2), A1c (t2), MBG (t2), GA / A1c, etc. More preferably, it is easy to understand using graphs and tables.
  • a function may be installed, and for example, the determination result of fulminant type 1 diabetes may be displayed.
  • the present invention requires blood glucose, GA, and A1c measurement values, but it is preferable that the above calculation can be performed by a device having the measurement function.
  • the device having a measurement function it is a general-purpose biochemical automatic analyzer or a device that can be easily measured on a desktop, preferably fully automatic simply by inserting a reagent or a measurement chip.
  • the measurement is preferably completed, and more preferably, the measurement is completed in about 10 minutes and can be applied to a pre-clinical examination.
  • Example 1 Calculation of GA predicted value and comparison with actual measurement ⁇ Subject> Of diabetic patients with poor glycemic control, 28 patients who started or changed diabetes treatment (19 men, 9 women, average age 60.7 ⁇ ) The predicted value was calculated for 13.1 years old. Excluded were cases in which improvement in blood glucose control was insufficient and treatment was added, and cases with liver disease / renal disease / anemia. Before these treatments, GA (0), HbA1c (0) and blood glucose were measured, and GA (t1), HbA1c (t1) and blood glucose were measured at the first medical examination after the start of treatment.
  • GA (t2) and HbA1c (t2) at the time of medical care were predicted.
  • Formulas 1 to 3 were used for prediction of GA (t2), and Formulas 4 to 7 were used for prediction of HbA1c (t2).
  • Dietary therapy, exercise therapy, oral drugs, and insulin were used for each treatment.
  • HbA1c, GA, and blood glucose were measured at the second medical examination after the start of treatment, and compared with predicted values.
  • TGA (1/2) is a constant indicating the period until glycoalbumin reaches (GA (0) + GA ( ⁇ )) / 2 when blood glucose changes rapidly.
  • k is a constant indicating the ratio of the change in blood glucose change due to a sudden change in blood glucose and the treatment, it can be similarly obtained by calculation using Equation 14.
  • Formula 14 can be easily calculated by setting the measured value of GA (0) and GA (t1), and GA (infinity). Since Expression 2 is obtained by substituting Expression 11 and Expression 14 into Expression 3, the same result can be obtained by using either Expression 2 or Expression 3.
  • FIG. 1 shows the average value of GA (t2) calculated using Equation 1 and actually measured GA.
  • FIG. 2 is a graph showing the relationship between the measured value of GA and GA (t2) calculated using Equation 1.
  • the average values of GA (t2) and measured GA which are calculated using an arithmetic expression, are 18.9% and 19.4%, respectively, and GA (t2) is about 98% of the measured value. You can see that they are in good agreement.
  • Example 2 Comparison between HbA1c predicted value and actual value ⁇ Target> Same as Example 1 ⁇ Details and results of calculation of A1c (t2)> In Example 2, 5% was used as the target value for treatment A1c ( ⁇ ).
  • A1c (0) is a measurement value before treatment
  • A1c (t1) is a measurement value on the t1 day after the start of treatment.
  • TA1c (1/2) is a constant indicating the period until HbA1c reaches (A1c (0) + A1c ( ⁇ )) / 2 when blood glucose changes rapidly. It can be calculated in advance by Equation 12. Since k is a constant indicating the ratio of blood glucose change due to abrupt change and blood glucose change due to treatment, it can be similarly obtained by calculation using Equation 15.
  • Equation 15 can be easily calculated by setting the measured values of A1c (0) and A1c (t1) and A1c ( ⁇ ) if TA1c (1/2) is obtained. Incidentally, if Expression 12 and Expression 15 are substituted into Expression 5, Expression 6 is obtained. Therefore, the same result can be obtained by using either Expression 5 or Expression 6.
  • FIG. 3 shows the average value of A1c (t2) calculated using Equation 4 and the measured HbA1c.
  • FIG. 4 is a graph showing the relationship between the measured value of HbA1c and A1c (t2) calculated using Equation 4. As shown in FIG. 3, the average values of A1c (t2) calculated using an arithmetic expression and the measured HbA1c were 8.1% and 8.1%, respectively, which were in good agreement.
  • Example 3 Calculation of MBG predicted value and comparison with actual measurement ⁇ Target> Same as Example 1 ⁇ Details and results of calculation of MBG (t2)>
  • MBG ( ⁇ ) 160 mg / dl was used as MBG ( ⁇ ), which is the target value for treatment.
  • MBG (0) is a measured value before treatment
  • MBG (t1) is a measured value on day t1 after the start of treatment. Equation 23 can be replaced with Equation 24 as described above.
  • TMBG (1/2) is a constant indicating a period until MBG reaches (MBG (0) + MBG ( ⁇ )) / 2 when blood glucose changes rapidly, and is calculated in advance by Equation 13. be able to. Since k is a constant indicating the ratio of blood glucose change due to abrupt change and blood glucose change due to treatment, it can be similarly obtained by calculation using Equation 21.
  • Equation 21 can be easily calculated by setting the measured values of MBG (0) and MBG (t1) and MBG ( ⁇ ). Note that, by substituting Equations 13 and 21 into Equation 24, Equation 24 is obtained, so the same result can be obtained using either Equation 23 or Equation 24.
  • the result of actually calculating MBG (t2) and comparing it with the actual measurement value shows that the average value of MBG (t2) calculated using the arithmetic expression and the actual measurement MBG agrees very well. The usefulness and accuracy of 24 were clear.
  • Example 4 Relationship between predicted values and actual measurement values of HbA1c and GA in various treatments ⁇ Subject> Patients who started treatment of diabetes ⁇ Method> HbA1c and the results of the same various treatments in Examples 1 and 2 Table 1 shows the relationship between the predicted GA value and the actually measured value. As shown in Table 1, it was clear that HbA1c and GA can be predicted in various treatments, and that the blood sample analysis method of the present invention can accurately predict HbA1c and GA.
  • HbA1c and GA patients who have started treatment of diabetes ⁇ Method> Prediction of HbA1c and GA when treated with the same various drugs as in Examples 1 and 2 (metformin, liraglitide, exenalide, sitagliptin, alpha GI, etc.) Table 2 shows the relationship between values and measured values. As shown in Table 2, it was clear that HbA1c and GA can be predicted in various treatments, and that the blood sample analysis method of the present invention can accurately predict HbA1c and GA.
  • FIG. 5 is a graph in which the transition of the measured value of GA is plotted against the number of days from the treatment start date.
  • Equation 7 is clear because it can accurately estimate future HbA1c using GA before HbA1c changes significantly. there were.
  • the following formulas 1, 4, 25, and 26 for estimating HbA1c and GA by MBG are also useful.
  • Equation 8-10 for estimating MBG using GA or HbA1c is also clear.
  • Example 7 Example of estimating HbA1c and GA values using HbA1c values before and after t2 days ⁇ Method> Administration examples of liraglitide 0.3 mg, 0.6 mg and 0.9 mg (Seino Y, DRCP, 81: 161 -168, 2008) was used for the calculation.
  • A1c (0) 8.24%
  • A1c (t2) 7.17%
  • A1c ( ⁇ 3) 7.0%
  • A1c (0) 8.21%
  • A1c (t2) 6.71%
  • A1c ( ⁇ 2) 6.5%
  • A1c (0) 8.12%
  • A1c (t2) 6.45%
  • A1c ( ⁇ 1) 6.0%
  • the k value was determined using Equation 23 below.
  • k ⁇ log2 ⁇ t1 / TA1c (1/2) / log ((A1c (t2) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ ))) (23)
  • k1 0.92 for the 0.9 mg formulation
  • k2 0.84 for the 0.6 mg formulation
  • k3 1.08 for the 0.3 mg formulation.
  • the hemoglobin A1c value (A1c (t1)) and glycoalbumin value (GA (GA) (GA) of the blood sample collected after t1 day from the treatment start date using the formulas (24), (25), (26), (27). t1)) is calculated.
  • Table 3 shows the calculated A1c (t1) and GA (t1).
  • Table 3 is an example of estimating HbA1c and GA values between HbA1c before and 14 weeks after treatment, and administration examples of liraglitide 0.3 mg, o.6 mg, and 0.9 mg (Seino Y, DRCP, 81: 161-168). , 2008). As shown in Table 3, the HbA1c and GA values during the treatment were predictable using the measured values of HbA1c before treatment and t2.
  • Example 8 Prediction when the dosage of a therapeutic agent is changed ⁇ Method>
  • administration examples of liraglitide 0.3 mg, 0.6 mg and 0.9 mg (Seino Y, DRCP, 81: 161-168, 2008) The calculation was performed using the published data.
  • the hemoglobin A1c values of the blood samples collected at the time when sufficient time has elapsed from the treatment start date are A1c ( ⁇ D1), A1c ( ⁇ D2), A1c ( ⁇ D3, respectively) )
  • A1c (0) 8.24%
  • A1c (t2) 7.17%
  • A1c ( ⁇ 3) 7.0%
  • A1c (0) 8.21%
  • A1c (t2) 6.71%
  • A1c ( ⁇ 2) 6.5%
  • A1c ( ⁇ 1) 6.0%
  • k1 0.92
  • k2 0.84
  • k3 1.08
  • A1c (t1) A1c ( ⁇ D1) + (A1c (0) ⁇ A1c ( ⁇ D1)) ⁇ 10 B (29)
  • B ⁇ log2 ⁇ t2 / (TA1c (1/2) ⁇ k) (6)
  • TA1c (1/2) is the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c ( ⁇ )) / 2 when treatment is performed to rapidly reduce blood sugar. It is a constant of 19 to 84 days shown.
  • A1c (t2) or GA (t2) is calculated using equations (30) and (31).
  • A1c (t2) A1c ( ⁇ D2) + (A1c (t1) ⁇ A1c ( ⁇ D2)) ⁇ 10 B
  • GA (t2) GA ( ⁇ D2) + (GA (t1) ⁇ GA ( ⁇ D2)) ⁇ 10 B (31)
  • B in formula (30) is calculated using formula (32)
  • B in formula (31) is calculated using formula (33).
  • TA1c (1/2) is the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c ( ⁇ )) / 2 when treatment is performed to rapidly reduce blood sugar.
  • the TGA (1/2) is a constant of 19 to 84 days shown, and when a treatment for rapidly lowering blood glucose is performed, the glycoalbumin value of the blood sample is (GA (0) + GA ( ⁇ )) / 2. It is a constant of 7 to 26 days indicating the period until reaching.
  • Table 4 shows the results of calculating the HbA1c value and GA value after 6 weeks, 10 weeks and 14 weeks from the start of treatment using the GA values after 2 weeks from the treatment start date.
  • Each table shows the calculation results when the dose of liraglitide from the start of treatment to the second week is 0.3 mg, and the dose after the second week is 0.3 mg, 0.6 mg, and 0.9 mg.
  • prediction was possible even when the dose of the therapeutic agent was changed. This allows the present invention not only to adjust the dosage, but also to change the treatment, such as changing from exercise to diet, strengthening exercise or diet, changing medication, etc. It became clear that it was useful.
  • the calculated GA and HbA1c values can be evaluated with reference to the diabetes treatment guide edited by the Japan Diabetes Society, and the dose of the drug can be increased or the treatment can be changed.
  • the HbA1c value changes after the start of treatment, and the change disappears for 1 month or more (t2> 1 month), preferably 2 months or more (t2> 2 months), more preferably 3 months (t2> March)
  • A1c (t2) less than 5.8% (excellent), less than 5.8-6.5% (good), less than 6.5-7.0% (insufficient), 7.0-8.0% Less than (bad), 8.0% or more (impossible).
  • the GA value changes after the start of treatment, and the change disappears for 2 weeks or more (t2> 2 weeks), preferably 1 or more (t2> 1 month), more preferably 2 months (t2>) (Feb) GA (t2) less than 17.0% (excellent), 17.0-20.0% (good), 20.0-21.0% (insufficient), 21.0-24.0% ), 24.0% or more (impossible).
  • the value of HbA1c is a value of JDS (Japan Diabetes Society) determined in accordance with the standardization program of the Japan Diabetes Society, but NGSP values and IFCC values that are different internationally are used. The NGSP value is calculated with a JDS value of -0.4%.
  • Example 9 Prediction of future HbA1c value using GA value change at the beginning of treatment
  • lists and graphs including nomograms
  • HbA1c and GA when the blood glucose index changes to a stable value several months ahead of changes in HbA1c and GA at the start of treatment.
  • An example is shown below.
  • Glycoalbumin levels (GA ( ⁇ )) of blood samples collected when sufficient time has passed since the start of treatment and hemoglobin A1c values (A1c (A1c () of blood samples collected when sufficient time has elapsed since the start of treatment) ⁇ )
  • blood serum sample collected before the start of treatment (GA (0))
  • blood sample collected after t1 day from the start of treatment (GA (t1))
  • treatment Temporarily set the hemoglobin A1c value (A1c (0)) of the blood sample collected on the start day, Using equation (4), the hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date is calculated.
  • A1c (t2) A1c ( ⁇ ) + (A1c (0) ⁇ A1c ( ⁇ )) ⁇ 10 B (4)
  • B in formula (4) is calculated using formula (7).
  • B t2 / t1 ⁇ TGA (1/2) / TA1c (1/2) ⁇ log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (7)
  • TGA (1/2) is the period until the glycoalbumin value of the blood sample reaches (GA (0) + GA ( ⁇ )) / 2 when treatment for rapidly lowering blood glucose is performed.
  • TA1c (1/2) indicates that the hemoglobin A1c value of the blood sample is (A1c (0) + A1c ( ⁇ )) / 2 when treatment for rapidly reducing blood glucose is performed. It is a constant of 19 to 84 days indicating the period until reaching. Further, t1 ⁇ t2.
  • Table 5 is a table showing the results of calculating A1c (t2) by substituting GA (t1) ⁇ GA (0) ( ⁇ GA2w) and A1c (0) (A1c value at the start of treatment). In the example shown in Table 5, t1 is 2 weeks and t2 is 14 weeks. By using Table 5, the future A1c value can be easily estimated using a computer or the like at a clinical site or the like.
  • FIG. 14 is a graph showing the relationship between GA (t1) -GA (0) and A1c (t2) for each A1c (0) shown in Table 5, but such a graph is used instead of the table. May be used.
  • Table 5 shows the result of calculating A1c (t2) by substituting GA (t1) ⁇ GA (0) and A1c (0).
  • GA (t1) ⁇ GA (0) and GA (0 ) Can be used to calculate GA (t2), or A1c (t1) -A1c (0), A1c (0) can be used to calculate A1c (t2)
  • a table obtained by substituting (t1) ⁇ MBG (0) and A1c (0) to calculate A1c (t2) may be used. The same applies to the graph.
  • Example 10 Prescription example of anti-diabetic drug liraglitide using the present invention ⁇ Method> Using the graphs shown in Examples 7 to 9 and the results of papers actually using liraglycide, the drug prescription from the initial GA value change Determine the amount. Administration of liraglitide begins with a minimum dose of 0.3 mg and is incrementally increased based on therapeutic effects. As shown in FIG. 14, when the change in GA value in the initial two weeks is 2.5%, if the initial value of HbA1c is about 8.0%, the HbA1c value after 14 weeks is about 6.5% (determination of the diabetes treatment guide It is estimated that the blood glucose level is good), and a sufficient blood glucose lowering effect is estimated.
  • the HbA1c value after 14 weeks is estimated to be about 6.5% or more from FIG. It is unlikely that hypoglycemia will be obtained.
  • Table 4 when the change in GA value in the initial 2 weeks was 2.0% and the initial value of HbA1c was about 8%, the dose of liraglitide was increased to 0.3 mg in the initial 2 weeks and then increased to 0.6 mg Then, the HbA1c value drops to 6.7% after 14 weeks, so if the change in GA value in the initial two weeks is 2.0% or more, then the prescription of 0.6 mg may be continued.
  • the change in GA value in the initial 2 weeks is less than 2.0%, it is difficult to determine that a dose of 0.6 mg has a sufficient blood glucose lowering effect, and the dose should be increased to 0.9 mg after 2 weeks.
  • the initial A1c value is 8% and the GA change in the initial two weeks is 1.0%
  • the HbA1c value after 14 weeks is 7% or more, and the effect of using liraglycide is small. Therefore, it is preferable to consider using other drugs instead of liraglycide.
  • the dosage at the start of treatment is 0.3 mg
  • the GA value change after 2 weeks from the start of treatment is 2.5%. In the above case, continue to be administered at 0.3 mg. If the change in GA level after 2 weeks from the start of treatment is 2.0-2.4%, increase the dose to 0.6 mg after 2 weeks and 2 weeks after the start of treatment. If the GA value change is 1.0-1.9%, increase the dosage to 0.6 mg after 2 weeks, then increase the dosage to 0.9 mg after 2 weeks, and if the GA value change is less than 1.0%, etc. Consider switching to other drugs.
  • Example 11 Differentiation of fulminant type 1 diabetes, calculation of GA (t) / A1c (t) Prediction of ⁇ GA / A1c> GA (t) / A1c (t) using formulas 1, 3, 4 and 6 was calculated.
  • GA (0) and A1c (0) are GA and HbA1c normal values of 15.0% and 5.0%.
  • GA ( ⁇ ) and HbA1c ( ⁇ ) are GA and HbA1c completely abnormal values of 90.0% and 30.0. % Was used.
  • TGA (1/2) and TA1c (1/2) 14 days and 42 days obtained in Example 3 were used, respectively.
  • GA (1) / HbA1c (1) is 3.2 to 3.6, and GA (0) is any number as long as it is 14.4% or more. It was clear that GA (t) / A1c (t) became 3.2 or more from the first day after onset even if set.
  • Example 12 Differentiation of fulminant type 1 diabetes ⁇ Subject> 35 subjects diagnosed with fulminant type 1 diabetes, type 2 diabetes as a control, HbA1c less than 8.5%, 21 subjects with no history of diabetes treatment (16 men) Nineteen women) and diabetic type in glucose tolerance test, HbA1c was less than 8.5%, 11 cases with no history of diabetes treatment, a total of 32 (25 men, 7 women). In both groups, pregnancy, renal disease, liver disease, blood disease, malignant disease, thyroid disease combined cases, and steroid treatment cases affecting HbA1C or GA measurement were excluded.
  • the ratio of GA for HbA 1C (GA / HbA 1C ratio) In fulminant type 1 diabetes against 2.76 ⁇ 0.29 in type 2 diabetes showed significant highs and 3.94 ⁇ 0.53 (p ⁇ 0.0001) .
  • the cases with a GA / HbA1c ratio of 3.2 or higher were 34 (97%) of 35 cases of fulminant type 1 diabetes, but only 1 (32%) of 32 cases of type 2 diabetes. The results are shown in FIG.
  • fulminant type 1 gluconic disease and type 2 diabetes can be differentiated by setting GA (t) / A1c (t) to 3.2. As can be seen from the figure, it was clear that GA (t) / A1c (t) 3.0-3.5 can distinguish fulminant type 1 glucosylosis from type 2 diabetes.
  • FIG. 9 shows an example of diagnosing fulminant type 1 diabetes by calculating GA / HbA1c at the first visit.
  • the program uses Microsoft and Excel 2000, and the calculation formula is GA / HbA1c. If the value is 3.2 or more, it can be displayed that there is a possibility of fulminant type 1 diabetes.
  • the equipment used was Toshiba, Dynabook SS 1620 12L / 2.
  • the blood sample analyzer according to the present invention may be any device such as a personal computer, a calculator, and a mobile phone as long as it has a calculation function.
  • Example 14 Prediction of GA and HbA1c using blood sample analyzer according to the present invention GA and HbA1c at the first visit and the first GA after the start of treatment were measured, and the next prediction was performed as shown in FIGS. And 12.
  • A1c (t2) and GA (t2) are calculated using Equations 1, 2, 4, and 7.
  • FIG. 10 shows an example in which the next predicted value is obtained with two measured values
  • FIG. 11 shows an example in which the prediction of 204 days after GA and HbA1c are disclosed
  • FIG. 12 shows a range of ⁇ 10% of HbA1c. This is an example obtained by comparison with actual measurement.
  • the predicted HbA1c and measured HbA1c are well constant on the 24th, 52nd and 80th days after the start of diabetes treatment, and the usefulness of this program is clear. It is also clear that treatment guidance is capable.
  • the blood sample analyzer according to the present invention may be any device such as a personal computer, a calculator, and a mobile phone as long as it has a calculation function.
  • Example 15 Blood sample analyzer capable of measuring blood glucose, GA, and HbA1c having an arithmetic function of MBG (t2), GA (t2), A1c (t2) The hemoglobin A1c reagent was loaded and the serum and hemolysis of the same person were measured.
  • Glycoalbumin reagent Lucika GA-L (Asahi Kasei Pharma) and a dedicated calibrator were used.
  • Hemoglobin A1c reagent Determiner HbA1c (manufactured by Kyowa Medex) and a dedicated calibrator were used.
  • the present invention relates to a therapeutic effect and a method for measuring the onset of fulminant type 1 diabetes, and a device having the function, which is useful in the treatment of diabetes, and in particular, future mean blood glucose useful for the treatment of diabetic patients, By calculating the ratio of glycoalbumin, hemoglobin A1c, or glycoalbumin and hemoglobin A1c, it is used in clinical examinations for the measurement and device of the therapeutic effect of diabetes and the onset of fulminant type 1 diabetes.
  • FIG. 13 is a block diagram showing a functional configuration of the blood sample device 10 according to the present invention.
  • the blood sample device 10 includes an input device 11, an input unit 12, a storage unit (first storage unit, second storage unit) 13, a calculation unit (first calculation unit, second calculation unit). Part) 14, a determination part 15, an output part 16, and an output device 17.
  • the blood sample apparatus 10 is obtained, for example, by causing a general-purpose personal computer to execute a predetermined program.
  • the input unit 12, the calculation unit 14, the determination unit 15, and the output unit 16 represent modules of operations performed by a computer processor according to a program, and these actually constitute a processor of the blood sample device 10 as a whole.
  • the storage unit 13 is a storage device such as a hard disk of the blood sample device 10.
  • the input device 11 is input means such as a keyboard, a mouse, and a touch panel, for example, and is used by a user to give an instruction for processing to the blood sample device 10 and to input data and parameters. It is also possible to read data from a memory medium or the like via a USB (Universal Serial Bus) interface. An operation by the user via the input device 11 is controlled by the input unit 12.
  • the output device 17 is a display device, a printer, or the like. Output processing to the output device 17 is controlled by the output unit 16.
  • the user uses the input device 11 to determine the glycoalbumin value (GA (0)) of the blood sample collected on the patient's treatment start date, the glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), enter the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date .
  • the storage unit 13 has a glycoalbumin value (GA ( ⁇ )) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and a blood sample collected when a sufficient time has elapsed from the treatment start date.
  • GA ( ⁇ ) glycoalbumin value
  • A1c ( ⁇ ) Hemoglobin A1c value
  • TGA (1/2) the period until the blood glucose sample reaches (GA (0) + GA ( ⁇ )) / 2 when blood glucose treatment is rapidly reduced
  • TGA (1/2) the period (TA1c (1/2)) until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c ( ⁇ )) / 2 are stored.
  • the computing unit 14 calculates the glycoalbumin value (GA (t2)) of the blood sample collected t2 days after the treatment start date according to the equation (1).
  • GA (t2) GA ( ⁇ ) + (GA (0) ⁇ GA ( ⁇ )) ⁇ 10 A (1)
  • the calculating part 14 calculates the hemoglobin A1c value (A1c (t2)) of the blood sample extract
  • A1c (t2) A1c ( ⁇ ) + (A1c (0) ⁇ A1c ( ⁇ )) ⁇ 10 B (4)
  • the GA (t2) and A1c (t2) calculated by the calculation unit 14 are output to the output device 17 via the output unit 16.
  • the computing unit 14 calculates A in the formula (1) by either the formula (2) or the formula (3).
  • A t2 / t1 ⁇ log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (2)
  • A ⁇ log 2 ⁇ t 2 / (TGA (1/2) ⁇ k) (3)
  • the calculating part 14 calculates B in said Formula (4) by either of Formula (5) to Formula (7).
  • B t2 / t1 ⁇ log ((A1c (t1) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ ))) (5)
  • B ⁇ log2 ⁇ t2 / (TA1c (1/2) ⁇ k) (6)
  • B t2 / t1 ⁇ TGA (1/2) / TA1c (1/2) ⁇ log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ ))) (7)
  • the calculating part 14 calculates k in Formula (3) and said Formula (6) using Formula (14) and Formula (15), respectively.
  • k ⁇ log2 ⁇ t1 / TGA (1/2) / log ((GA (t1) ⁇ GA ( ⁇ )) / (GA (0) ⁇ GA ( ⁇ )))
  • k ⁇ log2 ⁇ t1 / TA1c (1/2) / log ((A1c (t1) ⁇ A1c ( ⁇ )) / (A1c (0) ⁇ A1c ( ⁇ ))) (15)
  • the user uses the input device 11 to input the glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after the onset of diabetes and the hemoglobin A1c value (A1c (t1)) of the blood sample. To do.
  • G (t) glycoalbumin value
  • A1c (t1) hemoglobin A1c value
  • the computing unit 14 calculates GA (t) / A1c (t1) using the input GA (t) and A1c (t1).
  • the determination unit 15 determines whether or not GA (t) / A1c (t1) calculated by the calculation unit 14 is equal to or greater than a predetermined threshold value.
  • the determination result that the patient has developed fulminant type 1 diabetes is output via the output unit 16 Output to device 17.
  • Example 16 Blood sample analyzer having a calculation function of GA (t1) and A1c (t1) and capable of measuring blood glucose, GA, and HbA1c even at the time of treatment change.
  • the hemoglobin A1c reagent was loaded and the serum and hemolysis of the same person were measured.
  • A1c (t2) was output using equations (6) and (29) to (33).
  • the output of Excel is shown in FIG. Also, graphs may be used in combination as in FIGS.
  • A1c (0) measured before the start of treatment TGA (1/2) 13.7, TA1c (1/2) 36.3 (15.0%), GA (0) measured before the start of treatment, t1 last measured It can be calculated by inserting the number of days from the start of treatment to the current treatment, substituting the current measurement value into GA (t1), and the number of days after the start of treatment to be predicted into t2.
  • the functional configuration of the blood sample analyzer according to the sixteenth embodiment can be the same as the functional configuration of the blood sample apparatus 10 according to the fifteenth embodiment shown in FIG.
  • the user uses the input device 11 to determine the glycoalbumin value (GA (0)) of the blood sample collected on the patient's treatment start date, the glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), enter the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date .
  • the type of treatment and conditions (such as dosage) can be entered.
  • the storage unit 13 stores the glycoalbumin value (GA ( ⁇ )) of the blood sample collected when sufficient time has elapsed from the treatment start date for each treatment type and condition (dose, etc.), from the treatment start date.
  • the computing unit 14 calculates the glycoalbumin value (GA (t2)) of the blood sample collected t2 days after the treatment start date according to the equation (1).
  • GA (t2) GA ( ⁇ ) + (GA (0) ⁇ GA ( ⁇ )) ⁇ 10 A (1)
  • the calculation unit 14 calculates the hemoglobin A1c value (A1c (t2)) of the blood sample collected after t2 days from the treatment start date according to the equations (4), (30), and (31).
  • the calculation unit 14 calculates A in the formula (1) and B in the above formula (4) by the same method as in Example 15, and B in the above formulas (30) and (31) is calculated by the formula ( 32) and (33).
  • B ⁇ log2 ⁇ (t2 ⁇ t1) / (TA1c (1/2) ⁇ k ⁇ k2 / k1) (32)
  • B -log2 * (t2-t1) / (TGA (1/2) * k * k2 / k1) (33)
  • the calculating part 14 calculates k in Formula (32), (33) using Formula (34).
  • k ⁇ log2 ⁇ t1 / TGA (1/2) / log ((GA (t1) ⁇ GA ( ⁇ 1)) / (GA (0) ⁇ GA ( ⁇ 1))) (34)
  • the determination unit 15 determines which region of the predetermined determination value the A1c (t2) and GA (t2) calculated by the calculation unit 14 are in, and changes the determination result and the treatment method and the strength (medication) Change of the amount, etc.) is output to the output device 17 via the output unit 16.
  • A1c (t2) is based on the Diabetes Treatment Guide of the Japan Diabetes Society, but if the standard is changed or the value is changed in the future, it will be changed according to the appropriate standard such as the official guidelines. That's fine. Further, according to the analysis based on Example 10 of the present invention, when the drug is liraglitide, the dosage at the start of treatment is 0.3 mg, and the GA value change after 2 weeks of the treatment is 2.5% or more, the dosage is continued at 0.3 mg. When the GA change after 2 weeks of treatment is 2.0-2.4%, the dosage is increased to 0.6 mg after 2 weeks. When the GA value is 1.0-1.9%, the dosage is increased to 0.6 mg after 2 weeks. Further, after 2 weeks, the dosage may be increased to 0.9 mg, and if the change in GA value is less than 1.0%, it may be determined to switch to another drug and output.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Diabetes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

A blood sample analysis method comprising: a first step of obtaining average blood glucose levels (MBG(0)), (MBG(t1)) and (MBG(∞)), glycoalbumin levels (GA(0)), (GA(t1)) and (GA(∞)) and hemoglobin A1c levels (A1c(0)), (A1c(t1)) and (A1c(∞)) in a blood sample at a base time point, t1 day(s) after the base time point, and after sufficient time is elapsed after the base time point; and a second step of calculating an average glucose level, a glycoalbumin level, a hemoglobin A1c level, or a ratio of a glycoalbumin level to a hemoglobin A1c level on day t by utilizing the fact that logarithmic values of (GA(t) - GA(∞))/(GA(0) – GA(∞)), (A1c(t) – A1c(∞))/(A1c(0) – A1c(∞)) and (MBG(t) - MBG(0))/(MBG(0) – MBG (∞)) are proportional to the days (t) elapsed after the base time point.

Description

血液試料解析方法、血液試料解析装置、及びプログラムBlood sample analysis method, blood sample analysis device, and program
　本発明は、血液試料解析方法、血液試料解析装置、及びプログラムに関するものである。 The present invention relates to a blood sample analysis method, a blood sample analysis device, and a program.
　糖尿病は爆発的に患者が増えている疾患であり、その対策が急務である。インスリンの発見依頼、糖尿病そのものでの死亡はまれになったが、併発する全身の微小血管の障害により起こる腎症、網膜症、神経症に代表される合併症が、患者のQOL（生活の質）を損なうことからその予防の検討が進められている。一方、DECORDスタディや舟形スタディでは、糖尿病発症以前であっても食後高血糖の症状があれば心臓や脳を始めとする大血管の障害が進行することが示され、食後高血糖を是正することが説かれるようになった。 Diabetes is a disease in which the number of patients is increasing explosively, and countermeasures are urgently needed. Although the request for discovery of insulin and death due to diabetes itself became rare, complications such as nephropathy, retinopathy, and neuropathy caused by the complications of systemic microvessels that coexist may be related to the patient's quality of life (QOL). ) Is being investigated for prevention. On the other hand, DECORD studies and boat-shaped studies show that if there is a symptom of postprandial hyperglycemia even before the onset of diabetes, macrovascular disorders such as the heart and brain progress, and postprandial hyperglycemia is corrected. Came to be preached.
　糖尿病は高血糖を呈する疾患であるが、一般に症状は少なく放置されやすい。そこで検査による血糖値および血糖コントロール状態の把握が重要である。
　現在、糖尿病の検査では空腹時血糖（FBS）と随時血糖が基本検査項目であるが、これらの値は食事等の影響を受けることから、頻回採血を行うなどして平均血糖を求めるか、平均血糖を反映する血糖コントロールマーカー（HbA1c：HbA1c、GA、１，５アンヒドロール（1.5-AG）等）が測定されている。HbA1cは過去２～３ヶ月、ＧＡは２～４週間、1.5AGは数日の血糖コントロール状態を反映すると言われている。中でもHbA1cはＤＣＣＴ（Diabetes Control and Complications Trial）によりその値を７％にコントロールすると合併症の発症や進展が抑制されることが知られており、この値を何％に管理するかが現在の糖尿病治療のターゲットとなっている（例えば、非特許文献１参照）。なおＧＡおよび1.5AGにはHbA1cと同様なエビデンス（科学的根拠）はない。また、非特許文献１にも記載されているように、日本糖尿病学会の治療ガイドによる糖尿病治療指針では、糖尿病の治療は以下の手順で進められる。第１に、患者自身が糖尿病の病態を十分理解し、適切な食事療法と運動療法を行うように指導する。第２に、これらを２～３ヶ月続けても尚目標の血糖コントロールを達成できない場合には、経口血糖降下薬またはインスリン製剤を用いる。血糖コントールの目標は一般には優（HbA1c＝～6.8）ないし良（HbA1c＝6.9～7.5）とすべきであり、若年者では優とすべきである。 Diabetes is a disease that exhibits hyperglycemia, but generally has few symptoms and is easily left untreated. Therefore, it is important to know the blood glucose level and blood glucose control state by examination.
Currently, fasting blood glucose (FBS) and occasional blood glucose are basic test items in diabetes testing, but these values are affected by meals, etc. A blood glucose control marker (HbA1c: HbA1c, GA, 1,5-anhydrol (1.5-AG), etc.) reflecting average blood glucose is measured. HbA1c is said to reflect glycemic control for the past 2-3 months, GA for 2-4 weeks, and 1.5AG for several days. Among them, HbA1c is known to suppress the onset and progression of complications when its value is controlled to 7% by DCCT (Diabetes Control and Complications Trial). It is a target for treatment (see, for example, Non-Patent Document 1). GA and 1.5AG do not have the same evidence (scientific basis) as HbA1c. Further, as described in Non-Patent Document 1, in the diabetes treatment guideline by the treatment guide of the Japan Diabetes Society, treatment of diabetes proceeds in the following procedure. First, instruct the patient to fully understand the condition of diabetes and to take appropriate diet and exercise therapy. Second, if these continue for 2-3 months and still cannot achieve the target glycemic control, oral hypoglycemic or insulin preparations are used. The goal for glycemic control should generally be excellent (HbA1c = ~ 6.8) to good (HbA1c = 6.9 to 7.5), and should be good for young people.
　高血糖の患者に対して、最初の２～３ヶ月の間運動療法と食時療法を継続して施すことは、現在の糖尿病検査がHbA1cを基準として進んでいることと関係がある。つまり、前述のように過去２～３ヶ月の血糖コントロール状態を反映するHbA1cに基づいて診断が進められる以上、２～３ヶ月たたなければ検査に治療効果が反映されないからである。たとえば、０ヶ月と１ヶ月目のHbA1cの値から２～６ヶ月程度先までのHbA1cの推移が予測できれば、患者にとっても医者にとっても貴重な情報となる。 [Continuous exercise and dietary therapy for hyperglycemic patients for the first 2 to 3 months is related to the progress of current diabetes tests based on HbA1c. That is, as described above, since the diagnosis proceeds based on HbA1c reflecting the blood glucose control state in the past 2 to 3 months, the therapeutic effect is not reflected in the test unless it is in 2 to 3 months. For example, if the transition of HbA1c from 2 to 6 months ahead can be predicted from the value of HbA1c in the 0th and 1st months, it will be valuable information for both patients and doctors.
　ＧＡや1.5-AGを用いて将来の測定値の推移が予測できれば、HbA1cを用いるよりもさらに早く将来の変化が予想できることが期待されるが、前述のようにＧＡや1.5-AGにはエビデンスがないことが問題点である。GAや1.5AGの測定値により将来のHbA1cの値が推定できるならばこれに勝るものはない。尚、すぐに治療が必要なほどの高血糖を呈する患者において、つまり尿糖が観察される患者においては、1.5AGの値はほぼ０であることが知られており、変化が確認できないことからこのような推定には不向きと考えられる。なお、平均血糖が簡便に測定できれば血糖コントロールマーカーは不要と思われるが、平均血糖を求めるためには１日に何度も血糖を測定する必要があり現実的ではない。 If changes in future measurements can be predicted using GA or 1.5-AG, it is expected that future changes can be predicted even faster than using HbA1c. However, as described above, there is evidence for GA and 1.5-AG. There is no problem. If the value of HbA1c in the future can be estimated from the measured values of GA and 1.5AG, there is nothing better than this. It should be noted that the value of 1.5AG is known to be almost zero in patients with hyperglycemia that needs immediate treatment, that is, in patients whose urine sugar is observed. It is considered unsuitable for such estimation. It should be noted that if the average blood glucose can be easily measured, a blood glucose control marker is unnecessary, but in order to obtain the average blood glucose, it is necessary to measure the blood glucose several times a day, which is not realistic.
　血糖コントロールが悪くなり新患で紹介されてきた患者や、血糖コントロールが悪いが手術が必要な患者に対しては、すぐに血糖を下げる治療が必要であるが、前述のようにHbA1cを用いた場合はその効果の判定に２～３ヶ月を要してしまうという問題がある。
　加えて、順調に治療を開始しても、数ヵ月後に運動療法、食事療法や薬物療法が継続できなくなる場合があるが、あらかじめ将来のＧＡやHbA1c推移のパターンが計算できていれば、どの時点で問題が起こったのかが把握できることになり、医療側の管理が各段に行いやすくなる。また、患者としても、例えば最初の１月間HbA1cに変化がなくても、３ヶ月、６ヶ月先のHbA1cやＧＡの推移が予測されていれば、現在の治療が合っているのかいないのか、今の治療を継続するとどのような効果が期待できるのかが明確になり、治療の動機付けに大きな効果をもたらすと考えられる。 For patients who have been introduced to new patients due to poor glycemic control, or patients who have poor glycemic control but need surgery, treatment to lower blood glucose immediately is necessary, but as mentioned above, HbA1c was used. In some cases, it takes two to three months to determine the effect.
In addition, even if treatment is started smoothly, exercise therapy, diet therapy, and drug therapy may not be continued after several months. However, if the pattern of future GA or HbA1c transition can be calculated in advance, As a result, it is possible to grasp whether a problem has occurred, and the management on the medical side becomes easier to perform in each stage. Also, as a patient, for example, even if there is no change in HbA1c during the first month, if changes in HbA1c and GA in the third and sixth months are predicted, whether the current treatment is appropriate or not It is clear that what kind of effect can be expected by continuing this treatment, and it will have a great effect on motivation for treatment.
　このように将来の血糖を予測するには、平均血糖、GAやHbA1cの変化を関数で示すと良いが、個々のケースでその変化のスピードが異なることからこれまで良いモデルは確立されていなかった。また、平均血糖、GAやHbA1cの将来の値を簡便に計算する方法を用いて糖尿病の治療効果を測定する方法は知られていない。加えて、平均血糖やGAを用いてHbA1cの将来の値を計算する方法、GAやHbA1cを用いて将来の平均血糖を計算する方法も知られていない。 Thus, to predict future blood glucose, it is good to show changes in average blood glucose, GA and HbA1c as a function, but since the speed of the change differs in individual cases, a good model has not been established so far . In addition, there is no known method for measuring the therapeutic effect of diabetes using a method for simply calculating future values of mean blood glucose, GA and HbA1c. In addition, a method for calculating a future value of HbA1c using average blood glucose and GA, and a method for calculating a future average blood glucose using GA and HbA1c are not known.
　また、将来の血糖を予測することは劇症１型糖尿病の診断にも有用である。劇症１型糖尿病の場合、ある日突然膵臓が機能しなくなり血糖が急激に上昇して１型糖尿病を発症する。その症状は、最初は風邪に似た症状で、血糖が高くHbA1cは正常である。このようなケースにおいて、２型の糖尿病に風邪が合併したものと間違って診断され、糖尿病の経口薬と風邪薬を処方されて帰宅し、翌日死亡したというケースも認められており、昨今、劇症１型糖尿病発症の測定は非常に重要と考えられている。しかし、これまでGAやHbA1cの変化の予測に基づいた劇症１型糖尿病発症の測定方法は知られていなかった。 Predicting future blood glucose is also useful for diagnosing fulminant type 1 diabetes. In the case of fulminant type 1 diabetes, one day, the pancreas suddenly stops functioning and blood sugar rises rapidly, resulting in type 1 diabetes. The symptoms are initially similar to those of a cold, with high blood sugar and normal HbA1c. In such a case, it was mistakenly diagnosed that cold was combined with type 2 diabetes, and it was recognized that he died the next day after being prescribed an oral medicine and a cold medicine for diabetes. Measurement of the onset of type 1 diabetes is considered very important. However, there has been no known method for measuring the onset of fulminant type 1 diabetes based on the prediction of changes in GA and HbA1c.
　本発明は、平均血糖、GA、およびHbA1cの変化を計算することにより、糖尿病治療の効果および劇症１型糖尿病発症を測定することが可能な、血液試料解析方法、血液試料解析装置、およびプログラムを提供することを目的とする。 The present invention relates to a blood sample analysis method, blood sample analysis apparatus, and program capable of measuring the effects of diabetes treatment and the onset of fulminant type 1 diabetes by calculating changes in mean blood glucose, GA, and HbA1c. The purpose is to provide.
　本発明に係る血液試料解析方法は、血液試料中の血糖コントロールマーカーの値が変化する前の基準時点での血液試料中の平均血糖MBG（0）、グリコアルブミン値（GA（0））、ヘモグロビンA1c値（A1c（0））、前記基準時点からｔ1日後の血液試料中の平均血糖（MBG（t1））、グリコアルブミン値（GA（t1））、ヘモグロビンA1c値（A1c（t1））、基準時点から十分時間が経過した後の血液試料中の平均血糖（MBG（∞））、グリコアルブミン値（GA（∞））、及びヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、（GA（t）－GA（∞））／（GA（0）－GA（∞））の対数、（A1c（t）－A1c（∞））／（A1c（0）－A1c（∞））の対数、及び（MBG（t）－MBG（0））／（MBG（0）－MBG（∞））の対数それぞれが前記基準時点からの経過日数tに比例することを利用して、t日目の平均血糖、グリコアルブミン、ヘモグロビンA1c、またはグリコアルブミンとヘモグロビンA1cの比を算出する第２の工程と、を有する。 The blood sample analysis method according to the present invention includes a mean blood glucose MBG (0), glycoalbumin value (GA (0)), hemoglobin in a blood sample at a reference time before the value of a blood glucose control marker in the blood sample changes. A1c value (A1c (0)), mean blood glucose (MBG (t1)), glycoalbumin level (GA (t1)), hemoglobin A1c value (A1c (t1)), standard A first step of obtaining mean blood glucose (MBG (∞)), glycoalbumin value (GA (∞)), and hemoglobin A1c value (A1c (∞)) in a blood sample after sufficient time has elapsed from the time point; , (GA (t) -GA (∞)) / logarithm of (GA (0) -GA (∞)), (A1c (t) -A1c (∞)) / (A1c (0) -A1c (∞)) And the logarithm of (MBG (t) −MBG (0)) / (MBG (0) −MBG (∞)) are proportional to the elapsed time t from the reference time point. And use, with an average blood glucose of t-th day, glycated albumin, and a second step of calculating a ratio of hemoglobin A1c or glycated albumin and hemoglobin A1c,, a.
　本発明によれば、平均血糖、GA、およびHbA1cの変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。さらに、劇症１型糖尿病発症に関する有用な情報を提供することも可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。 According to the present invention, by calculating changes in average blood glucose, GA, and HbA1c, it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Furthermore, it becomes possible to provide useful information regarding the onset of fulminant type 1 diabetes. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
　本発明に係る血液試料解析方法は、治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））を取得する第１の工程と、式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する第２の工程と、を有し、
GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
前記第２の工程では、上記式（１）中のＡを、式（２）を用いて算出し、
Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
t1＜t2であることを特徴とする。
　本発明によれば、グリコアルブミンGAの変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。 The blood sample analysis method according to the present invention includes a glycoalbumin value (GA (0)) of a blood sample collected before the start of treatment, a glycoalbumin value (GA (0) of the blood sample collected t1 days after the start of treatment. t1)), and a first step of obtaining a glycoalbumin value (GA (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and using the formula (1), A second step of calculating a glycoalbumin value (GA (t2)) of a blood sample collected t2 days after the treatment start date,
GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
In the second step, A in the formula (1) is calculated using the formula (2),
A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
It is characterized by t1 <t2.
According to the present invention, by calculating the change in glycoalbumin GA, it is possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information that is effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
　また、前記第２の工程において、前記式（１）中のＡを、式（２）の代わりに式（３）を用いて算出し、
　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、
　前記式（３）中のｋを、式（１４）を用いて算出するようにしてもよい。
　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４） In the second step, A in the formula (1) is calculated using the formula (3) instead of the formula (2),
A = −log 2 × t 2 / (TGA (1/2) × k) (3)
TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. 26 days constant,
You may make it calculate k in said Formula (3) using Formula (14).
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
　本発明に係る血液試料解析方法は、治療開始前に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））を算出する第２の工程と、を有し、
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　前記第２の工程では、上記式（４）中のＢを、式（５）を用いて算出し、
　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
　t1＜t2であることを特徴とする。
　本発明によれば、ヘモグロビンA1c（HbA1c）の変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。 The blood sample analysis method according to the present invention includes a hemoglobin A1c value (A1c (0)) of a blood sample collected before the start of treatment, and a hemoglobin A1c value (A1c ( t1)), and a first step of obtaining a hemoglobin A1c value (A1c (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and using the equation (4), A second step of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date,
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
In the second step, B in the formula (4) is calculated using the formula (5),
B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
It is characterized by t1 <t2.
According to the present invention, by calculating the change in hemoglobin A1c (HbA1c), it is possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information that is effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
　また、前記第２の工程において、前記式（４）中のＡを、式（５）の代わりに式（６）を用いて算出し、
　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８６日の定数であり、前記式（６）中のｋを、式（１５）を用いて算出することを特徴とするようにしてもよい。
　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５） In the second step, A in the formula (4) is calculated using the formula (6) instead of the formula (5),
B = −log2 × t2 / (TA1c (1/2) × k) (6)
TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. The constant is 86 days, and k in the equation (6) may be calculated using the equation (15).
k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
　また、本発明に係る血液試料解析方法は、治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））を算出する第２の工程と、を有し、
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　前記第２の工程では、上記式（４）中のＢを、式（７）を用いて算出し、
　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８６日の定数であり、t1＜t2であることを特徴とする。
　本発明によれば、ヘモグロビンA1c（HbA1c）の変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。 Further, the blood sample analysis method according to the present invention includes a glycoalbumin value (GA (0)) of a blood sample collected before the start of treatment, and a glycoalbumin value (GA (0)) of a blood sample collected after t1 days from the start of treatment ( GA (t1)), glycoalbumin value (GA (∞)) of a blood sample collected when sufficient time has passed since the treatment start date, hemoglobin A1c value (A1c) of the blood sample collected on the treatment start date (0)), and a first step of obtaining a hemoglobin A1c value (A1c (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and using the formula (4), A second step of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date,
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
In the second step, B in the formula (4) is calculated using the formula (7),
B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
TGA (1/2) indicates the period until the blood glucose sample reaches (GA (0) + GA (∞)) / 2 when blood glucose is rapidly reduced. It is a constant for 26 days, and TA1c (1/2) reaches a value (A1c (0) + A1c (∞)) / 2 of the hemoglobin A1c value of the blood sample when treatment for rapidly lowering blood glucose is performed It is a constant of 19 to 86 days indicating the period until and t1 <t2.
According to the present invention, by calculating the change in hemoglobin A1c (HbA1c), it is possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information that is effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
　本発明に係る血液試料解析方法は、治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、前記治療開始前に採取された血液試料の平均血糖（MBG（0））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料の平均血糖（MBG（∞））を取得する第１の工程と、式（８）を用いて、前記治療開始日からt2日後に採取された血液試料の平均血糖（MBG（t2））を算出する第２の工程と、を有し、
　MBG（t2）＝MBG（∞）＋（MBG（0）－MBG（∞））×１０Ｃ　…（８）
　前記第２の工程では、上記式（８）中のＣを、式（９）を用いて算出し、
　Ｃ＝t2／t1×TGA（1/2）／TMBG（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（９）
　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、TMBG（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料の平均血糖が（MBG（0）＋MBG（∞））／２に到達するまでの期間を示す１～６日の定数であり、t1＜t2であることを特徴とする。
　本発明によれば、血液試料の平均血糖MBGの変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。また、本発明によれば、MBGは平均血糖のことであるので、その値を求めるには何度も採血して平均値を求める必要があり煩雑であるが、上述のGAを求める計算式を用いて、MBGを計算することもできる。GAは１回の採血で済むことから、簡便にMBGが計算に基づいて予測され得る。 The blood sample analysis method according to the present invention includes a glycoalbumin value (GA (0)) of a blood sample collected before the start of treatment, a glycoalbumin value (GA (0) of a blood sample collected after t1 days from the start of treatment. t1)), the glycoalbumin level (GA (∞)) of the blood sample collected when sufficient time has passed since the treatment start date, the mean blood glucose (MBG (0)) of the blood sample collected before the treatment start ), And a first step of obtaining an average blood glucose (MBG (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and using the formula (8), the treatment start date A second step of calculating an average blood glucose (MBG (t2)) of a blood sample collected after t2 days from
MBG (t2) = MBG (∞) + (MBG (0) −MBG (∞)) × 10 C (8)
In the second step, C in the formula (8) is calculated using the formula (9),
C = t2 / t1 × TGA (1/2) / TMBG (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (9)
TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant for 26 days, and TMBG (1/2) is the average blood sugar level of the blood sample reaches (MBG (0) + MBG (∞)) / 2 when treatment is performed to rapidly reduce blood sugar. Is a constant of 1 to 6 days indicating the period of time t1 <t2.
According to the present invention, by calculating the change in mean blood glucose MBG of a blood sample, it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information that is effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient. Further, according to the present invention, since MBG is an average blood sugar, it is complicated to obtain the average value by collecting blood many times in order to obtain the value. You can also use it to calculate MBG. Since GA requires only one blood collection, MBG can be easily predicted based on calculations.
　本発明に係る血液試料解析方法は、治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））、前記治療開始前に採取された血液試料の平均血糖（MBG（0））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料の平均血糖（MBG（∞））を取得する第１の工程と、式（８）を用いて、前記治療開始日からt2日後に採取された血液試料の平均血糖（MBG（t2））を算出する第２の工程と、を有し、
　MBG（t2）＝MBG（∞）＋（MBG（0）－MBG（∞））×１０Ｃ　…（８）
　前記第２の工程では、上記式（８）中のＣを、式（１０）を用いて算出し、
　Ｃ＝t2／t1×TA1c（1/2）／TMBG（1/2）×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１０）
　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８６日の定数であり、TMBG（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料の平均血糖が（MBG（0）＋MBG（∞））／２に到達するまでの期間を示す１～６日の定数であり、t1＜t2であることを特徴とする。
　本発明によれば、血液試料の平均血糖MBGの変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。また、本発明によれば、MBGは平均血糖のことであるので、その値を求めるには何度も採血して平均値を求める必要があり煩雑であるが、上述のA1cを求める計算式を用いて、MBGを計算することもできる。HbA1cは１回の採血で済むことから、簡便にMBGが計算に基づいて予測され得る。 The blood sample analysis method according to the present invention includes a hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, and a hemoglobin A1c value (A1c (A1c (0)) of the blood sample collected t1 days after the treatment start date. t1)), hemoglobin A1c value (A1c (∞)) of a blood sample collected when sufficient time has passed since the treatment start date, mean blood glucose (MBG (0)) of the blood sample collected before the treatment start ), And a first step of obtaining an average blood glucose (MBG (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and using the formula (8), the treatment start date A second step of calculating an average blood glucose (MBG (t2)) of a blood sample collected after t2 days from
MBG (t2) = MBG (∞) + (MBG (0) −MBG (∞)) × 10 C (8)
In the second step, C in the formula (8) is calculated using the formula (10),
C = t2 / t1 × TA1c (1/2) / TMBG (1/2) × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (10)
TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant for 86 days, and TMBG (1/2) is the average blood sugar of the blood sample reaches (MBG (0) + MBG (∞)) / 2 when treatment is performed to rapidly reduce blood sugar. Is a constant of 1 to 6 days indicating the period of time, and is characterized by t1 <t2.
According to the present invention, by calculating the change in mean blood glucose MBG of a blood sample, it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information that is effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient. Further, according to the present invention, since MBG is an average blood sugar, it is complicated to obtain an average value by collecting blood many times in order to obtain its value. You can also use it to calculate MBG. Since HbA1c only needs to be collected once, MBG can be easily predicted based on the calculation.
　本発明に係る血液試料解析方法は、治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））が既知である場合、式（２３）を用いてｋ値を決定する第１の工程と、
　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t2）－A1c（∞））／（A1c（0）－A1c（∞）））　…（２３）
　式（２４）、（２５）、（２６）、（２７）を用いて前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））およびグリコアルブミン値（GA（t1））を算出する第２の工程と、を有し、
A1c（t1）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（２４）
Ｂ＝－ｌｏｇ２×t1／（TA1c（1/2）×ｋ）　…（２６）
GA（t1）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（２５）
Ａ＝－ｌｏｇ２×t1／（TGA（1/2）×ｋ）　…（２７）
　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、t1＜t2であることを特徴とする。
 これにより、論文等でデータが公開されている治療法に関し、そのデータからA1c（0）、A1c（t2）およびA1c（∞）を読み取り、A1c（t1）、GA（t1）を予測することにより、初めて行う治療法であってもグリコアルブミンやヘモグロビンA1cを予測して使用することができ、治療方針の決定に有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上に有用情報を提供することができる。 The blood sample analysis method according to the present invention includes a hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, and a hemoglobin A1c value (A1c (A1c (0)) of the blood sample collected t2 days after the treatment start date. t2)), and when the hemoglobin A1c value (A1c (∞)) of a blood sample collected at the time when a sufficient time has elapsed from the treatment start date is known, the k value is determined using Equation (23) A first step;
k = −log2 × t1 / TA1c (1/2) / log ((A1c (t2) −A1c (∞)) / (A1c (0) −A1c (∞))) (23)
Hemoglobin A1c value (A1c (t1)) and glycoalbumin value (GA (t1) of blood samples collected after t1 day from the treatment start date using the formulas (24), (25), (26), (27) )) Calculating the second step,
A1c (t1) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (24)
B = −log2 × t1 / (TA1c (1/2) × k) (26)
GA (t1) = GA (∞) + (GA (0) −GA (∞)) × 10 A (25)
A = −log2 × t1 / (TGA (1/2) × k) (27)
TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant for 84 days, and TGA (1/2) reaches the level of (GA (0) + GA (∞)) / 2 in the blood sample when blood glucose is rapidly reduced. Is a constant of 7 to 26 days indicating the period of time until t1 <t2.
By doing this, by reading A1c (0), A1c (t2) and A1c (∞) from the data, and predicting A1c (t1) and GA (t1) Even for the first treatment, glycoalbumin and hemoglobin A1c can be predicted and used, and it is possible to provide information useful for determining a treatment policy in advance. Thus, useful information can be provided to improve the accuracy of diabetes medical care.
　本発明に係る血液試料解析方法は、治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））、及び投薬量がそれぞれD1、D2、D3の場合の前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値A1c（∞D1）、A1c（∞D2）、A1c（∞D3）が既知である場合、式（２８）を用いて、投薬量がD1である場合のk1、投薬量がD2である場合のk2、投薬量がD3である場合のk3を決定する第１の工程と、
　ｋ＝－ｌｏｇ２×ｔ3／TA1c（1/2）／ｌｏｇ（（A1c（t2）－A1c（∞））／（A1c（0）－A1c（∞）））　…（２８）
　前記治療開始日からt1日後までの投薬量をD1、t1日後からt2日後までの投薬量をD2として治療を実施した場合に、治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞D1）および（GA（∞D2）））、前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞D1）および（A1c（∞D2）））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））を取得する第２の工程と、式（２９）を用いて、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））を算出する第３の工程と、
　A1c（t1）＝A1c（∞1）＋（A1c（0）－A1c（∞1））×１０B　…（２９）
　式（３０）、（３１）を用いてA1c(t2)もしくはGA(t2)を計算する第４の工程を有し、
　A1c（t2）＝A1c（∞2）＋（A1c（t1）－A1c（∞2））×１０B　…（３０）
　GA(t2) ＝GA（∞2）＋（GA（t1）－GA（∞2））×１０B　…（３１）
　前記第３の工程では、上記式（２９）中のＢを式（６）により算出し、
　ただし、Ｂ＝－log２×t2／（TA1c（1/2）×ｋ）　…（６）
　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、前記第４の工程では、上記式（３０）中のＢを式（３２）により、式（３１）中のＢを式（３３）により算出し、
　Ｂ＝－log２×（t2-t1）／（TA1c（1/2）×ｋ×k2/k1）　…（３２）
Ｂ＝－log２×（t2-t1）／（TGA（1/2）×ｋ×k2/k1）　…（３３）
前記式（３２）、（３３）中のｋを、式（３４）を用いて算出し、
ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞1））／（GA（0）－GA（∞1）））　…（３４）
　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であることを特徴とする。
　これにより、投薬量を変化させた場合の血液試料のA1c(t2)もしくはGA(t2)を推定することが可能になり、治療方針の決定や患者のモチベーションアップに有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用な情報を提供することができる。
　また、本発明は薬剤投与量の変更のみならず、運動療法などの治療法の切り替えや、薬剤の切り替えなどにも使用することができ、糖尿病診療の正確性向上はもちろん、患者にとっても有用な情報を提供することができる。 The blood sample analysis method according to the present invention includes a hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, and a hemoglobin A1c value (A1c (A1c (0)) of the blood sample collected t2 days after the treatment start date. t2)), and hemoglobin A1c values A1c (∞D1), A1c (∞D2) of blood samples collected when a sufficient amount of time has elapsed from the treatment start date when the dosage is D1, D2, and D3, respectively. If A1c (∞D3) is known, use equation (28) to determine k1 when the dosage is D1, k2 when the dosage is D2, and k3 when the dosage is D3 A first step of:
k = −log2 × t3 / TA1c (1/2) / log ((A1c (t2) −A1c (∞)) / (A1c (0) −A1c (∞))) (28)
When treatment was performed with D1 as the dosage from day 1 to day 1 after the start of treatment, and D2 as the dosage from day 1 to day 2 after t1, the glycoalbumin value (GA (0 )), Glycoalbumin level (GA (t1)) of a blood sample collected after t1 day from the treatment start date, Glycoalbumin value (GA (GA) of a blood sample collected when sufficient time has elapsed from the treatment start date) (∞D1) and (GA (∞D2))), hemoglobin A1c values (A1c (∞D1) and (A1c (∞D2)) of blood samples collected when sufficient time has passed since the treatment start date) The blood collected after t1 day from the treatment start date using the second step of obtaining the hemoglobin A1c value (A1c (0)) of the blood sample collected at the treatment start date and the formula (29) A third step of calculating a hemoglobin A1c value (A1c (t1)) of the sample;
A1c (t1) = A1c (∞1) + (A1c (0) −A1c (∞1)) × 10 B (29)
A fourth step of calculating A1c (t2) or GA (t2) using equations (30) and (31);
A1c (t2) = A1c (∞2) + (A1c (t1) −A1c (∞2)) × 10 B (30)
GA (t2) = GA (∞2) + (GA (t1) −GA (∞2)) × 10 B (31)
In the third step, B in the formula (29) is calculated by the formula (6),
However, B = −log2 × t2 / (TA1c (1/2) × k) (6)
TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant of 84 days, and in the fourth step, B in the above formula (30) is calculated by formula (32), and B in formula (31) is calculated by formula (33).
B = −log2 × (t2−t1) / (TA1c (1/2) × k × k2 / k1) (32)
B = -log2 * (t2-t1) / (TGA (1/2) * k * k2 / k1) (33)
K in the equations (32) and (33) is calculated using the equation (34),
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞1)) / (GA (0) −GA (∞1))) (34)
TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant for 84 days, and TGA (1/2) reaches the level of (GA (0) + GA (∞)) / 2 in the blood sample when blood glucose is rapidly reduced. It is characterized by being a constant of 7 to 26 days indicating the period until.
This makes it possible to estimate the A1c (t2) or GA (t2) of a blood sample when the dosage is changed, and to provide information that is useful for deciding treatment strategies and increasing patient motivation in advance. Is possible. Thus, not only the accuracy of diabetes medical care can be improved, but also information useful for the patient can be provided.
Further, the present invention can be used not only for changing the drug dosage but also for switching therapy such as exercise therapy, switching drugs, etc., and is useful for patients as well as improving the accuracy of diabetes medical care. Information can be provided.
　また、t2が３ヶ月以上であり、A1c(t2)が5.8%未満の場合に（優）、5.8～6.5%未満の場合に（良）、6.5～7.0%未満の場合に（不十分）、7.0～8.0%未満の場合に（不良）、8.0%以上の場合に（不可）、GA(t2)が17.0%未満の場合に（優）、17.0～20.0%未満の場合に（良）、20.0～21.0%未満の場合に（不十分）、21.0～24.0%未満の場合に（不良）、24.0%以上の場合に（不可）と判定することが望ましい。
　このような判定を用いることにより、糖尿病診療の正確性向上はもちろん、患者にとっても有用な情報を提供することができる。 Also, when t2 is 3 months or more and A1c (t2) is less than 5.8% (excellent), when it is less than 5.8 to 6.5% (good), when it is less than 6.5 to 7.0% (insufficient), If it is 7.0 to less than 8.0% (bad), if it is 8.0% or more (impossible), GA (t2) is less than 17.0% (excellent), 17.0 to less than 20.0% (good), 20.0 It is desirable to judge that it is less than 21.0% (insufficient), 21.0 to less than 24.0% (bad), and 24.0% or more (impossible).
By using such a determination, it is possible not only to improve the accuracy of diabetes medical care but also to provide useful information for patients.
　また、t2が３ヶ月以上、t1が１～５週間であり、A1c(t2)が5.8%未満の場合に（優）、5.8～6.5%未満の場合に（良）、6.5～7.0%未満の場合に（不十分）、7.0～8.0%未満の場合に（不良）、8.0%以上の場合に（不可）、GA(t2)が17.0%未満の場合に（優）、17.0～20.0%未満の場合に（良）、20.0～21.0%未満の場合に（不十分）、21.0～24.0%未満の場合に（不良）、24.0%以上の場合に（不可）と判定し、GA(t1)-GA(0)を用いて治療の効果を判定するようにしてもよい。 Also, when t2 is 3 months or more, t1 is 1 to 5 weeks, and A1c (t2) is less than 5.8% (excellent), when 5.8 to less than 6.5% (good), less than 6.5 to 7.0% (Inadequate), 7.0 to less than 8.0% (Bad), 8.0% or more (Not possible), GA (t2) less than 17.0% (Excellent), 17.0 to less than 20.0% If it is (good), 20.0 to less than 21.0% (insufficient), 21.0 to less than 24.0% (bad), 24.0% or more (impossible), GA (t1) -GA The effect of treatment may be determined using (0).
　また、GA(t1)-GA(0) とA1c(O)を用いて算出したA1c(t2)を示す表、または、A1c(O)ごとに、GA(t1)-GA(0) とA1c(t2)の関係を示したグラフを用いて、治療の効果を判定するようにしてもよい。
本発明に使用しうる表としては、GA(t1)-GA(0) 、A1c(O)、A1c(t2)が表示してあればよく、わかりやすくは、縦、もしくは横の項目にGA(t1)-GA(0) 、A1c(O)が表示してあり、A1c(t2)がGA(t1)-GA(0)とA1c(O)の値に応じて表示されている表が好ましい。なおA1c(t2)の変わりにA1c(t2)-A1c(0)を用いても良い。
本発明に使用しうるグラフとしては、X軸もしくはY軸にGA(t1)-GA(0) 、A1c(t2)をとり、A1c(O)の値ごとにグラフが示され、GA(t1)-GA(0)とA1c(O)が決まればA1c(t2)が読み取れるグラフであれば良い。なおA1c(t2)の変わりにA1c(t2)-A1c(0)を用いても良い。 In addition, a table showing A1c (t2) calculated using GA (t1) -GA (0) and A1c (O), or for each A1c (O), GA (t1) -GA (0) and A1c ( You may make it determine the effect of a treatment using the graph which showed the relationship of t2).
As a table that can be used in the present invention, GA (t1) -GA (0), A1c (O), A1c (t2) need only be displayed.For easy understanding, GA (t A table in which t1) -GA (0) and A1c (O) are displayed and A1c (t2) is displayed according to the values of GA (t1) -GA (0) and A1c (O) is preferable. Note that A1c (t2) -A1c (0) may be used instead of A1c (t2).
As a graph that can be used in the present invention, GA (t1) -GA (0), A1c (t2) is taken on the X-axis or Y-axis, a graph is shown for each value of A1c (O), and GA (t1) -A graph that can read A1c (t2) if GA (0) and A1c (O) are determined. Note that A1c (t2) -A1c (0) may be used instead of A1c (t2).
　また、治療に用いる薬剤がリラグリチドであり、治療開始時の投薬量を0.3mgとし、治療開始２週間後のGA値の変化が2.5%以上の場合、0.3mgにて投薬を継続すると判定し、治療開始２週間後のGA値変化が2.0-2.4%の場合、２週間後に0.6mgに投薬量を増加すると判定し、治療開始２週間後のGA値変化が1.0-1.9%の場合、２週間後に0.6mgに投薬量を増加し、さらにその２週間後に0.9mgに投薬量を増加すると判定し、治療開始２週間後のGA値変化が1.0%未満の場合、他の薬剤への切り替えが必要と判定することが望ましい。
　これにより、治療開始時の投薬量を最低限とし、一定期間後に治療効果を判定した上で、効果が不足している場合には投薬の量を増量することができる。例えば、糖尿病治療薬であるリラグリチドは、最低用量から始めて効果を確認しつつ増量していくが、本発明によれば、初期のGAの変化、すなわちGA(t1)-GA(0)により、投薬量が一定である場合、もしくは順次増量した場合の効果を推定することができる。推定結果に基づき、たとえばA1c(t2)が5.8%未満なら（優）、5.8～6.5%未満なら（良）、6.5～7.0%未満なら（不十分）、7.0～8.0%未満なら（不良）、8.0%以上なら（不可）、また、GA(t2)が17.0%未満なら（優）、17.0～20.0%未満なら（良）、20.0～21.0%未満なら（不十分）、21.0～24.0%未満なら（不良）、24.0%以上なら（不可）と判定することにより、投薬量の目安を作成することができる。 In addition, when the drug used for treatment is liraglycide, the dosage at the start of treatment is 0.3 mg, and the change in GA value after 2 weeks of treatment is 2.5% or more, it is determined that the medication is continued at 0.3 mg, If the GA value change after 2 weeks of treatment is 2.0-2.4%, it will be determined that the dosage will be increased to 0.6 mg after 2 weeks, and if the GA value change after 2 weeks of treatment is 1.0-1.9%, 2 weeks If it is determined that the dosage will be increased to 0.6 mg later and further increased to 0.9 mg two weeks later, and the change in GA level is less than 1.0% 2 weeks after the start of treatment, switching to another drug is necessary. It is desirable to judge.
Thereby, the dosage at the start of treatment is minimized, and after determining the therapeutic effect after a certain period, the dosage can be increased if the effect is insufficient. For example, the therapeutic drug for diabetes, liraglitide, is increased while confirming the effect starting from the lowest dose, but according to the present invention, the initial GA change, i.e., GA (t1) -GA (0) When the amount is constant or when the amount is increased sequentially, the effect can be estimated. Based on the estimated results, for example, if A1c (t2) is less than 5.8% (excellent), 5.8-6.5% (good), 6.5-7.0% (insufficient), 7.0-8.0% (bad), If it is 8.0% or more (impossible), if GA (t2) is less than 17.0% (excellent), if it is less than 17.0-20.0% (good), if less than 20.0-21.0% (insufficient), if less than 21.0-24.0% By determining that it is (bad) or 24.0% or more (impossible), a guideline for the dosage can be created.
　前記GA（∞）は、１１～２０％であることが望ましい。
　また、前記A1c（∞）は、４～７％であることが望ましい。
　また、前記MBG（∞）は、８０～１８０mg/dlであることが望ましい。 The GA (∞) is preferably 11 to 20%.
The A1c (∞) is preferably 4 to 7%.
The MBG (∞) is preferably 80 to 180 mg / dl.
　本発明に係る血液試料解析方法は、糖尿病発症ｔ日後の血液試料のグリコアルブミン値（GA（t））、及び糖尿病発症ｔ日後の血液試料のヘモグロビンA1c値A1c（t）を取得する第１の工程と、GA（t）／A1c（t）を算出する第２の工程と、
　前記GA（t）／A1c（t）が所定の閾値以上の場合には、当該血液試料が劇症１型糖尿病患者由来血液試料であると判定する第３の工程と、を有する。
　本発明によれば、GA、およびHbA1cの値から、劇症１型糖尿病の発症を判定することができる。 The blood sample analysis method according to the present invention is a first method for acquiring a glycoalbumin value (GA (t)) of a blood sample after the onset of diabetes t and a hemoglobin A1c value A1c (t) of the blood sample after the onset of diabetes t. A step, a second step of calculating GA (t) / A1c (t),
A third step of determining that the blood sample is a blood sample derived from a patient with fulminant type 1 diabetes when GA (t) / A1c (t) is greater than or equal to a predetermined threshold value.
According to the present invention, the onset of fulminant type 1 diabetes can be determined from the values of GA and HbA1c.
　本発明に係る血液試料解析方法は、治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する第２の工程と、
　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））を算出する第３の工程と、
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　前記GA（t2）と前記A1c（t2）を用いてGA（t2）／A1c（t2）を算出し、GA（t2）／A1c（t2）が所定の閾値以上の場合には、当該血液試料が劇症１型糖尿病患者由来血液試料であると判定する第４の工程と、を有し、前記第２の工程では、上記式（１）中のＡを、式（２）または式（３）のいずれかを用いて算出し、
　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、前記第３の工程では、上記式（４）中のＢを、式（５）から式（７）のいずれかを用いて算出し、
　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８６日の定数であり、前記式（３）、前記式（６）中のｋは、それぞれ式（１４）、式（１５）を用いて算出し、
　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）
　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５）
　t1＜t2であることを特徴とする。
　本発明によれば、GA、およびHbA1cの値から、劇症１型糖尿病の発症を判定することができる。 The blood sample analysis method according to the present invention comprises a glycoalbumin value (GA (0)) of a blood sample collected on the treatment start date, a glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), the glycoalbumin value (GA (∞)) of the blood sample collected when sufficient time has passed since the treatment start date, and the hemoglobin A1c value (A1c (0) of the blood sample collected on the treatment start date )), Hemoglobin A1c value (A1c (t1)) of a blood sample collected after t1 day from the treatment start date, and hemoglobin A1c value of a blood sample collected when sufficient time has elapsed from the treatment start date ( The first step of obtaining A1c (∞) and the second step of calculating the glycoalbumin value (GA (t2)) of the blood sample collected t2 days after the treatment start date using the formula (1) And the process of
GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
A third step of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date using the formula (4);
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
GA (t2) / A1c (t2) is calculated using GA (t2) and A1c (t2). If GA (t2) / A1c (t2) is greater than or equal to a predetermined threshold, the blood sample is A fourth step of determining that the blood sample is derived from a patient with fulminant type 1 diabetes, and in the second step, A in the above formula (1) is replaced by formula (2) or formula (3) Using one of the
A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
A = −log 2 × t 2 / (TGA (1/2) × k) (3)
TGA (1/2) indicates the period until the blood glucose sample reaches (GA (0) + GA (∞)) / 2 when blood glucose is rapidly reduced. It is a constant for 26 days, and in the third step, B in the above formula (4) is calculated using any one of formula (5) to formula (7),
B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
B = −log2 × t2 / (TA1c (1/2) × k) (6)
B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant for 86 days, and k in the formula (3) and the formula (6) is calculated using the formula (14) and the formula (15), respectively.
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
It is characterized by t1 <t2.
According to the present invention, the onset of fulminant type 1 diabetes can be determined from the values of GA and HbA1c.
　また、前記TGA（∞）が３５～９０％であり、前記TA1c（∞）が１０～３０％であり、ｋが１～３であることが望ましい。 Further, it is desirable that the TGA (∞) is 35 to 90%, the TA1c (∞) is 10 to 30%, and k is 1 to 3.
　また、前記TGA（1/2）を式（１１）を用いて算出するようにしてもよい。
　TGA（1/2）＝－ｌｏｇ２×ｔ／ｌｏｇ（（GA（t）－GA（∞））／（GA（0）－GA（∞）））　…（１１） The TGA (1/2) may be calculated using the equation (11).
TGA (1/2) = − log2 × t / log ((GA (t) −GA (∞)) / (GA (0) −GA (∞))) (11)
　また、前記TA1c（1/2）を式（１２）を用いて算出するようにしてもよい。
　TA1c（1/2）＝－ｌｏｇ２×ｔ／ｌｏｇ（（A1c（t）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１２） The TA1c (1/2) may be calculated using the equation (12).
TA1c (1/2) = − log2 × t / log ((A1c (t) −A1c (∞)) / (A1c (0) −A1c (∞))) (12)
　また、前記TMBG（1/2）を式（１３）を用いて算出するようにしてもよい。
　TMBG（1/2）＝－ｌｏｇ２×ｔ／ｌｏｇ（（MBG（t）－MBG（∞））／（MBG（0）－MBG（∞）））　…（１３） Further, the TMBG (1/2) may be calculated using the equation (13).
TMBG (1/2) = − log2 × t / log ((MBG (t) −MBG (∞)) / (MBG (0) −MBG (∞))) (13)
　また、前記GA（t）／A1c（t）の閾値は3.0～3.5であることが望ましい。
　さらに、前記GA（t）／A1c（t）の閾値は3.2であることが望ましい。 The GA (t) / A1c (t) threshold is preferably 3.0 to 3.5.
Further, the threshold value of GA (t) / A1c (t) is preferably 3.2.
　本発明に係る血液試料解析装置は、治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、及び前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける入力部と、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を記憶する第１の記憶部と、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数（TGA（1/2））、及び血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８６日の定数（TA1c（1/2））を記憶する第２の記憶部と、式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する第１の演算部と、
　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c(t2)）を算出する第２の演算部と、
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　前記GA（t2）及び前記A1c（t2）を出力装置に出力する出力部と、を備え、前記第１の演算部は、上記式（１）中のＡを、式（２）または式（３）のいずれかを用いて算出し、
　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
　前記第２の演算部は、上記式（４）中のＢを、式（５）から式（７）のいずれかを用いて算出し、
　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
　前記第１の演算部及び前記第２の演算部は、それぞれ前記式（３）、前記式（６）中のｋを、式（１４）、式（１５）を用いて算出し、
　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）
　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５）
　t1＜t2であることを特徴とする。 The blood sample analyzer according to the present invention includes a glycoalbumin value (GA (0)) of a blood sample collected on the treatment start date, a glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date An input unit for accepting input, a glycoalbumin value (GA (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and a sample collected when a sufficient time has elapsed from the treatment start date When the first storage unit that stores the hemoglobin A1c value (A1c (∞)) of the blood sample and the treatment for rapidly lowering blood glucose is performed, the glycoalbumin value of the blood sample is (GA (0) + GA ( ∞)) / 2 indicates the period until reaching 7 to 26 days constant (TGA (1/2)), and 19 to 86 days constant indicating the period of time until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 Using the second storage unit that stores (TA1c (1/2)) and formula (1), the glycoalbumin value (GA (t2)) of the blood sample collected t2 days after the treatment start date is calculated. A first computing unit to calculate;
GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
A second arithmetic unit that calculates a hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date using Formula (4);
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
An output unit that outputs the GA (t2) and the A1c (t2) to an output device, wherein the first arithmetic unit represents A in the formula (1) as the formula (2) or the formula (3) )
A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
A = −log 2 × t 2 / (TGA (1/2) × k) (3)
The second calculation unit calculates B in the formula (4) using any one of the formulas (5) to (7),
B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
B = −log2 × t2 / (TA1c (1/2) × k) (6)
B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
The first calculation unit and the second calculation unit calculate k in the formula (3) and the formula (6) using the formula (14) and the formula (15), respectively.
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
It is characterized by t1 <t2.
　本発明によれば、グリコアルブミンGA及びヘモグロビンA1c（HbA1c）の変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。 According to the present invention, by calculating changes in glycoalbumin GA and hemoglobin A1c (HbA1c), it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
　本発明に係る血液試料解析装置は、糖尿病発症後ｔ日後の患者から採取された血液試料のグリコアルブミン値（GA（t））、及び前記血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける入力部と、前記GA（t）と前記A1c(t1)を用いて、GA（t）／A1c(t1)を算出する演算部と、前記演算部で算出されたGA（t）／A1c(t1)が所定の閾値以上であるか否かを判定する判定部と、前記判定部においてGA（t）／A1c(t1)が所定の閾値以上と判定された場合には、当該患者が劇症１型糖尿病を発症しているという判定結果を出力装置に出力する出力部と、を備えたものである。
　本発明によれば、GA、およびHbA1cの値から、劇症１型糖尿病の発症を判定することができる。
　また、前記閾値は3.0～3.5であることが望ましい。 The blood sample analyzer according to the present invention inputs a glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after the onset of diabetes and a hemoglobin A1c value (A1c (t1)) of the blood sample. An input unit that receives GA, a calculation unit that calculates GA (t) / A1c (t1) using GA (t) and A1c (t1), and GA (t) / A1c calculated by the calculation unit a determination unit that determines whether or not (t1) is equal to or greater than a predetermined threshold; and when the determination unit determines that GA (t) / A1c (t1) is equal to or greater than the predetermined threshold, An output unit that outputs to the output device a determination result indicating that type 1 diabetes has developed.
According to the present invention, the onset of fulminant type 1 diabetes can be determined from the values of GA and HbA1c.
The threshold is preferably 3.0 to 3.5.
　本発明に係るプログラムは、コンピュータに、治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、及び前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける機能と、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を記憶する機能と、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数（TGA（1/2））、及び血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８６日の定数（TA1c（1/2））を記憶する機能と、
　式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する機能と、
　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c(t2)）を算出する機能と、
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　前記GA（t2）及び前記A1c（t2）を出力装置に出力する機能と、を実行させるプログラムであって、上記式（１）中のＡは、式（２）または式（３）のいずれかを用いて算出し、
　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
　上記式（４）中のＢは、式（５）から式（７）のいずれかを用いて算出し、
　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
　前記式（３）、前記式（６）中のｋは、それぞれ式（１４）、式（１５）を用いて算出し、
　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）
　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５）
　t1＜t2であることを特徴とする。 The program according to the present invention stores, in a computer, a glycoalbumin value (GA (0)) of a blood sample collected on the treatment start date, a glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date A function that accepts input, a glycoalbumin value (GA (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and a sample collected when a sufficient time has elapsed from the treatment start date The function of memorizing the hemoglobin A1c value (A1c (∞)) of a blood sample and the treatment of reducing blood glucose abruptly, the glycoalbumin value of the blood sample is (GA (0) + GA (∞)) / 2 Indicates the time to reach 7 to 26 days constant (TGA (1/2)), and 19 to 86 days constant indicating the period of time until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 (TA1c (1/2)) memorize function,
A function of calculating a glycoalbumin value (GA (t2)) of a blood sample collected t2 days after the start of treatment using the formula (1);
GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
A function of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected after t2 days from the treatment start date using the formula (4);
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
A function of executing the function of outputting the GA (t2) and the A1c (t2) to an output device, wherein A in the formula (1) is either the formula (2) or the formula (3) Is calculated using
A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
A = −log 2 × t 2 / (TGA (1/2) × k) (3)
B in the formula (4) is calculated using any one of the formulas (5) to (7),
B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
B = −log2 × t2 / (TA1c (1/2) × k) (6)
B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
K in the formula (3) and the formula (6) is calculated using the formula (14) and the formula (15), respectively.
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
It is characterized by t1 <t2.
　本発明によれば、グリコアルブミンGA及びヘモグロビンA1c（HbA1c）の変化を計算することにより、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。このように、糖尿病診療の正確性向上はもちろん、患者にとっても有用情報を提供することができる。 According to the present invention, by calculating changes in glycoalbumin GA and hemoglobin A1c (HbA1c), it becomes possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Thus, not only the accuracy of diabetes medical care is improved, but also useful information can be provided for the patient.
　本発明に係るプログラムは、コンピュータに、糖尿病発症後ｔ日後の患者から採取された血液試料のグリコアルブミン値（GA（t））、及び前記血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける機能と、前記GA（t）と前記A1c(t1)を用いて、GA（t）／A1c(t1)を算出する機能と、前記演算部で算出されたGA（t）／A1c(t1)が所定の閾値以上であるか否かを判定する機能と、前記判定部においてGA（t）／A1c(t1)が所定の閾値以上と判定された場合には、当該患者が劇症１型糖尿病を発症しているという判定結果を出力装置に出力する機能と、を実行させるものである。
　本発明によれば、GA、およびHbA1cの値から、劇症１型糖尿病の発症を判定することができる。 The program according to the present invention inputs, to a computer, a glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after the onset of diabetes and a hemoglobin A1c value (A1c (t1)) of the blood sample. , A function of calculating GA (t) / A1c (t1) using GA (t) and A1c (t1), and GA (t) / A1c (t1 calculated by the arithmetic unit ) Is greater than or equal to a predetermined threshold value, and if the determination unit determines that GA (t) / A1c (t1) is equal to or greater than the predetermined threshold value, the patient is fulminant type 1 And a function of outputting a determination result that diabetes is developed to an output device.
According to the present invention, the onset of fulminant type 1 diabetes can be determined from the values of GA and HbA1c.
　本発明によれば、従来２～３ヶ月を要した糖尿病の治療効果の判定を約２週間で行うことが可能となる。また、治療方針の決定や患者のモチベーションアップにも有効な情報をあらかじめ提供することが可能になる。さらに、劇症１型糖尿病発症に関する有用な情報を提供することも可能になる。 According to the present invention, it is possible to determine the therapeutic effect of diabetes that has conventionally required 2 to 3 months in about 2 weeks. In addition, it is possible to provide in advance information effective for determining a treatment policy and improving patient motivation. Furthermore, it becomes possible to provide useful information regarding the onset of fulminant type 1 diabetes.
本発明の実施例１に基づく実測GAと予測GA平均値の比較図である。It is a comparison figure of measured GA based on Example 1 of this invention, and prediction GA average value. 本発明の実施例１に基づく実測GAと予測GAの比較図である。It is a comparison figure of measurement GA and prediction GA based on Example 1 of the present invention. 本発明の実施例２に基づく実測HbA1cと予測HbA1c平均値の比較図である。It is a comparison figure of measured HbA1c based on Example 2 of the present invention, and predicted HbA1c average value. 本発明の実施例２に基づく実測HbA1cと予測HbA1cの比較図である。It is a comparison figure of actual measurement HbA1c based on Example 2 of this invention, and prediction HbA1c. 本発明の実施例５に基づく治療日数とGA値の関係である。It is the relationship between the treatment days based on Example 5 of this invention, and GA value. 本発明の実施例５に基づく治療日数とHbA1c値の関係である。It is the relationship between the treatment days based on Example 5 of this invention, and a HbA1c value. 本発明の実施例６に基づく予測HbA1cと実測値の関係である。It is the relationship between prediction HbA1c based on Example 6 of this invention, and a measured value. 本発明の実施例１２に基づくGA/HbA1cと糖尿病型の関係である。It is the relationship between GA / HbA1c and diabetes type based on Example 12 of this invention. 本発明の実施例１３に基づくGA/HbA1cを計算例である。It is a calculation example about GA / HbA1c based on Example 13 of this invention. 本発明の実施例１４に基づく予測GA及びHbA1cの計算例である。It is an example of calculation of prediction GA and HbA1c based on Example 14 of the present invention. 本発明の実施例１４に基づく予測GA及びHbA1cの計算例である。It is an example of calculation of prediction GA and HbA1c based on Example 14 of the present invention. 本発明の実施例１４に基づく予測GA及びHbA1cの計算例である。It is an example of calculation of prediction GA and HbA1c based on Example 14 of the present invention. 本発明による、血液試料装置の機能構成を示すブロック図である。It is a block diagram which shows the function structure of the blood sample apparatus by this invention. 本発明の実施例９に基づく予測GA及びHbA1cの計算例である。It is an example of calculation of prediction GA and HbA1c based on Example 9 of the present invention. 本発明の実施例１６に基づく予測GA及びHbA1cの計算例である。It is an example of calculation of prediction GA and HbA1c based on Example 16 of the present invention.
　以下、本発明の実施の形態について図面を参照して説明する。
実施の形態１．
　本実施形態において、血糖値とは、通常の臨床検査で測定される血糖値であればいかなるものを用いても良く、空腹時血糖、随時血糖、食後血糖、１日の最高血糖、平均血糖（Mean Blood Glucose;MBG）等を用いることができるが、好ましくは１日の平均血糖である。平均血糖とは、１日に数回の測定を行った血糖の平均値であり、好ましくは食前、食後の６回と睡眠前の７回の測定の平均を用いても良いし、連続血糖測定装置（CGMS）などを用いて測定した血糖の平均を用いても良い。血糖測定の採血方法は問わないが、フッ化ナトリウムやクエン酸が封入された採血管や血清用採血管が使用でき、また指先の血液などをそのまま電極で測定しても良い。血糖の測定方法は酵素法、HPLC法、電極法など公知の方法を用いて測定することができる。本実施形態において、血液試料解析とは、血液試料に含まれる各種生体分子（例えば、グリコアルブミン、ヘモグロビンＡ１ｃ、平均血糖）測定値に基づき、各種疾病の有無やその程度、疾病治療の効果の有無やその程度等を予測または判定することなどを意味する。このような予測又は判定される対象の疾病として、例えば、糖尿病（劇症１型糖尿病等）が挙げられる。ここで、糖尿病治療とは、薬物による糖尿病治療に限られず、運動や食事による治療も含まれる。糖尿病の薬物療法に用いる薬剤も特に限定されず、例えば、インスリンや経口糖尿病薬（スルホニル尿素薬、速攻型インスリン分泌促進薬、α―グルコシダーゼ阻害薬、ビグアナイド薬、インスリン抵抗性改善薬など）が例示され得る。血液試料解析として、例えば、血液試料に含まれる各種生体分子の含有量を予測する方法、血液試料が劇症１型糖尿病患者由来であるか否かを判定する方法が例示される。 Hereinafter, embodiments of the present invention will be described with reference to the drawings.
Embodiment 1 FIG.
In the present embodiment, the blood glucose level may be any blood glucose level measured in a normal clinical test. Fasting blood glucose, occasional blood glucose, postprandial blood glucose, daily maximum blood glucose, average blood glucose ( Mean Blood Glucose (MBG) or the like can be used, but the daily average blood sugar is preferable. The average blood glucose is the average value of blood glucose measured several times a day, preferably the average of 6 measurements before meal, after meal and 7 before sleep, or continuous blood glucose measurement You may use the average of the blood glucose measured using the apparatus (CGMS) etc. A blood collection method for blood glucose measurement is not limited, but a blood collection tube or a serum blood collection tube in which sodium fluoride or citric acid is enclosed may be used, and blood of a fingertip may be directly measured with an electrode. The blood glucose can be measured using a known method such as an enzymatic method, an HPLC method, or an electrode method. In the present embodiment, blood sample analysis is based on the measured values of various biomolecules (eg, glycoalbumin, hemoglobin A1c, average blood glucose) contained in the blood sample, and the presence or absence of various diseases and the presence or absence of the effect of disease treatment. Or predicting the degree or the like. Examples of such diseases to be predicted or determined include diabetes (fulminant type 1 diabetes and the like). Here, diabetes treatment is not limited to diabetes treatment with drugs, but also includes treatment with exercise and diet. Drugs used for pharmacotherapy for diabetes are not particularly limited, and examples include insulin and oral diabetes drugs (sulfonylurea drugs, rapid-acting insulin secretagogues, α-glucosidase inhibitors, biguanides, insulin resistance improvers, etc.) Can be done. Examples of the blood sample analysis include a method for predicting the content of various biomolecules contained in the blood sample and a method for determining whether or not the blood sample is derived from a patient with fulminant type 1 diabetes.
　本実施形態において、グリコアルブミン（GA）とは、アルブミンに糖が結合した糖化タンパクのことを指し、その測定はいかなる方法を用いても良く、酵素法、免疫法、質量分析法、キャピラリー電気泳動法、ミニカラム法若しくは高速液体クロマトグラフィ法（ＨＰＬＣ法）等を用いることができる。特に、最も良く使用されている酵素法を用いることが好ましい。ＧＡ測定用の試料としては血清、血漿が好ましいが、それ以外の試料が好ましい場合もある。 In the present embodiment, glycoalbumin (GA) refers to a glycated protein in which a saccharide is bound to albumin, and any method may be used for the measurement. Enzymatic method, immunization method, mass spectrometry, capillary electrophoresis Method, mini-column method, high performance liquid chromatography method (HPLC method) or the like can be used. In particular, it is preferable to use the most commonly used enzymatic method. As a sample for GA measurement, serum and plasma are preferable, but other samples may be preferable.
　本実施形態において、ヘモグロビンA1c（HbA1c）とは、ヘモグロビンβ鎖のN末端バリンに糖が結合したヘモグロビンのことを指し、その測定はいかなる方法を用いても良く、酵素法、免疫法、質量分析法、キャピラリー電気泳動法、ミニカラム法若しくはＨＰＬＣ法等を用いることができる。特に、最も良く使用されている免疫法、酵素法、ＨＰＬＣ法を用いることが好ましい。HbA1c測定用の試料としては全血、血球、溶血液が好ましいが、それ以外の試料が好ましい場合もある。 In the present embodiment, hemoglobin A1c (HbA1c) refers to hemoglobin in which sugar is bound to the N-terminal valine of hemoglobin β chain, and any method may be used for the measurement. Enzyme method, immunization method, mass spectrometry Method, capillary electrophoresis, mini-column method, HPLC method or the like can be used. In particular, it is preferable to use the most commonly used immunization method, enzyme method, and HPLC method. As a sample for measuring HbA1c, whole blood, blood cells, and hemolyzed blood are preferable, but other samples may be preferable.
　なお、本発明の表記において、MBG、GA、及びHbA1cの右に付与される（）内の０、t1、t2は、治療開始後あるいは劇症１型糖尿病発症後の日数を示し、治療開始前あるいは劇症１型糖尿病発症前のMBG、GA、及びHbA1cの測定値はそれぞれMBG（0）、GA（0）、A1c（0）、治療開始あるいは劇症１型糖尿病発症からt1日後のMBG、GA、HbA1cの測定値はそれぞれMBG（t1）、GA（t1）、A1c（t1）、同様にt2日後の測定値はMBG（t2）、GA（t2）、A1c（t2）と表記する。 In the notation of the present invention, 0, t1, and t2 in parentheses given to the right of MBG, GA, and HbA1c indicate the number of days after the start of treatment or after the onset of fulminant type 1 diabetes, and before the start of treatment. Alternatively, the measured values of MBG, GA, and HbA1c before the onset of fulminant type 1 diabetes are MBG (0), GA (0), A1c (0), MBG at the start of treatment or after the onset of fulminant type 1 diabetes, The measured values of GA and HbA1c are expressed as MBG (t1), GA (t1), and A1c (t1), respectively, and similarly the measured values after t2 days are expressed as MBG (t2), GA (t2), and A1c (t2).
　MBG（0）、GA(0)、A1c（0）は、糖尿病治療開始からの日数に用いる場合、糖尿病治療前の測定値であればよく、血糖コントロール状態が変わらない限り、治療開始前であれば特に０日目でなくとも良い。なお、劇症１型糖尿病発症からの日数に用いる場合は、0日目は測定値がないことが一般的であるので、正常値を代入することが望ましい。 MBG (0), GA (0), A1c (0) should be measured before diabetes treatment when used for the number of days from the start of diabetes treatment. In particular, it may not be the 0th day. When used for the number of days since the onset of fulminant type 1 diabetes, there is generally no measured value on day 0, so it is desirable to substitute a normal value.
　劇症１型糖尿病の場合に0日目の正常値として代入できるGA（0）は、個人や治療によって異なるが、正常血糖若しくは正常血糖に近い血糖に対応するＧＡを設定すれば良く、例えば13.7～20％、好ましくは14.0～20％、より好ましくは14.5～19.0％である。また、単純に14.0、14.5、15.0、15.5、16.0、16.5もしくは17.0％を用いても良く、年齢や症状を考慮して18.0、18.5、19.0、19.5もしくは20.0％など高めに設定しても良い。 GA (0) that can be substituted as the normal value on day 0 in the case of fulminant type 1 diabetes is different depending on the individual and treatment, but it is sufficient to set GA corresponding to normal blood glucose or blood glucose close to normal blood glucose, for example 13.7 -20%, preferably 14.0-20%, more preferably 14.5-19.0%. Alternatively, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, or 17.0% may be simply used, and may be set higher as 18.0, 18.5, 19.0, 19.5, or 20.0% in consideration of age and symptoms.
　同様に、劇症１型糖尿病における、HbA1c（0）は個人や治療によって異なるが、正常血糖若しくは正常血糖に近い血糖に対応するHbA1cを設定すれば良く、例えば3.0～6.0％、好ましくは4.0～5.8％、より好ましくは4.0～5.5％である。また、単純に正常範囲の上限付近である5.0、5.3、5.5もしくは6.0％を用いても良い。また、年齢や症状を考慮して6.5、7.0もしくは7.5％など高めに設定する場合もある。 Similarly, in fulminant type 1 diabetes, HbA1c (0) varies depending on the individual and treatment, but HbA1c corresponding to normoglycemia or blood glucose close to normoglycemia may be set, for example, 3.0 to 6.0%, preferably 4.0 to It is 5.8%, more preferably 4.0 to 5.5%. Alternatively, 5.0, 5.3, 5.5, or 6.0% that is near the upper limit of the normal range may be used. In addition, considering the age and symptoms, it may be set higher, such as 6.5, 7.0, or 7.5%.
　同様に、劇症１型糖尿病における、平均血糖を低下させる目標値MBG（0）は、個人や治療によって異なるが、正常血糖若しくは正常血糖に近い血糖に対応するMBGを設定すれば良く、例えば80～180mg/dl、好ましくは90～170mg/dl、より好ましくは100～160mg/dlである。また、単純に80、90、100、110、120、130もしくは140mg/dlを用いても良く、年齢や症状を考慮して150、160、170もしくは180mg/dlなど高めに設定しても良い。 Similarly, the target value MBG (0) for lowering the average blood glucose in fulminant type 1 diabetes may vary depending on the individual or treatment, but an MBG corresponding to normal blood glucose or blood glucose close to normal blood glucose may be set. It is ˜180 mg / dl, preferably 90 to 170 mg / dl, more preferably 100 to 160 mg / dl. Moreover, 80, 90, 100, 110, 120, 130 or 140 mg / dl may be simply used, or 150, 160, 170 or 180 mg / dl may be set higher considering the age and symptoms.
　また、本実施形態において、十分時間が経過した後のMBG、GA、HbA1cをそれぞれMBG（∞）、GA（∞）、HbA1c（∞）と表記する。ここで十分時間が経過した後とは、血糖コントロール状態がある状態から次の状態に変化して一定に保たれた場合に、最終的にMBG、GA、及びHbA1cが安定するまでに要する十分な時間が経過した後のことである。十分な時間とはMBGの場合数日、GAの場合１～４週間、HbA1cの場合１～３ヶ月以上の時間とすることができる。また、糖尿病の治療の場合、GA（∞）、A1c（∞）、A1c（∞）には、例えば治療によってMBG、GA、HbA1cを低下させる目標値を用いると良く、一般的には正常値もしくは正常値に近い値を用いるとよい。また、劇症１型糖尿病の場合には、高血糖を放置した場合の異常高値を設定すると良い。 Also, in this embodiment, MBG, GA, and HbA1c after a sufficient time has elapsed are denoted as MBG (∞), GA (∞), and HbA1c (∞), respectively. Here, after a sufficient time has elapsed, when the blood glucose control state is changed from one state to the next state and kept constant, sufficient for the MBG, GA, and HbA1c to finally stabilize It is after time has passed. Sufficient time can be several days for MBG, 1 to 4 weeks for GA, and 1 to 3 months or more for HbA1c. In the case of treatment of diabetes, for GA (∞), A1c (∞), A1c (∞), for example, a target value that decreases MBG, GA, HbA1c by treatment may be used. A value close to the normal value should be used. Further, in the case of fulminant type 1 diabetes, it is preferable to set an abnormally high value when hyperglycemia is left unattended.
　さらに詳しく説明すると、たとえば糖尿病治療の場合、ＧＡを低下させる目標値GA（∞）は個人や治療によって異なるが、血糖若しくは正常血糖に近い血糖に対応するＧＡを設定すれば良い。その意味で劇症１型糖尿病のGA（∞）に近いが、正常値の下限付近の数字でも良く、例えば11～20％、好ましくは12～19％、より好ましくは13～18％であり、最も好ましくは14～17％を選択することができる。また、単純に11.0、12.0、13.0、14.0、15.0、16.0もしくは17.0％の数値を用いても良く、年齢や症状を考慮して18.0、19.0もしくは20.0％など高めに設定しても良い。一方、劇症１型糖尿病の場合の異常高値としてのGA（∞）は例えば30～90％であり、より好ましくは40～90％であり、さらに好ましくは50～90％であり、単純に60、70、80もしくは90％などを設定しても良い。 More specifically, for example, in the case of diabetes treatment, the target value GA (∞) for lowering the GA differs depending on the individual or treatment, but it is sufficient to set a GA corresponding to blood sugar or blood sugar close to normal blood sugar. In that sense, it is close to GA (∞) of fulminant type 1 diabetes, but it may be a number near the lower limit of the normal value, for example, 11 to 20%, preferably 12 to 19%, more preferably 13 to 18%. Most preferably, 14 to 17% can be selected. In addition, a numerical value of 11.0, 12.0, 13.0, 14.0, 15.0, 16.0, or 17.0% may be simply used, or may be set higher as 18.0, 19.0, or 20.0% in consideration of age and symptoms. On the other hand, GA (∞) as an abnormally high value in fulminant type 1 diabetes is, for example, 30 to 90%, more preferably 40 to 90%, still more preferably 50 to 90%, and simply 60 , 70, 80 or 90% may be set.
　また、糖尿病治療の場合のHbA1cを低下させる目標値、HbA1c（∞）は個人や治療によって異なるが、正常血糖若しくは正常血糖に近い血糖に対応するHbA1cを設定すれば良く、例えば4.0～7.0％、好ましくは4.5～6.5％、より好ましくは5.0～6.0％である。また、単純に4.0、4.5、5.0、5.5もしくは6.0％を用いても良く、年齢や症状を考慮して6.5、7.0もしくは7.5％など高めに設定しても良い。一方、劇症１型糖尿病の場合の異常高値としてのA1c（∞）としては例えば10～30％であり、より好ましくは15～30％であり、さらに好ましくは20～30％であり、単純に15、20、25もしくは30％等を設定しても良い。 In addition, the target value for reducing HbA1c in the case of diabetes treatment, HbA1c (∞) varies depending on the individual and treatment, but HbA1c corresponding to normoglycemia or blood glucose close to normoglycemia may be set, for example, 4.0 to 7.0%, Preferably it is 4.5 to 6.5%, more preferably 5.0 to 6.0%. Also, 4.0, 4.5, 5.0, 5.5, or 6.0% may be simply used, and may be set higher such as 6.5, 7.0, or 7.5% in consideration of age and symptoms. On the other hand, A1c (∞) as an abnormally high value in the case of fulminant type 1 diabetes is, for example, 10 to 30%, more preferably 15 to 30%, still more preferably 20 to 30%. You may set 15, 20, 25 or 30%.
　また、糖尿病治療における平均血糖を低下させる目標値、MBG（∞）は個人や治療によって異なるが、正常血糖若しくは正常血糖に近い血糖に対応するMBGを設定すれば良く、例えば80～180mg/dl、好ましくは90～170mg/dl、より好ましくは100～160mg/dlである。また、単純に正常範囲の上限付近である100、110もしくは120mg/dlを用いても良く、年齢や症状を考慮して130、140もしくは150mg/dlなど高めに設定しても良い。一方、劇症１型糖尿病の場合の異常高値としてのMBG（∞）は例えば300～1000mg/dlであり、より好ましくは400～1000mg/dlであり、さらに好ましくは500～1000mg/dlであり、単純に600、700、800、900もしくは1000mg/dlを設定しても良い。 The target value for reducing average blood sugar in diabetes treatment, MBG (∞) varies depending on the individual and treatment, but MBG corresponding to normal blood sugar or blood sugar close to normal blood sugar may be set, for example, 80 to 180 mg / dl, The dosage is preferably 90 to 170 mg / dl, more preferably 100 to 160 mg / dl. Alternatively, 100, 110, or 120 mg / dl, which is near the upper limit of the normal range, may be used, and may be set higher, such as 130, 140, or 150 mg / dl in consideration of age and symptoms. On the other hand, MBG (∞) as an abnormally high value in the case of fulminant type 1 diabetes is, for example, 300 to 1000 mg / dl, more preferably 400 to 1000 mg / dl, still more preferably 500 to 1000 mg / dl, You may simply set 600, 700, 800, 900 or 1000 mg / dl.
　本実施形態において、TMBG（1/2）、TGA（1/2）、THbA1c（1/2）は、血糖を急速に変化させた場合に、MBG、GA、HbA1cがそれぞれ（MBG（0）＋MBG（∞））／２、（GA（0）＋GA（∞））／２及び（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す定数である。TMBG（1/2）、TGA（1/2）、THbA1c（1/2）は、後述する計算式を用いて導き出しても良く、血糖、アルブミン及びヘモグロビンの半減期から推定したおおよその数字を代入しても良い。 In this embodiment, TMBG (1/2), TGA (1/2), and THbA1c (1/2) indicate that MBG, GA, and HbA1c are (MBG (0) + MBG) when blood glucose is changed rapidly. (∞)) / 2, (GA (0) + GA (∞)) / 2, and (A1c (0) + A1c (∞)) / 2 are constants indicating periods until reaching. TMBG (1/2), TGA (1/2), and THbA1c (1/2) may be derived using the formulas described below, and approximate numbers estimated from the half-lives of blood glucose, albumin, and hemoglobin are substituted. You may do it.
　TMBG（1/2）、TGA（1/2）、及びTHbA1c（1/2）に代入できる数字としては、例えば、TMBG（1/2）の場合、糖尿病の治療で急激に血糖を低下させる場合、通常1～6日で血糖が低下することから、1～6日、好ましくは1～5日であり、さらに好ましくは1～4日である。または、単純に1、2、3、4、5もしくは6日等を代入しても良い。劇症１型の場合は急激に血糖が悪化した場合の数字を代入する必要があるが、低下させる場合と同じ数字を用いることが出来る。 For numbers that can be substituted into TMBG (1/2), TGA (1/2), and THbA1c (1/2), for example, in the case of TMBG (1/2), when blood sugar is drastically decreased in the treatment of diabetes Since blood glucose usually decreases in 1 to 6 days, it is 1 to 6 days, preferably 1 to 5 days, and more preferably 1 to 4 days. Alternatively, 1, 2, 3, 4, 5 or 6 days may be simply substituted. In the case of fulminant type 1, it is necessary to substitute the number when blood glucose rapidly deteriorates, but the same number as that used for lowering can be used.
　また、TGA(1/2)の場合はTMBG（1/2）の変化に加えてアルブミンの半減期約1～3週間、つまり約6日～20日を考慮する必要があり、TMBG（1/2）1～6日にこの数字を足し、7～26日を用いることが出来、好ましくは9～24日であり、最も好ましくは11～22日である。単純に11～26日等の整数を代入しても良い。また、TA1c（1/2）の場合は同様にヘモグロビンの半減期を考慮し、19～84日を用いることが出来、好ましくは22～81日であり、最も好ましくは28～77日である。単純に19～84日等の整数を代入しても良い。 In addition, in the case of TGA (1/2), in addition to the change of TMBG (1/2), it is necessary to consider the half-life of albumin about 1 to 3 weeks, that is, about 6 to 20 days. 2) Add this number to days 1-6 and 7-26 days can be used, preferably 9-24 days, most preferably 11-22 days. An integer such as 11 to 26 days may be simply substituted. In the case of TA1c (1/2), in consideration of the half-life of hemoglobin, 19 to 84 days can be used, preferably 22 to 81 days, and most preferably 28 to 77 days. An integer such as 19 to 84 days may be simply substituted.
　本発明は、血糖コンロトール状態が変化した場合に、MBG、GA及びA1cがどのように変化するかを関数で示し、簡便にその計算及び計算に基づく予測ができるようにしたことに特徴がある。その関数とは、血糖コントロール状態変化前、変化後ｔ日及び十分時間が経過した場合の平均血糖、グリコアルブミン及びヘモグロビンA1cの値がそれぞれMBG（0）、MBG（t）、MBG（∞）、GA（0）、GA（t）、GA（∞）、A1c（0）、A1c（t）及びA1c（∞）である場合に、（GA（t）－GA（∞））／（GA（0）－GA（∞））の対数、（A1c（t）－A1c（∞））／（A1c（0）－A1c（∞））の対数若しくは（MBG（t）－MBG（0））／（MBG（0）－MBG（∞））の対数が変化後の経過日数tに対して直線になることを利用して、変化後t日目の平均血糖、グリコアルブミン、ヘモグロビンA1cを計算及び計算に基づく予測することが特徴である。 The present invention is characterized in that MBG, GA, and A1c change as a function when a blood glucose control state changes, and that the calculation and prediction based on the calculation can be easily performed. . The function is the average blood glucose level before the change in glycemic control state, t days after change, and the values of glycoalbumin and hemoglobin A1c are MBG (0), MBG (t), MBG (∞), When GA (0), GA (t), GA (∞), A1c (0), A1c (t), and A1c (∞), (GA (t) −GA (∞)) / (GA (0 ) -GA (∞)), logarithm of (A1c (t) -A1c (∞)) / (A1c (0) -A1c (∞)) or (MBG (t) -MBG (0)) / (MBG Based on the fact that the logarithm of (0) -MBG (∞)) is linear with the elapsed time t after the change, the average blood glucose, glycoalbumin, and hemoglobin A1c on the tth day after the change are calculated and calculated Predicting is a feature.
　さらに詳しく例示すると、例えば、GAの計算式の導出方法を例示すると、（GA（t）－GA（∞））／（GA（0）－GA（∞））の対数が直線を示すことから、直線の傾きをａ、切片をｂとすると、以下の式（１６）が得られる。 To illustrate in more detail, for example, to illustrate a method for deriving a calculation formula for GA, since the logarithm of (GA (t) −GA (∞)) / (GA (0) −GA (∞)) shows a straight line, If the slope of the straight line is a and the intercept is b, the following equation (16) is obtained.
　ｌｏｇ（（GA（t）－GA（∞））／（GA（0）－GA（∞）））＝ａｔ＋ｂ　…（１６）
　ただし、ｌｏｇは常用対数である。
　ここで、治療開始時t＝0においてGAはGA（0）であるから、この式の切片ｂはｂ＝ｌｏｇ（（GA（0）－GA（∞））／（GA（0）－GA（∞）））＝ｌｏｇ１＝０である。よって、式（１６）にｂ＝０を代入すると式（１７）が得られる。
　ａ＝ｌｏｇ（（GA（t）－GA（∞））／（GA（0）－GA（∞）））／t　…（１７） log ((GA (t) −GA (∞)) / (GA (0) −GA (∞))) = at + b (16)
However, log is a common logarithm.
Here, since GA is GA (0) at the start of treatment t = 0, the intercept b of this equation is b = log ((GA (0) −GA (∞)) / (GA (0) −GA ( ∞))) = log1 = 0. Therefore, when b = 0 is substituted into the equation (16), the equation (17) is obtained.
a = log ((GA (t) −GA (∞)) / (GA (0) −GA (∞))) / t (17)
　ここで、血糖を急激に低下させた場合に、GAが（GA（0）＋GA（∞））／２に到達するまでの期間をTGA（1/2）とする。式（１７）にGA(ｔ)＝（GA（0）＋GA（∞））／２、ｔ＝TGA（1/2）を代入すると式（１８）が得られる。
　ｌｏｇ１／２＝ａ×TGA（1/2）　…（１８）
　式（１８）のａに式（１７）を代入すると下記の式（１１）を得る。
　TGA（1/2）=－ｌｏｇ２×ｔ／ｌｏｇ（（GA（t）－GA（∞））／（GA（0）－GA（∞）））　…（１１） Here, let TGA (1/2) be a period until GA reaches (GA (0) + GA (∞)) / 2 when blood sugar is rapidly lowered. Substituting GA (t) = (GA (0) + GA (∞)) / 2 and t = TGA (1/2) into equation (17) yields equation (18).
log1 / 2 = a × TGA (1/2) (18)
Substituting equation (17) into a in equation (18) yields the following equation (11).
TGA (1/2) = − log2 × t / log ((GA (t) −GA (∞)) / (GA (0) −GA (∞))) (11)
　また、GAをA1cおよびMBGに置き換えるとTA1c(1/2)を求める式（１２）、TMBG(1/2)を求める式（１３）となる。
　TA1c（1/2）=－ｌｏｇ２×ｔ／ｌｏｇ（（A1c（t）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１２）
　TMBG（1/2）=－ｌｏｇ２×ｔ／ｌｏｇ（（MBG（t）－MBG（∞））／（MBG（0）－MBG（∞）））　…（１３） When GA is replaced with A1c and MBG, Equation (12) for obtaining TA1c (1/2) and Equation (13) for obtaining TMBG (1/2) are obtained.
TA1c (1/2) = − log2 × t / log ((A1c (t) −A1c (∞)) / (A1c (0) −A1c (∞))) (12)
TMBG (1/2) = − log2 × t / log ((MBG (t) −MBG (∞)) / (MBG (0) −MBG (∞))) (13)
　また、式（１１）をGA（t）に関して解くと
　GA（t）＝GA（∞）＋（GA（0）－GA（∞））×１０A　…（１９）
　A＝－ｌｏｇ２×ｔ／TGA（1/2）　…（２０） Further, when equation (11) is solved with respect to GA (t), GA (t) = GA (∞) + (GA (0) −GA (∞)) × 10 A (19)
A = −log2 × t / TGA (1/2) (20)
　ここで、通常の治療が、血糖を急激に低下させた場合に比してｋ倍遅いとすると、式（２０）を以下の式（２１）の様に記述できる。
　A＝－ｌｏｇ２×ｔ／（TGA（1/2）×ｋ）　…（２１） Here, assuming that normal treatment is k times slower than when blood glucose is drastically lowered, Equation (20) can be described as Equation (21) below.
A = −log 2 × t / (TGA (1/2) × k) (21)
　測定値として、GA（0）およびGA（t1）の２点が揃った場合に、式（２１）よりｋを解くと式（１４）が得られる。
　ｋ＝－ｌｏｇ２×t1／TGA（1/2）／（ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４） As a measured value, when two points of GA (0) and GA (t1) are prepared, equation (14) is obtained by solving k from equation (21).
k = −log2 × t1 / TGA (1/2) / (log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
　ここで、GAをA1cおよびMBGに置き換えるとA1cを用いたｋを求める式（１５）およびMBGを用いたｋを求める式となる。
　ｋ＝－ｌｏｇ２×t1／A1c（1/2）／（ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５） Here, when GA is replaced with A1c and MBG, Equation (15) for obtaining k using A1c and Equation for obtaining k using MBG are obtained.
k = −log2 × t1 / A1c (1/2) / (log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
　また、MBGを用いたｋを求める式は以下の式（２２）である。
　ｋ＝－ｌｏｇ２×t1／MBG（1/2）／（ｌｏｇ（（MBG（t1）－MBG（∞））／（MBG（0）－MBG（∞）））　…２２ The equation for obtaining k using MBG is the following equation (22).
k = −log2 × t1 / MBG (1/2) / (log ((MBG (t1) −MBG (∞)) / (MBG (0) −MBG (∞))) 22
　そこで将来のt2におけるGA値であるGA（t2）は、式１９、２１より以下の式１、３として示すことができる。
　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０A　…（１）
　A＝－ｌｏｇ２×ｔ2／（GA（1/2）×ｋ）　…（３） Therefore, GA (t2), which is the GA value at the future t2, can be expressed as the following formulas 1 and 3 from the formulas 19 and 21.
GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
A = -log2 * t2 / (GA (1/2) * k) (3)
　さらに式３に式１４を代入すると、式（２）が導出される。
　A=ｔ２／ｔ１×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２） Further, when Expression 14 is substituted into Expression 3, Expression (2) is derived.
A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
　よって、本発明におけるGA（t2）を求める計算式としては、GA（0）およびGA（t1）が測定されている場合に、十分時間が経過した場合のGAをGA（∞）とすると、上記の式１と式２を用いて計算することができる。
　また、式１、式３の組み合わせを用いて、TGA（1/2）、ｋを式１１、式１４に実測値を代入することによりあらかじめ求めておいて式３に代入し、次いで式１に式３の計算結果を代入しGA（t2）を求めることもできる。 Therefore, as a calculation formula for obtaining GA (t2) in the present invention, when GA (0) and GA (t1) are measured, and GA when a sufficient time has passed is GA (∞), It can be calculated using Equation 1 and Equation 2.
Also, using the combination of Equations 1 and 3, TGA (1/2), k is obtained in advance by substituting the actually measured values into Equations 11 and 14, and then substituted into Equation 3, and then into Equation 1. GA (t2) can also be obtained by substituting the calculation result of Equation 3.
　また、HbA1cの導出方法も同様であり、GAをA1cと置き換えれば、式４、式５、式６が導出される。
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６） The method for deriving HbA1c is also the same. If GA is replaced with A1c, equations 4, 5 and 6 are derived.
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
B = −log2 × t2 / (TA1c (1/2) × k) (6)
　さらにMBGの導出方法も同様であり、GAをMBGと置き換えれば、以下の式８、式２３、式２４が導出される。
　MBG（t2）＝MBG（∞）＋（MBG（0）－MBG（∞））×１０C　…（８）
　C＝t2／t1×ｌｏｇ（（MBG（t1）－MBG（∞））／（MBG（0）－MBG（∞）））　…（２３）
　C＝－ｌｏｇ２×t2／（TMBG（1/2）×ｋ）　…（２４） Further, the MBG deriving method is the same. If GA is replaced with MBG, the following equations 8, 23 and 24 are derived.
MBG (t2) = MBG (∞) + (MBG (0) −MBG (∞)) × 10 C (8)
C = t2 / t1 × log ((MBG (t1) −MBG (∞)) / (MBG (0) −MBG (∞))) (23)
C = -log2 * t2 / (TMBG (1/2) * k) (24)
　なお、A1c（t2）は式４、式５を用いて計算できるが、式５はHbA1cの関数であり、上述したようにHbA1cは過去２～４週間の血糖を反映することから値が変化するまでに時間がかかり、結果判定が遅くなる。よってGAやMBGを用いて計算するとさらに短期間でA1c（t2）を計算できる。 A1c (t2) can be calculated using Equations 4 and 5. Equation 5 is a function of HbA1c, and as described above, HbA1c changes in value because it reflects blood glucose in the past 2 to 4 weeks. Takes a long time and results are slow to judge. Therefore, A1c (t2) can be calculated in a shorter period of time by calculating using GA or MBG.
　例えば、A1c式４及び式６を以下に示す。
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　Ｂ＝－ｌｏｇ２×ｔ2／（TA1c（1/2）×ｋ）　…（６）
　これらの式を用いてA1c（t2）を計算する場合に、式６のｋをGAを用いた以下に示す式１４で示すことができる。
　ｋ＝－ｌｏｇ２×t1／TGA（1/2）／（ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４） For example, A1c Formula 4 and Formula 6 are shown below.
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
B = -log2 * t2 / (TA1c (1/2) * k) (6)
When A1c (t2) is calculated using these equations, k in Equation 6 can be expressed by the following Equation 14 using GA.
k = −log2 × t1 / TGA (1/2) / (log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
　式１４を式６に代入すると、式７が得られる。
　Ｂ＝t2／t1×TGA（1/2）／A1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞））　…（７） Substituting Equation 14 into Equation 6 yields Equation 7.
B = t2 / t1 × TGA (1/2) / A1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞)) (7)
　同様に、HbA1cの関数をMBGを用いて示しても良い。この場合ｋをMBGを用いて表現すればよく、MBGを用いることによりさらに早く予測することが可能になる。ここで、式６のGAをMBGに置き換えると以下の式２５が得られる。
　B=t2／t1×MBG（1/2）／TA1c（1/2）×ｌｏｇ（（MBG（t1）－MBG（∞））／（MBG（0）－MBG（∞）））　…（２５） Similarly, the function of HbA1c may be indicated using MBG. In this case, k may be expressed using MBG, and by using MBG, it becomes possible to predict it more quickly. Here, when the GA in Expression 6 is replaced with MBG, the following Expression 25 is obtained.
B = t2 / t1 × MBG (1/2) / TA1c (1/2) × log ((MBG (t1) −MBG (∞)) / (MBG (0) −MBG (∞))) (25)
　同様に、GAの関数をMBGを一部用いて示しても良い。この場合ｋをMBGを用いて表現すればよく、MBGを用いることによりさらに早く予測することが可能になる。ここで、式３のGAをMBGに置き換えると以下の式２６が得られる。
　A=t2／t1×MBG（1/2）／TGA（1/2）×ｌｏｇ（（MBG（t1）－MBG（∞））／（MBG（0）－MBG（∞）））　…（２６） Similarly, the GA function may be indicated using part of MBG. In this case, k may be expressed using MBG, and by using MBG, it becomes possible to predict it more quickly. Here, when the GA in Equation 3 is replaced with MBG, the following Equation 26 is obtained.
A = t2 / t1 × MBG (1/2) / TGA (1/2) × log ((MBG (t1) −MBG (∞)) / (MBG (0) −MBG (∞))) (26)
　またMBGは平均血糖のことであるので、その値を求めるには何度も採血して平均値を求める必要があり煩雑であるが、上述のGAやA1cを求める計算式を用いて、MBGを計算することもできる。GAやHbA1cは１回の採血で済むことから、簡便にMBGが求められることになる。つまり、式４のHbA1cをMBGに置き換え、式７のTA1c（1/2）をTMBG（1/2）に置き換え、糖尿病の治療開始前、治療開始後t1日、及び十分時間が経過した場合のグリコアルブミン及びヘモグロビンA1cがそれぞれGA（0）、GA（t1）、GA（∞）、A1c（0）、A1c（t1）及びA1c（∞）であり、治療開始前及び十分時間が経過した場合の平均血糖がそれぞれ、MBG（0）及びMBG（∞）であるとすると、以下の式８及び式９若しくは式１０を用いて治療開始後t2日の平均血糖値MBG（t2）を計算することができる。 MBG is an average blood sugar, so it is complicated to obtain the average value by collecting blood many times, but using the above formulas for calculating GA and A1c, MBG is calculated. It can also be calculated. Since GA and HbA1c need only be collected once, MBG is easily required. In other words, when HbA1c in Formula 4 is replaced with MBG, TA1c (1/2) in Formula 7 is replaced with TMBG (1/2), before treatment for diabetes, t1 days after the start of treatment, and when sufficient time has elapsed Glycoalbumin and hemoglobin A1c are GA (0), GA (t1), GA (∞), A1c (0), A1c (t1), and A1c (∞), respectively, before the start of treatment and when sufficient time has elapsed Assuming that the average blood glucose is MBG (0) and MBG (∞), respectively, the average blood glucose level MBG (t2) on t2 after the start of treatment can be calculated using the following formula 8 and formula 9 or formula 10. it can.
　MBG（t2）＝MBG（∞）＋（MBG（0）－MBG（∞））×１０Ｃ　…（８）
　Ｃ＝t2／t1×TGA（1/2）／TMBG（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）
GA（∞）））　…（９） MBG (t2) = MBG (∞) + (MBG (0) −MBG (∞)) × 10 C (8)
C = t2 / t1 × TGA (1/2) / TMBG (1/2) × log ((GA (t1) −GA (∞)) / (GA (0)
GA (∞))) (9)
　ここで、TGA（1/2）、TA1c（1/2）及びTMBG（1/2）は血糖を急速に変化させた場合に、グリコアルブミン、ヘモグロビンA1c及び平均血糖がそれぞれ（GA（0）＋GA（∞））／２、（A1c（0）＋A1c（∞））／２及び（MBG（0）＋MBG（∞））／２に到達するまでの期間を示す定数である。 Here, when TGA (1/2), TA1c (1/2), and TMBG (1/2) change blood glucose rapidly, glycoalbumin, hemoglobin A1c, and average blood glucose are (GA (0) + GA (∞)) / 2, (A1c (0) + A1c (∞)) / 2, and (MBG (0) + MBG (∞)) / 2 are constants indicating periods until reaching.
　同様に、式９のTGA（1/2）をTA1c（1/2）に、GA（0）、GA（t1）、GA（∞）をA1c（0）、A1c（t1）、A1c（∞）に置き換えれば、以下の式１０に示すHbA1cの関数で示すことができる。
　Ｃ＝t2／t1×TA1c（1/2）／TMBG（1/2）×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１０） Similarly, TGA (1/2) in Equation 9 is TA1c (1/2), GA (0), GA (t1), and GA (∞) are A1c (0), A1c (t1), A1c (∞) Can be expressed by the function of HbA1c shown in the following formula 10.
C = t2 / t1 × TA1c (1/2) / TMBG (1/2) × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (10)
　本発明における劇症１型糖尿病とは、１型糖尿病における劇症型のことであり、数日で膵臓が機能しなくなる、極めて急速に進行する１型糖尿病のことである。劇症１型糖尿病は血糖が急速に悪化し、HbA1cは正常であることが通常であるが、風邪を合併した２型糖尿病と見分けがつきにくい。また、劇症１型糖尿病は急激に血糖が悪化することから、GA/A1cの比率が特徴的な値以上である場合に２型糖尿病と鑑別することができる。GA/A1cの特徴的な値は本発明の式を用いて求めることができる。 The fulminant type 1 diabetes in the present invention is a fulminant type in type 1 diabetes, which is type 1 diabetes that progresses very rapidly, in which the pancreas stops functioning in a few days. In fulminant type 1 diabetes, blood sugar rapidly deteriorates and HbA1c is usually normal, but it is difficult to distinguish from type 2 diabetes combined with a cold. Further, since fulminant type 1 diabetes rapidly deteriorates blood glucose, it can be differentiated from type 2 diabetes when the ratio of GA / A1c is not less than a characteristic value. The characteristic value of GA / A1c can be obtained using the formula of the present invention.
　すなわち、本発明の計算式１、３、４、６、を用いてGA（t）及びA1c（t）を算出し、GA(t)／A1c（t）を求めて特徴的な値を設定すると良い。たとえば、GA（0）、A1c（0）にGA、HbA1cの正常値15.0％、5.0％を代入し、GA（∞）、HbA1c（∞）にGA、HbA1cの完全な異常値である90.0％、30.0％、を代入し、TGA（1/2）、TA1c（1/2）に仮に14日、42日を代入し、ｋ＝1.8、ｔ＝1とすると、
　GA（1）＝90＋（15－90）×10A
　A＝－ｌｏｇ2×1／（14×1.8）＝－0.01195
　GA（1）＝90－75×10－０．０１１９５＝17.04
　A1c（1）＝30＋（5－30）×10B
　B＝－ｌｏｇ2×1／（42×1.8）＝－0.00398
　A1c（1）＝30－25×10－０．００３９８＝5.228
となり、GA(1)／HbA1c（1）＝17.04／5.228＝3.259となる。同様にGA（2）／A1c（2）＝3.49、GA（3）／A1c（3）＝3.68、GA（4）／A1c（4）＝3.87、GA（5）／A1c（5）＝4.03、GA（6）／A1c（6）＝4.17、GA（7）／A1c（7）＝4.29であり、GA（14）／A1c（14）＝4.86、GA（21）／A1c（21）＝5.11、GA（28）／A1c（28）＝5.19、GA（35）／A1c（35）＝5.17であり、例えばGA/HbA1cを3.2以上に設定すれば発症後1日から少なくとも35日間、実際はさらに長期間劇症１型糖尿病を拾い上げることができる。 That is, GA (t) and A1c (t) are calculated using the calculation formulas 1, 3, 4, 6 of the present invention, and GA (t) / A1c (t) is obtained to set characteristic values. good. For example, GA (0) and A1c (0) are assigned normal values 15.0% and 5.0% of GA and HbA1c, and GA (∞) and HbA1c (∞) are GA and HbA1c 90.0% Substituting 30.0%, substituting 14 days and 42 days into TGA (1/2) and TA1c (1/2), and assuming k = 1.8 and t = 1,
GA (1) = 90 + (15-90) × 10 A
A = −log2 × 1 / (14 × 1.8) = − 0.01195
GA (1) = 90−75 × 10 −0.01195 = 17.04
A1c (1) = 30 + (5-30) x 10 B
B = −log2 × 1 / (42 × 1.8) = − 0.00398
A1c (1) = 30-25 x 10 -0.00398 = 5.228
Thus, GA (1) / HbA1c (1) = 17.04 / 5.228 = 2.259. Similarly, GA (2) / A1c (2) = 3.49, GA (3) / A1c (3) = 3.68, GA (4) / A1c (4) = 3.87, GA (5) / A1c (5) = 4.03, GA (6) / A1c (6) = 4.17, GA (7) / A1c (7) = 4.29, GA (14) / A1c (14) = 4.86, GA (21) / A1c (21) = 5.11, GA (28) / A1c (28) = 5.19, GA (35) / A1c (35) = 5.17. For example, if GA / HbA1c is set to 3.2 or higher, it will be at least 35 days from the first day after the onset, actually longer Can pick up fulminant type 1 diabetes.
　また、上記の計算においてGA（0）15.0％の代わりに14.4、15.5、16.0、16.5、17.0％を代入するとGA(1)／HbA1c（1）はそれぞれ3.15、3.35、3.44、3.54、3.63であり、例えばGA/HbA1cを3.2以上に設定すれば、GA（0）は14.4％以上の数字であればいかなる数字を設定しても発症後1日目より劇症１型糖尿病を検出することができる。また、実際発症当日に受診することはなかなかまれであることからｔ＝２、GA（0）15.0％の代わりに、14.0、13.7％を代入すると、GA（2）／A1c（2）はそれぞれ＝3.20、3.15であり、同様に例えばGA/HbA1cを3.2以上に設定すれば、GA（0）は13.7％以上の数字であればいかなる数字を設定しても発症後２日目より劇症１型糖尿病を検出することができる。尚、GAの基準範囲は11～17％であり、また20％以上より糖尿病が強く疑われることから、上限には20％を設定することができる。つまり劇症１型の場合の正常値GA（0）としては13.7～20％の間で設定することができる。尚、GA（0）が大きくなるほどGA／A1cは大きくなることから、17以上の数字を設定することも出来る。 In the above calculation, substituting 14.4, 15.5, 16.0, 16.5, 17.0% for GA (0) 15.0%, GA (1) / HbA1c (1) is 3.15, 3.35, 3.44, 3.54, 3.63, respectively. For example, if GA / HbA1c is set to 3.2 or higher, fulminant type 1 diabetes can be detected from the first day after onset if GA (0) is 14.4% or higher. . In addition, since it is very rare to visit on the day of actual onset, t = 2, GA (0) 15.0% instead of 14.0, 13.7%, GA (2) / A1c (2) = 3.20, 3.15. Similarly, if GA / HbA1c is set to 3.2 or higher, for example, GA (0) is 13.7% or higher. Diabetes can be detected. Note that the standard range of GA is 11 to 17%, and since diabetes is strongly suspected from 20% or more, the upper limit can be set to 20%. In other words, the normal value GA (0) for fulminant type 1 can be set between 13.7 and 20%. Since GA / A1c increases as GA (0) increases, a number of 17 or more can be set.
　また、上記の計算においてA1c（0）5.0％の代わりに4.0～5.1％、を代入するとGA(1)／HbA1c（1）は4.02～3.20であり、例えばGA/HbA1cを3.2以上に設定すれば、A1c（0）は5.1％以下の数字であればいかなる数字を設定しても発症後１日目より劇症１型糖尿病を検出することができる。また、実際発症当日に受診することはなかなかまれであることからｔ＝２、A1c（0）、5.0％の代わりに、5.3～5.5％を代入すると、GA（2）／A1c（2）はそれぞれ＝3.31～3.20であり、同様に例えばGA/HbA1cを3.2以上に設定すれば、A1c（0）は5.5％以下の数字であればいかなる数字を設定しても発症後２日目より劇症１型糖尿病を検出することができる。尚、A1cの基準範囲は4.0～5.8％であり、下限には4.0％を設定することができる。つまり劇症１型の場合の正常値A1c（0）としては4.0～5.5％の間で設定することができる。尚、A1c（0）が小さくなるほどGA／A1cは大きくなることから、4.0％以下の数字を設定することも出来る。 In the above calculation, substituting 4.0 to 5.1% instead of A1c (0) 5.0%, GA (1) / HbA1c (1) is 4.02 to 3.20. For example, if GA / HbA1c is set to 3.2 or higher As long as A1c (0) is a number of 5.1% or less, fulminant type 1 diabetes can be detected from the first day after onset regardless of the number set. In addition, since it is very rare to visit on the day of actual onset, substituting 5.3 to 5.5% instead of t = 2, A1c (0), 5.0%, GA (2) / A1c (2) is respectively = 3.31-3.20. Similarly, if GA / HbA1c is set to 3.2 or higher, for example, A1c (0) is 5.5% or lower. Type diabetes can be detected. The reference range of A1c is 4.0 to 5.8%, and the lower limit can be set to 4.0%. That is, the normal value A1c (0) in the case of fulminant type 1 can be set between 4.0 and 5.5%. Note that GA / A1c increases as A1c (0) decreases, so a value of 4.0% or less can be set.
　また、上記の計算において、例えばGA（∞）90％の代わりに、85～70％を設定すると、ｔ＝１日の場合GA(1)／HbA1c（1）＝3.23～3.15であり、GA/HbA1cを3.2以上に設定すれば発症後１日から劇症１型糖尿病を拾い上げることができる。また、実際発症当日に受診することはなかなかまれであることからｔ＝２、GA（∞）90％の代わりに、60～70％を代入すると、GA（2）／A1c（2）＝3.19～3.29であり同様にGA/HbA1cを3.2以上に設定すれば劇症１型糖尿病を拾い上げることができる。 In the above calculation, for example, if 85-70% is set instead of GA (∞) 90%, GA (1) / HbA1c (1) = 3.23-3.15 when t = 1 day, and GA / If HbA1c is set to 3.2 or higher, fulminant type 1 diabetes can be picked up from 1 day after onset. In addition, since it is very rare to visit on the day of actual onset, t = 2, GA (∞) instead of 90%, substituting 60-70%, GA (2) / A1c (2) = 3.19- Similarly, if GA / HbA1c is set to 3.2 or higher, fulminant type 1 diabetes can be picked up.
　さらにｔ＝２において、A1c（∞）の設定を10%に下げればGA（∞）35～45％とするとGA（2）／A1c（2）＝3.16～3.26であり、35％以上であれば劇症１型糖能病を選択できることになり、実質的にはGA(∞)は35～90％であればいかなる数字を用いても良い。尚、GA（∞）が大きくなるほどGA／A1cは大きくなることから、90％以上の数字を設定することも出来る。 Furthermore, at t = 2, if A1c (∞) is reduced to 10%, GA (∞) is 35-45%, then GA (2) / A1c (2) = 3.16-3.26. Fulminant type 1 glycosylation can be selected, and virtually any number of GA (∞) may be used as long as it is 35 to 90%. Since GA / A1c increases as GA (∞) increases, a value of 90% or more can be set.
　一方、A1c（∞）30％の代わりに、25～10％を設定すると、ｔ＝１日の場合GA(1)／HbA1c（1）＝3.29～3.38であり、GA/HbA1cを3.2以上若しくは3.3以上に設定すれば発症後１日から劇症１型糖尿病を拾い上げることができる。よってA1c（∞）は10％以上であればいかなる数字を用いても良いが、臨床的にHbA1c30％を越えることはないこと、A1c（∞）は数字が低いほどGA（t）／A1c（t）は増加する傾向にあり低く設定しても構わないが、臨床的に未治療で高血糖が持続した場合HbA1c10％を超えることが多いことから、実質的にはA1c（∞）は10～30％が好ましい。 On the other hand, if 25 to 10% is set instead of A1c (∞) 30%, GA (1) / HbA1c (1) = 3.29 to 3.38 when t = 1 day, and GA / HbA1c is 3.2 or higher or 3.3 If it is set as described above, fulminant type 1 diabetes can be picked up from the first day after onset. Therefore, A1c (∞) can be any number as long as it is 10% or more, but clinically it should never exceed HbA1c30%. A1c (∞) is GA (t) / A1c (t ) Tends to increase and may be set low, but if it is clinically untreated and hyperglycemia persists, it often exceeds HbA1c10%, so A1c (∞) is practically 10-30 % Is preferred.
　本発明におけるTGA（1/2）は、前述のように血糖を急速に変化させた場合に、GAが（GA（0）＋GA（∞））／２に到達するまでの期間を示す定数であるが、式１４を用いて導き出しても良く、アルブミンの半減期から推定したおおよその数字を代入しても良い。 TGA (1/2) in the present invention is a constant indicating a period until GA reaches (GA (0) + GA (∞)) / 2 when blood glucose is rapidly changed as described above. However, it may be derived using Equation 14, or an approximate number estimated from the half-life of albumin may be substituted.
　例えばおおよその数字を代入する場合に、アルブミンの半減期が約２週間であることから、7～26日、好ましくは9～24日であり、最も好ましくは11～17日であり、単純に11、12、13、14、15、16、17日等を代入しても良い。例えば、劇症１型糖尿病を検出する場合に、TGA（1/2）に14日の変わりに7か、9、11、12、13、15、16、17、19日を代入すると、それぞれ、GA（1）／A1c（1）＝3.63、3.47、3.36、3.32、3.29、3.32、3.21、3.19、3.16であり、また、実際発症当日に受診することはなかなかまれであることからｔ＝2、TGA（1/2）14日の代わりに、19、21、24、26日を代入すると、GA（2）／A1c（2）はそれぞれ＝3.30、3.24、3.18、3.15であり、同様に例えばGA/HbA1cを3.2以上に設定すれば、TGA（1/2）は7～26日の数字であればいかなる数字を設定しても発症後2日目より劇症１型糖尿病を検出することができる。なお、TGA（1/2）が小さくなるほどGA／A1cは大きくなることから、7日以下の数字を設定することも出来る。 For example, when substituting an approximate number, the half-life of albumin is about 2 weeks, so it is 7 to 26 days, preferably 9 to 24 days, most preferably 11 to 17 days, and simply 11 , 12, 13, 14, 15, 16, 17 etc. may be substituted. For example, when detecting fulminant type 1 diabetes, substituting 7 or 9, 11, 12, 13, 15, 16, 17, 19 for TGA (1/2) instead of 14 days, GA (1) / A1c (1) = 3.63, 3.47, 3.36, 3.32, 3.29, 3.32, 3.21, 3.19, 3.16, and since it is very rare to visit on the day of actual onset, t = 2 Substituting for 19, 21, 24, 26 days instead of TGA (1/2) 14 days, GA (2) / A1c (2) is 3.30, 3.24, 3.18, 3.15, respectively. If / HbA1c is set to 3.2 or higher, TGA (1/2) can detect fulminant type 1 diabetes from the second day after onset regardless of the number of 7-26 days. . Since GA / A1c increases as TGA (1/2) decreases, it is possible to set a number of 7 days or less.
　また本発明におけるTA1c（1/2）は、前述のように血糖を急速に変化させた場合に、HbA1cが（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す定数であるが、式１５を用いて導き出しても良く、アルブミンの半減期から推定したおおよその数字を代入しても良い。 TA1c (1/2) in the present invention is a constant indicating a period until HbA1c reaches (A1c (0) + A1c (∞)) / 2 when blood glucose is rapidly changed as described above. However, it may be derived using Equation 15, or an approximate number estimated from the half-life of albumin may be substituted.
　例えばおおよその数字を代入する場合に、ヘモグロビンの半減期が約2ヶ月であることから、1～3月つまり、4～12週間、若しくは19～84日を用いることが出来、好ましくは5～11週間つまり、25～77日であり、最も好ましくは6～10週間つまり54～70日である。単純に4、5、6、7、8、9、10、11、12週間つまり28、35、42、49、56、63、70、77、84日などを代入しても良い。たとえば、劇症１型糖尿病を検出する場合に、TA1c（1/2）に42日の変わりに23～84日を代入すると、それぞれ、GA（1）／A1c（1）＝3.15～3.33である。 For example, when assigning approximate numbers, the half-life of hemoglobin is about 2 months, so 1 to 3 months, ie 4 to 12 weeks, or 19 to 84 days can be used, preferably 5 to 11 Weeks or 25 to 77 days, most preferably 6 to 10 weeks or 54 to 70 days. Simply 4, 5, 6, 7, 8, 9, 10, 11, 12 weeks, that is, 28, 35, 42, 49, 56, 63, 70, 77, 84 days, etc. may be substituted. For example, when detecting fulminant type 1 diabetes, substituting 23 to 84 days for TA1c (1/2) instead of 42 days results in GA (1) / A1c (1) = 3.15 to 3.33, respectively. .
　また、実際発症当日に受診することはなかなかまれであることからｔ＝２、TA1c（1/2）、４２日の代わりに、19、21、23日を代入すると、GA（2）／A1c（2）はそれぞれ＝3.17、3.22、3.27日であり、同様に例えばGA/HbA1cを3.2以上に設定すれば、TA1c（1/2）は19～84日の数字であればいかなる数字を設定しても発症後２日目より劇症１型糖尿病を検出することができる。加えて、TA1c（1/2）が大きくなるほどGA／A1cは大きくなることから、84日以上の数字を設定することも出来る。 In addition, since it is very rare to see a doctor on the day of actual onset, substituting 19-21 days instead of t = 2, TA1c (1/2), 42 days, GA (2) / A1c ( 2) = 3.17, 3.22, and 3.27 days respectively. Similarly, if GA / HbA1c is set to 3.2 or higher, for example, TA1c (1/2) can be set to any number from 19 to 84 days. Also, fulminant type 1 diabetes can be detected from the second day after onset. In addition, GA / A1c increases as TA1c (1/2) increases, so it is possible to set a number of 84 days or more.
　本発明におけるｋ値は、急激に血糖を変化させた場合と、実際の治療や劇症１型糖尿病における血糖変化のスピードの差を示す定数であり、患者個人、治療の種類によって異なる値をとり、一般には１よりも大きな数字である。尚、劇症１型糖尿病の場合には急激に血糖が上昇し、かつ治療が行われていない場合の診断であるので、ｋ値を容易に設定することができ、これまでに発表のある劇症１型糖尿病患者のｋ値を平均するとほぼ1.8であった。 The k value in the present invention is a constant indicating a difference in blood glucose change speed in a case where blood glucose is suddenly changed and in actual treatment or fulminant type 1 diabetes, and takes a different value depending on the individual patient and the type of treatment. Generally, it is a number larger than 1. In addition, in the case of fulminant type 1 diabetes, since blood glucose increases rapidly and no treatment is performed, the k value can be easily set. The average k value of patients with type 1 diabetes was approximately 1.8.
　例えば、劇症１型糖尿病を検出する場合に、ｋ＝1.8の変わりに0.8～3.0を代入すると、それぞれ、GA（1）／A1c（1）＝3.54～3.16であり、同様に例えばGA/HbA1cを3.2以上に設定すれば、ｋは0.8～3.0の数字であればいかなる数字を設定しても劇症１型糖尿病を検出することができる。また、ｋが小さくなるほどGA（1）／A1c（1）は大きくなることから、0.8以下の数字を設定することも出来る。 For example, when detecting fulminant type 1 diabetes, substituting 0.8 to 3.0 instead of k = 1.8, GA (1) / A1c (1) = 3.54 to 3.16, respectively, for example GA / HbA1c If 3.2 is set to 3.2 or higher, fulminant type 1 diabetes can be detected by setting any number as long as k is a number from 0.8 to 3.0. Moreover, since GA (1) / A1c (1) increases as k decreases, a number of 0.8 or less can be set.
　本発明における劇症１型糖尿病を判別するGA（t）／A1c（t）としては通常2型糖尿病のGA/HbA1cが2.8～3.0程度であり、劇症１型糖尿病はそれ以上の値にあることから、3.0以上の数字であればいかなる数字を用いても良いが、好ましくは3.0～4.0であり、より好ましくは3.0～3.5であり、さらに好ましくは3.1～3.4であり、最も好ましくは3.1～3.3である。また、3.2を用いても良い。 As GA (t) / A1c (t) for distinguishing fulminant type 1 diabetes in the present invention, GA / HbA1c of type 2 diabetes is usually about 2.8 to 3.0, and fulminant type 1 diabetes is higher than that. Therefore, any number may be used as long as it is 3.0 or more, but it is preferably 3.0 to 4.0, more preferably 3.0 to 3.5, still more preferably 3.1 to 3.4, and most preferably 3.1 to 3.3. Also, 3.2 may be used.
　本発明に係る演算装置は、例えば血糖、GA、HbA1cを代入するとGA（t2）、A1c（t2）、MBG（t2）またはGA/A1c等を自動で計算できる電卓のようなものであれば良く、パ－ソナルコンピュター、携帯電話等演算機能を備えた装置であればいかなる装置を用いても良い。また、好ましくはGA（t2）、A1c（t2）、MBG（t2）またはGA/A1c等を計算する専用ボタン等の工夫があると使いやすく、さらに好ましくはグラフや表を用いて分かりやすく表示する機能が搭載され、例えば劇症１型糖尿病の判定結果を表示されても良い。 The arithmetic device according to the present invention may be a calculator that can automatically calculate GA (t2), A1c (t2), MBG (t2), GA / A1c, etc. by substituting blood glucose, GA, and HbA1c, for example. Any device having an arithmetic function such as a personal computer or a mobile phone may be used. Also, it is easy to use if there is a special button for calculating GA (t2), A1c (t2), MBG (t2), GA / A1c, etc. More preferably, it is easy to understand using graphs and tables. A function may be installed, and for example, the determination result of fulminant type 1 diabetes may be displayed.
　加えて、本発明には血糖、GA、A1cの測定値が必要であるが、その測定機能を持った装置で前記の演算ができると好ましい。測定機能を持った装置とは特に限定はされないが、汎用の生化学自動分析装置や卓上で簡便に測定できる装置であり、好ましくは試薬や測定用のチップを挿入するなどするのみで全自動で測定が終了するものが好ましく、より好ましくは１０分程度で測定が終了し、診療前検査に適用できるものである。 In addition, the present invention requires blood glucose, GA, and A1c measurement values, but it is preferable that the above calculation can be performed by a device having the measurement function. Although there is no particular limitation on the device having a measurement function, it is a general-purpose biochemical automatic analyzer or a device that can be easily measured on a desktop, preferably fully automatic simply by inserting a reagent or a measurement chip. The measurement is preferably completed, and more preferably, the measurement is completed in about 10 minutes and can be applied to a pre-clinical examination.
　以下に、本発明の実施例を説明するが、本発明は以下の例によって何ら限定されるものではない。
（実施例１）GA予測値の計算および実測値との比較＜対象＞血糖コントロール不良の糖尿病患者のうち、糖尿病治療の開始あるいは変更した28例（男性19例、女性9例、平均年齢60.7±13.1歳）を対象とし、予測値を計算した。血糖コントロールの改善が不十分で治療の追加をした例や肝疾患・腎疾患・貧血合併例は除外した。これら28名の治療前のGA（0）、HbA1c（0）、血糖を測定し、治療開始後第１回目の診療時にGA（t1）、HbA1c（t1）、血糖を測定し、第２回目の診療時のGA（t2）、HbA1c（t2）を予測した。なおGA（t2）の予測には式１～３を、HbA1c（t2）の予測には式４～７を用い、それぞれの治療は食事療法、運動療法、経口薬およびインスリンが用いられていた。次いで、治療開始後第２回目の診療時にHbA1c、GA、血糖を測定し、予測値と比較した。 Examples of the present invention will be described below, but the present invention is not limited to the following examples.
(Example 1) Calculation of GA predicted value and comparison with actual measurement <Subject> Of diabetic patients with poor glycemic control, 28 patients who started or changed diabetes treatment (19 men, 9 women, average age 60.7 ±) The predicted value was calculated for 13.1 years old. Excluded were cases in which improvement in blood glucose control was insufficient and treatment was added, and cases with liver disease / renal disease / anemia. Before these treatments, GA (0), HbA1c (0) and blood glucose were measured, and GA (t1), HbA1c (t1) and blood glucose were measured at the first medical examination after the start of treatment. GA (t2) and HbA1c (t2) at the time of medical care were predicted. Formulas 1 to 3 were used for prediction of GA (t2), and Formulas 4 to 7 were used for prediction of HbA1c (t2). Dietary therapy, exercise therapy, oral drugs, and insulin were used for each treatment. Next, HbA1c, GA, and blood glucose were measured at the second medical examination after the start of treatment, and compared with predicted values.
　これら28名の治療前の平均のHbA1c＝10.8±2.3%、GA＝33.7±9.4%、GA/HbA1c＝3.11±0.36であり、治療前と第一回の診療までの平均期間 (t1)は19.9±5.4日（14-28日）であり、第１回目と第２回目の間隔の平均期間は26.9±4.9日（16-35日）であった。
＜GA（t2）の計算の詳細および結果＞
　ここで、治療の目標値であるGA（∞）は15%を用いた。GA（0）は治療前の測定値、GA（t1）は治療開始後t1日目の測定値であり、これらを式１，２に代入し予測値であるGA（t2）を求めた。なお、式２は前述のように式３に置き換えることができる。
　ここでTGA（1/2）は、血糖が急激に変化した場合にグリコアルブミンが（GA（0）＋GA（∞））／２に到達するまでの期間を示す定数であり、実施例４に示すように式１１によりあらかじめ算出することができる。ｋは急激に血糖が変化した場合と治療による血糖変化の変化の比率を示す定数であることから、同様に式１４を用いて計算で求めることができる。 The average preoperative HbA1c = 10.8 ± 2.3%, GA = 33.7 ± 9.4%, and GA / HbA1c = 3.11 ± 0.36. It was ± 5.4 days (14-28 days), and the average period between the first and second intervals was 26.9 ± 4.9 days (16-35 days).
<Details and results of GA (t2) calculation>
Here, GA (∞), which is the target value for treatment, was 15%. GA (0) is a measurement value before treatment, and GA (t1) is a measurement value on the t1 day after the start of treatment. Equation 2 can be replaced with Equation 3 as described above.
Here, TGA (1/2) is a constant indicating the period until glycoalbumin reaches (GA (0) + GA (∞)) / 2 when blood glucose changes rapidly. As shown in FIG. Since k is a constant indicating the ratio of the change in blood glucose change due to a sudden change in blood glucose and the treatment, it can be similarly obtained by calculation using Equation 14.
　式１４はTGA（1/2）が求められていれば、GA（0）、GA（t1）の測定値及びGA（∞）を設定することにより容易に計算することができる。
　なお、式３に式１１と式１４を代入すると式２が得られることから、式２と式３どちらを用いても同じ結果が得られる。 If TGA (1/2) is calculated | required, Formula 14 can be easily calculated by setting the measured value of GA (0) and GA (t1), and GA (infinity).
Since Expression 2 is obtained by substituting Expression 11 and Expression 14 into Expression 3, the same result can be obtained by using either Expression 2 or Expression 3.
　図１に、式１を用いて算出したGA(t2)と実測したGAの平均値を示す。また、図２にGAの実測値と式１を用いて算出したGA(t2)との関係を表すグラフを示す。
　図１に示すように演算式を用いて計算したGA(t2)と実測のGAの平均値はそれぞれ18.9％、19.4%、であり、GA（t2）は実測値の約98%であり、きわめて良く一致していることが分かる。 FIG. 1 shows the average value of GA (t2) calculated using Equation 1 and actually measured GA. FIG. 2 is a graph showing the relationship between the measured value of GA and GA (t2) calculated using Equation 1.
As shown in Fig. 1, the average values of GA (t2) and measured GA, which are calculated using an arithmetic expression, are 18.9% and 19.4%, respectively, and GA (t2) is about 98% of the measured value. You can see that they are in good agreement.
　図２は、ｘ軸に実測値GA、Y軸に予測値GA（t2）をとり、個々のデータをグラフにしたものである。図２に示すように、実測値と予測値には予測値＝０．７４×実測値＋４．６２、ｒ＝０．７５、ｐ＜０．０００１の極めて強い相関が認められ、本発明の計算式１～３、１１、１４の有用性、正確性は明らかである。 Fig. 2 is a graph of individual data with the measured value GA on the x-axis and the predicted value GA (t2) on the Y-axis. As shown in FIG. 2, the measured value and the predicted value have a very strong correlation of predicted value = 0.74 × measured value + 4.62, r = 0.75, p <0.0001, and the calculation of the present invention. The usefulness and accuracy of Formulas 1-3, 11, and 14 are clear.
（実施例２）HbA1c予測値と実測値との比較＜対象＞実施例１に同じ
＜A1c（t2）の計算の詳細および結果＞
　実施例２では、治療の目標値であるA1c（∞）は5%を用いた。A1c（0）は治療前の測定値、A1c（t1）は治療開始後t1日目の測定値であり、これらを式４、５に代入して予測値であるA1c（t2）を求めた。尚、式５は前述のように式６に置き換えることができる。 (Example 2) Comparison between HbA1c predicted value and actual value <Target> Same as Example 1 <Details and results of calculation of A1c (t2)>
In Example 2, 5% was used as the target value for treatment A1c (∞). A1c (0) is a measurement value before treatment, and A1c (t1) is a measurement value on the t1 day after the start of treatment. These values are substituted into Equations 4 and 5 to obtain A1c (t2) which is a predicted value. Note that Equation 5 can be replaced with Equation 6 as described above.
　ここでTA1c（1/2）は、血糖が急激に変化した場合にHbA1cが（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す定数であり、実施例４に示すように式１２によりあらかじめ算出することができる。ｋは急激に血糖が変化した場合と治療による血糖変化の比率を示す定数であることから、同様に式１５を用いて計算で求めることができる。 Here, TA1c (1/2) is a constant indicating the period until HbA1c reaches (A1c (0) + A1c (∞)) / 2 when blood glucose changes rapidly. It can be calculated in advance by Equation 12. Since k is a constant indicating the ratio of blood glucose change due to abrupt change and blood glucose change due to treatment, it can be similarly obtained by calculation using Equation 15.
　式１５はTA1c（1/2）が求められていればA1c（0）、A1c（t1）の測定値及びA1c（∞）を設定すれば容易に計算することができる。
　ちなみに、式５に式１２と式１５を代入すると式６が得られることから、式５と式６どちらを用いても同じ結果が得られる。 Equation 15 can be easily calculated by setting the measured values of A1c (0) and A1c (t1) and A1c (∞) if TA1c (1/2) is obtained.
Incidentally, if Expression 12 and Expression 15 are substituted into Expression 5, Expression 6 is obtained. Therefore, the same result can be obtained by using either Expression 5 or Expression 6.
　図３に、式４を用いて算出したA1c（t2）と実測したHbA1cの平均値を示す。また、図４にHbA1cの実測値と式４を用いて算出したA1c（t2）との関係を表すグラフを示す。
　図３に示すように、演算式を用いて計算したA1c(t2)と実測のHbA1cの平均値はそれぞれ8.1%、8.1％であり、きわめて良く一致した。 FIG. 3 shows the average value of A1c (t2) calculated using Equation 4 and the measured HbA1c. FIG. 4 is a graph showing the relationship between the measured value of HbA1c and A1c (t2) calculated using Equation 4.
As shown in FIG. 3, the average values of A1c (t2) calculated using an arithmetic expression and the measured HbA1c were 8.1% and 8.1%, respectively, which were in good agreement.
　図４はｘ軸に実測値、Y軸に予測値A1c（t2）をとり、個々のデータをグラフにしたものである。図４に示すように実測値と予測値には予測値＝０．９５×実測値＋０．３７、ｒ＝０．８４、ｐ＜０．０００１の極めて強い相関が認められ、本発明の計算式４～６、１２、１５の有用性、正確性が明らかである。 Fig. 4 is a graph of individual data with actual values on the x-axis and predicted values A1c (t2) on the Y-axis. As shown in FIG. 4, the measured value and the predicted value have a very strong correlation of predicted value = 0.95 × actual value + 0.37, r = 0.84, p <0.0001, and the calculation formula of the present invention. The usefulness and accuracy of 4-6, 12, 15 are clear.
（実施例３）MBG予測値の計算および実測値との比較
＜対象＞実施例１に同じ
＜MBG（t2）の計算の詳細および結果＞
　実施例４では、治療の目標値であるMBG（∞）は160mg/dlを用いた。MBG（0）は治療前の測定値、MBG（t1）は治療開始後t1日目の測定値であり、これらを式８、２３に代入して予測値であるMBG（t2）を求めた。なお、式２３は前述のように式２４に置き換えることができる。 (Example 3) Calculation of MBG predicted value and comparison with actual measurement <Target> Same as Example 1 <Details and results of calculation of MBG (t2)>
In Example 4, 160 mg / dl was used as MBG (∞), which is the target value for treatment. MBG (0) is a measured value before treatment, and MBG (t1) is a measured value on day t1 after the start of treatment. Equation 23 can be replaced with Equation 24 as described above.
　ここでTMBG（1/2）は、血糖が急激に変化した場合にMBGが（MBG（0）＋MBG（∞））／２に到達するまでの期間を示す定数であり、式１３によりあらかじめ算出することができる。ｋは急激に血糖が変化した場合と治療による血糖変化の比率を示す定数であることから、同様に式２１を用いて計算で求めることができる。 Here, TMBG (1/2) is a constant indicating a period until MBG reaches (MBG (0) + MBG (∞)) / 2 when blood glucose changes rapidly, and is calculated in advance by Equation 13. be able to. Since k is a constant indicating the ratio of blood glucose change due to abrupt change and blood glucose change due to treatment, it can be similarly obtained by calculation using Equation 21.
　式２１はTA1c（1/2）が求められていればMBG（0）、MBG（t1）の測定値及びMBG（∞）を設定することにより、容易に計算することができる。
　なお、式２４に式１３と２１を代入すると式２４が得られることから、式２３と式２４どちらを用いても同じ結果が得られる。実際にMBG（t2）を計算して実測値と比較した結果は演算式を用いて計算したMBG(t2)と実測のMBGの平均値はきわめて良く一致し、本発明の計算式１３、２１～２４の有用性、正確性が明らかであった。 If TA1c (1/2) is obtained, Equation 21 can be easily calculated by setting the measured values of MBG (0) and MBG (t1) and MBG (∞).
Note that, by substituting Equations 13 and 21 into Equation 24, Equation 24 is obtained, so the same result can be obtained using either Equation 23 or Equation 24. The result of actually calculating MBG (t2) and comparing it with the actual measurement value shows that the average value of MBG (t2) calculated using the arithmetic expression and the actual measurement MBG agrees very well. The usefulness and accuracy of 24 were clear.
（実施例４）様々な治療におけるHbA1c及びGAの予測値と実測値の関係
＜対象＞糖尿病の治療を開始した患者
＜方法＞実施例１及び２に同じ
様々な治療を行った場合のHbA1c及びGAの予測値と実測値の関係を表１に示す。
Figure JPOXMLDOC01-appb-T000001
 　表１に示すように、様々な治療においてHbA1c、GAの予測が可能であり本発明の血液試料解析方法が正確にHbA1c及びGAを予測できることが明白であった。 (Example 4) Relationship between predicted values and actual measurement values of HbA1c and GA in various treatments <Subject> Patients who started treatment of diabetes <Method> HbA1c and the results of the same various treatments in Examples 1 and 2 Table 1 shows the relationship between the predicted GA value and the actually measured value.
Figure JPOXMLDOC01-appb-T000001
 As shown in Table 1, it was clear that HbA1c and GA can be predicted in various treatments, and that the blood sample analysis method of the present invention can accurately predict HbA1c and GA.
＜対象＞糖尿病の治療を開始した患者
＜方法＞実施例１及び２に同じ
様々な薬剤（メトホルミン、リラグリチド、エクセナリド、シタグリプチン、アルファＧＩ等）を用いて治療を行った場合のHbA1c及びGAの予測値と実測値の関係を表２に示す。
Figure JPOXMLDOC01-appb-T000002
 　表２に示すように、様々な治療においてHbA1c、GAの予測が可能であり本発明の血液試料解析方法が正確にHbA1c及びGAを予測できることが明白であった。 <Subject> Patients who have started treatment of diabetes <Method> Prediction of HbA1c and GA when treated with the same various drugs as in Examples 1 and 2 (metformin, liraglitide, exenalide, sitagliptin, alpha GI, etc.) Table 2 shows the relationship between values and measured values.
Figure JPOXMLDOC01-appb-T000002
 As shown in Table 2, it was clear that HbA1c and GA can be predicted in various treatments, and that the blood sample analysis method of the present invention can accurately predict HbA1c and GA.
（実施例５）GA（1/2）、HbA1c（1/2）、MBG(1/2)の算出
＜対象＞合併症を有しない血糖コントロール不良の糖尿病患者のうち、入院の上初期治療としてインスリン強化療法を施行した9例（男性8例、女性1例、平均年齢59.4±13.4歳）を対象とし、入院時及び12-22日後にHbA1c、GAを測定した。その後４週間毎に３ヶ月間HbA1c、GAを測定した。
＜A1c（1/2）の計算の詳細および結果＞
　図５は、GAの測定値の推移を治療開始日からの日数に対してプロットした図である。また、図６は、HbA1cの測定値の推移を治療開始日からの日数に対してプロットした図である。また、式１１に、GA（∞）＝15、実測のGA（0）、GA（t）を代入（但しｔは１ヶ月以内）すると、TGA（1/2）＝13.7日が得られた。 (Example 5) Calculation of GA (1/2), HbA1c (1/2), MBG (1/2) <Subject> Among diabetic patients with poor glycemic control without complications, as initial treatment after hospitalization Nine patients (8 males, 1 female, average age 59.4 ± 13.4 years) who underwent insulin-enhanced therapy were targeted, and HbA1c and GA were measured at the time of hospitalization and 12-22 days later. Thereafter, HbA1c and GA were measured every 3 weeks for 3 months.
<Details and results of A1c (1/2) calculation>
FIG. 5 is a graph in which the transition of the measured value of GA is plotted against the number of days from the treatment start date. FIG. 6 is a graph in which the transition of the measured value of HbA1c is plotted against the number of days from the treatment start date. Further, when GA (∞) = 15 and measured GA (0), GA (t) are substituted into Equation 11 (where t is within one month), TGA (1/2) = 13.7 days is obtained.
　式１、式３にTGA(1/2)=13.7、ｋ＝１を代入した曲線を図５中の実線で示す。
　図５に示すように、TGA(1/2)=13.7を代入した実線は実際の測定値に良く一致し、式１、３及び１１の有用性、正確性が明らかであった。 Curves obtained by substituting TGA (1/2) = 13.7 and k = 1 into Equations 1 and 3 are indicated by solid lines in FIG.
As shown in FIG. 5, the solid line into which TGA (1/2) = 13.7 was in good agreement with the actual measurement value, and the usefulness and accuracy of Equations 1, 3 and 11 were clear.
　また、式１２にA1c（∞）＝5を代入し、実測のA1c（0）、A1c（t）を代入（但しｔは２～３ヶ月）すると、TA1c（1/2）＝36.3日が得られた。 Substituting A1c (∞) = 5 into Equation 12 and substituting the measured A1c (0) and A1c (t) (where t is 2 to 3 months), TA1c (1/2) = 36.3 days is obtained. It was.
　式４，６にTA1c(1/2)=36.3、ｋ＝１を代入した曲線を図６中の実線で示す。
　図６に示すように、TA1c（1/2）＝36.3を代入した実線は実際の測定値に良く一致し、式４，６及び１２の有用性、正確性が明らかであった。 A curve obtained by substituting TA1c (1/2) = 36.3 and k = 1 into Equations 4 and 6 is shown by a solid line in FIG.
As shown in FIG. 6, the solid line into which TA1c (1/2) = 36.3 was substituted closely matched the actual measurement value, and the usefulness and accuracy of equations 4, 6 and 12 were clear.
　また、TMBG(1/2)についても同様の群で検討を行った結果、TMBG（1/2）＝3.6日が得られ、式８、２４に代入したプロットは実測と良く一致した。このことから、式８、１３及び２４の有用性、正確性が明らかであった。 Also, as a result of examination of TMBG (1/2) in the same group, TMBG (1/2) = 3.6 days was obtained, and the plots assigned to Equations 8 and 24 agreed well with the actual measurement. From this, the usefulness and accuracy of Formulas 8, 13 and 24 were clear.
　なお、別の同様の群8例（男性6例、女性2例、平均年齢62.3±16.1歳）を対象とし、同様の計算を行ったところ、TGA（1/2）＝14.0日、TA1c(1/2)＝42.0日が得られ、前記の群とほぼ同じ結果となった。 The same calculation was performed on 8 other similar groups (6 males, 2 females, average age 62.3 ± 16.1 years), and TGA (1/2) = 14.0 days, TA1c (1 /2)=42.0 days was obtained, which was almost the same as the above group.
（実施例６）A1c（t2）のGAを用いた演算
＜対象＞　血糖コントロールが悪化した糖尿病患者
＜方法＞　インスリン治療を開始し、GA（0）、A1c（0）、GA（t1）を測定しそれぞれ35.5%、9.9%、25.18%であった。また、A1c（∞）＝5、GA（∞）＝15、GA(1/2)=13.7 、A1c（1/2）＝36.3を用いた。これらの値を用いて、式１、２、４、及び７を用いてA1c（t2）、GA（t2）を計算した。結果を図７に示す。 (Example 6) Calculation using GA of A1c (t2) <Subject> Diabetic patient with impaired glycemic control <Method> Insulin treatment was started and GA (0), A1c (0), and GA (t1) were measured They were 35.5%, 9.9%, and 25.18%, respectively. Further, A1c (∞) = 5, GA (∞) = 15, GA (1/2) = 13.7 and A1c (1/2) = 36.3 were used. Using these values, A1c (t2) and GA (t2) were calculated using Equations 1, 2, 4, and 7. The results are shown in FIG.
　図７に示すように治療前のGA、HbA1cおよび治療後15日目のGAの３点によるGA及びHbA1cの予測値と実測値がほぼ一致しており、式１、２、４及び７を用いてGA、HbA1cの予測が98日目まで正確に行われることが確認された。 As shown in FIG. 7, the predicted values of GA and HbA1c by three points of GA before treatment, HbA1c, and GA on the 15th day after treatment almost coincide with the actual measurement values, and the formulas 1, 2, 4 and 7 are used. As a result, it was confirmed that the GA and HbA1c were accurately predicted until the 98th day.
　このことから、式１，２，４及び７の有用性が明確であり、特に式７はHbA1cが大きく変化する前にGAを用いて将来のHbA1cを正確に推定できることからその有用性は明らかであった。
　同様にHbA1c、GAをMBGで推定する以下の式１、４、２５、２６についても有用であることは明らかであった。
　さらに、MBGをGAやHbA1cを用いて推定する式8-10についての有用性も明らかである。 From this, the usefulness of Equations 1, 2, 4 and 7 is clear. Especially, the usefulness of Equation 7 is clear because it can accurately estimate future HbA1c using GA before HbA1c changes significantly. there were.
Similarly, it is clear that the following formulas 1, 4, 25, and 26 for estimating HbA1c and GA by MBG are also useful.
Furthermore, the usefulness of Equation 8-10 for estimating MBG using GA or HbA1c is also clear.
（実施例７）治療前及びt2日後のHbA1c値を用いて、その間のHbA1c, GA値を推測する例
＜方法＞リラグリチド0.3mg,0.6mg,0.9mg投与例（Seino Y, DRCP, 81: 161-168, 2008）の以下の発表データを用いて計算を行った。
0.3mg 処方の場合、A1c（0）=8.24%、A1c（t2）=7.17%、A1c（∞3）=7.0%
0.6mg 処方の場合、A1c（0）=8.21%、A1c（t2）=6.71%、A1c（∞2）=6.5%
0.9mg 処方の場合、A1c（0）=8.12%、A1c（t2）=6.45%、A1c（∞1）=6.0%
ｋ値は以下の式２３を用いて決定した。
　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t2）－A1c（∞））／（A1c（0）－A1c（∞）））　…（２３）
　計算の結果、0.9mg 処方の場合のｋ1=0.92、0.6mg 処方の場合のｋ2=0.84、0.3mg 処方の場合のｋ3=1.08であった。
次いで、式（２４）、（２５）、（２６）、（２７）を用いて治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））およびグリコアルブミン値（GA（t1））を算出する。
A1c（t1）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（２４）
Ｂ＝－ｌｏｇ２×t1／（TA1c（1/2）×ｋ）　…（２６）
GA（t1）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（２５）
Ａ＝－ｌｏｇ２×t1／（TGA（1/2）×ｋ）　…（２７）
　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数である。
　計算したA1c(t1)、GA(t1)を表３に示す。表３は、治療前及び14週後のHbA1cで、その間のHbA1c, GA値を推測する例であり、リラグリチド0.3mg,o.6mg,0.9mg投与例（Seino Y, DRCP, 81: 161-168, 2008）をベースに試算している。
Figure JPOXMLDOC01-appb-T000003
 　表３に示すように治療前及びt2のHbA1c測定値を用いて、その間のHbA1c, GA値を予測可能であった。 (Example 7) Example of estimating HbA1c and GA values using HbA1c values before and after t2 days <Method> Administration examples of liraglitide 0.3 mg, 0.6 mg and 0.9 mg (Seino Y, DRCP, 81: 161 -168, 2008) was used for the calculation.
In the case of 0.3mg prescription, A1c (0) = 8.24%, A1c (t2) = 7.17%, A1c (∞3) = 7.0%
In the case of 0.6mg prescription, A1c (0) = 8.21%, A1c (t2) = 6.71%, A1c (∞2) = 6.5%
In the case of 0.9mg prescription, A1c (0) = 8.12%, A1c (t2) = 6.45%, A1c (∞1) = 6.0%
The k value was determined using Equation 23 below.
k = −log2 × t1 / TA1c (1/2) / log ((A1c (t2) −A1c (∞)) / (A1c (0) −A1c (∞))) (23)
As a result of the calculation, k1 = 0.92 for the 0.9 mg formulation, k2 = 0.84 for the 0.6 mg formulation, and k3 = 1.08 for the 0.3 mg formulation.
Next, the hemoglobin A1c value (A1c (t1)) and glycoalbumin value (GA (GA) (GA) of the blood sample collected after t1 day from the treatment start date using the formulas (24), (25), (26), (27). t1)) is calculated.
A1c (t1) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (24)
B = −log2 × t1 / (TA1c (1/2) × k) (26)
GA (t1) = GA (∞) + (GA (0) −GA (∞)) × 10 A (25)
A = −log2 × t1 / (TGA (1/2) × k) (27)
TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant for 84 days, and TGA (1/2) reaches the level of (GA (0) + GA (∞)) / 2 in the blood sample when blood glucose is rapidly reduced. It is a constant of 7 to 26 days indicating the period until.
Table 3 shows the calculated A1c (t1) and GA (t1). Table 3 is an example of estimating HbA1c and GA values between HbA1c before and 14 weeks after treatment, and administration examples of liraglitide 0.3 mg, o.6 mg, and 0.9 mg (Seino Y, DRCP, 81: 161-168). , 2008).
Figure JPOXMLDOC01-appb-T000003
 As shown in Table 3, the HbA1c and GA values during the treatment were predictable using the measured values of HbA1c before treatment and t2.
（実施例８）治療薬の投与量を変化させた場合の予測
＜方法＞実施例７同様、リラグリチド0.3mg,0.6mg,0.9mg投与例（Seino Y, DRCP, 81: 161-168, 2008）の発表データを用いて計算を行った。
　投薬量がそれぞれD1、D2、D3で、治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値がそれぞれ、A1c（∞D1）、A1c（∞D2）、A1c（∞D3）で既知であるとき、式２８を用いて、投薬量がD1である場合のk1、投薬量がD2である場合のk2、投薬量がD3である場合のk3を算出する。
　ｋ＝－ｌｏｇ２×ｔ3／TA1c（1/2）／ｌｏｇ（（A1c（t2）－A1c（∞））／（A1c（0）－A1c（∞）））　…（２８）
　実施例７で示したように、A1c（0）A1c（t2）A1c（∞）及びｋ値は以下に示すとおりである。
0.3mg 処方の場合、A1c（0）=8.24%、A1c（t2）=7.17%、A1c（∞3）=7.0%
0.6mg 処方の場合、A1c（0）=8.21%、A1c（t2）=6.71%、A1c（∞2）=6.5%
0.9mg 処方の場合、A1c（0）=8.12%、A1c（t2）=6.45%、A1c（∞1）=6.0%
　ｋ1=0.92、ｋ2=0.84、ｋ3=1.08 (Example 8) Prediction when the dosage of a therapeutic agent is changed <Method> As in Example 7, administration examples of liraglitide 0.3 mg, 0.6 mg and 0.9 mg (Seino Y, DRCP, 81: 161-168, 2008) The calculation was performed using the published data.
The hemoglobin A1c values of the blood samples collected at the time when sufficient time has elapsed from the treatment start date are A1c (∞D1), A1c (∞D2), A1c (∞D3, respectively) ) To calculate k1 when the dosage is D1, k2 when the dosage is D2, and k3 when the dosage is D3.
k = −log2 × t3 / TA1c (1/2) / log ((A1c (t2) −A1c (∞)) / (A1c (0) −A1c (∞))) (28)
As shown in Example 7, A1c (0) A1c (t2) A1c (∞) and k value are as shown below.
In the case of 0.3mg prescription, A1c (0) = 8.24%, A1c (t2) = 7.17%, A1c (∞3) = 7.0%
In the case of 0.6mg prescription, A1c (0) = 8.21%, A1c (t2) = 6.71%, A1c (∞2) = 6.5%
In the case of 0.9mg prescription, A1c (0) = 8.12%, A1c (t2) = 6.45%, A1c (∞1) = 6.0%
k1 = 0.92, k2 = 0.84, k3 = 1.08
　次に、治療開始日からt1日後までの投薬量D1、t1日後からt2日後までの投薬量をD2として治療を実施した場合に、
　治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞D1）および（GA（∞D2）））、治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞D1）および（A1c（∞D2）））、治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））とすると、
　式（２９）を用いて、治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））算出することができる。
　A1c（t1）＝A1c（∞D1）＋（A1c（0）－A1c（∞D1））×１０B　…（２９）
　ただし、Ｂ＝－log２×t2／（TA1c（1/2）×ｋ）　…（６）
　ここで、TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数である。 Next, when the treatment was carried out with the dose D1 from the treatment start date to t1 day later, the dose from t1 day to t2 day later as D2,
Glycoalbumin level (GA (0)) of blood sample collected before the start of treatment, Glycoalbumin level (GA (t1)) of blood sample collected after t1 day from the start date of treatment, sufficient time from the start date of treatment Glycoalbumin levels (GA (∞D1) and (GA (∞D2))) of blood samples collected at the time elapsed, and hemoglobin A1c values of blood samples collected when sufficient time has elapsed from the start of treatment ( A1c (∞D1) and (A1c (∞D2))), the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date,
Using equation (29), the hemoglobin A1c value (A1c (t1)) of a blood sample collected t1 days after the treatment start date can be calculated.
A1c (t1) = A1c (∞D1) + (A1c (0) −A1c (∞D1)) × 10 B (29)
However, B = −log2 × t2 / (TA1c (1/2) × k) (6)
Here, TA1c (1/2) is the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment is performed to rapidly reduce blood sugar. It is a constant of 19 to 84 days shown.
　次いで、式（３０）、（３１）を用いてA1c(t2)もしくはGA(t2)を計算する。
　A1c（t2）＝A1c（∞D2）＋（A1c（t1）－A1c（∞D2））×１０B　…（３０）
　GA(t2) ＝GA（∞D2）＋（GA（t1）－GA（∞D2））×１０B　…（３１）
　式（３０）中のＢは式（３２）を用いて、式（３１）中のＢは式（３３）を用いて算出する。
　Ｂ＝－log２×（t2-t1）／（TA1c（1/2）×ｋ×k2/k1）　…（３２）
Ｂ＝－log２×（t2-t1）／（TGA（1/2）×ｋ×k2/k1）　…（３３）
式（３２）、（３３）中のｋは、式（３４）を用いて算出する。
ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞D1））／（GA（0）－GA（∞D1）））　…（３４）
　ここで、TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数である。 Next, A1c (t2) or GA (t2) is calculated using equations (30) and (31).
A1c (t2) = A1c (∞D2) + (A1c (t1) −A1c (∞D2)) × 10 B (30)
GA (t2) = GA (∞D2) + (GA (t1) −GA (∞D2)) × 10 B (31)
B in formula (30) is calculated using formula (32), and B in formula (31) is calculated using formula (33).
B = −log2 × (t2−t1) / (TA1c (1/2) × k × k2 / k1) (32)
B = -log2 * (t2-t1) / (TGA (1/2) * k * k2 / k1) (33)
K in the equations (32) and (33) is calculated using the equation (34).
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞D1)) / (GA (0) −GA (∞D1))) (34)
Here, TA1c (1/2) is the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment is performed to rapidly reduce blood sugar. The TGA (1/2) is a constant of 19 to 84 days shown, and when a treatment for rapidly lowering blood glucose is performed, the glycoalbumin value of the blood sample is (GA (0) + GA (∞)) / 2. It is a constant of 7 to 26 days indicating the period until reaching.
　表４は治療開始日から２週間後のGA値を用いて、治療開始から６週間後、１０週間後、１４週間後のHbA1c値及びGA値を計算した結果を示している。それぞれの表は、治療開始から２週間目までのリラグリチド投与量を0.3mgとし、２週間目以降の投与量は0.3mg、0.6mg、0.9mgとした場合の計算結果を示している。
Figure JPOXMLDOC01-appb-T000004
 　表４に示すように、治療薬の投与量を変化させた場合でも予測は可能であった。このことにより、本発明は、投薬量の調整のみならず、治療法の変更、たとえば運動療法から食事療法への変更、運動療法や食事療法の強化、薬剤の変更などの様々な治療の変更に有用であることが明らかとなった。 Table 4 shows the results of calculating the HbA1c value and GA value after 6 weeks, 10 weeks and 14 weeks from the start of treatment using the GA values after 2 weeks from the treatment start date. Each table shows the calculation results when the dose of liraglitide from the start of treatment to the second week is 0.3 mg, and the dose after the second week is 0.3 mg, 0.6 mg, and 0.9 mg.
Figure JPOXMLDOC01-appb-T000004
 As shown in Table 4, prediction was possible even when the dose of the therapeutic agent was changed. This allows the present invention not only to adjust the dosage, but also to change the treatment, such as changing from exercise to diet, strengthening exercise or diet, changing medication, etc. It became clear that it was useful.
　また、計算したGAやHbA1cの値は日本糖尿病学会編の糖尿病治療ガイドを参考にして評価し、薬剤の増量や治療の変更を行うことができる。例えば、HbA1c値で判断する場合は、治療開始後HbA1c値が変化し、その変化がなくなる１月以上(t2>1月)、好ましくは２月以上(t2>2月)、さらに好ましくは３ヶ月(t2>3月)以上一定の治療を行った場合、A1c(t2)が5.8%未満（優）、5.8～6.5%未満（良）、6.5～7.0%未満（不十分）、7.0～8.0%未満（不良）、8.0%以上（不可）と判断することができる。 Also, the calculated GA and HbA1c values can be evaluated with reference to the diabetes treatment guide edited by the Japan Diabetes Society, and the dose of the drug can be increased or the treatment can be changed. For example, when judging by the HbA1c value, the HbA1c value changes after the start of treatment, and the change disappears for 1 month or more (t2> 1 month), preferably 2 months or more (t2> 2 months), more preferably 3 months (t2> March) A1c (t2) less than 5.8% (excellent), less than 5.8-6.5% (good), less than 6.5-7.0% (insufficient), 7.0-8.0% Less than (bad), 8.0% or more (impossible).
　GA値で判断する場合は、治療開始後GA値が変化し、その変化がなくなる２週間以上(t2>2週間)、好ましくは１以上(t2>１月)、さらに好ましくは２ヶ月(t2>２月)以上一定の治療を行った場合、GA(t2)が17.0%未満（優）、17.0～20.0%未満（良）、20.0～21.0%未満（不十分）、21.0～24.0未満%（不良）、24.0%以上（不可）と判定することができる。ここでHbA1cの値は日本糖尿病学会の標準化プログラムに則って決定されたJDS(日本糖尿病学会)の値であるが、国際的には異なる基準であるNGSP値やIFCC値が用いられる。なお、NGSP値はJDS値-0.4%で計算される。
　GA値についても将来標準化法が決定された場合に、現在の値と新しい方法の値の相関を求め、その関係を用いて値を換算し、その換算値に基づき判定すればよい。 When judging by the GA value, the GA value changes after the start of treatment, and the change disappears for 2 weeks or more (t2> 2 weeks), preferably 1 or more (t2> 1 month), more preferably 2 months (t2>) (Feb) GA (t2) less than 17.0% (excellent), 17.0-20.0% (good), 20.0-21.0% (insufficient), 21.0-24.0% ), 24.0% or more (impossible). Here, the value of HbA1c is a value of JDS (Japan Diabetes Society) determined in accordance with the standardization program of the Japan Diabetes Society, but NGSP values and IFCC values that are different internationally are used. The NGSP value is calculated with a JDS value of -0.4%.
When a standardization method is determined for the GA value in the future, the correlation between the current value and the value of the new method is obtained, the value is converted using the relationship, and the determination is made based on the converted value.
（実施例９）
　治療開始初期のGA値変化を用いた将来のHbA1c値の予測
　本発明による方法を用いて計算やプログラムの実行などを行う際、予め様々なケースに応じて一覧表やグラフ（ノモグラムを含む）を作成しておけば簡便である。具体的には治療開始時のHbA1cの変化、GAの変化より、数ヶ月先に血糖指標が変化して安定した値になった時点でのHbA1c、GAを予測することができればよい。以下にその例を示す。
＜方法＞
　治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））および治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を用い、治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））を仮に設定し、
式（４）を用いて、治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））を算出する。
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
　式（４）中のＢは、式（７）を用いて算出する。
　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
　ここで、TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数である。また、t1＜t2である。
　表５は、GA(t1)－GA(0)（ΔGA2w）、A1c(0)（治療開始時のA1c値）を代入してA1c(t2)を計算した結果を示す表である。なお、表５に示す例では、t1は２週間であり、t2は１４週間である。
Figure JPOXMLDOC01-appb-T000005
 　表５を用いることにより、診療現場等において、計算機等を用いて簡便に将来のA1c値を推定することができる。 Example 9
Prediction of future HbA1c value using GA value change at the beginning of treatment When performing calculation or program execution using the method according to the present invention, lists and graphs (including nomograms) according to various cases in advance It is convenient if created. Specifically, it is only necessary to be able to predict HbA1c and GA when the blood glucose index changes to a stable value several months ahead of changes in HbA1c and GA at the start of treatment. An example is shown below.
<Method>
Glycoalbumin levels (GA (∞)) of blood samples collected when sufficient time has passed since the start of treatment and hemoglobin A1c values (A1c (A1c () of blood samples collected when sufficient time has elapsed since the start of treatment) ∞)), blood serum sample collected before the start of treatment (GA (0)), blood sample collected after t1 day from the start of treatment (GA (t1)), treatment Temporarily set the hemoglobin A1c value (A1c (0)) of the blood sample collected on the start day,
Using equation (4), the hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date is calculated.
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
B in formula (4) is calculated using formula (7).
B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
Here, TGA (1/2) is the period until the glycoalbumin value of the blood sample reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. The constant of 7 to 26 days shown, TA1c (1/2) indicates that the hemoglobin A1c value of the blood sample is (A1c (0) + A1c (∞)) / 2 when treatment for rapidly reducing blood glucose is performed. It is a constant of 19 to 84 days indicating the period until reaching. Further, t1 <t2.
Table 5 is a table showing the results of calculating A1c (t2) by substituting GA (t1) −GA (0) (ΔGA2w) and A1c (0) (A1c value at the start of treatment). In the example shown in Table 5, t1 is 2 weeks and t2 is 14 weeks.
Figure JPOXMLDOC01-appb-T000005
 By using Table 5, the future A1c value can be easily estimated using a computer or the like at a clinical site or the like.
　また、図１４は、表５に示す各々のA1c(0)について、GA(t1)-GA(0) とA1c(t2)の関係を示したグラフであるが、表の代わりにこのようなグラフを用いても良い。 FIG. 14 is a graph showing the relationship between GA (t1) -GA (0) and A1c (t2) for each A1c (0) shown in Table 5, but such a graph is used instead of the table. May be used.
　なお、表５はGA(t1)－GA(0)、A1c(0)を代入してA1c(t2)を計算した結果を表しているが、GA(t1)－GA(0)とGA(0)を代入してGA(t2)を算出した表を利用しても良いし、A1c(t1)－A1c(0)、A1c(0)を代入してA1c(t2)を算出した表や、MGB(t1)－MBG(0)、A1c(0)を代入してA1c(t2)を算出した表を用いても良い。グラフについても同様である。 Table 5 shows the result of calculating A1c (t2) by substituting GA (t1) −GA (0) and A1c (0). GA (t1) −GA (0) and GA (0 ) Can be used to calculate GA (t2), or A1c (t1) -A1c (0), A1c (0) can be used to calculate A1c (t2) A table obtained by substituting (t1) −MBG (0) and A1c (0) to calculate A1c (t2) may be used. The same applies to the graph.
（実施例１０）本発明を用いた糖尿病治療薬リラグリチドの処方例
＜方法＞実施例７～９に示されるグラフ及び実際にリラグリチドを使用した論文の結果を用いて初期のGA値変化より薬剤処方量を決定する。
　リラグリチドの投与は最低用量の0.3mgから開始され、治療効果に基づいて順次増量が行われる。図１４に示すように、初期の２週間のGA値変化が2.5％である場合、HbA1cの初期値が約8.0％であれば、１４週間後のHbA1c値は約6.5％（糖尿病治療ガイドの判定では良）になると推定され、十分な血糖低下の効果が推定される。また、HbA1c8.0％以上であっても順調にHbA1c値が低下していることから、初期の２週間のGA値変化が2.5%以上の場合には、リラグリチドの投与量を0.3mgで継続すると良く、GA値変化が2.5%未満の場合には0.6mgへの増量を検討すると良い。 (Example 10) Prescription example of anti-diabetic drug liraglitide using the present invention <Method> Using the graphs shown in Examples 7 to 9 and the results of papers actually using liraglycide, the drug prescription from the initial GA value change Determine the amount.
Administration of liraglitide begins with a minimum dose of 0.3 mg and is incrementally increased based on therapeutic effects. As shown in FIG. 14, when the change in GA value in the initial two weeks is 2.5%, if the initial value of HbA1c is about 8.0%, the HbA1c value after 14 weeks is about 6.5% (determination of the diabetes treatment guide It is estimated that the blood glucose level is good), and a sufficient blood glucose lowering effect is estimated. In addition, even if HbA1c is 8.0% or higher, the HbA1c value is steadily decreasing. Therefore, if the change in GA value in the initial two weeks is 2.5% or higher, the dose of liraglitide should be continued at 0.3 mg. Well, if the change in GA value is less than 2.5%, consider increasing the dose to 0.6 mg.
　また、初期の２週間のGA値変化が2.0%である場合、HbA1cの初期値が約８％であれば、図１４から１４週間後のHbA1c値は約6.5％以上になると推定され、十分な血糖低下が得られるとは考え難い。一方、表４に示すように、初期２週間のGA値変化が2.0%、HbA1cの初期値が約８％である場合に、リラグリチドの投与量を初期２週間は0.3mg、その後0.6mgに増量すると、１４週間後にHbA1c値は6.7%まで低下することから、初期２週間のGA値変化が2.0%以上である場合は0.6mgの処方を続ければよい。また、初期２週間のGA値変化が2.0%未満の場合には、0.6mgの投与量では十分な血糖低下の効果があるとは判定しがたく、更に２週間後に0.9mgまで増量すると良い。 In addition, when the GA value change in the initial two weeks is 2.0%, if the initial value of HbA1c is about 8%, the HbA1c value after 14 weeks is estimated to be about 6.5% or more from FIG. It is unlikely that hypoglycemia will be obtained. On the other hand, as shown in Table 4, when the change in GA value in the initial 2 weeks was 2.0% and the initial value of HbA1c was about 8%, the dose of liraglitide was increased to 0.3 mg in the initial 2 weeks and then increased to 0.6 mg Then, the HbA1c value drops to 6.7% after 14 weeks, so if the change in GA value in the initial two weeks is 2.0% or more, then the prescription of 0.6 mg may be continued. In addition, when the change in GA value in the initial 2 weeks is less than 2.0%, it is difficult to determine that a dose of 0.6 mg has a sufficient blood glucose lowering effect, and the dose should be increased to 0.9 mg after 2 weeks.
　最後に、初期のA1c値が8%、初期２週間のGA値変化が1.0%の場合、１４週間後のHbA1c値は7%以上であり、リラグリチド使用の効果は小さい。よってリラグリチドではなくほかの薬剤を使用することを検討することが好ましい。 Finally, if the initial A1c value is 8% and the GA change in the initial two weeks is 1.0%, the HbA1c value after 14 weeks is 7% or more, and the effect of using liraglycide is small. Therefore, it is preferable to consider using other drugs instead of liraglycide.
　以上をまとめると、治療開始時のHbA1c値が8%以上の患者にリラグリチドを投与する場合には、治療開始時の投薬量を0.3mgとし、治療開始から２週間後のGA値変化が2.5%以上の場合は0.3mgにて投薬を継続、治療開始から２週間後のGA値変化が2.0-2.4%の場合には、２週間後に0.6mgに投薬量を増加、治療開始から２週間後のGA値変化が1.0-1.9%の場合には、２週間後に0.6mgに投薬量を増加し、さらにその２週間後に0.9mgに投薬量を増加し、GA値変化が1.0%未満の場合、他の薬剤に切り替えることを検討すると良い。 In summary, when Liraglitide is administered to patients whose HbA1c value at the start of treatment is 8% or more, the dosage at the start of treatment is 0.3 mg, and the GA value change after 2 weeks from the start of treatment is 2.5%. In the above case, continue to be administered at 0.3 mg. If the change in GA level after 2 weeks from the start of treatment is 2.0-2.4%, increase the dose to 0.6 mg after 2 weeks and 2 weeks after the start of treatment. If the GA value change is 1.0-1.9%, increase the dosage to 0.6 mg after 2 weeks, then increase the dosage to 0.9 mg after 2 weeks, and if the GA value change is less than 1.0%, etc. Consider switching to other drugs.
（実施例１１）劇症１型糖尿病の鑑別、GA（t）／A1c（t）の計算
＜GA/A1c＞の予測
　式１、３、４及び６を用いGA(t)／A1c（t）を計算した。なお、GA（0）、A1c（0）はGA、HbA1cの正常値15.0％、5.0％を用い、GA（∞）、HbA1c（∞）にGA、HbA1cの完全な異常値である90.0％、30.0％、を用いた。TGA（1/2）、TA1c（1/2）はそれぞれ実施例３で得られた14日、42日を用いた。ｋを実測値より1.8とし、発症後の経過日数ｔはt＝1日～35日まで計算した。式１０、１１にこれらの数字を代入すると
　GA（1）＝90＋（15－90）×10A
　A＝－ｌｏｇ2×1／（14×1.8）＝－0.01195
　GA（1）＝90－75×10－０．０１１９５＝17.04
　A1c（1）＝30＋（5－30）×10B
　B＝－ｌｏｇ2×1／（42×1.8）＝－0.00398
　A1c（1）＝30－25×10－０．００３９８＝5.228
となり、GA(1)／HbA1c（1）＝17.04／5.228＝3.259となる。同様にGA（2）／A1c（2）＝4.49、GA（3）／A1c（3）＝3.68、GA（5）／A1c（5）＝4.03、GA（7）／A1c（7）＝4.29であり、GA（14）／A1c（14）＝4.86、GA（35）／A1c（35）＝5.17であり、GA/HbA1cを３．２以上に設定すれば発症後1日から少なくとも35日間、実際はさらに長期間劇症１型糖尿病を拾い上げることができることが明らかであった。 (Example 11) Differentiation of fulminant type 1 diabetes, calculation of GA (t) / A1c (t) Prediction of <GA / A1c> GA (t) / A1c (t) using formulas 1, 3, 4 and 6 Was calculated. GA (0) and A1c (0) are GA and HbA1c normal values of 15.0% and 5.0%. GA (∞) and HbA1c (∞) are GA and HbA1c completely abnormal values of 90.0% and 30.0. % Was used. As TGA (1/2) and TA1c (1/2), 14 days and 42 days obtained in Example 3 were used, respectively. k was set to 1.8 from the measured value, and the elapsed time t after the onset was calculated from t = 1 day to 35 days. Substituting these numbers into Equations 10 and 11, GA (1) = 90 + (15-90) × 10 A
A = −log2 × 1 / (14 × 1.8) = − 0.01195
GA (1) = 90−75 × 10 −0.01195 = 17.04
A1c (1) = 30 + (5-30) x 10 B
B = −log2 × 1 / (42 × 1.8) = − 0.00398
A1c (1) = 30-25 x 10 -0.00398 = 5.228
Thus, GA (1) / HbA1c (1) = 17.04 / 5.228 = 2.259. Similarly, GA (2) / A1c (2) = 4.49, GA (3) / A1c (3) = 3.68, GA (5) / A1c (5) = 4.03, GA (7) / A1c (7) = 4.29 Yes, GA (14) / A1c (14) = 4.86, GA (35) / A1c (35) = 5.17, and if GA / HbA1c is set to 3.2 or higher, it will actually be at least 35 days from 1 day after onset. It was also clear that fulminant type 1 diabetes can be picked up for a long time.
　また、GA（0）15.0％の代わりに14.4％～17.0％を代入するとGA(1)／HbA1c（1）は3.2～3.6であり、GA（0）は14.4%以上の数字であればいかなる数字を設定しても発症後1日目よりGA（t）/A1c（t）は3.2以上となることが明らかであった。 In addition, substituting 14.4% to 17.0% for GA (0) 15.0%, GA (1) / HbA1c (1) is 3.2 to 3.6, and GA (0) is any number as long as it is 14.4% or more. It was clear that GA (t) / A1c (t) became 3.2 or more from the first day after onset even if set.
　上記計算においてA1c（0）5％の代わりに４.0～5.1％、を代入するとGA(1)／HbA1c（1）は4.0～3.2であり、A1c（0）は5.1％以下の数字であればいかなる数字を設定しても発症後１日目よりGA（t）/A1c（t）は3.2以上となることが明らかであった。また、実際発症当日に受診することはなかなかまれであることからt＝2、A1c（0）、5.0％の代わりに、5.3％、5.5％を代入すると、GA（2）／A1c（2）はそれぞれ＝3.3、3.2であり、A1c（0）は5.5％以下の数字であればいかなる数字を設定しても発症後２日目よりGA（t）/A1c（t）は3.2以上となることが明らかであった。 Substituting 4.0 to 5.1% instead of A1c (0) 5% in the above calculation, GA (1) / HbA1c (1) is 4.0 to 3.2, and A1c (0) is 5.1% or less. In any case, it was clear that GA (t) / A1c (t) was 3.2 or more from the first day after onset regardless of the number. In addition, since it is very rare to visit on the day of actual onset, substituting 5.3% and 5.5% instead of t = 2, A1c (0), 5.0%, GA (2) / A1c (2) is As long as each number is 3.3 and 3.2, and A1c (0) is 5.5% or less, GA (t) / A1c (t) may be 3.2 or more from the second day after onset regardless of the number. It was clear.
　上記計算において、例えばGA（∞）90％の代わりに、85～70％を設定すると、ｔ＝1日の場合GA(1)／HbA1c（1）＝3.2～3.2であり、GA（∞）85～70%において発症後１日からGA/HbA1cは3.2以上であることが明らかであった。また、実際発症当日に受診することはなかなかまれであることから、ｔ＝2、GA（∞）90％の代わりに60～70％を代入すると、GA（2）／A1c（2）＝3.2～3.3であり、発症後２日目よりGA（∞）60%以上であればGA（t）/A1c（t）は3.2以上となることが明らかであった。さらにｔ＝2において、A1c（∞）の設定を10に下げれば、GA（∞）35～45％とするとGA（2）／A1c（2）＝3.2～3.3であり、発症後２日目よりGA（∞）35%以上であればGA（t）/A1c（t）は3.2以上となることが明らかであった。 In the above calculation, for example, if 85-70% is set instead of GA (∞) 90%, GA (1) / HbA1c (1) = 3.2-3.2 when t = 1 day, and GA (∞) 85 It was clear that GA / HbA1c was 3.2 or more from 1 day after onset in ~ 70%. In addition, since it is very rare to see a doctor on the day of actual onset, substituting 60 to 70% for t = 2 and GA (∞) 90%, GA (2) / A1c (2) = 3.2 ~ From the second day after the onset, it was clear that GA (t) / A1c (t) was 3.2 or more when GA (∞) was 60% or more. Furthermore, at t = 2, if the setting of A1c (∞) is lowered to 10, GA (∞) 35-45%, GA (2) / A1c (2) = 3.2-3.3, from the second day after onset It was clear that GA (t) / A1c (t) was 3.2 or more when GA (∞) was 35% or more.
　上記計算において、A1c（∞）30％の代わりに25～10％を設定すると、ｔ＝1日の場合GA(1)／HbA1c（1）＝3.3～3.4であり、A1c（∞）は１０％以上であればいかなる数字を用いても発症１日目よりGA（t）/A1c（t）は3.2以上となることが明らかであった。 In the above calculation, if 25 to 10% is set instead of A1c (∞) 30%, GA = (1) / HbA1c (1) = 3.3 to 3.4 when t = 1 day, and A1c (∞) is 10% It was clear that GA (t) / A1c (t) was 3.2 or higher from the first day of onset, regardless of what number was used.
　上記計算においてTGA（1/2）14日の変わりに7～19日を代入すると、それぞれGA（1）／A1c（1）＝3.6～3.2であり、また、実際発症当日に受診することはなかなかまれであることからｔ＝2、TGA（1/2）14日の代わりに19～26日を代入すると、GA（2）／A1c（2）は＝3.3～3.2であり、TGA（1/2）は26日以下の数字であればいかなる数字を設定してもGA（t）/A1c（t）は3.2以上となることが明らかであった。 Substituting 7-19 days instead of 14 days for TGA (1/2) in the above calculation, GA (1) / A1c (1) = 3.6-3.2, respectively, and it is quite common to visit on the day of actual onset Since t = 2 and substituting 19-26 days instead of 14 days for TGA (1/2), GA (2) / A1c (2) is 3.3-3.2 and TGA (1/2 ) Is clear that GA (t) / A1c (t) will be 3.2 or higher, no matter what number is set as long as it is 26 days or less.
　上記計算において、TA1c（1/2）に42日の変わり23～84日を代入すると、それぞれ、GA（1）／A1c（1）＝3.15～3.33であり、また、実際発症当日に受診することはなかなかまれであることからｔ＝２、A1c（1/2）、42日の代わり19～23日を代入すると、GA（2）／A1c（2）はそれぞれ＝3.17～3.27日であり、加えて、TA1c（1/2）が大きくなるほどGA／A1cは大きくなることから、TA1c（1/2）は19～84日もしくは19日以上の数字であればいかなる数字を設定してもGA（t）/A1c（t）は3.2以上となることが明らかであった。 In the above calculation, substituting 23 to 84 days for 42 days into TA1c (1/2), GA (1) / A1c (1) = 3.15 to 3.33, respectively, and should be consulted on the day of actual onset Since it is quite rare, substituting t = 2, A1c (1/2), and 19-23 days instead of 42 days, GA (2) / A1c (2) is 3.17-3.27 days respectively, Since GA / A1c increases as TA1c (1/2) increases, TA1c (1/2) can be set to GA (t as long as it is 19 to 84 days or more than 19 days. ) / A1c (t) was clearly 3.2 or more.
　上記計算において、ｋ＝1.8の変わりに0.8～3.0を代入すると、それぞれ、GA（1）／A1c（1）＝3.54～3.16であり、ｋが小さくなるほどGA（1）／A1c（1）は大きくなることから、ｋは0.8～3.0もしくは3.0以下の数字であればいかなる数字を設定してもGA（t）/A1c（t）は3.2以上となることが明らかであった。
　以上よりGA（t）／A1c（t）は3.2以上であれば劇症１型糖尿病と２型糖能病との鑑別が可能であることが明白であった。 In the above calculation, substituting 0.8 to 3.0 instead of k = 1.8, respectively, GA (1) / A1c (1) = 3.54 to 3.16, and GA (1) / A1c (1) increases as k decreases Therefore, it was clear that GA (t) / A1c (t) would be 3.2 or more even if k is a number of 0.8 to 3.0 or 3.0 or less.
From the above, it was clear that if GA (t) / A1c (t) is 3.2 or more, it is possible to distinguish fulminant type 1 diabetes from type 2 glycosylation.
（実施例１２）劇症１型糖尿病の鑑別
＜対象＞劇症１型糖尿病と診断された35名、対照として２型糖尿病で、HbA1c8.5%未満、糖尿病治療歴のない21名（男性16名、女性19名）及びブドウ糖負荷試験で糖尿病型を示し、HbA1cが8.5%未満であり糖尿病治療歴のない11例、計32（男性25例、女性7例）。
　なお、両群においてHbA1CあるいはGA測定に影響する妊娠、腎疾患、肝疾患、血液疾患、悪性疾患、甲状腺疾患の合併例、ステロイド治療例は除外した。 (Example 12) Differentiation of fulminant type 1 diabetes <Subject> 35 subjects diagnosed with fulminant type 1 diabetes, type 2 diabetes as a control, HbA1c less than 8.5%, 21 subjects with no history of diabetes treatment (16 men) Nineteen women) and diabetic type in glucose tolerance test, HbA1c was less than 8.5%, 11 cases with no history of diabetes treatment, a total of 32 (25 men, 7 women).
In both groups, pregnancy, renal disease, liver disease, blood disease, malignant disease, thyroid disease combined cases, and steroid treatment cases affecting HbA1C or GA measurement were excluded.
＜方法＞対象者のGA値及びHbA1c値を測定し、GA／HbA1cを計算し、劇症1型糖尿病と２型糖尿病の比較を行った。 <Method> The GA and HbA1c values of the subjects were measured, GA / HbA1c was calculated, and fulminant type 1 diabetes was compared with type 2 diabetes.
＜結果＞劇症1型糖尿病は2型糖尿病に比し、HbA1Cは有意に低値であった（6.0±0.8％ vs 6.8±0.8％; p=0.0002）が、血清GAは有意に高値であった（23.6±4.3％ vs 18.7±3.1％; p<0.0001）。HbA1Cに対するGAの比（GA/HbA1C比）は2型糖尿病では2.76±0.29に対して劇症1型糖尿病では3.94±0.53と著明な高値を示した（ｐ<0.0001）。GA/HbA1c比が3.2以上の症例は、劇症1型糖尿病では35例中34例（97％）であったが、2型糖尿病では32例中1例（3％）のみであった。結果を図８に示す。 <Results> HbA 1C was significantly lower in fulminant type 1 diabetes than in type 2 diabetes (6.0 ± 0.8% vs 6.8 ± 0.8%; p = 0.0002), but serum GA was significantly higher (23.6 ± 4.3% vs 18.7 ± 3.1%; p <0.0001). The ratio of GA for HbA 1C (GA / HbA 1C ratio) In fulminant type 1 diabetes against 2.76 ± 0.29 in type 2 diabetes showed significant highs and 3.94 ± 0.53 (p <0.0001) . The cases with a GA / HbA1c ratio of 3.2 or higher were 34 (97%) of 35 cases of fulminant type 1 diabetes, but only 1 (32%) of 32 cases of type 2 diabetes. The results are shown in FIG.
　図８に示すようにGA（t）／A1c（t）を3.2に設定することで劇症１型糖能病と２型糖尿病の鑑別ができることが明白であった。尚、図から読み取れるようにGA（t）／A1c（t）3.0～3.5において劇症１型糖能病と２型糖尿病の鑑別ができることが明白であった。 As shown in FIG. 8, it was clear that fulminant type 1 gluconic disease and type 2 diabetes can be differentiated by setting GA (t) / A1c (t) to 3.2. As can be seen from the figure, it was clear that GA (t) / A1c (t) 3.0-3.5 can distinguish fulminant type 1 glucosylosis from type 2 diabetes.
（実施例１３）本発明による血液試料解析装置を用いた劇症１型糖尿病の判定
　初診時にGA/HbA1cを計算し、劇症１型糖尿病を診断する例を図９に示す。プログラムはマイクロソフト、エクセル2000を用い、計算式はGA/HbA1cを計算し、その値が3.2以上であれば、劇症１型糖尿病の可能性があると表示できるようにした。装置は東芝、ダイナブックSS 1620 12L/2を用いた。
　本発明による血液試料解析装置は、演算機能を有するものであればパソコン、電卓、携帯電話等いかなる装置であってもよい。 (Example 13) Determination of fulminant type 1 diabetes using blood sample analyzer according to the present invention FIG. 9 shows an example of diagnosing fulminant type 1 diabetes by calculating GA / HbA1c at the first visit. The program uses Microsoft and Excel 2000, and the calculation formula is GA / HbA1c. If the value is 3.2 or more, it can be displayed that there is a possibility of fulminant type 1 diabetes. The equipment used was Toshiba, Dynabook SS 1620 12L / 2.
The blood sample analyzer according to the present invention may be any device such as a personal computer, a calculator, and a mobile phone as long as it has a calculation function.
（実施例１４）本発明による血液試料解析装置を用いたGA、HbA1cの予測
　初診時のGA、HbA1cと治療開始後１回目のGAを測定し、次回の予測を行った例を図１０、１１及び１２に示す。プログラムはマイクロソフト、エクセル2000を用い、装置は東芝、ダイナブックSS 1620 12L/2を用いた。 (Example 14) Prediction of GA and HbA1c using blood sample analyzer according to the present invention GA and HbA1c at the first visit and the first GA after the start of treatment were measured, and the next prediction was performed as shown in FIGS. And 12. The program used Microsoft and Excel 2000, and the device used Toshiba and Dynabook SS 1620 12L / 2.
　式１、２、４、及び７を用いてA1c（t2）、GA（t2）を計算する。なお、A1c（∞）＝5、GA（∞）＝15、GA(1/2)=13.7 、A1c（1/2）＝36.3を用いた。
　図１０は２回の測定値で次回の予測値を求める例、図１１は、GA及びHbA1cを治療開示後204日までの予測を求めた例、図１２は、HbA1cの±10％の範囲を求め、実測と比べた例である。図１２では糖尿病治療を開始して２４日目、５２日目および８０日目で予測HbA1cと実測HbA1cが良く一定しておりこのプログラムの有用性が明白であると共に、実測と予測を比較して治療の指導化が能であることも明白である。
　本発明による血液試料解析装置は、演算機能を有するものであればパソコン、電卓、携帯電話等いかなる装置であってもよい。 A1c (t2) and GA (t2) are calculated using Equations 1, 2, 4, and 7. A1c (∞) = 5, GA (∞) = 15, GA (1/2) = 13.7 and A1c (1/2) = 36.3 were used.
FIG. 10 shows an example in which the next predicted value is obtained with two measured values, FIG. 11 shows an example in which the prediction of 204 days after GA and HbA1c are disclosed, and FIG. 12 shows a range of ± 10% of HbA1c. This is an example obtained by comparison with actual measurement. In FIG. 12, the predicted HbA1c and measured HbA1c are well constant on the 24th, 52nd and 80th days after the start of diabetes treatment, and the usefulness of this program is clear. It is also clear that treatment guidance is capable.
The blood sample analyzer according to the present invention may be any device such as a personal computer, a calculator, and a mobile phone as long as it has a calculation function.
（実施例１５）MBG（t2）、GA（t2）、A1c（t2）の演算機能を備えた血糖、GA、HbA1cを測定可能な血液試料解析装置
　日立自動分析装置７１７０Ｓ型にグリコアルブミン測定試薬、ヘモグロビンＡ１ｃ試薬を搭載して同一者の血清および溶血液を測定した。
＜試薬＞
　グリコアルブミン試薬：ルシカＧＡ－Ｌ（旭化成ファーマ社製）および専用キャリブレーターを使用した。
　ヘモグロビンＡ１ｃ試薬：デターミナーＨｂＡ１ｃ（協和メデックス社製）及び専用キャリブレーターを使用した。 (Example 15) Blood sample analyzer capable of measuring blood glucose, GA, and HbA1c having an arithmetic function of MBG (t2), GA (t2), A1c (t2) The hemoglobin A1c reagent was loaded and the serum and hemolysis of the same person were measured.
<Reagent>
Glycoalbumin reagent: Lucika GA-L (Asahi Kasei Pharma) and a dedicated calibrator were used.
Hemoglobin A1c reagent: Determiner HbA1c (manufactured by Kyowa Medex) and a dedicated calibrator were used.
＜項目間演算式＞
１）劇症1型鑑別診断としてGA/A1ｃを入力して計算するように設定した。
２）GA測定値をデータ通信を用いてエクセルに添付。
その際に、式４、７を用いてA1c（t2）を出力した。エクセルの出力は図９～１１と同じである。なお、式４と７はA1c（∞）＝5.0、A1c（0）＝前回の測定値、TGA(1/2)=13.7、TA1c（1/2）＝36.3、GA（∞）＝15.0％、GA（0）＝前回の測定値、t1に前回の治療開始から今回の診療まで日数を入れ、GA（t1）に今回の測定値を、t2に予測したい治療開始後日数を代入すれば計算可能である。 <Calculation between items>
1) GA / A1c was input and calculated for differential diagnosis of fulminant type 1.
2) Attach GA measurement values to Excel using data communication.
At that time, A1c (t2) was output using equations 4 and 7. The output of Excel is the same as in FIGS. Equations 4 and 7 are A1c (∞) = 5.0, A1c (0) = previous measurement, TGA (1/2) = 13.7, TA1c (1/2) = 36.3, GA (∞) = 15.0%, GA (0) = previous measurement, t1 can be calculated by inserting the number of days from the start of the previous treatment to the current medical treatment, and substituting the current measurement value for GA (t1) and the number of days after the start of treatment to be predicted for t2. It is.
　本発明は、本発明は、糖尿病の治療において有用な、治療効果および劇症１型糖尿病発症の測定方法、およびその機能を有した装置に関し、特に糖尿病患者の治療に有用な将来の平均血糖、グリコアルブミン、ヘモグロビンＡ１ｃ若しくはグリコアルブミンとヘモグロビンA1cの比を計算することにより糖尿病治療効果及び劇症1型糖尿病発症の測定及び装置に関し、臨床検査に用いられる。 The present invention relates to a therapeutic effect and a method for measuring the onset of fulminant type 1 diabetes, and a device having the function, which is useful in the treatment of diabetes, and in particular, future mean blood glucose useful for the treatment of diabetic patients, By calculating the ratio of glycoalbumin, hemoglobin A1c, or glycoalbumin and hemoglobin A1c, it is used in clinical examinations for the measurement and device of the therapeutic effect of diabetes and the onset of fulminant type 1 diabetes.
　図１３は、本発明による、血液試料装置１０の機能構成を示すブロック図である。図に示すように、血液試料装置１０は、入力装置１１、入力部１２、記憶部（第１の記憶部、第２の記憶部）１３、演算部（第１の演算部、第２の演算部）１４、判定部１５、出力部１６、出力装置１７を備えている。 FIG. 13 is a block diagram showing a functional configuration of the blood sample device 10 according to the present invention. As shown in the figure, the blood sample device 10 includes an input device 11, an input unit 12, a storage unit (first storage unit, second storage unit) 13, a calculation unit (first calculation unit, second calculation unit). Part) 14, a determination part 15, an output part 16, and an output device 17.
　血液試料装置１０は、例えば汎用的なパーソナルコンピュータに所定のプログラムを実行させたものである。入力部１２、演算部１４、判定部１５、及び出力部１６は、プログラムに従ってコンピュータのプロセッサが行う動作のモジュールを表しており、これらは実際には一体として血液試料装置１０のプロセッサを構成する。 The blood sample apparatus 10 is obtained, for example, by causing a general-purpose personal computer to execute a predetermined program. The input unit 12, the calculation unit 14, the determination unit 15, and the output unit 16 represent modules of operations performed by a computer processor according to a program, and these actually constitute a processor of the blood sample device 10 as a whole.
　記憶部１３は、血液試料装置１０のハードディスク等の記憶装置である。
　入力装置１１は、例えばキーボード、マウス、タッチパネル等の入力手段であり、ユーザが血液試料装置１０に処理の指示を与えたり、データやパラメータを入力するために用いられる。また、USB(Universal Serial Bus)インターフェイスを介して、メモリ媒体などからデータを読み込むことも可能である。ユーザによる入力装置１１を介した操作は入力部１２によって制御される。　出力装置１７は、表示装置やプリンタ等である。出力装置１７への出力処理は出力部１６によって制御される。 The storage unit 13 is a storage device such as a hard disk of the blood sample device 10.
The input device 11 is input means such as a keyboard, a mouse, and a touch panel, for example, and is used by a user to give an instruction for processing to the blood sample device 10 and to input data and parameters. It is also possible to read data from a memory medium or the like via a USB (Universal Serial Bus) interface. An operation by the user via the input device 11 is controlled by the input unit 12. The output device 17 is a display device, a printer, or the like. Output processing to the output device 17 is controlled by the output unit 16.
　ユーザは、入力装置１１を用いて患者の治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、及び治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）を入力する。 The user uses the input device 11 to determine the glycoalbumin value (GA (0)) of the blood sample collected on the patient's treatment start date, the glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), enter the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date .
　記憶部１３には、治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、及び治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間（TGA（1/2））、及び血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間（TA1c（1/2））が記憶されている。 The storage unit 13 has a glycoalbumin value (GA (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and a blood sample collected when a sufficient time has elapsed from the treatment start date. Hemoglobin A1c value (A1c (∞)), the period until the blood glucose sample reaches (GA (0) + GA (∞)) / 2 when blood glucose treatment is rapidly reduced ( TGA (1/2)) and the period (TA1c (1/2)) until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 are stored.
　演算部１４は、式（１）により、治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する。
　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１） The computing unit 14 calculates the glycoalbumin value (GA (t2)) of the blood sample collected t2 days after the treatment start date according to the equation (1).
GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
　また、演算部１４は、式（４）により、治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c(t2)）を算出する。
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４） Moreover, the calculating part 14 calculates the hemoglobin A1c value (A1c (t2)) of the blood sample extract | collected t2 days after the treatment start date by Formula (4).
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
　演算部１４によって算出された、GA（t2）及びA1c（t2）は、出力部１６を介して出力装置１７に出力される。 The GA (t2) and A1c (t2) calculated by the calculation unit 14 are output to the output device 17 via the output unit 16.
　演算部１４は、式（１）中のＡを、式（２）または式（３）のいずれかによって算出する。
　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３） The computing unit 14 calculates A in the formula (1) by either the formula (2) or the formula (3).
A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
A = −log 2 × t 2 / (TGA (1/2) × k) (3)
　また、演算部１４は、上記式（４）中のＢを、式（５）から式（７）のいずれかによって算出する。
　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７） Moreover, the calculating part 14 calculates B in said Formula (4) by either of Formula (5) to Formula (7).
B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
B = −log2 × t2 / (TA1c (1/2) × k) (6)
B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
　また、演算部１４は、式（３）、前記式（６）中のｋを、それぞれ式（１４）、式（１５）を用いて算出する。
　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）
　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５） Moreover, the calculating part 14 calculates k in Formula (3) and said Formula (6) using Formula (14) and Formula (15), respectively.
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
　また、ユーザは、入力装置１１を用いて糖尿病発症後ｔ日後の患者から採取された血液試料のグリコアルブミン値（GA（t））、及び血液試料のヘモグロビンA1c値（A1c(t1)）を入力する。 In addition, the user uses the input device 11 to input the glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after the onset of diabetes and the hemoglobin A1c value (A1c (t1)) of the blood sample. To do.
　演算部１４は、入力されたGA（t）とA1c(t1)を用いて、GA（t）／A1c(t1)を算出する。
　判定部１５は、演算部１４で算出されたGA（t）／A1c(t1)が所定の閾値以上であるか否かを判定する。
　判定部１５においてGA（t）／A1c(t1)が所定の閾値以上と判定された場合には、当該患者が劇症１型糖尿病を発症しているという判定結果を出力部１６を介して出力装置１７に出力する。 The computing unit 14 calculates GA (t) / A1c (t1) using the input GA (t) and A1c (t1).
The determination unit 15 determines whether or not GA (t) / A1c (t1) calculated by the calculation unit 14 is equal to or greater than a predetermined threshold value.
When the determination unit 15 determines that GA (t) / A1c (t1) is equal to or greater than a predetermined threshold value, the determination result that the patient has developed fulminant type 1 diabetes is output via the output unit 16 Output to device 17.
（実施例１６）GA（t1）、A1c（t1）の演算機能を備え、治療変更時においても血糖、GA、HbA1cを測定可能な血液試料解析装置
　日立自動分析装置７１７０Ｓ型にグリコアルブミン測定試薬、ヘモグロビンＡ１ｃ試薬を搭載して同一者の血清および溶血液を測定した。
＜試薬＞
　実施例１５に同じ。
＜項目間演算式＞
１）GA測定値をデータ通信を用いてエクセルに添付。
その際に、式（６）、（２９）～（３３）を用いてA1c（t2）を出力した。エクセルの出力を図１５に示す。また、図１０～１２と同様にグラフを併用しても良い。 (Example 16) Blood sample analyzer having a calculation function of GA (t1) and A1c (t1) and capable of measuring blood glucose, GA, and HbA1c even at the time of treatment change. The hemoglobin A1c reagent was loaded and the serum and hemolysis of the same person were measured.
<Reagent>
Same as Example 15.
<Calculation between items>
1) Attach GA measurement value to Excel using data communication.
At that time, A1c (t2) was output using equations (6) and (29) to (33). The output of Excel is shown in FIG. Also, graphs may be used in combination as in FIGS.
　なお、A1c（∞）、GA（∞）は既知の臨床試験結果から数値を引用すればよく、たとえば薬剤治療としてリラグリチドを用いた場合、0.3mg処方ではA1c（∞）=7.0%、0.6 mg処方ではA1c（∞）=6.5% 、0.9mg処方ではA1c（∞）=6.0%であり、GA（∞）はその３倍の値を使用することができる。A1c（0）に治療開始前の測定値、TGA(1/2)に13.7、TA1c（1/2）に36.3（15.0％）、GA（0）に治療開始前の測定値、t1に前回の治療開始から今回の診療まで日数を入れ、GA（t1）に今回の測定値を、t2に予測したい治療開始後日数を代入すれば計算可能である。 In addition, A1c (∞), GA (∞) may be quoted from the values of known clinical trials. For example, when liraglycide is used as a drug treatment, A1c (∞) = 7.0%, 0.6 mg Is A1c (∞) = 6.5%, 0.9mg prescription is A1c (∞) = 6.0%, and GA (∞) can use three times that value. A1c (0) measured before the start of treatment, TGA (1/2) 13.7, TA1c (1/2) 36.3 (15.0%), GA (0) measured before the start of treatment, t1 last measured It can be calculated by inserting the number of days from the start of treatment to the current treatment, substituting the current measurement value into GA (t1), and the number of days after the start of treatment to be predicted into t2.
　また、実施例１６による血液試料解析装置の機能構成は、図１３に示す実施例１５による血液試料装置１０の機能構成と同様のものとすることができる。　ユーザは、入力装置１１を用いて患者の治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、及び治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）を入力する。加えて、治療の種類、条件（投薬量など）を入力することができる。 The functional configuration of the blood sample analyzer according to the sixteenth embodiment can be the same as the functional configuration of the blood sample apparatus 10 according to the fifteenth embodiment shown in FIG. The user uses the input device 11 to determine the glycoalbumin value (GA (0)) of the blood sample collected on the patient's treatment start date, the glycoalbumin value (GA (0) of the blood sample collected t1 days after the treatment start date. t1)), enter the hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, and the hemoglobin A1c value (A1c (t1)) of the blood sample collected t1 days after the treatment start date . In addition, the type of treatment and conditions (such as dosage) can be entered.
　記憶部１３には、治療の種類、条件（投薬量など）ごとに、治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））、急激に血糖を低下させる治療を行った場合に血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間（TGA（1/2））、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間（TA1c（1/2））、ｋ値が記憶されている。 The storage unit 13 stores the glycoalbumin value (GA (∞)) of the blood sample collected when sufficient time has elapsed from the treatment start date for each treatment type and condition (dose, etc.), from the treatment start date. Blood samples collected when sufficient time has passed, hemoglobin A1c value (A1c (∞)), when blood glucose abruptly treatment to reduce blood glucose level (GA (0) + GA (∞ )) / 2 period to reach (TGA (1/2)), blood sample hemoglobin A1c value to reach (A1c (0) + A1c (∞)) / 2 (TA1c (1/2) )), K value is stored.
　演算部１４は、式（１）により、治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する。
　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
　また、演算部１４は、式（４）、（３０）、（３１）により、治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c(t2)）を算出する。
　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
A1c（t2）＝A1c（∞2）＋（A1c（t1）－A1c（∞2））×１０B　…（３０）
GA(t2) ＝GA（∞2）＋（GA（t1）－GA（∞2））×１０B　…（３１）
　さらに、演算部１４によって算出された、GA（t2）及びA1c（t2）は、出力部１６を介して出力装置１７に出力される。
　演算部１４は、式（１）中のＡ、上記式（４）中のＢを、実施例１５と同じ方法で計算し、上記式（３０）、（３１）中のＢを、それぞれ式（３２）、（３３）により算出する。
　Ｂ＝－log２×（t2-t1）／（TA1c（1/2）×ｋ×k2/k1）　…（３２）
　Ｂ＝－log２×（t2-t1）／（TGA（1/2）×ｋ×k2/k1）　…（３３）
　また、演算部１４は、式（３２）、（３３）中のｋを、式（３４）を用いて算出する。
ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞1））／（GA（0）－GA（∞1）））　…（３４） The computing unit 14 calculates the glycoalbumin value (GA (t2)) of the blood sample collected t2 days after the treatment start date according to the equation (1).
GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
In addition, the calculation unit 14 calculates the hemoglobin A1c value (A1c (t2)) of the blood sample collected after t2 days from the treatment start date according to the equations (4), (30), and (31).
A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
A1c (t2) = A1c (∞2) + (A1c (t1) −A1c (∞2)) × 10 B (30)
GA (t2) = GA (∞2) + (GA (t1) −GA (∞2)) × 10 B (31)
Further, GA (t2) and A1c (t2) calculated by the calculation unit 14 are output to the output device 17 via the output unit 16.
The calculation unit 14 calculates A in the formula (1) and B in the above formula (4) by the same method as in Example 15, and B in the above formulas (30) and (31) is calculated by the formula ( 32) and (33).
B = −log2 × (t2−t1) / (TA1c (1/2) × k × k2 / k1) (32)
B = -log2 * (t2-t1) / (TGA (1/2) * k * k2 / k1) (33)
Moreover, the calculating part 14 calculates k in Formula (32), (33) using Formula (34).
k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞1)) / (GA (0) −GA (∞1))) (34)
　判定部１５は、演算部１４で算出されたA1c（t2）、GA（t2）が所定の判定値のどの領域に入っているかを判定し、判定結果及び治療方法の変更や、その強度（投薬量等）の変更等を、出力部１６を介して出力装置１７に出力する。
　なお、所定の判定値のどの領域に入っているかを判定する際には、A1c(t2)の場合、5.8%未満なら（優）、5.8～6.5%未満なら（良）、6.5～7.0%未満なら（不十分）、7.0～8.0%未満なら（不良）、8.0%以上なら（不可）、GA(t2)の場合、17.0%未満なら（優）、17.0～20.0%未満なら（良）、20.0～21.0%未満なら（不十分）、21.0～24.0%未満なら（不良）、24.0%以上なら（不可）と判定するとよい。 The determination unit 15 determines which region of the predetermined determination value the A1c (t2) and GA (t2) calculated by the calculation unit 14 are in, and changes the determination result and the treatment method and the strength (medication) Change of the amount, etc.) is output to the output device 17 via the output unit 16.
When determining which region of the specified judgment value is included, in the case of A1c (t2), if it is less than 5.8% (excellent), if it is less than 5.8 to 6.5% (good), less than 6.5 to 7.0% If it is (insufficient), 7.0 to less than 8.0% (bad), 8.0% or more (impossible), GA (t2), less than 17.0% (excellent), 17.0 to less than 20.0% (good), 20.0 If it is less than ~ 21.0% (insufficient), if it is less than 21.0 ~ 24.0% (defect), it is better to judge that it is 24.0% or more (impossible).
　なお、A1c(t2)による判定は、日本糖尿病学会の糖尿病治療ガイドに基づくものであるが、将来的に基準の変更や値の変更がなされた場合には公のガイドライン等の適宜基準に従って変更すればよい。また、本発明の実施例１０に基づく解析により、薬剤がリラグリチドで、治療開始の投薬量が0.3mg、治療開始２週間後のGA値変化が2.5%以上の場合、0.3mgにて投薬を継続、治療開始２週間後のGA値変化が2.0-2.4%の場合、２週間後に0.6mgに投薬量を増加、GA値変化が1.0-1.9%の場合、２週間後に0.6mgに投薬量を増加し、さらにその２週間後に0.9mgに投薬量を増加、GA値変化が1.0%未満の場合、他の薬剤に切り替えることを判定し、出力するようにしても良い。 The determination by A1c (t2) is based on the Diabetes Treatment Guide of the Japan Diabetes Society, but if the standard is changed or the value is changed in the future, it will be changed according to the appropriate standard such as the official guidelines. That's fine. Further, according to the analysis based on Example 10 of the present invention, when the drug is liraglitide, the dosage at the start of treatment is 0.3 mg, and the GA value change after 2 weeks of the treatment is 2.5% or more, the dosage is continued at 0.3 mg. When the GA change after 2 weeks of treatment is 2.0-2.4%, the dosage is increased to 0.6 mg after 2 weeks. When the GA value is 1.0-1.9%, the dosage is increased to 0.6 mg after 2 weeks. Further, after 2 weeks, the dosage may be increased to 0.9 mg, and if the change in GA value is less than 1.0%, it may be determined to switch to another drug and output.
　１０　血液試料装置、１１　入力装置、１２　入力部、１３　記憶部、１４　演算部、１５　判定部、１６　出力部、１７　出力装置 10 blood sample device, 11 input device, 12 input unit, 13 storage unit, 14 calculation unit, 15 determination unit, 16 output unit, 17 output device

Claims (30)

  1. 　血液試料中の血糖コントロールマーカーの値が変化する前の基準時点での血液試料中の平均血糖MBG（0）、グリコアルブミン値（GA（0））、ヘモグロビンA1c値（A1c（0））、前記基準時点からｔ1日後の血液試料中の平均血糖（MBG（t1））、グリコアルブミン値（GA（t1））、ヘモグロビンA1c値（A1c（t1））、基準時点から十分時間が経過した後の血液試料中の平均血糖（MBG（∞））、グリコアルブミン値（GA（∞））、及びヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、
    　（GA（t）－GA（∞））／（GA（0）－GA（∞））の対数、（A1c（t）－A1c（∞））／（A1c（0）－A1c（∞））の対数、及び（MBG（t）－MBG（0））／（MBG（0）－MBG（∞））の対数各々が前記基準時点からの経過日数tに比例することを利用して、t日目の平均血糖、グリコアルブミン、ヘモグロビンA1c、またはグリコアルブミンとヘモグロビンA1cの比を算出する第２の工程と、を有する血液試料解析方法。     Mean blood glucose MBG (0), glycoalbumin value (GA (0)), hemoglobin A1c value (A1c (0)) in the blood sample at the reference time before the value of the blood glucose control marker in the blood sample changes, Mean blood glucose (MBG (t1)), glycoalbumin level (GA (t1)), hemoglobin A1c level (A1c (t1)), and blood after sufficient time has elapsed since the reference point A first step of obtaining mean blood glucose (MBG (∞)), glycoalbumin level (GA (∞)), and hemoglobin A1c level (A1c (∞)) in the sample;
    Logarithm of (GA (t) -GA (∞)) / (GA (0) -GA (∞)), (A1c (t) -A1c (∞)) / (A1c (0) -A1c (∞)) Using the logarithm and the logarithm of (MBG (t) −MBG (0)) / (MBG (0) −MBG (∞)) are proportional to the number of days elapsed from the reference time point, A blood sample analysis method comprising: calculating a mean blood glucose, glycoalbumin, hemoglobin A1c, or ratio of glycoalbumin to hemoglobin A1c.
  2. 　治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））を取得する第１の工程と、
    　式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する第２の工程と、を有し、
    　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
    　前記第２の工程では、上記式（１）中のＡを、式（２）を用いて算出し、
    　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
    　t1＜t2であることを特徴とする血液試料解析方法。     Glycoalbumin value (GA (0)) of a blood sample collected before the start of treatment, Glycoalbumin value (GA (t1)) of a blood sample collected after t1 day from the treatment start date, and the treatment start date A first step of obtaining a glycoalbumin value (GA (∞)) of a blood sample collected when a sufficient time has elapsed;
    A second step of calculating a glycoalbumin value (GA (t2)) of a blood sample collected t2 days after the start of treatment using the formula (1),
    GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
    In the second step, A in the formula (1) is calculated using the formula (2),
    A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
    A blood sample analysis method, wherein t1 <t2.
  3. 　前記第２の工程において、
    　前記式（１）中のＡを、式（２）の代わりに式（３）を用いて算出し、
    　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
    　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、　前記式（３）中のｋを、式（１４）を用いて算出することを特徴とする請求項２に記載の血液試料解析方法。
    　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）     In the second step,
    A in the formula (1) is calculated using the formula (3) instead of the formula (2),
    A = −log 2 × t 2 / (TGA (1/2) × k) (3)
    TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. The blood sample analysis method according to claim 2, wherein the constant is 26 days, and k in the formula (3) is calculated using the formula (14).
    k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
  4. 　治療開始前に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、
    　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））を算出する第２の工程と、を有し、
    　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
    　前記第２の工程では、上記式（４）中のＢを、式（５）を用いて算出し、
    　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
    　t1＜t2であることを特徴とする血液試料解析方法。     Hemoglobin A1c value (A1c (0)) of a blood sample collected before the start of treatment, hemoglobin A1c value (A1c (t1)) of a blood sample collected after t1 day from the treatment start date, and from the treatment start date A first step of obtaining a hemoglobin A1c value (A1c (∞)) of a blood sample collected at a sufficient time;
    A second step of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected after t2 days from the treatment start date using the formula (4),
    A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
    In the second step, B in the formula (4) is calculated using the formula (5),
    B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
    A blood sample analysis method, wherein t1 <t2.
  5. 　前記第２の工程において、
    　前記式（４）中のＡを、式（５）の代わりに式（６）を用いて算出し、
    　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
    　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、
    　前記式（６）中のｋを、式（１５）を用いて算出することを特徴とする請求項４に記載の血液試料解析方法。
    　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５）     In the second step,
    A in Formula (4) is calculated using Formula (6) instead of Formula (5),
    B = −log2 × t2 / (TA1c (1/2) × k) (6)
    TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant of 84 days,
    The blood sample analysis method according to claim 4, wherein k in the equation (6) is calculated using the equation (15).
    k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
  6. 　治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、
    　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））を算出する第２の工程と、を有し、
    　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
    　前記第２の工程では、上記式（４）中のＢを、式（７）を用いて算出し、
    　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
    　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、
    　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、
    　t1＜t2であることを特徴とする血液試料解析方法。     Glycoalbumin level of blood sample collected before the start of treatment (GA (0)), Glycoalbumin level of blood sample collected after t1 day from the start of treatment (GA (t1)), sufficient from the start date of treatment Glycoalbumin value (GA (∞)) of blood sample collected at the time when time passed, hemoglobin A1c value (A1c (0)) of blood sample collected on the treatment start date, and sufficient from the treatment start date A first step of obtaining a hemoglobin A1c value (A1c (∞)) of a blood sample collected at the time point;
    A second step of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected after t2 days from the treatment start date using the formula (4),
    A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
    In the second step, B in the formula (4) is calculated using the formula (7),
    B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
    TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. 26 days constant,
    TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant of 84 days,
    A blood sample analysis method, wherein t1 <t2.
  7. 　治療開始前に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、前記治療開始前に採取された血液試料の平均血糖（MBG（0））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料の平均血糖（MBG（∞））を取得する第１の工程と、
    　式（８）を用いて、前記治療開始日からt2日後に採取された血液試料の平均血糖（MBG（t2））を算出する第２の工程と、を有し、
    　MBG（t2）＝MBG（∞）＋（MBG（0）－MBG（∞））×１０Ｃ　…（８）
    　前記第２の工程では、上記式（８）中のＣを、式（９）を用いて算出し、
    　Ｃ＝t2／t1×TGA（1/2）／TMBG（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（９）
    　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、
    　TMBG（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料の平均血糖が（MBG（0）＋MBG（∞））／２に到達するまでの期間を示す１～６日の定数であり、
    　t1＜t2であることを特徴とする血液試料解析方法。     Glycoalbumin level of blood sample collected before the start of treatment (GA (0)), Glycoalbumin level of blood sample collected after t1 day from the start of treatment (GA (t1)), sufficient from the start date of treatment Glycoalbumin level (GA (∞)) of blood sample collected at the time when time passed, mean blood glucose (MBG (0)) of blood sample collected before the start of treatment, and sufficient time from the start date of treatment A first step of obtaining an average blood glucose (MBG (∞)) of a blood sample collected at the time when
    A second step of calculating an average blood glucose (MBG (t2)) of a blood sample collected after t2 days from the treatment start date using the formula (8),
    MBG (t2) = MBG (∞) + (MBG (0) −MBG (∞)) × 10 C (8)
    In the second step, C in the formula (8) is calculated using the formula (9),
    C = t2 / t1 × TGA (1/2) / TMBG (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (9)
    TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. 26 days constant,
    TMBG (1/2) indicates the period until blood sugar average blood sugar reaches (MBG (0) + MBG (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant for the day,
    A blood sample analysis method, wherein t1 <t2.
  8. 　治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））、前記治療開始前に採取された血液試料の平均血糖（MBG（0））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料の平均血糖（MBG（∞））を取得する第１の工程と、
    　式（８）を用いて、前記治療開始日からt2日後に採取された血液試料の平均血糖（MBG（t2））を算出する第２の工程と、を有し、
    　MBG（t2）＝MBG（∞）＋（MBG（0）－MBG（∞））×１０Ｃ　…（８）
    　前記第２の工程では、上記式（８）中のＣを、式（１０）を用いて算出し、
    　Ｃ＝t2／t1×TA1c（1/2）／TMBG（1/2）×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１０）
    　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、
    　TMBG（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料の平均血糖が（MBG（0）＋MBG（∞））／２に到達するまでの期間を示す１～６日の定数であり、
    　t1＜t2であることを特徴とする血液試料解析方法。     Hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, hemoglobin A1c value (A1c (t1)) of a blood sample collected t1 days after the treatment start date, sufficient from the treatment start date Hemoglobin A1c value (A1c (∞)) of the blood sample collected at the time when the time has elapsed, mean blood glucose (MBG (0)) of the blood sample collected before the start of treatment, and sufficient time from the treatment start date A first step of obtaining an average blood glucose (MBG (∞)) of a blood sample collected at the time when
    A second step of calculating an average blood glucose (MBG (t2)) of a blood sample collected after t2 days from the treatment start date using the formula (8),
    MBG (t2) = MBG (∞) + (MBG (0) −MBG (∞)) × 10 C (8)
    In the second step, C in the formula (8) is calculated using the formula (10),
    C = t2 / t1 × TA1c (1/2) / TMBG (1/2) × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (10)
    TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant of 84 days,
    TMBG (1/2) indicates the period until blood sugar average blood sugar reaches (MBG (0) + MBG (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant for the day,
    A blood sample analysis method, wherein t1 <t2.
  9. 　治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））が既知である場合、
    　式（２３）を用いてｋ値を決定する第１の工程と、
    　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t2）－A1c（∞））／（A1c（0）－A1c（∞）））　…（２３）
    　式（２４）、（２５）、（２６）、（２７）を用いて前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））およびグリコアルブミン値（GA（t1））を算出する第２の工程と、を有し、
    A1c（t1）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（２４）
    Ｂ＝－ｌｏｇ２×t1／（TA1c（1/2）×ｋ）　…（２６）
    GA（t1）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（２５）
    Ａ＝－ｌｏｇ２×t1／（TGA（1/2）×ｋ）　…（２７）
    　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、
    　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、
    　t1＜t2であることを特徴とする血液試料解析方法。     Hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start date, hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date, and from the treatment start date If the hemoglobin A1c value (A1c (∞)) of a blood sample collected at a sufficient time has been known,
    A first step of determining a k value using equation (23);
    k = −log2 × t1 / TA1c (1/2) / log ((A1c (t2) −A1c (∞)) / (A1c (0) −A1c (∞))) (23)
    Hemoglobin A1c value (A1c (t1)) and glycoalbumin value (GA (t1) of blood samples collected after t1 day from the treatment start date using the formulas (24), (25), (26), (27) )) Calculating the second step,
    A1c (t1) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (24)
    B = −log2 × t1 / (TA1c (1/2) × k) (26)
    GA (t1) = GA (∞) + (GA (0) −GA (∞)) × 10 A (25)
    A = −log2 × t1 / (TGA (1/2) × k) (27)
    TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant of 84 days,
    TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. 26 days constant,
    A blood sample analysis method, wherein t1 <t2.
  10. 　治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））、及び投薬量がそれぞれD1、D2、D3の場合の前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値A1c（∞D1）、A1c（∞D2）、A1c（∞D3）が既知である場合、式（２８）を用いて、投薬量がD1である場合のk1、投薬量がD2である場合のk2、投薬量がD3である場合のk3を決定する第１の工程と、
    　ｋ＝－ｌｏｇ２×ｔ3／TA1c（1/2）／ｌｏｇ（（A1c（t2）－A1c（∞））／（A1c（0）－A1c（∞）））　…（２８）
    　前記治療開始日からt1日後までの投薬量をD1、t1日後からt2日後までの投薬量をD2として治療を実施した場合に、
    治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞D1）および（GA（∞D2）））、前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞D1）および（A1c（∞D2）））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c（0））を取得する第２の工程と、
    　式（２９）を用いて、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c（t1））を算出する第３の工程と、
    　A1c（t1）＝A1c（∞1）＋（A1c（0）－A1c（∞1））×１０B　…（２９）
    　式（３０）、（３１）を用いてA1c(t2)もしくはGA(t2)を計算する第４の工程を有し、
    　A1c（t2）＝A1c（∞2）＋（A1c（t1）－A1c（∞2））×１０B　…（３０）
    　GA(t2) ＝GA（∞2）＋（GA（t1）－GA（∞2））×１０B　…（３１）
    　前記第３の工程では、上記式（２９）中のＢを式（６）により算出し、
    　ただし、Ｂ＝－log２×t2／（TA1c（1/2）×ｋ）　…（６）
    　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、
    　前記第４の工程では、上記式（３０）中のＢを式（３２）により、式（３１）中のＢを式（３３）により算出し、
    　Ｂ＝－log２×（t2-t1）／（TA1c（1/2）×ｋ×k2/k1）　…（３２）
    Ｂ＝－log２×（t2-t1）／（TGA（1/2）×ｋ×k2/k1）　…（３３）
    前記式（３２）、（３３）中のｋを、式（３４）を用いて算出し、
    ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞1））／（GA（0）－GA（∞1）））　…（３４）
    　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数である、血液試料解析方法。     The hemoglobin A1c value (A1c (0)) of the blood sample collected on the treatment start date, the hemoglobin A1c value (A1c (t2)) of the blood sample collected t2 days after the treatment start date, and the dosage are D1 When hemoglobin A1c values A1c (∞D1), A1c (∞D2), and A1c (∞D3) of blood samples collected when sufficient time has elapsed since the start of treatment in the case of D2, D3, and D3 A first step of using formula (28) to determine k1 when the dosage is D1, k2 when the dosage is D2, and k3 when the dosage is D3;
    k = −log2 × t3 / TA1c (1/2) / log ((A1c (t2) −A1c (∞)) / (A1c (0) −A1c (∞))) (28)
    When the treatment is performed with D1 as the dosage from the start date of treatment to t1 day later, and D2 as the dosage from t1 day to t2 day later,
    Glycoalbumin level (GA (0)) of the blood sample collected on the treatment start date, Glycoalbumin level (GA (t1)) of the blood sample collected t1 days after the treatment start date, sufficient from the treatment start date Glycoalbumin levels (GA (∞D1) and (GA (∞D2))) of blood samples collected when time has passed, hemoglobin of blood samples collected when sufficient time has passed since the treatment start date A1c value (A1c (∞D1) and (A1c (∞D2))), a second step of obtaining a hemoglobin A1c value (A1c (0)) of a blood sample collected on the treatment start day;
    A third step of calculating a hemoglobin A1c value (A1c (t1)) of a blood sample collected after t1 day from the treatment start date using Formula (29);
    A1c (t1) = A1c (∞1) + (A1c (0) −A1c (∞1)) × 10 B (29)
    A fourth step of calculating A1c (t2) or GA (t2) using equations (30) and (31);
    A1c (t2) = A1c (∞2) + (A1c (t1) −A1c (∞2)) × 10 B (30)
    GA (t2) = GA (∞2) + (GA (t1) −GA (∞2)) × 10 B (31)
    In the third step, B in the formula (29) is calculated by the formula (6),
    However, B = −log2 × t2 / (TA1c (1/2) × k) (6)
    TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant of 84 days,
    In the fourth step, B in the formula (30) is calculated from the formula (32), and B in the formula (31) is calculated from the formula (33).
    B = −log2 × (t2−t1) / (TA1c (1/2) × k × k2 / k1) (32)
    B = -log2 * (t2-t1) / (TGA (1/2) * k * k2 / k1) (33)
    K in the equations (32) and (33) is calculated using the equation (34),
    k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞1)) / (GA (0) −GA (∞1))) (34)
    TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. It is a constant for 84 days, and TGA (1/2) reaches the level of (GA (0) + GA (∞)) / 2 in the blood sample when blood glucose is rapidly reduced. A blood sample analysis method, which is a constant of 7 to 26 days indicating the period until.
  11. 　t2が３ヶ月以上であり、
    　A1c(t2)が5.8%未満の場合に（優）、5.8～6.5%未満の場合に（良）、6.5～7.0%未満の場合に（不十分）、7.0～8.0%未満の場合に（不良）、8.0%以上の場合に（不可）、GA(t2)が17.0%未満の場合に（優）、17.0～20.0%未満の場合に（良）、20.0～21.0%未満の場合に（不十分）、21.0～24.0%未満の場合に（不良）、24.0%以上の場合に（不可）と判定することを特徴とする請求項２～６、９、１０のいずれかに記載の血液試料解析方法。     t2 is 3 months or more,
    A1c (t2) is less than 5.8% (excellent), 5.8 to less than 6.5% (good), less than 6.5 to 7.0% (insufficient), and less than 7.0 to 8.0% (bad) ), 8.0% or more (impossible), GA (t2) less than 17.0% (excellent), 17.0-20.0% (good), 20.0-21.0% (insufficient) The blood sample analysis method according to any one of claims 2 to 6, 9, and 10, wherein 21.0 to less than 24.0% (defect) is determined and 24.0% or more is determined to be (impossible) .
  12. 　t2が３ヶ月以上、t1が１～５週間であり、
    　A1c(t2)が5.8%未満の場合に（優）、5.8～6.5%未満の場合に（良）、6.5～7.0%未満の場合に（不十分）、7.0～8.0%未満の場合に（不良）、8.0%以上の場合に（不可）、GA(t2)が17.0%未満の場合に（優）、17.0～20.0%未満の場合に（良）、20.0～21.0%未満の場合に（不十分）、21.0～24.0%未満の場合に（不良）、24.0%以上の場合に（不可）と判定し、GA(t1)-GA(0)を用いて治療の効果を判定する請求項２～６、９、１０のいずれかに記載の血液試料解析方法。     t2 is more than 3 months, t1 is 1 to 5 weeks,
    A1c (t2) is less than 5.8% (excellent), 5.8 to less than 6.5% (good), less than 6.5 to 7.0% (insufficient), and less than 7.0 to 8.0% (bad) ), 8.0% or more (impossible), GA (t2) less than 17.0% (excellent), 17.0-20.0% (good), 20.0-21.0% (insufficient) ), 21.0 to less than 24.0% (bad), 24.0% or more (impossible), and GA (t1) -GA (0) is used to determine the effect of treatment. The blood sample analysis method according to any one of 9, 9 and 10.
  13. 　GA(t1)-GA(0) とA1c(O)を用いて算出したA1c(t2)を示す表、または、A1c(O)ごとに、GA(t1)-GA(0) とA1c(t2)の関係を示したグラフを用いて、治療の効果を判定する請求項１２に記載の血液試料解析方法。 Table showing A1c (t2) calculated using GA (t1) -GA (0) and A1c (O), or GA (t1) -GA (0) and A1c (t2) for each A1c (O) The blood sample analysis method according to claim 12, wherein the effect of treatment is determined using a graph showing the relationship of
  14. 　治療に用いる薬剤がリラグリチドであり、治療開始時の投薬量を0.3mgとし、
    　治療開始２週間後のGA値の変化が2.5%以上の場合、0.3mgにて投薬を継続すると判定し、
    　治療開始２週間後のGA値変化が2.0-2.4%の場合、２週間後に0.6mgに投薬量を増加すると判定し、
    　治療開始２週間後のGA値変化が1.0-1.9%の場合、２週間後に0.6mgに投薬量を増加し、さらにその２週間後に0.9mgに投薬量を増加すると判定し、
    　治療開始２週間後のGA値変化が1.0%未満の場合、他の薬剤への切り替えが必要と判定することを特徴とする請求項１３に記載の血液試料解析方法。     The drug used for treatment is liraglitide, the dosage at the start of treatment is 0.3 mg,
    If the change in GA level after 2 weeks from the start of treatment is 2.5% or more, it is determined that the medication will be continued at 0.3 mg,
    If the GA change after 2 weeks of treatment is 2.0-2.4%, it will be decided to increase the dosage to 0.6 mg after 2 weeks.
    When GA change after 2 weeks of treatment is 1.0-1.9%, it is determined that the dosage is increased to 0.6 mg after 2 weeks and further increased to 0.9 mg after 2 weeks,
    The blood sample analysis method according to claim 13, wherein it is determined that switching to another drug is necessary when the change in GA value after 2 weeks from the start of treatment is less than 1.0%.
  15. 　前記GA（∞）は、１１～２０％であることを特徴とする、請求項１、２、３、６、７、９、１０のいずれかに記載の血液試料解析方法。 The blood sample analysis method according to any one of claims 1, 2, 3, 6, 7, 9, and 10, wherein the GA (∞) is 11 to 20%.
  16. 　前記A1c（∞）は、４～７％であることを特徴とする、請求項１、４、５、６、８～１０のいずれかに記載の血液試料解析方法。 The blood sample analysis method according to any one of claims 1, 4, 5, 6, and 8 to 10, wherein the A1c (∞) is 4 to 7%.
  17. 　前記MBG（∞）は、８０～１８０mg/dlであることを特徴とする、請求項１、７または８のいずれかに記載の血液試料解析方法。 9. The blood sample analysis method according to claim 1, 7 or 8, wherein the MBG (∞) is 80 to 180 mg / dl.
  18. 　糖尿病発症ｔ日後の血液試料のグリコアルブミン値（GA（t））、及び糖尿病発症ｔ日後の血液試料のヘモグロビンA1c値A1c（t）を取得する第１の工程と、
    　GA（t）／A1c（t）を算出する第２の工程と、
    　前記GA（t）／A1c（t）が所定の閾値以上の場合には、当該血液試料が劇症１型糖尿病患者由来血液試料であると判定する第３の工程と、を有する血液試料解析方法。     A first step of obtaining a glycoalbumin value (GA (t)) of a blood sample after the onset of diabetes, and a hemoglobin A1c value A1c (t) of the blood sample after the onset of diabetes;
    A second step of calculating GA (t) / A1c (t);
    And a third step of determining that the blood sample is a blood sample derived from a patient with fulminant type 1 diabetes when GA (t) / A1c (t) is equal to or greater than a predetermined threshold value. .
  19. 　治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を取得する第１の工程と、
    　式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する第２の工程と、
    　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
    　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c（t2））を算出する第３の工程と、
    　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
    　前記GA（t2）と前記A1c（t2）を用いてGA（t2）／A1c（t2）を算出し、GA（t2）／A1c（t2）が所定の閾値以上の場合には、当該血液試料が劇症１型糖尿病患者由来血液試料であると判定する第４の工程と、を有し、
    　前記第２の工程では、上記式（１）中のＡを、式（２）または式（３）のいずれかを用いて算出し、
    　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
    　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
    　TGA（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間を示す７～２６日の定数であり、
    　前記第３の工程では、上記式（４）中のＢを、式（５）から式（７）のいずれかを用いて算出し、
    　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
    　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
    　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
    　TA1c（1/2）は、急激に血糖を低下させる治療を行った場合に、血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間を示す１９～８４日の定数であり、
    　前記式（３）、前記式（６）中のｋは、それぞれ式（１４）、式（１５）を用いて算出し、
    　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）
    　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５）
    　t1＜t2であることを特徴とする血液試料解析方法。     Glycoalbumin value (GA (0)) of blood sample collected on the treatment start date, Glycoalbumin value (GA (t1)) of blood sample collected t1 day after the treatment start date, sufficient from the treatment start date Glycoalbumin level (GA (∞)) of blood sample collected at the time elapsed, hemoglobin A1c value (A1c (0)) of blood sample collected on the start date of treatment, t1 day from the start date of treatment The first obtains the hemoglobin A1c value (A1c (t1)) of a blood sample collected later and the hemoglobin A1c value (A1c (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date. And the process of
    A second step of calculating a glycoalbumin value (GA (t2)) of a blood sample collected t2 days after the start of treatment using the formula (1);
    GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
    A third step of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date using the formula (4);
    A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
    GA (t2) / A1c (t2) is calculated using GA (t2) and A1c (t2). If GA (t2) / A1c (t2) is greater than or equal to a predetermined threshold, the blood sample is A fourth step of determining that the blood sample is derived from a patient with fulminant type 1 diabetes,
    In the second step, A in the formula (1) is calculated using either the formula (2) or the formula (3),
    A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
    A = −log 2 × t 2 / (TGA (1/2) × k) (3)
    TGA (1/2) indicates the period until blood glucose level reaches (GA (0) + GA (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. 26 days constant,
    In the third step, B in the formula (4) is calculated using any one of the formulas (5) to (7),
    B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
    B = −log2 × t2 / (TA1c (1/2) × k) (6)
    B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
    TA1c (1/2) indicates the period until the hemoglobin A1c value of the blood sample reaches (A1c (0) + A1c (∞)) / 2 when treatment for rapidly lowering blood glucose is performed. A constant of 84 days,
    K in the formula (3) and the formula (6) is calculated using the formula (14) and the formula (15), respectively.
    k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
    k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
    A blood sample analysis method, wherein t1 <t2.
  20. 　前記GA（∞）が３５～９０％であり、前記A1c（∞）が１０～３０％であり、ｋが１～３であることを特徴とする請求項１９に記載の血液試料解析方法。 The blood sample analysis method according to claim 19, wherein the GA (∞) is 35 to 90%, the A1c (∞) is 10 to 30%, and k is 1 to 3.
  21. 　前記TGA（1/2）を式（１１）を用いて算出することを特徴とする請求項３、６、７、９、１０、１９のいずれかに記載の血液試料解析方法。
    　TGA（1/2）＝－ｌｏｇ２×ｔ／ｌｏｇ（（GA（t）－GA（∞））／（GA（0）－GA（∞）））　…（１１）     The blood sample analysis method according to any one of claims 3, 6, 7, 9, 10, and 19, wherein the TGA (1/2) is calculated using the formula (11).
    TGA (1/2) = − log2 × t / log ((GA (t) −GA (∞)) / (GA (0) −GA (∞))) (11)
  22. 　前記TA1c（1/2）を式（１２）を用いて算出することを特徴とする請求項５、６、８、９、１０、１９のいずれかに記載の血液試料解析方法。
    　TA1c（1/2）＝－ｌｏｇ２×ｔ／ｌｏｇ（（A1c（t）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１２）     The blood sample analysis method according to any one of claims 5, 6, 8, 9, 10, and 19, wherein the TA1c (1/2) is calculated using the formula (12).
    TA1c (1/2) = − log2 × t / log ((A1c (t) −A1c (∞)) / (A1c (0) −A1c (∞))) (12)
  23. 　前記TMBG（1/2）を式（１３）を用いて算出することを特徴とする請求項７または８に記載の血液試料解析方法。
    　TMBG（1/2）＝－ｌｏｇ２×ｔ／ｌｏｇ（（MBG（t）－MBG（∞））／（MBG（0）－MBG（∞）））　…（１３）     9. The blood sample analysis method according to claim 7 or 8, wherein the TMBG (1/2) is calculated using the formula (13).
    TMBG (1/2) = − log2 × t / log ((MBG (t) −MBG (∞)) / (MBG (0) −MBG (∞))) (13)
  24. 　前記GA（t）／A1c（t）の閾値が3.0～3.5であることを特徴とする請求項１８または１９に記載の血液試料解析方法。 The blood sample analysis method according to claim 18 or 19, wherein a threshold value of the GA (t) / A1c (t) is 3.0 to 3.5.
  25. 　前記GA（t）／A1c（t）の閾値が3.2であることを特徴とする請求項２４に記載の血液試料解析方法。 The blood sample analysis method according to claim 24, wherein the threshold value of GA (t) / A1c (t) is 3.2.
  26. 　治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、及び前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける入力部と、
    　前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を記憶する第１の記憶部と、
    　前記治療開始後に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間（TGA（1/2））、及び血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間（TA1c（1/2））を記憶する第２の記憶部と、
    　式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する第１の演算部と、
    　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
    　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c(t2)）を算出する第２の演算部と、
    　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
    　前記GA（t2）及び前記A1c（t2）を出力装置に出力する出力部と、を備え、
    　前記第１の演算部は、上記式（１）中のＡを、式（２）または式（３）のいずれかを用いて算出し、
    　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
    　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
    　前記第２の演算部は、上記式（４）中のＢを、式（５）から式（７）のいずれかを用いて算出し、
    　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
    　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
    　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
    　前記第１の演算部及び前記第２の演算部は、それぞれ前記式（３）、前記式（６）中のｋを、式（１４）、式（１５）を用いて算出し、
    　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）
    　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５）
    　t1＜t2であることを特徴とする血液試料解析装置。     Glycoalbumin value (GA (0)) of a blood sample collected on the treatment start date, Glycoalbumin value (GA (t1)) of a blood sample collected t1 days after the treatment start date, collected on the treatment start date An input unit for receiving an input of a hemoglobin A1c value (A1c (0)) of a blood sample obtained and a hemoglobin A1c value (A1c (t1)) of a blood sample collected after t1 day from the treatment start date;
    Glycoalbumin value (GA (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and a hemoglobin A1c value of a blood sample collected when a sufficient time has elapsed from the treatment start date A first storage unit for storing (A1c (∞));
    After the start of the treatment, the period (TGA (1/2)) until the glycoalbumin value of the blood sample reaches (GA (0) + GA (∞)) / 2, and the hemoglobin A1c value of the blood sample is (A1c ( 0) + A1c (∞)) / 2, a second storage unit that stores a period (TA1c (1/2)) until it reaches 2;
    A first arithmetic unit that calculates a glycoalbumin value (GA (t2)) of a blood sample collected after t2 days from the treatment start date using the formula (1);
    GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
    A second arithmetic unit that calculates a hemoglobin A1c value (A1c (t2)) of a blood sample collected t2 days after the treatment start date using Formula (4);
    A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
    An output unit that outputs the GA (t2) and the A1c (t2) to an output device;
    The first calculation unit calculates A in the formula (1) using either the formula (2) or the formula (3),
    A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
    A = −log 2 × t 2 / (TGA (1/2) × k) (3)
    The second calculation unit calculates B in the formula (4) using any one of the formulas (5) to (7),
    B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
    B = −log2 × t2 / (TA1c (1/2) × k) (6)
    B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
    The first calculation unit and the second calculation unit calculate k in the formula (3) and the formula (6) using the formula (14) and the formula (15), respectively.
    k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
    k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
    A blood sample analyzer, wherein t1 <t2.
  27. 　糖尿病発症後ｔ日後の患者から採取された血液試料のグリコアルブミン値（GA（t））、及び前記血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける入力部と、
    　前記GA（t）と前記A1c(t1)を用いて、GA（t）／A1c(t1)を算出する演算部と、
    　前記演算部で算出されたGA（t）／A1c(t1)が所定の閾値以上であるか否かを判定する判定部と、
    　前記判定部においてGA（t）／A1c(t1)が所定の閾値以上と判定された場合には、当該患者が劇症１型糖尿病を発症しているという判定結果を出力装置に出力する出力部と、を備えた血液試料解析装置。     An input unit for receiving input of a glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after onset of diabetes, and a hemoglobin A1c value (A1c (t1)) of the blood sample;
    An arithmetic unit that calculates GA (t) / A1c (t1) using the GA (t) and the A1c (t1);
    A determination unit that determines whether or not GA (t) / A1c (t1) calculated by the calculation unit is equal to or greater than a predetermined threshold;
    When the determination unit determines that GA (t) / A1c (t1) is equal to or greater than a predetermined threshold, the output unit outputs a determination result that the patient has developed fulminant type 1 diabetes to the output device And a blood sample analyzer.
  28. 　前記閾値が3.0～3.5であることを特徴とする請求項２７に記載の血液試料解析装置。 The blood sample analyzer according to claim 27, wherein the threshold value is 3.0 to 3.5.
  29. 　コンピュータに、
    　治療開始日に採取された血液試料のグリコアルブミン値（GA（0））、前記治療開始日からt1日後に採取された血液試料のグリコアルブミン値（GA（t1））、前記治療開始日に採取された血液試料のヘモグロビンA1c値（A1c(0)）、及び前記治療開始日からt1日後に採取された血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける機能と、
    　前記治療開始日から十分時間が経過した時点で採取された血液試料のグリコアルブミン値（GA（∞））、及び前記治療開始日から十分時間が経過した時点で採取された血液試料のヘモグロビンA1c値（A1c（∞））を記憶する機能と、
    　前記治療開始後に、血液試料のグリコアルブミン値が（GA（0）＋GA（∞））／２に到達するまでの期間（TGA（1/2））、及び血液試料のヘモグロビンA1c値が（A1c（0）＋A1c（∞））／２に到達するまでの期間（TA1c（1/2））を記憶する機能と、
    　式（１）を用いて、前記治療開始日からt2日後に採取された血液試料のグリコアルブミン値（GA（t2））を算出する機能と、
    　GA（t2）＝GA（∞）＋（GA（0）－GA（∞））×１０Ａ　…（１）
    　式（４）を用いて、前記治療開始日からt2日後に採取された血液試料のヘモグロビンA1c値（A1c(t2)）を算出する機能と、
    　A1c（t2）＝A1c（∞）＋（A1c（0）－A1c（∞））×１０B　…（４）
    　前記GA（t2）及び前記A1c（t2）を出力装置に出力する機能と、を実行させるプログラムであって、
    　上記式（１）中のＡは、式（２）または式（３）のいずれかを用いて算出し、
    　Ａ＝t2／t1×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（２）
    　Ａ＝－ｌｏｇ２×t2／（TGA（1/2）×ｋ）　…（３）
    　上記式（４）中のＢは、式（５）から式（７）のいずれかを用いて算出し、
    　Ｂ＝t2／t1×ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（５）
    　Ｂ＝－ｌｏｇ２×t2／（TA1c（1/2）×ｋ）　…（６）
    　Ｂ＝t2／t1×TGA（1/2）／TA1c（1/2）×ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（７）
    　前記式（３）、前記式（６）中のｋは、それぞれ式（１４）、式（１５）を用いて算出し、
    　ｋ＝－ｌｏｇ２×ｔ１／TGA（1/2）／ｌｏｇ（（GA（t1）－GA（∞））／（GA（0）－GA（∞）））　…（１４）
    　ｋ＝－ｌｏｇ２×ｔ１／TA1c（1/2）／ｌｏｇ（（A1c（t1）－A1c（∞））／（A1c（0）－A1c（∞）））　…（１５）
    　t1＜t2であることを特徴とするプログラム。     On the computer,
    Glycoalbumin value (GA (0)) of a blood sample collected on the treatment start date, Glycoalbumin value (GA (t1)) of a blood sample collected t1 days after the treatment start date, collected on the treatment start date A function of accepting an input of a hemoglobin A1c value (A1c (0)) of a blood sample obtained and a hemoglobin A1c value (A1c (t1)) of a blood sample collected after t1 day from the treatment start date;
    Glycoalbumin value (GA (∞)) of a blood sample collected when a sufficient time has elapsed from the treatment start date, and a hemoglobin A1c value of a blood sample collected when a sufficient time has elapsed from the treatment start date (A1c (∞)) function,
    After the start of the treatment, the period (TGA (1/2)) until the glycoalbumin value of the blood sample reaches (GA (0) + GA (∞)) / 2, and the hemoglobin A1c value of the blood sample is (A1c ( 0) + A1c (∞)) / 2 A function for storing a period (TA1c (1/2)) until reaching 2;
    A function of calculating a glycoalbumin value (GA (t2)) of a blood sample collected t2 days after the start of treatment using the formula (1);
    GA (t2) = GA (∞) + (GA (0) −GA (∞)) × 10 A (1)
    A function of calculating a hemoglobin A1c value (A1c (t2)) of a blood sample collected after t2 days from the treatment start date using the formula (4);
    A1c (t2) = A1c (∞) + (A1c (0) −A1c (∞)) × 10 B (4)
    A function of outputting the GA (t2) and the A1c (t2) to an output device,
    A in the formula (1) is calculated using either the formula (2) or the formula (3),
    A = t2 / t1 × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (2)
    A = −log 2 × t 2 / (TGA (1/2) × k) (3)
    B in the formula (4) is calculated using any one of the formulas (5) to (7),
    B = t2 / t1 × log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (5)
    B = −log2 × t2 / (TA1c (1/2) × k) (6)
    B = t2 / t1 × TGA (1/2) / TA1c (1/2) × log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (7)
    K in the formula (3) and the formula (6) is calculated using the formula (14) and the formula (15), respectively.
    k = −log2 × t1 / TGA (1/2) / log ((GA (t1) −GA (∞)) / (GA (0) −GA (∞))) (14)
    k = −log2 × t1 / TA1c (1/2) / log ((A1c (t1) −A1c (∞)) / (A1c (0) −A1c (∞))) (15)
    A program characterized by t1 <t2.
  30. 　コンピュータに、
    　糖尿病発症後ｔ日後の患者から採取された血液試料のグリコアルブミン値（GA（t））、及び前記血液試料のヘモグロビンA1c値（A1c(t1)）の入力を受け付ける機能と、
    　前記GA（t）と前記A1c(t1)を用いて、GA（t）／A1c(t1)を算出する機能と、
    　前記演算部で算出されたGA（t）／A1c(t1)が所定の閾値以上であるか否かを判定する機能と、
    　前記判定部においてGA（t）／A1c(t1)が所定の閾値以上と判定された場合には、当該患者が劇症１型糖尿病を発症しているという判定結果を出力装置に出力する機能と、を実行させるプログラム。     On the computer,
    A function of accepting an input of a glycoalbumin value (GA (t)) of a blood sample collected from a patient t days after onset of diabetes and a hemoglobin A1c value (A1c (t1)) of the blood sample;
    A function of calculating GA (t) / A1c (t1) using the GA (t) and the A1c (t1);
    A function of determining whether GA (t) / A1c (t1) calculated by the calculation unit is equal to or greater than a predetermined threshold;
    A function of outputting, to the output device, a determination result indicating that the patient has developed fulminant type 1 diabetes when GA (t) / A1c (t1) is determined to be equal to or greater than a predetermined threshold in the determination unit; , A program to execute.
PCT/JP2009/005208 2008-10-08 2009-10-07 Blood sample analysis method, blood sample analysis apparatus, and program WO2010041439A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2010532814A JP5323853B2 (en) 2008-10-08 2009-10-07 Blood sample analysis method, blood sample analysis device, and program

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2008-261559 2008-10-08
JP2008261559 2008-10-08

Publications (1)

Publication Number Publication Date
WO2010041439A1 true WO2010041439A1 (en) 2010-04-15

Family

ID=42100400

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2009/005208 WO2010041439A1 (en) 2008-10-08 2009-10-07 Blood sample analysis method, blood sample analysis apparatus, and program

Country Status (2)

Country Link
JP (1) JP5323853B2 (en)
WO (1) WO2010041439A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016042024A (en) * 2014-08-13 2016-03-31 学校法人大阪医科大学 Detection method for fulminant type 1 diabetes mellitus, biomarker, and kit
JP2016511038A (en) * 2013-02-21 2016-04-14 ユニバーシティ・オブ・ヴァージニア・パテント・ファウンデーション Tracking changes in mean blood glucose in diabetic patients
JPWO2020013230A1 (en) * 2018-07-11 2020-01-16
WO2023147522A1 (en) * 2022-01-28 2023-08-03 GATC Health Corp Biomarkers for early detection of diabetes

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10332704A (en) * 1997-05-30 1998-12-18 Nokia Mobile Phones Ltd Diabetes control
JP2003079723A (en) * 2001-07-31 2003-03-18 F Hoffmann-La Roche Ag Diabetes management system
WO2005106446A1 (en) * 2004-04-30 2005-11-10 Matsushita Electric Industrial Co., Ltd. Blood sugar level measuring device

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10332704A (en) * 1997-05-30 1998-12-18 Nokia Mobile Phones Ltd Diabetes control
JP2003079723A (en) * 2001-07-31 2003-03-18 F Hoffmann-La Roche Ag Diabetes management system
WO2005106446A1 (en) * 2004-04-30 2005-11-10 Matsushita Electric Industrial Co., Ltd. Blood sugar level measuring device

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
IZUMI TAKEI: "Shitte Okitai Kensa Glycoalbumin", LAB. CLIN. PRACT., vol. 21, no. 2, 30 October 2003 (2003-10-30), pages 80 - 84 *
TAKUJI KOZUMA: "Atarashii Rinsho Kensa-Mirai no Rinsho Kensa 2. Seikagaku Kensa 6 Glycoalbumin", KENSA TO GIJUTSU, vol. 34, no. 11, 15 October 2006 (2006-10-15), pages 1138 - 1141 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016511038A (en) * 2013-02-21 2016-04-14 ユニバーシティ・オブ・ヴァージニア・パテント・ファウンデーション Tracking changes in mean blood glucose in diabetic patients
JP2016042024A (en) * 2014-08-13 2016-03-31 学校法人大阪医科大学 Detection method for fulminant type 1 diabetes mellitus, biomarker, and kit
JPWO2020013230A1 (en) * 2018-07-11 2020-01-16
WO2020013230A1 (en) * 2018-07-11 2020-01-16 株式会社Ｐｒｏｖｉｇａｔｅ Healthcare management method
CN112771378A (en) * 2018-07-11 2021-05-07 株式会社普欧威盖特 Health care management method
JP7477875B2 (en) 2018-07-11 2024-05-02 株式会社Provigate Healthcare Management Methodology
WO2023147522A1 (en) * 2022-01-28 2023-08-03 GATC Health Corp Biomarkers for early detection of diabetes

Also Published As

Publication number Publication date
JPWO2010041439A1 (en) 2012-03-08
JP5323853B2 (en) 2013-10-23

Similar Documents

Publication Publication Date Title
American Diabetes Association Tests of glycemia in diabetes
Buse et al. Serum 1, 5-anhydroglucitol (GlycoMark™): a short-term glycemic marker
Secrest et al. Association of socioeconomic status with mortality in type 1 diabetes: the Pittsburgh epidemiology of diabetes complications study
Kimberly et al. Variability among five over-the-counter blood glucose monitors
Sinning et al. Association of glycated hemoglobin A 1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium
Pan et al. Serum glycated albumin predicts the progression of diabetic retinopathy—a five year retrospective longitudinal study
JP5054674B2 (en) Combination of 1,5-anhydroglucitol (1,5-AG) assay and A1C / 1,5-AG assay to measure blood glucose variability in general and postprandial hyperglycemia in diabetic patients
Ogata et al. The lack of long-range negative correlations in glucose dynamics is associated with worse glucose control in patients with diabetes mellitus
JP5323853B2 (en) Blood sample analysis method, blood sample analysis device, and program
Janghorbani et al. Incidence of metabolic syndrome and its risk factors among type 2 diabetes clinic attenders in Isfahan, Iran
Janssen et al. Importance of the pre-analytical phase in blood glucose analysis
Wahl How accurately do we measure blood glucose levels in intensive care unit (ICU) patients?
Yoshino et al. Assessment of factors that determine the mean absolute relative difference in flash glucose monitoring with reference to plasma glucose levels in Japanese subjects without diabetes
Isobe et al. Diabetes with preserved renal function is an independent risk factor for renal function deterioration after coronary computed tomography angiography
Yamada et al. Evaluation of the relationship between glycated hemoglobin A1c and mean glucose levels derived from the professional continuous flash glucose monitoring system
JP4889116B2 (en) Method for calculating accurate blood glucose control status and liver function in liver disease
Wahl et al. Diabetes diagnostics including analytical methods for glucose monitoring
Nichols What is accuracy and how close must the agreement be?
Schumacher A misdiagnosis of type 2 diabetes mellitus: Using continuous glucose monitoring to improve patient-centered care
JP7383259B2 (en) Method for determining sensitivity to SGLT2 inhibitors and markers for sensitivity to SGLT2 inhibitors
Ng et al. Aberrantly high glycated haemoglobin measurement due to the haemoglobin
Ling et al. Impact of Body Composition and Anemia on Accuracy of a Real-Time Continuous Glucose Monitor in Diabetes Patients on Continuous Ambulatory Peritoneal Dialysis
Edelman et al. Multisite evaluation of a new diabetes self-test for glucose and glycated protein (fructosamine)
JP7282298B2 (en) Estimation method and average blood glucose level estimation system
Chantler et al. Self-prepared heparinized syringes for measuring ionized magnesium in critical care patients.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09818979

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2010532814

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09818979

Country of ref document: EP

Kind code of ref document: A1