Postprandial hyperglycemia marker, method of measuring the same, and usage thereof

• US 8,637,275 B2
• Filed: 08/10/2007
• Issued: 01/28/2014
• Est. Priority Date: 08/11/2006
• Status: Active Grant

• Current Assignee: ARKRAY, Inc
• Original Assignee: ARKRAY, Inc
• Inventors: Yonehara, Satoshi, Imai, Toshihiro
• Primary Examiner(s): Shen, Bin
• Application Number:
  US12/376,914
• Publication Number:
  US 20100190194A1
• Time in Patent Office: 2,363 Days
• Field of Search: 435/69.6
• US Class Current: 435/69.6
• CPC Class Codes: G01N 2030/027 Liquid chromatography
• CPC Class Codes: G01N 2333/906 acting on nitrogen containing compounds as donors (1.4, 1.5, 1.7)
• CPC Class Codes: G01N 27/447 using electrophoresis
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 33/723 Glycosylated haemoglobin

Abstract

A new method of diagnosing postprandial hyperglycemia by indirectly measuring a blood glucose level is provided. Postprandial hyperglycemia is detected by measuring a glycation degree of lysine in hemoglobin, in which a side chain amino group of lysine is glycated (GHbLys %). Measurement of GHbLys % can be performed by cleaving hemoglobin by protease, treating a glycated part of a lysine residue in the obtained cleavage product of hemoglobin with fructosyl amino acid oxidase, and measuring a redox reaction between the glycated part and fructosyl amino acid oxidase.

Claims

1. A method of determining a risk for a specimen to develop diabetes, wherein the method of determining a risk comprises following process (a) and (b):

(a1) a process of measuring a postprandial hyperglycemia marker, wherein the postprandial hyperglycemia marker comprises hemoglobin having a glycated lysine residue, by measuring a glycation degree of a lysine residue of hemoglobin by a method comprising a step of at least one selected from the group consisting of applying a high-performance liquid chromatography method, an immunization method, an enzymatic method and an electrophoresis method with respect to a blood sample obtained from the specimen;

(a2) a process of determining a risk for the specimen based on the postprandial hyperglycemia marker measured by the step (a1); and

(b) a process of determining a risk for the specimen to develop diabetes by at least one method selected from the group consisting of (b1) to (b5) using the glycation degree of the lysine residue of hemoglobin measured in the process (a);

(b1) setting a boundary value between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a glycation degree of a lysine residue of hemoglobin in blood collected from a postprandial hyperglycemia patient as an evaluation criterion, and determining the risk for developing diabetes being relatively high in a case where the glycation degree of the lysine residue of the specimen measured in the process (a) is relatively higher than the evaluation criterion;

(b2) setting a calculation value of a glycation degree of a lysine residue of hemoglobin, which is obtained by substituting a blood glucose level of blood collected from the specimen in the fasting state into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a blood glucose level of blood collected from a healthy subject in the fasting state, as an evaluation criterion, and determining the risk for developing diabetes being relatively high in a case where the glycation degree of the lysine residue of the specimen measured in the process (a) is relatively higher than the evaluation criterion;

(b3) setting a blood glucose level of blood collected from the specimen in the fasting state as an evaluation criterion, on the other hand, obtaining a calculation value of the blood glucose level of the specimen in the fasting state by substituting the glycation degree of the lysine residue of the specimen measured in the process (a) into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a blood glucose level of blood collected from a healthy subject in the fasting state, and determining the risk for developing diabetes being relatively high in a case where the calculation value of the blood glucose level of the specimen in the fasting state is relatively higher than the evaluation criterion;

(b4) setting a calculation value of a glycation degree of a lysine residue of hemoglobin, which is obtained by substituting a glycation degree of a 13 chain N-terminal amino acid residue of hemoglobin in blood collected from the specimen into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a glycation degree of a 13 chain N-terminal amino acid residue of hemoglobin in blood collected from a healthy subject, as an evaluation criterion, and determining the risk for developing diabetes being relatively high in a case where the glycation degree of the lysine residue of the specimen measured in the process (a) is relatively higher than the evaluation criterion; and

(b5) setting a glycation degree of a β

chain N-terminal amino acid residue of hemoglobin in blood collected from the specimen as an evaluation criterion, on the other hand, obtaining a calculation value of the glycation degree of a β

chain N-terminal amino acid residue of hemoglobin of the specimen by substituting the glycation degree of the lysine residue of the specimen measured in the process (a) into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a glycation degree of a β

chain N-terminal amino acid residue of hemoglobin in blood collected from a healthy subject, and determining the risk for developing diabetes being relatively high in a case where the calculation value of the glycation degree of the β

chain N-terminal amino acid of hemoglobin is relatively higher than the evaluation criterion.

2. A method of diagnosing postprandial hyperglycemia of a specimen, wherein the method comprises the processes (c) and (d):

(c1) a process of measuring a postprandial hyperglycemia marker, wherein the postprandial hyperglycemia marker comprises hemoglobin having a glycated lysine residue, by measuring a glycation degree of a lysine residue of hemoglobin by a method of measuring comprising a step of at least one selected from the group consisting of applying a high-performance liquid chromatography method, an immunization method, an enzymatic method and an electrophoresis method with respect to a blood sample obtained from the specimen; and

(c2) a process of determining a risk for the specimen based on the postprandial hyperglycemia marker measured by the step (c1) by at least one method selected from the group consisting of (d1) to (d5);

(d1) setting a boundary value between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a glycation degree of a lysine residue of hemoglobin in blood collected from a postprandial hyperglycemia patient as an evaluation criterion, and determining the specimen being postprandial hyperglycemia in a case where the glycation degree of the lysine residue of the specimen measured in the process (c) is relatively higher than the evaluation criterion;

(d2) setting a calculation value of a glycation degree of a lysine residue of hemoglobin, which is obtained by substituting a blood glucose level of blood collected from a specimen in the fasting state into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a blood glucose level of blood collected from a healthy subject in the fasting state, as an evaluation criterion, and determining the specimen being postprandial hyperglycemia in a case where the glycation degree of the lysine residue of the specimen measured in the process (c) is relatively higher than the evaluation criterion;

(d3) setting a blood glucose level of blood collected from the specimen in the fasting state as an evaluation criterion, on the other hand, obtaining a calculation value of the blood glucose level of the specimen in the fasting state by substituting the glycation degree of the lysine residue of the specimen measured in the process (c) into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a blood glucose level of blood collected from a healthy subject in the fasting state, and determining the specimen being postprandial hyperglycemia in a case where the calculation value of the blood glucose level of the specimen in the fasting state is relatively higher than the evaluation criterion;

(d4) setting a calculation value of a glycation degree of a lysine residue of hemoglobin, which is obtained by substituting a glycation degree of a 13 chain N-terminal amino acid residue of hemoglobin in blood collected from the specimen into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a glycation degree of a 13 chain N-terminal amino acid residue of hemoglobin in blood collected from a healthy subject, as an evaluation criterion, and determining the specimen being postprandial hyperglycemia in a case where the glycation degree of the lysine residue of the specimen measured in the process (c) is relatively higher than the evaluation criterion; and

(d5) setting a glycation degree of a 13 chain N-terminal amino acid residue of hemoglobin in blood collected from a specimen as an evaluation criterion, on the other hand, obtaining a calculation value of the glycation degree of the β

chain N-terminal amino acid residue of hemoglobin of the specimen by substituting the glycation degree of the lysine residue of the specimen measured in the process (a) into a relational expression between a glycation degree of a lysine residue of hemoglobin in blood collected from a healthy subject and a glycation degree of a β

chain N-terminal amino acid residue of hemoglobin in blood collected from a healthy subject, and determining the risk being relatively high in a case where a calculation value of the glycation degree of the β

chain N-terminal amino acid of hemoglobin is relatively higher than the evaluation criterion.

3. A method of measuring an average blood glucose level reflecting a postprandial blood glucose level, wherein the method comprises following processes (x) and (y):

(x) a process of measuring a glycation degree of a lysine residue of hemoglobin by a method of measuring a postprandial hyperglycemia marker comprising a step of at least one selected from the group consisting of applying a high-performance liquid chromatography method, an immunization method, an enzymatic method and an electrophoresis method with respect to a blood sample obtained from a specimen, wherein the postprandial hyperglycemia marker comprises hemoglobin having a glycated lysine residue; and

(y) a process of calculating the average blood glucose level reflecting a postprandial blood glucose level by substituting the glycation degree of the lysine residue of hemoglobin measured in the process (x) to a standard curve showing a relationship between a glycation degree of a lysine residue of hemoglobin and an average blood glucose level reflecting postprandial blood glucose level, wherein the standard curve is formed by plotting with respect to each of plural patients having postprandial blood glucose levels different from each other, a glycation degree of lysine residue (GHbLys %) and an average blood glucose level calculated based on blood glucose levels in blood samples collected two or more times from the same patient.