Method for measuring carbohydrate metabolism ability, and composition for use in said method

• US 10,228,365 B2
• Filed: 08/20/2013
• Issued: 03/12/2019
• Est. Priority Date: 08/20/2012
• Status: Active Grant

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Inventors: Inada, Makoto, Kunizaki, Jun-ichi, Tobita, Kazuki, Akamatsu, Suguru
• Primary Examiner(s): Wallenhorst, Maureen
• Application Number:
  US14/423,021
• Publication Number:
  US 20150204852A1
• Time in Patent Office: 2,030 Days
• Field of Search: 436 8, 436 14, 436 56, 436 57, 436 95, 436133, 435 14
• CPC Class Codes: A61B 5/0813 Measurement of pulmonary parameters by tracers, e.g. radioactive tracers
• CPC Class Codes: A61B 5/0836 Measuring rate of CO2 production
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: G01N 2400/00 Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath
• CPC Class Codes: G01N 33/5038 involving detection of metabolites per se
• CPC Class Codes: G01N 33/5088 of vertebrates
• CPC Class Codes: G01N 33/60 involving radioactive labelled substances
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/204998 Inorganic carbon compounds

Abstract

A method is provided for measuring and evaluating rapidly and with high accuracy a subject'"'"'s glucose metabolism. The method uses a labeled C-breath test and a composition that is suitably used in the method. The composition contains as active ingredient glucose labeled with at least one isotope of C, wherein the glucose is converted in the subject to labeled carbon dioxide that is excreted in expired air. This method also allows for the determination of a stage of a patient in whom diabetes has developed as well as for a stage before the onset of diabetes, and monitors the state (diabetes condition including a state before onset of diabetes) over time.

Claims

1. A method for measuring glucose metabolism of a subject comprising:

(a) administering a composition to the subject and collecting expired air of the subject after the administration of the composition, wherein the composition comprises glucose labeled with at least one isotope of C; and

(b) determining a ratio of labeled CO₂ amount to unlabeled CO₂ amount or a ratio of labeled CO₂ amount to total CO₂ amount contained in the expired air of step (a) to generate a subject value;

(c) comparing the subject value, which is “

the ratio of labeled CO₂ amount to unlabeled CO₂ amount or the ratio of labeled CO₂ amount to total CO₂ amount”

obtained in the subject in step (b), to a control value, which is “

a ratio of labeled CO₂ amount to unlabeled CO₂ amount or a ratio of labeled CO₂ amount to total CO₂ amount”

of a non-diabetic subject;

(d) detecting that the glucose metabolism of the subject is enhanced when the subject value is higher than the control value and (e) determining that the subject whose glucose metabolism is detected to be enhanced in step (d) is in a stage before onset of diabetes.

2. The method according to claim 1, wherein the subject is in a glucose-loaded state.

3. The method according to claim 2, wherein the glucose-loaded subject has taken, before step (a), a saccharide, a food or beverage comprising a saccharide, or a food or beverage comprising a component that is metabolized to a saccharide.

4. The method according to claim 1, wherein the expired air is collected at least at one point in time within 120 minutes after administration of the composition to the subject.

5. The method according to claim 1, wherein the non-diabetic subject is a subject in which diabetes has not developed, and that is not in a stage before onset of diabetes.

6. A method for detecting a stage before onset of diabetes in a subject comprising, using, as an index, glucose metabolism of the subject obtained by a method for measuring glucose metabolism of a subject comprising:

(a) administering a composition to the subject and collecting expired air of the subject after the administration of the composition, wherein the composition comprises glucose labeled with at least on isotope of C; and

(b) determining a ratio of labeled CO₂ amount to unlabeled CO₂ amount or a ratio of labeled CO₂ amount to total CO₂ amount contained in the expired air of step (a) to generate a subject value; and

(c) comparing the subject value, which is “

the ratio of labeled CO₂ amount to unlabeled CO₂ amount or the ratio of labeled CO₂ amount to total CO₂ amount”

obtained in the subject in step (b), to a control value, which is “

a ratio of labeled CO₂ amount to unlabeled CO₂ amount or a ratio of labeled CO₂ amount to total CO₂ amount”

of a non-diabetic subject, wherein when the subject value is higher than the control value, the glucose metabolism of the subject is enhanced; and

determining that the subject is in a stage before onset of diabetes when the glucose metabolism of the subject is enhanced.

7. The method according to claim 6, wherein the non-diabetic subject is a subject in which diabetes has not developed, and that is not in a stage before onset of diabetes.