13C glucose breath test for the diagnosis of diabetic indications and monitoring glycemic control

• US 7,118,919 B2
• Filed: 02/28/2005
• Issued: 10/10/2006
• Est. Priority Date: 05/06/1998
• Status: Expired due to Fees

• Current Assignee: Isotechnika Inc. (Endo International PLC)
• Original Assignee: Isotechnika Inc. (Endo International PLC)
• Inventors: Aspeslet, Launa J., Foster, Robert T., Yatscoff, Randall W., Lewanczuk, Richard
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US11/069,169
• Publication Number:
  US 20050147560A1
• Time in Patent Office: 589 Days
• Field of Search: 436/56, 436/181, 436/8, 436/14, 422/61, 435/14
• US Class Current: 436/56
• 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 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61K 51/1206 Administration of radioactive gases, aerosols or breath tests
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath
• CPC Class Codes: Y10T 436/104998 Glucose, ketone, nitrate standard or control
• CPC Class Codes: Y10T 436/13 Tracers or tags
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
• CPC Class Codes: Y10T 436/25875 Gaseous sample or with change of physical state

Abstract

Use of ¹³C glucose in an analytical assay to monitor glucose metabolism by measurement of labeled exhaled CO₂ is provided. A breath test and kit for performing the breath test are described for the diagnosis of diabetic indications and monitoring of glycemic control. The breath test utilizes the measurement of expired ¹³C-labeled CO₂ following the ingestion of a ¹³C-enriched glucose source.

Claims

1. A method of diagnosing insulin resistance in a subject, said method comprising:

a) collecting a first breath sample from said subject in a first breath collection container;

b) administering ¹³C-enriched glucose to said subject;

c) collecting a second breath sample from said subject in a second breath container at a time point after administration of said ¹³C-enriched glucose;

d) measuring the ¹³CO₂ in each of said first and second breath samples; and

e) comparing the amount of ¹³CO₂in said second breath sample with the amount of ¹³CO₂in said first breath sample, wherein the presence of less ¹³CO₂in said second breath sample compared to normal control comparison values indicates insulin resistance in the subject wherein said comparison is made by choosing a cutoff of receiver operated characteristics (ROC) values wherein the sensitivity and specificity are such as to maximize diagnostic accuracy.

2. The method of claim 1, wherein said cutoff of ROC values is 8 to 10.

3. The method of claim 2, wherein said ROC value is 9 to 10.

4. A method of diagnosing insulin resistance in a subject, said method comprising:

a) collecting a first breath sample from said subject in a first breath collection container;

b) administering ¹³C-enriched glucose to said subject;

c) collecting a second breath sample from said subject in a second breath container at a time point after administration of said ¹³C-enriched glucose;

d) measuring the ¹³CO₂ in each of said first and second breath samples;

e) comparing the amount of ¹³CO₂ in said second breath sample with the amount of 13CO2 in said first breath sample to calculate a delta over baseline; and

f) diagnosing insulin resistance if the calculated delta over baseline for the subject is less than a standard delta over baseline of a normal individual or of a typical diabetic individual.

5. A method of diagnosing insulin resistance in a subject, said method comprising:

a) collecting a first breath sample from the subject in a first breath collection container;

b) administering ¹³C-enriched glucose to the subject;

c) collecting a second breath sample from the subject in a second breath container at a first time point after administration of the ¹³C-enriched glucose;

d) collecting a third breath sample from the subject in a third breath container at a second time point after administration of the ¹³C -enriched glucose;

e) measuring the ¹³CO₂ in each of the first, second and third breath samples to generate a breath test curve;

f) determining a blood glucose level of the subject prior to administration of the ¹³C-enriched glucose and at the first and second time points after administration to generate a blood glucose test curve;

g) diagnosing insulin resistance if the area between the breath test curve and the blood glucose test curve is less than that of a standard individual or of a typical diabetic individual.