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

• US 6,468,802 B1
• Filed: 02/08/2001
• Issued: 10/22/2002
• 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: Foster, Robert T., Yatscoff, Randall W., Lewanczuk, Richard, Aspeslet, Launa J.
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US09/674,806
• Time in Patent Office: 621 Days
• Field of Search: 436/814, 436/56, 436/173, 436/181, 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

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 diagnostic kit for the determination of glycemic control in a subject comprising:

a predetermined quantity of uniformly labeled ¹³C-enriched glucose; and

a breath collection container.

2. A diagnostic kit according to claim 1, which comprises a first breath collection container for receiving a baseline breath sample taken from the subject prior to ingestion of any of the predetermined quantity of the uniformly labeled ¹³C-enriched glucose;

and a second breath collection container for receiving a breath sample after the uniformly labeled ¹³C-enriched glucose is ingested.

3. A diagnostic kit according to claim 2, further comprising a set of instructions wherein the instructions direct the subject to collect a first breath sample in said first breath collection container, ingest the uniformly labeled ¹³C-enriched glucose and collect a second breath sample at a time point that is after ingestion of the uniformly labeled ¹³C-enriched glucose, in said second breath collection container.

4. A diagnostic kit according to claim 1, wherein the determination of glycemic control is indicative for the diagnosis of diabetes in the subject.

5. A diagnostic kit according to claim 1, wherein the determination of glycemic control is indicative for the diagnosis of insulin resistance in the subject.

6. A diagnostic kit according to claim 1, wherein the determination of glycemic control is indicative for the diagnosis of gestational diabetes in the subject.

7. A diagnostic kit according to claim 1, wherein the determination of glycemic control is indicative for the determination of adequacy of antihyperglycemic therapy in the subject.

8. A diagnostic kit according to claim 1, further comprising a tube that transfers the breath of the subject into the breath collection container.

9. A diagnostic kit according to claim 1 further including analysis means for measuring ¹³CO₂ metabolized from said uniformly labeled ¹³C-enriched glucose, in a breath sample, said analysis means being selected from the group consisting of an isotope ratio mass spectroscope (IRMS), a continuous flow isotope ratio mass spectroscope (CF-IRMS) and a non-dispersive infrared spectroscopy (NDIRS).

10. The diagnostic kit of claim 9 wherein said analysis means is CF-IRMS.

11. The diagnostic kit of claim 9 wherein said analysis means is NDIRS.

12. A diagnostic kit according to claim 1, wherein said predetermined quantity contains 25 mg or less of the uniformly labeled ¹³C-enriched glucose.

13. A diagnostic kit according to claim 12, further comprising about 15 g of unlabeled glucose.

14. A diagnostic kit according to claim 1, wherein said predetermined quantity comprises about 25 mg of the uniformly labeled ¹³C-enriched glucose.

15. A method for the determination of glycemic control in a subject comprising:

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

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

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

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

e) comparing the amount of ¹³CO₂ in said second breath sample with the amount of ¹³CO₂ in said first breath sample wherein the difference between said amounts of ¹³CO₂ determines the glycemic control in the subject.

16. The method according to claim 15, wherein the determination of glycemic control is indicative for the detection of diabetes in the subject.

17. The method according to claim 15, wherein the determination of glycemic control is indicative for the detection of gestational diabetes in the subject.

18. The method according to claim 15, wherein the determination of glycemic control is indicative for the detection of insulin resistance in the subject.

19. The method according to claim 15, wherein the determination of glycemic control is indicative for the determination of adequacy of antihyperglycemic therapy in the subject.

20. A diagnostic kit for the determination of glycemic control in normal, diabetic and insulin resistant subjects by comparing blood glucose levels with breath levels of ¹³C-enriched CO₂ comprising:

a predetermined quantity of uniformly labeled ¹³C-enriched glucose;

a breath collection container; and

a blood sampling device.

21. A diagnostic kit according to claim 20, which comprises a first breath collection container for receiving a baseline breath sample taken from the subject prior to ingestion of any of the predetermined quantity of the uniformly labeled ¹³C-enriched glucose;

and a second breath collection container for receiving a breath sample after the uniformly labeled ¹³C-enriched glucose is ingested.