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

• US 20050147560A1
• Filed: 02/28/2005
• Published: 07/07/2005
• Est. Priority Date: 05/06/1998
• Status: Active Grant

• 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.
• Granted Patent: US 7,118,919 B2
• Time in Patent Office: Days
• US Class Current: 424/9.100
• 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

1-23. -23. (canceled)

24. A diagnostic kit for the determination of insulin resistance in a subject by comparing blood glucose levels with breath levels of ¹³C-enriched CO₂ comprising:

(a) a predetermined quantity of ¹³C-enriched glucose; and

(b) a plurality of breath collection containers.

25. 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 ¹³CO₂ in said second breath sample with the amount of ¹³CO₂ in said first breath sample, wherein the presence of less ¹³CO₂ in said second breath sample compared to normal control values indicates insulin resistance in the subject.

26. The method of claim 25, 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.

27. The method of claim 26, wherein said cutoff of ROC values is 8 to 10.

28. The method of claim 27, wherein said ROC value is 9 to 10.

29. A diagnostic kit for the diagnosis of insulin resistance in a subject comprising:

(a) a predetermined quantity of ¹³C-enriched glucose; and

(b) a breath collection container.

30. A diagnostic kit according to claim 29 comprising at least two breath collection containers.

31. A diagnostic kit according to claim 30 further comprising a tube that is adapted for the transfer of the breath of a subject into the breath collection containers.

32. A diagnostic kit according to claim 30, further comprising a set of instructions, wherein the instructions direct the subject to:

(i) collect a first breath sample in a first breath collection container;

(ii) ingest the ¹³C-enriched glucose; and

(iii) collect a second breath sample in a second breath collection container at a time point that is after ingestion of the ¹³C-enriched glucose.

33. A diagnostic kit according to claim 29 further comprising analysis means for measuring ¹³CO₂ metabolized from said ¹³C-enriched glucose in a breath sample.

34. A diagnostic kit according to claim 29, further comprising a blood sampling device.

35. A diagnostic kit for monitoring the effect of insulin resistance therapy in a subject comprising:

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

(b) a breath collection container.

36. A diagnostic kit according to claim 35, wherein the insulin resistance therapy is selected from the group consisting of diet, exercise, and pharmacological.

37. A diagnostic kit according to claim 35 comprising at least two breath collection containers.

38. A diagnostic kit according to claim 37 further comprising a tube that is adapted for the transfer of the breath of a subject into the breath collection containers.

39. A diagnostic kit according to claim 35 further comprising a set of instructions, wherein the instructions direct the subject to:

(i) collect a first breath sample in a first breath collection container;

(ii) ingest the ¹³C-enriched glucose; and

(iii) collect a second breath sample in a second breath collection container at a time point that is after ingestion of the ¹³C-enriched glucose.

40. 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.

41. 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.