Biomarkers

1. A method for diagnosing or monitoring diabetes in a subject, the method comprising:

(a) measuring the level of an insulin signal peptide (INS-SP) fragment defined by INS-SP (1-9) SEQ ID NO:16 in a biological sample from the subject; and

(b) comparing the level of INS-SP fragment with the INS-SP fragment level from a control,

wherein a measured level of INS-SP fragment lower than the control level is indicative of diabetes.

2. A method for diagnosing or monitoring an acute cardiac disorder (ACD) in a subject, the method comprising:

(a) measuring the level of on insulin signal peptide (INS-SP) fragment defined by INS-SP (1-9) SEQ ID NO:16 in a biological sample from the subject; and

(b) comparing the level of said INS-SP fragment with the INS-SP fragment level from a control,

wherein a measured level of INS-SP fragment higher than the control level is indicative of ACD.

3. A method of claim 2 , wherein said method is used to monitor a response to treatment of an acute cardiac disorder (ACD) in a subject, wherein a change in the measured level of INS-SP fragment from the control level is indicative of a response to the treatment.

4. A method of claim 2 , the method comprising measuring the level of INS-SP fragment in a biological sample from the subject within the first six hours of onset of, or clinical presentation with, acute cardiac disorder (ACD).

5. A method according to claim 2 , wherein the level of INS-SP fragment is measured within the first hour of onset of ACD, or clinical presentation with, acute cardiac disorder (ACD).

6. A method according to claim 2 , wherein a level of INS-SP fragment in the sample in the range 40 to 250 pmol/L, is indicative of ACD.

7. A method according to claim 2 , wherein a level of INS-SP fragment in the sample which is 5 to 15 times higher than the control level is indicative of ACD.

8. A method according to claim 2 , wherein the acute cardiac disorder is an acute myocardial infarction (AMI) with ST-elevation on presenting ECG, unstable angina, an acute non ST-elevated myocardial infarction; cardiac ischemia, acute cardiac injury, acute cardiac damage resulting from acute drug toxicity, an acute cardiomyopathy, or a cardiac transplant rejection episode.

9. A method according to claim 2 , wherein the biological sample is a blood, plasma, serum, saliva, interstitial fluid, urine or heart tissue sample.

10. A method according to claim 2 , wherein the measuring step comprises

(a) binding INS-SP fragment with a binding agent; and

(b) measuring the level of bound INS-SP fragment.

11. A method according to claim 2 , wherein the binding agent is a binding agent that specifically binds INS-SP (1-9) (SEQ ID NO:16).

12. A method according to claim 2 , wherein the level of INS-SP fragment is measured using an assay selected from mass spectroscopy (including SELDI, ESI, MALDI or FTIC), RIA, ELISA, fluoroimmunoassay, immunofluorometric assay, and immunoradiometric assay.

13. A method according to claim 2 , which further comprises measuring the level of one or more non-INS-SP fragment markers of said ACD, and comparing the levels against marker levels from a control wherein a deviation in the measured level from the control level, together with a measured level of INS-SP fragment which is higher than the control level of INS-SP fragment, is predictive or diagnostic of the ACD, or can be used to monitor said ACD.

14. A method as claimed in claim 13 wherein the non-INS-SP fragment markers are selected from the group consisting of troponin T, troponin I, creatine kinase-MB, myoglobin, ANP, ANP-SP, BNP, NT-BNP, BNP-SP, LDH, aspartate aminotransferase, H-FABP, endothelin, adrenomedullin, renin, ischemia modified albumin and angiotensin II.

15. A method according to claim 1 , which further comprises measuring the level of one or more non-INS-SP fragment markers of diabetes and comparing the levels against marker levels from a control wherein a deviation in the measured level from the control level of non-INS-SP fragment marker, together with a measured level of INS-SP fragment which is lower than the control level of INS-SP fragment, is predictive or diagnostic of diabetes or can be used to monitor diabetes.

16. A method as claimed in claim 15 wherein the non-INS-SP fragment markers are selected from the group consisting of glucose, insulin, lactate, trigyclerides and fatty acids or markers therefor.

17. The method of claim 2 wherein measuring the level of the INS-SP fragment is performed using an antibody or antigen-binding fragment of the antibody, which antibody or antigen-binding fragment selectively binds INS-SP (1-9) SEQ ID NO:16.

18. A method according to claim 1 , wherein said method is used to monitor a response to treatment of diabetes in a subject, wherein a change in the measured level of INS-SP fragment from the control level is indicative of a response to the treatment.

19. A method according to claim 1 , wherein the biological sample is a blood, plasma, serum, saliva, interstitial fluid, or urine.

20. A method according to claim 1 , wherein the measuring step comprises

(a) binding INS-SP fragment with a binding agent; and

(b) measuring the level of bound INS-SP fragment.

21. A method according to claim 20 , wherein the binding agent is a binding agent that specifically binds INS-SP (1-9) (SEQ ID NO:16).

22. A method according to claim 1 , wherein the level of INS-SP fragment is measured using an assay selected from mass spectroscopy (including SELDI, ESI, MALDI or FTIC), RIA, ELISA, fluoroimmunoassay, immunofluorometric assay, and immunoradiometric assay.

23. The method of claim 1 , wherein measuring the level of the INS-SP fragment is performed using an antibody or antigen-binding fragment of the antibody, which antibody or antigen-binding fragment selectively binds INS-SP (1-9) SEQ ID NO:16.