Biomarkers for Cardiodiabetes
The invention provides compositions and methods for determining cardiodiabetes status in a subject. The invention also provides compositions and methods for treating a subject experiencing cardiodiabetes.
1 . A composition comprising a solid support comprising:
(a) a capture binding ligand selective for adiponectin,
(b) a capture binding ligand selective for hsCRP, and
(c) a capture binding ligand selective for intact proinsulin.
2 . The composition of claim 1 wherein one of the capture binding ligands comprises an antibody.
3 . The composition of claim 1 wherein the composition further comprises:
(a) a soluble capture ligand selective for adiponectin,
(b) a soluble capture ligand selective for hsCRP, and
(c) a soluble capture ligand selective for intact proinsulin.
4 . The composition of claim 3 wherein each of the soluble capture ligands comprises a detectable marker.
5 . The composition of claim 4 wherein a detectable marker is a fluorophore.
6 . The composition of claim 4 wherein a detectable marker is a conjugated enzyme.
7 . The composition of claim 6 Wherein the conjugated enzyme is horseradish peroxidase.
8 . The composition of claim 1 further comprising a detector.
9 . A method of treating cardiodiabetes in a subject comprising
(a) measuring the concentration of a biomarker panel in a sample from the subject, the biomarker panel consisting of adiponectin, hsCRP and intact proinsulin; and
(b) effecting a therapy with respect to the subject.
10 . The method of claim 9 wherein if the risk level associated with each of the concentrations of adiponectin, hsCRP and intact proinsulin respectively is selected from (a) high, high and high; (b) high, medium and high; (c) medium, high and high; (d) low, high and high; (e) low, medium and high; and (0 low, low and high, then the subject is administered a glitazone and a drug or combination of drugs selected from a GLP-1 analog and an insulin.
11 . The method of claim 9 wherein if the risk level associated with each of the concentrations of adiponectin, hsCRP and intact proinsulin respectively is selected from. (a) high, low and high; (b) medium, medium and high; and (c) medium, low and high, then the subject is administered a glitazone and a drug or combination of drugs selected from a GLP-1 analog, an insulin and a DPPIV inhibitor.
12 . The method of claim 9 if the risk level associated with each of the concentrations of adiponectin, hsCRP and intact proinsulin respectively is selected from (a) high, high and low;
(b) medium, high and low; (c) low, high and low; (d) low, medium and low; and (e) low, low and low, then the subject is administered metformin and a drug or combination of drugs selected from a glitazone, a GLP-1 analog, a DPPIV inhibitor and an insulin,
13 . The method of claim 9 wherein it' the risk level associated with each of the concentrations of adiponectin, hsCRP and intact proinsulin respectively is selected from (a) high, medium and low; (b) high, low and low; (c) medium, medium and low; and (d) medium, low and low, then the therapy comprises administering metformin and a drug or combination of drugs selected from a glitazone, a DPPIV inhibitor and an insulin.
14 . The method of any of claims 9 - 12 wherein the subject is not administered a drug or combination of drugs selected from a sulfonylurea and a glinide.
15 . The method of any of claims 9 - 14 wherein the subject is administered one or more additional drugs comprising one or more glucose lowering drugs.
16 . The method of claim 9 wherein the sample comprises blood.
17 . The method of claim 9 claim further comprising taking a measurement of at least one additional biomarker.
18 . The method of claim 17 wherein the additional biomarker is selected from the group consisting of leptin, mRNAx, NFκB, m IL-6, MMP-9, TNFα, NFκB, eNOS, PPARγ, MCP-1, PAI-1, ICAM/VCAM, E-selectin, P-selectin, von Willebrand factor, sCD40L, insulin, glucose, HbAlc, free fatty acids, triglycerides, VLDL, small dense LDL, oxidized LDL, resistin, HDL, NO, IκB-α, p105, Re1A, TNFα, MIF, inflammatory cytokines and molecules involved in signaling pathways.
19 . The method of claim 18 wherein the additional biomarker is MMP-9.
20 . The method of claim 19 wherein the concentration of intact proinsulin, hsCRP and adiponectin in the sample is measured and each is a high risk concentration.
21 . The method of claim 18 wherein the additional biomarker is leptin.
22 . A method of treating cardiodiabetes in a subject comprising:
(a) contacting a sample from the subject with the composition of claim 1 :
(b) measuring the concentration of a biomarker panel in the sample from the subject, the biomarker panel consisting of adiponectin, hsCRP and intact proinsulin: and
(c) effecting a therapy with respect to the subject.