Biomarkers for Cardiodiabetes

Abstract

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.

We claim: 
     
         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.