Biomarkers associated with pre-diabetes, diabetes and diabetes related conditions

Abstract

Biomarkers for pre-Diabetes, Diabetes and/or a Diabetes related conditions, and methods of their use, including the biomarkers in Tables 1 and 2 such as peroxiredoxin-2, complement C1q subcomponent subunit B, sulfhydryl oxidase 1 and apolipoprotein A-IV.

1 - 42 . (canceled) 
     
     
         43 . A method of assessing a subject for diabetic nephropathy comprising measuring at least one biomarker in a sample from the subject, wherein said at least one biomarker is selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV. 
     
     
         44 . A method according to  claim 43  wherein the at least one biomarker is at least two, three or four biomarkers selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV. 
     
     
         45 . A method according to  claim 43  wherein the at least one biomarker comprises Apoliprotein A-IV, Insulin-like growth factor-binding protein, Protein AMBP and Complement C1q. 
     
     
         46 . A method according to  claim 43  wherein the at least one biomarker comprises Peroxiredoxin-2, Protein AMBP and Complement C1q. 
     
     
         47 . A method according to  claim 43  wherein the at least one biomarker is Peroxiredoxin-2, Protein AMBP and Complement C1q. 
     
     
         48 . A method according to  claim 43  wherein the step of measuring at least one biomarker in a sample from the subject comprises the use of mass spectrometry to measure a peptide fragment of the at least one biomarker. 
     
     
         49 . A method according to  claim 48  where the peptide fragment is a 5-25 amino acid peptide of a protein selected from the list of proteins comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV. 
     
     
         50 . A method according to  claim 48  wherein the peptide fragment comprises at least two of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO:  9) 
                 
                     
                   ATAVVDGAFK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  10) 
                 
                     
                   TVAACNLPIVR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  11) 
                 
                     
                   EYCGVPGDGDEELLR; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  14) 
                 
                     
                   IAFSATR. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         51 . A method according to  claim 48  wherein the peptide fragment comprises at least two of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO:  17) 
                 
                     
                   FLNVLSPR 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  3) 
                 
                     
                   ISASAEELR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  10) 
                 
                     
                   TVAACNLPIVR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  11) 
                 
                     
                   EYCGVPGDGDEELLR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  7) 
                 
                     
                   SVSLPSLDPASAK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  14) 
                 
                     
                   IAFSATR; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO:  8) 
                 
                     
                   TEVIPPLIENR. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         52 . A method according to  claim 43  wherein the subject is asymptomatic for or only exhibits non-specific indicators of diabetic nephropathy. 
     
     
         53 . A method according to  claim 43  wherein the subject has been diagnosed with diabetic nephropathy. 
     
     
         54 . A method according  claim 43  wherein the subject has kidney disease. 
     
     
         55 . A method according to  claim 43  wherein the subject has microalbuminuria, macroalbuminuria or end stage renal disease. 
     
     
         56 . The method according to  claim 43  wherein the sample comprises a blood sample. 
     
     
         57 . A kit comprising reagents for measuring at least one biomarker in a sample from a subject, wherein said at least one biomarker is selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV. 
     
     
         58 . A computer readable medium having computer executable instructions for assessing a subject for diabetic nephropathy, the computer readable medium comprising: a routine, stored on the computer readable medium and adapted to be executed by a processor, to store biomarker measurement data representing at least one biomarker selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV. 
     
     
         59 . A method of assessing a treatment for diabetic nephropathy comprising measuring at least one biomarker, in a sample from a subject undergoing the treatment, selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV, at least twice over the course of the treatment. 
     
     
         60 . A test system comprising:
 means for obtaining test results data representing levels of at least one biomarker selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV, in a sample from the subject;   means for collecting and tracking the test results data generated in step (i);   means for calculating a diabetic nephropathy risk index value from the test results data, wherein said risk index value is representative of the risk of an individual developing or having diabetic nephropathy; and   means for reporting said risk index value.   
     
     
         61 . A method of evaluating the risk of a subject developing diabetic nephropathy comprising measuring at least one biomarker in a sample from the subject, wherein said at least one biomarker is selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV. 
     
     
         62 . A method of treating diabetic nephropathy in a subject comprising: evaluating risk, for the subject, of developing diabetic nephropathy using at least one biomarker selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV and treating the subject when identified as being at elevated risk for diabetic nephropathy related condition with a treatment regimen to delay or prevent the onset of diabetic nephropathy. 
     
     
         63 . A method of identifying or assessing an agent for treating or reducing the risk of developing diabetic nephropathy comprising:
 contacting cells expressing at least one biomarker selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV with a putative agent; and   comparing expression and/or levels of the at least one biomarker in the cells prior to contact with the putative agent to expression and/or levels of the at least one biomarker in the cells after contact with the putative agent;   wherein a change in the level or expression identifies the agent as an agent for treating diabetic nephropathy.   
     
     
         64 . Use of at least one biomarker selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV as a drug target for diabetic nephropathy. 
     
     
         65 . Use of an agent adapted to change the expression or level of at least one biomarker selected from the list of biomarkers comprising: Peroxiredoxin-2, Protein AMBP, Complement C1q, Insulin-like growth factor-binding protein, Complement factor H-related protein 2, Apolipoprotein B-100, Sulfhydryl oxidase 1 and Apolipoprotein A-IV for preparing a medication for treating or reducing the risk of developing diabetic nephropathy.