Biomarkers Related to Insulin Resistance Progression and Methods Using the Same

Abstract

Biomarkers relating to insulin resistance and insulin resistance-related disorders are provided, as well as methods for using such biomarkers as biomarkers for insulin resistance, dysglycemia, type-2 diabetes, and cardiovascular disease. In addition, methods for monitoring the respective disorders or conditions of a subject are also provided. Also provided are suites of small molecule entities as biomarkers for insulin resistance, dysglycemia, type-2 diabetes, and cardiovascular disease.

1 - 40 . (canceled) 
     
     
         41 . A method of determining the level of two or more metabolites in a sample from a subject, the method comprising:
 extracting small molecules from a biological sample obtained from the subject to produce an analytical sample; and   performing mass spectrometry on the analytical sample to determine a level of 3-hydroxypropanoate and one or more additional metabolites in the sample, wherein the one or more additional metabolites are selected from the group consisting of cinnamoylglycine, 5alpha-androstan-3beta, 17alpha-diol disulfate, adrenate, and 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca).   
     
     
         42 . A method of determining the level of four or more metabolites in a sample from a subject, the method comprising:
 extracting small molecules from a biological sample obtained from the subject to produce an analytical sample; and   performing mass spectrometry on the analytical sample to determine a level of four or more metabolites, wherein the four or more metabolites are selected from the group consisting of 3-hydroxypropanoate, cinnamoylglycine, 5alpha-androstan-3beta, 17alpha-diol disulfate, adrenate, and 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca).   
     
     
         43 . The method of  claim 41 , wherein the one or more additional metabolites is cinnamoylglycine. 
     
     
         44 . The method of  claim 41 , wherein the one or more additional metabolites is 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca). 
     
     
         45 . The method of  claim 41 , wherein the method comprises determining the level of three metabolites. 
     
     
         46 . The method of  claim 45 , wherein the three metabolites comprise 3-hydroxypropanoate, cinnamoylglycine, and 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca). 
     
     
         47 . The method of  claim 45 , wherein the three metabolites comprise 3-hydroxypropanoate, cinnamoylglycine, and adrenate. 
     
     
         48 . The method of  claim 45 , wherein the three metabolites comprise 3-hydroxypropanoate, adrenate, and 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca). 
     
     
         49 . The method of  claim 41 , wherein the method comprises determining the level of four metabolites. 
     
     
         50 . The method of  claim 41 , wherein the method comprises determining the level of five metabolites. 
     
     
         51 . The method of  claim 41 , wherein the method further comprises performing liquid chromatography on the analytical sample. 
     
     
         52 . The method of  claim 41 , wherein the mass spectrometry is tandem mass spectrometry. 
     
     
         53 . The method of  claim 42 , wherein the method further comprises performing liquid chromatography on the analytical sample. 
     
     
         54 . The method of  claim 42 , wherein the mass spectrometry is tandem mass spectrometry.