Methods for the diagnosis of metabolic disorders using epimetabolic shifters, multidimensional intracellular molecules, or environmental influencers

Abstract

Methods and formulations for diagnosing metabolic disorders in humans using epimetabolic shifters, multidimensional intracellular molecules or environmental influencers are described.

1 - 55 . (canceled) 
     
     
         56 . A method of assessing whether a subject is afflicted with a CoQ10 responsive state, the method comprising:
 (1) determining the level of expression of at least one marker present in a biological sample obtained from the subject, wherein the biological sample obtained from the subject is exposed to CoQ10; and wherein the at least one marker is selected from the group consisting of the markers listed in Tables 2-4, 6-29 and 64-69; and   (2) comparing the level of expression of the at least one marker present in the biological sample obtained from the subject with the level of expression of the at least one marker present in a control sample,   wherein a modulation in the level of expression of the at least one marker in the biological sample obtained from the subject relative to the level of expression of the at least one marker in the control sample is an indication that the subject is afflicted with the CoQ10 responsive state, thereby assessing whether the subject is afflicted with a CoQ10 responsive state.   
     
     
         57 . The method of  claim 56 , wherein the CoQ10 responsive state is a metabolic disorder. 
     
     
         58 . The method of  claim 57 , wherein the metabolic disorder is selected from the group consisting of diabetes, obesity, pre-diabetes, Metabolic Syndrome, satiety and endocrine abnormalities. 
     
     
         59 . The method of  claim 58 , wherein the metabolic disorder is diabetes. 
     
     
         60 . The method of  claim 56 , wherein the at least one marker is selected from the group consisting of AGT, BCL2L1, CCL5, CEACAM1, DUSP4, ENPP1, GRPEL1, IL6, INSR, MFN1, NFKB1, PIK3C2B, PMAIP1, PRKCB, SELL, SLC25A1, SLC25A3, SLC25A13, SLC25A19, SLC25A22, SNAP25, TIMM44, TNF, TOMM40 and TSPO. 
     
     
         61 . The method of  claim 60 , wherein the at least one marker is selected from the group consisting of BCL2L1, CCL5, DUSP4, ENPP1, GRPEL1, IL6, INSR, MFN1, NFKB1, PIK3C2B, PMAIP1, PRKCB, SELL, SLC25A1, SLC25A3, SLC25A13, SLC25A19, SLC25A22, SNAP25, TIMM44, TOMM40 and TSPO. 
     
     
         62 . The method of  claim 61 , wherein the at least one marker is selected from the group consisting of BCL2L1, CCL5, GRPEL1, MFN1, PMAIP1, SLC25A1, SLC25A13, SLC25A19, SLC25A22, SLC25A3, TIMM44, TOMM40 and TSPO. 
     
     
         63 . The method of  claim 61 , wherein the at least one marker is selected from the group consisting of DUSP4, ENPP1, IL6, INSR, NFKB1, PIK3C2B, PRKCB, SELL and SNAP25. 
     
     
         64 . The method of  claim 56 , wherein the sample comprises a fluid obtained from the subject. 
     
     
         65 . The method of  claim 64 , wherein the fluid is selected from the group consisting of blood fluids, vomit, saliva, lymph and urine. 
     
     
         66 . The method of  claim 65 , wherein the sample is a blood sample or a component thereof. 
     
     
         67 . The method of  claim 56 , wherein the sample comprises a tissue or component thereof obtained from the subject. 
     
     
         68 . The method of  claim 67 , wherein the tissue is selected from the group consisting of bone, connective tissue, cartilage, lung, liver, kidney, muscle tissue, heart, pancreas and skin. 
     
     
         69 . The method of  claim 56 , wherein the subject is a human. 
     
     
         70 . The method of  claim 56 , wherein the level of expression of the at least one marker in the biological sample is determined by assaying a transcribed polynucleotide or a portion thereof in the sample. 
     
     
         71 . The method of  claim 70 , wherein assaying the transcribed polynucleotide comprises amplifying the transcribed polynucleotide. 
     
     
         72 . The method of  claim 56 , wherein the level of expression of the at least one marker in the subject sample is determined by assaying a protein or a portion thereof in the sample. 
     
     
         73 . The method of  claim 56 , wherein the at least one marker is assayed using a reagent which specifically binds the at least one marker. 
     
     
         74 . The method of  claim 73 , wherein the reagent is labeled. 
     
     
         75 . The method of  claim 73 , wherein the reagent is selected from the group consisting of an antibody and an antigen-binding antibody fragment. 
     
     
         76 . The method of  claim 56 , wherein the level of expression of the at least one marker in the sample is determined using a technique selected from the group consisting of polymerase chain reaction (PCR) amplification reaction, reverse-transcriptase PCR analysis, single-strand conformation polymorphism analysis (SSCP), mismatch cleavage detection, heteroduplex analysis, Southern blot analysis, Northern blot analysis, Western blot analysis, in situ hybridization, array analysis, deoxyribonucleic acid sequencing, restriction fragment length polymorphism analysis, and combinations or sub-combinations thereof, of said sample. 
     
     
         77 . The method of  claim 56 , wherein the level of expression of the at least one marker in the sample is determined using a technique selected from the group consisting of immunohistochemistry, immunocytochemistry, flow cytometry, ELISA and mass spectrometry. 
     
     
         78 . The method of  claim 56 , wherein the levels of expression of a plurality of markers are determined. 
     
     
         79 . A method of assessing the efficacy of CoQ10 for treating a metabolic disorder in a subject, the method comprising: comparing
 (1) the level of expression of at least one marker present in a first sample obtained from the subject prior to administering at least a portion of CoQ10 to the subject, wherein the at least one marker is selected from the group consisting of the markers listed in Tables 2-4, 6-29 and 64-69; with   (2) the level of expression of at least one corresponding marker present in a second sample obtained from the subject following administration of at least the portion of CoQ10,   wherein a modulation in the level of expression of the marker in the second sample as compared to the first sample is an indication that CoQ10 is efficacious for treating the metabolic disorder in the subject.   
     
     
         80 . A method of assessing the efficacy of CoQ10 for treating a metabolic disorder in a subject in need thereof, the method comprising:
 (1) determining the level of expression of at least one marker present in a biological sample obtained from the subject, wherein the biological sample is exposed to CoQ10, and wherein the at least one marker is selected from the group consisting of the markers listed in Tables 2-4, 6-29 and 64-69 with a positive fold change and/or with a negative fold change;   (2) determining the level of expression of the at least one corresponding marker present in a second biological sample obtained from the subject, wherein the sample is not exposed to CoQ10; and   (3) comparing the level of expression of the at least one marker in the biological sample exposed to CoQ10 and the level of expression of the at least one corresponding marker in the biological sample not exposed to CoQ10,   (4) wherein a decrease in the level of expression of the at least one marker with a negative fold change present in the biological sample exposed to CoQ10 relative to the level of expression of the at least one corresponding marker present in the second sample is an indication that CoQ10 is efficacious for treating the metabolic disorder in the subject in need thereof, and,   wherein an increase in the level of expression of the at least one marker with a positive fold change present in the biological sample exposed to CoQ10 relative to the level of expression of the at least one corresponding marker present in the second sample is an indication that CoQ10 is efficacious for treating the metabolic disorder in the subject in need thereof,   thereby assessing the efficacy of CoQ10 for treating the metabolic disorder.