Biomarkers for pre-diabetes, cardiovascular diseases, and other metabolic-syndrome related disorders and methods using the same

A method of classifying a subject according to glucose tolerance from normal glucose tolerance (NGT), impaired fasting glucose tolerance (IFG), or impaired glucose tolerance (IGT), to type-2 diabetes, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for glucose tolerance in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Tables 4, 5, 6, 7, 8, 9A, 9B, and combinations thereof, and comparing the level(s) of the one or more biomarkers in the sample to glucose tolerance reference levels of the one or more biomarkers in order to classify the subject as having NGT, IFG, IGT, or diabetic.

A method of determining susceptibility of a subject to type-2 diabetes, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for pre-diabetes in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Tables 4, 5, 6, 7, 8, 9A, 9B, and combinations thereof;
• and comparing the level(s) of the one or more biomarkers in the sample to diabetes-positive and/or diabetes-negative reference levels of the one or more biomarkers in order to diagnose whether the subject is susceptible to developing type-2 diabetes.

A method of determining an insulin resistance score in a subject, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Tables 4, 5, 6, 7, 8, 9A, 9B, and combinations thereof;
• and comparing the level(s) of the one or more biomarkers in the sample to insulin resistance reference levels of the one or more biomarkers in order to determine an insulin resistance score for the subject.

A method of monitoring the progression or regression of pre-diabetes in a subject, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for pre-diabetes in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Tables 4, 5, 6, 7, 8, 9A, 9B, and combinations thereof;
• and comparing the level(s) of the one or more biomarkers in the sample to pre-diabetes progression and/or pre-diabetes-regression reference levels of the one or more biomarkers in order to monitor the progression or regression of pre-diabetes in a subject.

A method of diagnosing whether a subject has metabolic syndrome, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for metabolic syndrome in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Tables 12 and 13, analyzing the biological sample to determine the level(s) of one or more biomarkers for glucose disposal, obesity, and/or cardiovascular disease, wherein the one or more biomarkers for glucose disposal, obesity, and/or cardiovascular disease are selected from one or more biomarkers identified in Tables 4, 5, 6, 7, 8, 9A, 9B, 14, 15, 16, 17, 21, 22, 23, 25, 26, 27, 28, and combinations thereof, and
• comparing the level(s) of the one or more biomarkers in the sample to the respective disorder-positive and/or disorder-negative reference levels of the one or more biomarkers in order to diagnose whether the subject has the metabolic syndrome.

A method of diagnosing a cardiovascular disease in a subject, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for a cardiovascular disease in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Tables 14, 15, 16, 17, 21, 22, 23, 25, and combinations thereof;
• and comparing the level(s) of the one or more biomarkers in the sample to disease-positive and/or disease-negative reference levels of the one or more biomarkers in order to diagnose whether the subject has cardiomyopathy or atherosclerosis.

A method for determining whether a subject is predisposed to becoming obese, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for obesity in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Table 26;
• and comparing the level(s) of the one or more biomarkers in the sample to obesity-positive and/or obesity-negative and/or lean-positive and/or lean-negative reference levels of the one or more biomarkers in order to determine whether the subject is susceptible to obesity.

A method for determining whether a therapeutic agent is capable of inducing weight gain in a subject, the method comprising:

• analyzing a biological sample from a subject receiving a therapeutic agent to determine the level(s) of one or more biomarkers for obesity in the sample, wherein the one or more biomarkers are selected from one or more biomarkers listed in Table 26;
• and comparing the level(s) of the one or more biomarkers in the sample to obesity-positive and/or obesity-negative and/or lean-positive and/or lean-negative reference levels of the one or more biomarkers in order to determine whether the subject is susceptible to gaining weight.

A method for predicting a subject's response to a course of treatment for pre-diabetes or diabetes, the method comprising:

• analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for pre-diabetes, wherein the one or more biomarkers are selected from one or more biomarkers listed in Table 27;
• comparing the level(s) of one or more biomarkers in the sample to treatment-positive and/or treatment-negative reference levels of the one or more biomarkers to predict whether the subject is likely to respond to a course of treatment.