Method of determination of risk of 2 hour blood glucose equal to or greater than 140 mg/dL

1. A method of treating and/or preventing diabetes or a related cardio-diabetes condition and comorbidity in a subject, comprising: administering to the subject a drug or supplement in an amount effective to treat diabetes or the related cardio-diabetes condition and comorbidity, wherein the subject has been determined to have abnormal glucose tolerance or to be at risk for developing abnormal glucose tolerance by:

a) obtaining a biological sample from the subject;

b) processing the biological sample by one of the following:

i) concentrating the biological sample to obtain a concentrated biological sample;

ii) fractionating the biological sample to obtain a fractionated biological sample; or

iii) separating the biological sample to obtain a separated biological sample;

c) obtaining, from the concentrated biological sample, the fractionated biological sample, or the separated biological sample, a measured level of a combination of biomarkers selected from the group consisting of, free fatty acids, glucose, myeloperoxidase, insulin, fibrinogen, and leptin, that predict and/or provide information about at least three physiological processes selected from the group consisting of, adipose tissue insulin resistance, pancreatic beta cell dysfunction and/or exhaustion, muscle and/or hepatic insulin resistance, functional enhancement of insulin secretion by beta cells, inhibition of beta cell function, adipokine function, total glycemic control, and inflammation,

d) calculating a score based on the measured levels of the combination of biomarkers, wherein the score calculation comprises:

ln

[

FFA

2.374

×

Glucose

5.248

×

MPO

1.7415

×

Insulin

1.037

×

Fibrinogen

3.037

Leptin

0.601

]

e) comparing the score to reference values from a population of randomly chosen subjects, with or without normal glucose tolerance, and

f) identifying the subject as likely to develop abnormal glucose tolerance if the calculated score is elevated, wherein an elevated score correlates with an increased likelihood of elevation of blood glucose to ≥140 mg/dL at 2 hours after oral glucose tolerance test.

2. The method of claim 1 , wherein the likelihood can be predicted by a single measurement of a single fasting sample.

3. The method of claim 1 , wherein the score replaces the oral glucose tolerance test (OGTT) to predict likelihood of the subject having abnormal glucose tolerance.

4. The method of claim 1 , wherein at least one of the biomarkers of the combination of biomarkers is a protein in a form of a monomer, a multimer, a complex with one or more other organic molecules, a normal (wild-type) form, a genetic variant with altered amino acid sequence or conformation, an isoform, a glycoform, a post-translationally modified form, an oxidized form, a form with altered biological function, a fragment/product of enzymatic cleavage, or an adduct with another chemical moiety.

5. The method of claim 1 , wherein at least one of the biomarkers of the combination of biomarkers predicts and/or provides information about adipose tissue insulin resistance, and wherein the at least one biomarker that predicts and/or provides information about adipose tissue insulin resistance is a total free fatty acid or a component fatty acid species of a total free fatty acid.

6. The method of claim 1 , wherein the mathematical transformation comprises:

i) multiplying the measured level of each biomarker of the combination of biomarkers by a pre-determined exponent;

ii) multiplying the products of the exponentiation generated from step i); and

iii) logarithmically transforming the multiplied product generated from step ii).

7. The method of claim 1 , further comprising:

obtaining values for one or more base model factors selected from the group consisting of age, sex, body mass index (BMI), and fasting glucose, to predict the likelihood of the subject having abnormal glucose tolerance;

calculating a based model score for the subject based on one or more values of the base model factors; and

combining the score obtained from step b) with the calculated base model score, wherein the combined score is compared to reference values from a population.

8. The method of claim 7 , wherein the base model factor is fasting glucose, and wherein the base model score is calculated by logarithmically transforming a measured level of fasting glucose in the subject.

9. The method of claim 7 , wherein the combining the score obtained from step b) with the base model score provides an improved likelihood prediction than the base model score alone.

10. The method of claim 7 , wherein the combining the score obtained from step b) with the base model score causes a net reclassification improvement (NRI) of the subject from having normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), or from having MT to NGT.

11. The method of claim 10 , wherein the NRI is at least about 10%.

12. The method of claim 1 , further comprising monitoring the levels of the biomarkers in the subject to assess progression, improvement, normalization, and/or treatment efficacy, wherein the monitoring step comprises repeating steps a)-c) based on the levels of the combination of biomarkers from a biological sample in the subject obtained at a later time.