Dynamic hepatic recycling glucose tolerance test

A method for diagnosing diabetes mellitus, comprising:

• administering a plurality of labeled glucose molecules to a patient;
• quantifying the glucose flux and glucose recycling over time after said administration of labeled glucose;
• comparing quantified glucose flux and recycling with a standard to assess the status of the health of the patient;
• measuring insulin levels at time points after said administration of labeled glucose to said patient;
• and
• correlating said insulin levels with said quantified glucose flux and glucose recycling.

A method for screening drug candidates for biological activity for potential use in treating a hyperglycemic patient, comprising:

• labeling at least one carbon atom of a glucose molecule;
• introducing labeled glucose molecules into a mammalian test subject;
• introducing a candidate drug into said mammalian test subject;
• determining the rate of glucose flux through metabolic pathways in the liver and the peripheral muscles;
• and
• comparing determined flux rates with known baseline flux rates in the absence of said candidate drug.

A method for screening drug candidates for biological activity for potential use in treating a hyperglycemic patient, comprising:

• labeling at least one carbon atom of a glucose molecule;
• introducing labeled glucose molecules into a mammalian test subject;
• introducing a candidate drug into said mammalian test subject;
• determining the rate of glucose flux through metabolic pathways in the liver and the peripheral muscles;
• comparing determined flux rates with known baseline flux rates in the absence of said candidate drug;
• measuring hormone and metabolite levels of said test subject;
• and
• comparing said measured hormone and metabolite levels with known baseline levels of said hormone and metabolites in the absence of said candidate drug.

A method for screening drug candidates for biological activity for potential use in treating a hyperglycemic patient, comprising:

• labeling at least one carbon atom of a glucose molecule;
• introducing labeled glucose molecules into a mammalian test subject;
• introducing a candidate drug into said mammalian test subject;
• determining the rate of glucose flux through metabolic pathways in the liver and the peripheral muscles;
• comparing determined flux rates with known baseline flux rates in the absence of said candidate drug;
• measuring insulin levels at time points after introduction of labeled glucose into said test subject;
• and
• correlating said insulin levels with said rates of glucose flux in the presence of said candidate drug.

A method for screening drug candidates for biological activity for potential use in treating a hyperglycemic patient, comprising:

• labeling at least one carbon atom of a glucose molecule;
• introducing labeled glucose molecules into a mammalian test subject;
• introducing a candidate drug into said mammalian test subject;
• determining the rate of glucose flux through metabolic pathways in the liver and the peripheral muscles;
• comparing determined flux rates with known baseline flux rates in the absence of said candidate drug;
• collecting an array of measurements of flux rates, insulin, hormones and metabolite concentrations from a plurality of healthy individuals;
• collecting an array of measurements of flux rates, insulin, hormones and metabolite concentrations from a plurality of individuals with diagnosed hyperglycemia;
• and
• comparing said measurements of flux rates, insulin, hormones and metabolite concentrations from said test subject with said array of measurements from healthy individuals and said array of measurements from individuals diagnosed with hyperglycemia.

A method for screening drug candidates for biological activity for potential use in treating a hyperglycemic patient, comprising:

• labeling at least one carbon atom of a glucose molecule;
• introducing labeled glucose molecules into a mammalian test subject;
• introducing a candidate drug into said mammalian test subject;
• determining the rate of glucose flux through metabolic pathways in the liver and the peripheral muscles;
• and
• comparing determined flux rates with known baseline flux rates in the absence of said candidate drug;
• wherein said label of said glucose comprises [1, 2-13C2]-glucose.

A method for screening drug candidates for biological activity for potential use in treating a hyperglycemic patient, comprising:

• labeling at least one carbon atom of a glucose molecule;
• introducing labeled glucose molecules into a mammalian test subject;
• introducing a candidate drug into said mammalian test subject;
• determining the rate of glucose flux through metabolic pathways in the liver and the peripheral muscles;
• comparing determined flux rates with known baseline flux rates in the absence of said candidate drug;
• and
• monitoring glucose flux and recycling levels at different concentration levels of candidate drug to determine a minimum effective dose of candidate drug.

A method for screening drug candidates for biological activity for potential use in treating a hyperglycemic patient, comprising:

• labeling at least one carbon atom of a glucose molecule;
• introducing labeled glucose molecules into a mammalian test subject;
• introducing a candidate drug into said mammalian test subject;
• determining the rate of glucose flux through metabolic pathways in the liver and the peripheral muscles;
• comparing determined flux rates with known baseline flux rates in the absence of said candidate drug;
• and
• determining the rate of glucose recycling through metabolic pathways in the liver and the peripheral tissues.