Diabetes-related biomarkers and methods of use thereof

• US 8,119,358 B2
• Filed: 04/18/2008
• Issued: 02/21/2012
• Est. Priority Date: 10/11/2005
• Status: Expired due to Fees

• Current Assignee: True Health Diagnostics LLC (True Health Group LLC)
• Original Assignee: Tethys Bioscience, Inc.
• Inventors: Urdea, Michael S., McKenna, Michael P., Arensdorf, Patrick A.
• Primary Examiner(s): COOK, LISA V
• Application Number:
  US12/106,070
• Publication Number:
  US 20090012716A1
• Time in Patent Office: 1,404 Days
• Field of Search: None
• US Class Current: 435/7.21
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/48714 for determining substances foreign to the organism, e.g. drugs or heavy metals drugs by chemical analysis G01N33/94
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The invention describes biomarkers which can be used to predict the likelihood that an individual will develop Diabetes. The biomarkers can also be used to screen large groups in order to identify individuals at risk of developing Diabetes.

Claims

1. A method comprising:

(a) obtaining measurements of biomarkers from at least one biological sample isolated from an individual, wherein said biomarkers comprise;

(i) at least three biomarkers, where three of the biomarkers are selected from the RDMARKER sets listed in FIG. 6A;

or

(ii) at least four biomarkers selected from RDMARKERS;

or

(iii) at least three biomarkers, where two biomarkers are selected from ADIPOQ;

CRP;

GLUCOSE;

GPT;

HBA1C;

HSPA1B;

IGFBP1;

IGFBP2;

INS, LEP; and

TRIG; and

one biomarker is selected from the ALLDBRISKS, CPs, and TLRFs of Table 1, Table 2, and Table 3;

or

(iv) at least three biomarkers, where at least one biomarker is selected from GLUCOSE and HBA1C;

at least one biomarker is selected from ADIPOQ, CRP, GPT, HSPA1B, IGFBP1, IGFBP2, INS, LEP, and TRIG; and

at least one biomarker is selected from the ALLDBRISKS, CPs, and TLRFs of Table 1, Table 2, and Table 3;

or

(v) at least three biomarkers, where at least two biomarkers are selected from the biomarkers within the group consisting of Core Biomarkers I and Core Biomarkers II and at least a third biomarker is selected from any of the biomarkers listed in Table 4;

or

(vi) ADIPOQ, GLUCOSE, CRP and one biomarker selected from the group consisting of HBA1C, IGFBP1, IGFBP2, Insulin, LEP and TRIG;

(b) calculating an index value from the output of a model, wherein the inputs to said model comprise said measurements, and further wherein said model was developed by fitting data from a longitudinal study of a selected population of individuals and said fitted data comprises levels of said biomarkers and an end point in said selected population of individuals, wherein said end point is selected from risk for developing a diabetic condition, the diagnosis of a diabetic condition, response to a Diabetes-modulating drugs, a surrogate diabetes endpoint, glucose class, a complication of a diabetic condition; and

(c) administering to said individual a Diabetes-modulating drug.

2. In a method of treating an individual with a Diabetes-modulating drug, the improvement comprising:

(a) obtaining measurements of biomarkers from at least one biological sample isolated from siad individual, wherein said biomarkers comprise;

(i) at least three biomarkers, where three of the biomarkers are selected from the RDMARKER sets listed in FIG. 6A;

or

(ii) at least four biomarkers selected from RDMARKERS;

or

(iii) at least three biomarkers, where two biomarkers are selected from ADIPOQ;

CRP;

GLUCOSE;

GPT;

HBA1C;

HSPA1B;

IGFBP1;

IGFBP2;

INS, LEP; and

TRIG; and

one biomarker is selected from the ALLDBRISKS, CPs, and TLRFs of Table 1, Table 2, and Table 3;

or

(iv) at least three biomarkers, where at least one biomarker is selected from GLUCOSE and HBAIC;

at least one biomarker is selected from ADIPOQ, CRP, GPT, HSPA1B, IGFBP1, IGFBP2, INS, LEP, and TRIG; and

at least one biomarker is selected from the ALLDBRISKS, CPs, and TLRFs of Table 1, Table 2, and Table 3;

or

(v) at least three biomarkers, where at least two biomarkers are selected from the biomarkers within the group consisting of Core Biomarkers I and Core Biomarkers II and at least a third biomarker is selected from any of the biomarkers listed in Table 4;

or

(vi) ADIPOQ, GLUCOSE, CRP and one biomarker selected from the group consisting of HBA1C, IGFBP1, IGFBP2, Insulin, LEP and TRIG; and

(b) calculating an index value from the output of a model, wherein the inputs to said model comprise said measurements, and further wherein said model was developed by fitting data from a longitudinal study of a selected population of individuals and said fitted data comprises levels of said biomarkers and an end point in said selected population of individuals, wherein said end point is selected from risk for developing a diabetic condition, the diagnosis of a diabetic condition, response to a Diabetes-modulating drugs, a surrogate diabetes endpoint, glucose class, and a complication of a diabetic condition.

3. A method according to claim 2 wherein said diabetes is Type II.

4. A method according to claim 3 wherein said individual has not converted to frank diabetes.

5. A method according to claim 4 wherein said end point is risk for developing a diabetic condition.

6. A method according to claim 4 wherein said end point is diagnosis of a diabetic condition.

7. A method according to claim 3 wherein said end point is response to a Diabetes-modulating drug.

8. A method according to claim 7 wherein said individual has not converted to frank diabetes and said drug administration is for diabetes prophylaxis.

9. A method according to claim 7 wherein said individual has converted to frank diabetes and said drug administration is for diabetes treatment.

10. A method according to any one of claims 2, 3, and 4, 9 wherein the Diabetes-modulating drug is liraglutide.