Diabetes-related biomarkers and methods of use thereof

• US 9,034,585 B2
• Filed: 03/14/2013
• Issued: 05/19/2015
• Est. Priority Date: 10/11/2005
• Status: Active Grant

• Current Assignee: True Health Diagnostics LLC (True Health Group LLC)
• Original Assignee: Health Diagnostic Laboratory Incorporated (True Health Group LLC)
• Inventors: Urdea, Michael S., McKenna, Michael P., Arensdorf, Patrick A.
• Primary Examiner(s): COOK, LISA V
• Application Number:
  US13/826,398
• Publication Number:
  US 20140147850A1
• Time in Patent Office: 796 Days
• 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 of evaluating risk for developing a diabetic condition, the method comprising:

obtaining biomarker measurement data, wherein the biomarker measurement data is representative of measurements of biomarkers in at least one biological sample from an individual; and

evaluating risk for developing a diabetic condition based on an output from a model, wherein the model is executed based on an input of the biomarker measurement data;

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.

3. The method of claim 1, wherein evaluating risk comprises computing an index value using the model based on the biomarker measurement data, and

wherein the index value is correlated with risk of developing a diabetic condition in the subject.

4. The method of claim 1, wherein evaluating risk comprises normalizing the biomarker measurement data to one or more reference values.

5. The method of claim 1, wherein the diabetic condition is Type 2 Diabetes.

6. The method of claim 1, wherein the diabetic condition is pre-Diabetes.

7. The method of claim 1, wherein the diabetic condition is selected from the group consisting of Metabolic Syndrome, Impaired Glucose Tolerance, and Impaired Fasting Glycemia.

8. The method of claim 1, wherein the obtaining biomarker measurement data step comprises measuring the level of at least one of the biomarkers in at least one biological sample from said individual.

9. The method of claim 1, further comprising a step prior to the step of obtaining biomarker measurement data, of obtaining at least one biological sample from the individual.

10. The method of claim 1, wherein the at least one biological sample comprises a blood sample.

11. The method of claim 1, wherein obtaining biomarker measurement data comprises obtaining data representative of a measurement of the level of at least one biomarker from a preexisting record.

12. The method of claim 1, wherein evaluating risk comprises computing a Diabetes risk score.

13. The method of claim 12, further comprising reporting the Diabetes risk score to at least one entity selected from:

the individual, an organization, or a database.

14. The method of claim 1, wherein the individual has not been diagnosed to have Diabetes.

2. A method of evaluating the risk of developing a diabetic condition in a subject by comprising:

measuring one or more of Clinical Parameters and Traditional Laboratory Risk Factors;

obtaining biomarker measurement data that is representative of measurements of at least two biomarkers in a sample from the subject, wherein the at least two biomarkers are selected from the group consisting of Core Biomarkers I and Core Biomarkers II; and

evaluating the risk of developing a diabetic condition in the subject based on an output from a model, wherein the model is executed based on an input of the biomarker measurement data.

15. A computer readable medium having computer executable instructions for evaluating risk for developing a diabetic condition, the computer readable medium comprising:

a routine, stored on the computer readable medium and adapted to be executed by a processor, to store biomarker measurement data representing;

(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; and

a routine stored on the computer readable medium and adapted to be executed by a processor to analyze the biomarker measurement data to evaluate a risk for developing a diabetic condition.

16. A diagnostic test system comprising:

means for obtaining test results data representing levels of multiple biomarkers in at least one biological sample;

means for collecting and tracking test results data for one or more individual biological samples;

means for computing an index value from biomarker measurement data according to a DRS Formula, wherein said biomarker measurement data is representative of measured levels of biomarkers, and further wherein said measured levels of biomarkers comprise the levels of;

(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,

and means for reporting said index value.

17. The diagnostic test system of claim 16, where said index value is a Diabetes risk score.

18. The diagnostic test system of claim 16, where Diabetes risk score is computed according to the method of evaluating risk for developing a diabetic condition, the method comprising:

obtaining biomarker measurement data, wherein the biomarker measurement data is representative of measurements of biomarkers in at least one biological sample from the individual; and

evaluating risk for developing a diabetic condition based on an output from a model, wherein the model is executed based on an input of the biomarker measurement data and comprises computing a Diabetes risk score;

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.

19. The diagnostic test system of claim 16, where the means for collecting and tracking test results data representing for one or more individuals comprises a data structure or database.

20. The diagnostic test system of claim 16, wherein the means for computing a Diabetes risk score comprises a computer or microprocessor.

21. The diagnostic test system of claim 16, wherein the means for reporting the Diabetes risk score comprises a visible display, an audio output, a link to a data structure or database, or a printer.

22. A medical diagnostic test system for evaluating risk for developing a diabetic condition, the system comprising:

a data collection tool adapted to collect biomarker measurement data representative of measurements of biomarkers in at least one biological sample from an individual; and

an analysis tool comprising a statistical analysis engine adapted to generate a representation of a correlation between a risk for developing a diabetic condition and measurements of the biomarkers, wherein the representation of the correlation is adapted to be executed to generate a result; and

an index computation tool adapted to analyze the result to determine the individual'"'"'s risk for developing a diabetic condition and represent the result as an index value;

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.

23. The system of claim 22, wherein the analysis tool comprises a first analysis tool comprising a first statistical analysis engine, the system further comprising a second analysis tool comprising a second statistical analysis engine adapted to select the representation of the correlation between the risk for developing a diabetic condition and measurements of the biomarkers from among a plurality of representations capable of representing the correlation.

24. The system of claim 22, further comprising a reporting tool adapted to generate a report comprising the index value.

25. A method of evaluating the current status of a diabetic condition in an individual, the method comprising:

obtaining biomarker measurement data, wherein the biomarker measurement data is representative of measurements of biomarkers in at least one biological sample from the individual; and

evaluating the current status of a diabetic condition in the individual based on an output from a model, wherein the model is executed based on an input of the biomarker measurement data;

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.

26. The method of claim 25, where the current status of the diabetic condition in the individual is type II Diabetes Mellitus.

27. The method of claim 25, where the current status of the diabetic condition in the individual is Impaired Glucose Tolerance (IGT).

28. The method of claim 25, where the current status of the diabetic condition in the individual is Impaired Fasting Glucose (IFG).

29. The method of claim 25, where the individual is pregnant.

30. The method of claim 25, where the current status of the diabetic condition in the individual is normal glucose tolerance (NCT).