Method for determining risk of diabetes

• US 9,740,819 B2
• Filed: 10/28/2010
• Issued: 08/22/2017
• Est. Priority Date: 10/29/2009
• Status: Expired due to Fees

• Current Assignee: True Health Diagnostics LLC (True Health Group LLC)
• Original Assignee: True Health Diagnostics LLC (True Health Group LLC)
• Inventors: McKenna, Michael P., Rowe, Michael, Moler, Jr., Edward J., Gerwien, Robert W.
• Primary Examiner(s): Riggs, II, Larry D
• Application Number:
  US13/504,478
• Publication Number:
  US 20120309030A1
• Time in Patent Office: 2,490 Days
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/30 Unsupervised data analysis
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

A method of determining risk of diabetes is provided. In one embodiment, the method comprises: a) measuring the levels of a plurality of biomarkers in a blood samples obtained from a patient, wherein the plurality of biomarkers comprises at least five of the following biomarkers: glucose, adiponectin, CRP, IL2RA, ferritin, insulin and HbAIc; b) calculating a diabetes risk score for the patients using the levels and, optionally, patient age and/or gender. Results obtained from performing the assay on a reference population are similar or identical to those obtained using Formula I.

Claims

1. A method of preventing development of diabetes in a subject, comprising:

a) measuring levels of a plurality of biomarkers in a blood sample obtained from the human subject, wherein said plurality of biomarkers comprises at least five of the following biomarkers;

glucose, adiponectin, CRP, IL2RA, ferritin, insulin and HbA1c;

b) calculating a diabetes risk score for said subject as a function of said measured levels and optionally, the subject'"'"'s age and/or gender;

c) applying the function of measured biomarker levels and optional age and/or gender of the subject to measured biomarker levels and optional age and/or gender of a human reference population to generate a risk profile associated with the reference population, the risk profile has a 95% confidence interval of a Spearman rank correlation coefficient squared (R²) that is entirely above or includes a correlation value of 0.5 with a comparative risk profile associated with the reference population generated from the formula;

D=X+0.062*Age−

0.64*Gender+1.62*GLUCOSE−

3.37*ADIPOQ+0.60*CRP+0.70*FTH1+1.35*IL2RA+0.49*INSULIN+0.26*HBA1C,

wherein;

0.062*Age is subject age in years multiplied by 0.062;

0.64*Gender is subject gender, wherein female=0 and male=1, multiplied by 0.64;

1.62*GLUCOSE is the square root of the level of subject blood glucose in mg/dL, multiplied by 1.62;

3.37*ADIPOQ is the log10 of the level of subject blood adiponectin in μ

g/mL, multiplied by 3.37;

0.60*CRP is the log10 of level of subject blood CRP in mg/L, multiplied by 0.60;

0.70*FTH1 is the log10 of the level of subject blood level ferritin in ng/mL, multiplied by 0.70;

1.35*IL2RA is the log10 of the level of subject blood IL2RA in U/mL, multiplied by 1.35;

0.49*INSULIN is the log10 of the level of subject blood insulin in ulU/mL, multiplied by 0.49;

0.26*HBA1C is the level of subject blood Hb1Ac measured in as a percentage of total hemoglobin in blood multiplied by 0.26; and

X is any number.

2. The method of claim 1, wherein said human reference population comprises at least 25 subjects.

3. The method of claim 1, wherein the subjects of said human reference population are randomly chosen from a larger population of human subjects.

4. The method of claim 1, further comprising:

initiating a therapeutic intervention or a treatment regimen to delay, reduce or prevent the human subject'"'"'s conversion to a diabetes disease state is performed if the calculated diabetes risk score indicates a risk that the subject has a high risk of developing diabetes.

5. The method of claim 1, further comprising:

initiating a therapeutic intervention or a treatment regimen to delay, reduce or prevent the human subject'"'"'s conversion to a diabetes disease state is performed if the calculated diabetes risk score indicates a risk that the subject has a moderate risk of developing diabetes.

6. A method of preventing a human subject from developing diabetes if a categorical risk assessment associated with the human subject falls within a high risk mutually exclusive ordered risk category or a moderate risk mutually exclusive ordered risk category from among a plurality of mutually exclusive ordered risk categories consisting of high risk, moderate risk and low risk, comprising:

a) measuring levels of a plurality of biomarkers in a sample obtained from the human subject, wherein said plurality of biomarkers comprises at least five of the following biomarkers;

glucose, adiponectin, CRP, IL2RA, ferritin, insulin and HbA1c;

b) generating a categorical risk assessment associated with the human subject generated as a function of a diabetes risk score (D) using said measured levels and optionally, the subject'"'"'s age and/or gender by the formula;

D=X+0.062*Age−

0.64*Gender+1.62*GLUCOSE−

3.37*ADIPOQ+0.60*CRP+0.70*FTH1+1.35*IL2RA+0.49*INSULIN+0.26*HBA1C,

wherein;

0.062*Age is subject age in years multiplied by 0.062;

0.64*Gender is subject gender, wherein female=0 and male=1, multiplied by 0.64;

1.62*GLUCOSE is the square root of the level of subject blood glucose in mg/dL, multiplied by 1.62;

3.37*ADIPOQ is the log10 of the level of subject blood adiponectin in μ

g/mL, multiplied by 3.37;

0.60*CRP is the log10 of level of subject blood CRP in mg/L, multiplied by 0.60;

0.70*FTH1 is the log10 of the level of subject blood level ferritin in ng/mL, multiplied by 0.70;

1.35*IL2RA is the log10 of the level of subject blood IL2RA in U/mL, multiplied by 1.35;

0.49*INSULIN is the log10 of the level of subject blood insulin in ulU/mL, multiplied by 0.49;

0.26*HBA1C is the level of subject blood Hb1Ac measured in as a percentage of total hemoglobin in blood multiplied by 0.26; and

X is any number,

wherein when a plurality of categorized risk assessments from a plurality of human subjects calculated as a function of the formula is compared to a plurality of comparative categorized risk assessments from a human reference population each generated as a function of levels of at least five of;

glucose, adiponectin, CRP, IL2RA, ferritin, insulin and HbA1c associated with each human reference population subject, and optionally each human reference population subject'"'"'s age and/or gender, the plurality of comparative categorized risk assessments from the human reference population;

is not independent with 95% confidence, using a chi-squared test, from the categorical risk assessments generated as a function of the formula, and

each mutually exclusive ordered risk category includes a range of diabetes risk scores (D) selected such that each individual mutually exclusive ordered risk category generated by the formula includes an identical number of human subjects as a number of human reference population subjects included in a corresponding mutually exclusive ordered risk category generated as a function of the levels of at least five of;

glucose, adiponectin, CRP, IL2RA, ferritin, insulin and HbA1c associated with each human reference population subject, and optionally each human reference population subject'"'"'s age and/or gender.

7. The method of claim 6, wherein said subject is categorized into one of said risk categories using at least the levels of glucose, adiponectin, CRP and HbA1c in the blood of said subject, and subject age.

8. The method of claim 6, wherein said human reference population comprises at least 25 subjects.

9. The method of claim 6, wherein the subjects of said human reference population are randomly chosen from a larger population of human subjects.

10. The method of claim 6, further comprising:

c) initiating a therapeutic intervention or a treatment regimen to delay, reduce or prevent the human subject'"'"'s conversion to a diabetes disease state if the calculated diabetes risk score indicates a risk that the subject will develop diabetes.

11. The method of claim 6, further comprising:

c) initiating a therapeutic intervention or a treatment regimen to delay, reduce or prevent the human subject'"'"'s conversion to a diabetes disease state if the calculated diabetes risk score indicates a high risk or moderate risk that the subject will develop diabetes.