Methods for detecting pre-diabetes and diabetes using differential protein glycosylation

• US 8,530,175 B2
• Filed: 04/26/2012
• Issued: 09/10/2013
• Est. Priority Date: 05/11/2009
• Status: Active Grant

• Current Assignee: DiabetOmics, Inc.
• Original Assignee: Diabetomics, LLC
• Inventors: Nagalla, Srinivasa R., Roberts, Charles T.
• Primary Examiner(s): Cheu, Jacob
• Application Number:
  US13/457,225
• Publication Number:
  US 20120214179A1
• Time in Patent Office: 502 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: G01N 2333/42 Lectins, e.g. concanavalin, phytohaemagglutinin
• CPC Class Codes: G01N 2400/00 Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
• CPC Class Codes: G01N 2440/38 addition of carbohydrates, e.g. glycosylation, glycation
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• 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 33/6893 related to diseases not provided for elsewhere

Abstract

Methods for identifying individuals who are not yet diabetic (pre-diabetic), but who are at significant risk of developing diabetes, such as type 2 diabetes, are disclosed herein. Methods are also provided for the identification of diabetic subjects. Also disclosed are methods for identifying individuals with diabetic complications. The methods include the identification of an overall glycosylation profile of proteins in a biological fluid, such as saliva, urine, or serum. In some examples, the methods include determining the amount of one or more protein in a biological fluid or determining the glycosylation pattern of one or more proteins in a biological fluid.

Claims

1. A method of monitoring efficacy of a treatment of a diabetes or pre-diabetes condition in a subject, comprising:

measuring binding of a plurality of lectins to a first sample from the subject;

administering a treatment to the subject;

measuring binding of the plurality of lectins to a second sample from the subject after administering the treatment to the subject; and

comparing the binding of the plurality of lectins to the first sample to the binding of the plurality of lectins to the second sample,

wherein the plurality of lectins comprises Aleuria aurantia lectin, Concanavalin A, Phaseolus vulgaris agglutinin, Datura stramonium lectin, and Sambucus nigra lectin; and

wherein a decrease in the binding of each of the plurality of lectins to the second sample relative to the binding of each of the plurality of lectins to the first sample indicates that the treatment is effective, and/or wherein an increase in the binding of each of the plurality of lectins to the second sample relative to the binding of each of the plurality of lectins to the first sample indicates that the treatment is ineffective.

2. The method of claim 1, wherein the first and second samples each comprise urine, saliva, or serum.

3. The method of claim 1, further comprising determining a quantity of at least one protein in both the first and second samples from the subject, wherein determining the quantity of at least one protein comprises determining the quantity of alpha-1antitrypsin (A1AT) protein in the first and second samples.

4. The method of claim 3, wherein an increase in the quantity of A1AT in the second sample as compared to the first sample indicates that the treatment is ineffective.

5. The method of claim 3, wherein a decrease in the quantity of A1AT in the second sample as compared to first sample indicates that the treatment is effective.

6. The method of claim 3, wherein determining the quantity of at least one protein comprises using an immunoassay to measure the quantity of the at least one protein.

7. The method of claim 1, wherein the plurality of lectins comprises one or more lectins that bind alpha-1 acid glycoprotein.

8. The method of claim 1, wherein measuring binding of a plurality of lectins to a first or second sample comprises contacting the first and/or second sample from the subject with a lateral flow device comprising one or more lectins.

9. The method of claim 1, wherein the metabolic condition is a diabetic complication.

10. The method of claim 9, wherein the diabetic complication is a microvascular complication or a macrovascular complication.

11. The method of claim 9, wherein the diabetic complication is a microvascular complication comprising one or more of diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy.

12. The method of claim 1, further comprising determining a quantity of at least one protein in both the first and second samples from the subject, wherein determining the quantity of at least one protein comprises determining the quantity of alpha-1 acid glycoprotein (A1AG) protein in the first and second samples.

13. The method of claim 12, wherein an increase in the quantity of A1AG in the second sample as compared to the first sample indicates that the treatment is ineffective.

14. The method of claim 13, wherein a decrease in the quantity of A1AG in the second sample as compared to the first sample indicates that the treatment is effective.