GLYCEMIC CONTROL FOR REDUCTION OF CARDIOVASCULAR DISEASE RISK IN DIABETIC PATIENTS EXPRESSING HAPTOGLOBIN 2-2
This invention relates to methods of reducing risk of developing cardiovascular complications in diabetic patients. Specifically, the invention relates to the use of haptoglobin genotyping for determining the importance of maintaining tight glycemic control in diabetic subjects expressing Hp 2-2 allele.
1 . A method of reducing the risk of a diabetic subject developing a cardiovascular disease, comprising the steps of obtaining a biological sample from the subject; determining the subject's haptoglobin allelic genotype; and controlling the level of HbA1c below a predetermined threshold in a subject expressing the Hp-2-2 genotype.
2 . The method of claim 1 , wherein said step of determining said haptoglobin genotype is effected by a method selected from a signal amplification method, a direct detection method, detection of at least one sequence change, immunological method or a combination thereof.
3 . The method of claim 3 , wherein said signal amplification method amplifies a molecule selected from the group consisting of a DNA molecule and an RNA molecule.
4 . The method of claim 3 , wherein said signal amplification method is selected from the group consisting of PCR, LCR (LAR), Self-Sustained Synthetic Reaction (3SR/NASBA) and Q-Beta (Qβ) Replicase reaction.
5 . The method of claim 3 , wherein said direct detection method is selected from the group consisting of a cycling probe reaction (CPR) and a branched DNA analysis.
6 . The method of claim 3 , wherein said detection of at least one sequence change employs a method selected from the group consisting of restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis and Dideoxy fingerprinting (ddF).
7 . The method of claim 3 , wherein step of determining said haptoglobin genotype is effected by an immunological detection method.
8 . The method of claim 7 , wherein said immunological detection method is a radio-immunoassay (RIA), an enzyme linked immunosorbent assay (ELISA), a sandwhich immunoassay, a western blot, an immunohistochemical analysis, or fluorescence activated cell sorting (FACS).
9 . The method of claim 1 , whereby the diabetic subject exhibits type II diabetes.
10 . The method of claim 1 , whereby the reducing the risk comprises determining the importance of reducing oxidative stress.
11 . The method of claim 1 , wherein the HbA 1c level is below about 7.0%.
12 . The method of claim 1 , wherein the HbA 1c level is below about 6.5%.
13 . The method of claim 1 , whereby the cardiovascular disease is angina, myocardial infarct, peripheral vascular disease, cerebrovascular disease or a combination thereof.
14 . A method of determining prognosis for a diabetic subject, to benefit from a glycemic control comprising the step of obtaining a biological sample from the subject; and determining the subject's haptoglobin allelic genotype, whereby a subject expressing the Hp-2-2 genotype will benefit from a glycemic control.
15 . The method of claim 14 , wherein the glycemic control comprises lowering the level of HbA1c to below the predetermined threshold
16 . The method of claim 14 , wherein lowering the level of HbA1c is done by contacting the subject with a composition comprising: a biguanide, a sulphonylureas, a meglitinides, an α-glucosidase inhibitor, a PPARγ-agonists, a GLP-1 agonist, a DPP-IV inhibitor, an insulin or their combination.
17 . The method in claim 15 wherein the lowering of the level of Hb1Ac is done by exercise, diet or their combination.
18 . The method of claim 15 , wherein the HbA 1c level is below about 7.0%.
19 . The method of claim 15 , wherein the HbA 1c level is below about 6.5%.
20 . The method of claim 14 , wherein said step of determining said haptoglobin genotype is effected by a method selected from a signal amplification method, a direct detection method, detection of at least one sequence change, immunological method or a combination thereof.
21 . The method of claim 20 , wherein said signal amplification method amplifies a molecule selected from the group consisting of a DNA molecule and an RNA molecule.
22 . The method of claim 20 , wherein said signal amplification method is selected from the group consisting of PCR, LCR (LAR), Self-Sustained Synthetic Reaction (3SR/NASBA) and Q-Beta (Qβ) Replicase reaction.
23 . The method of claim 20 , wherein said direct detection method is selected from the group consisting of a cycling probe reaction (CPR) and a branched DNA analysis.
24 . The method of claim 20 , wherein said detection of at least one sequence change employs a method selected from the group consisting of restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis and Dideoxy fingerprinting (ddF).
25 . The method of claim 14 , wherein step of determining said haptoglobin genotype is effected by an immunological detection method.
26 . The method of claim 25 , wherein said immunological detection method is a radio-immunoassay (RIA), an enzyme linked immunosorbent assay (ELISA), a sandwhich immunoassay, a western blot, an immunohistochemical analysis, or fluorescence activated cell sorting (FACS).
27 . The method of claim 14 , whereby the diabetic subject exhibits type II diabetes.