Aims/hypothesis. To determine if the haptoglobin 2 allele is associated with an increased risk for the development of diabetic nephropathy. Methods. This study included 110 consecutive normotensive subjects with Type I (insulin-dependent) diabetes mellitus and Type II (non-insulin-dependent) diabetes mellitus seen in two outpatient clinics in Israel. Diabetes duration was greater than 10 years for Type I diabetes and more than 5 years for Type II diabetic subjects. Microalbuminuria was defined as urinary protein excretion of 30 to 300 mg/24 h, and macroalbuminuria was defined as urinary protein excretion of greater than 300 mg/24 h. Serum was taken from subjects for haptoglobin typing by gel electrophoresis. Results. Of the participating subjects 54 had Type I and 56 had Type II diabetes. None (0/18) of the subjects homozygous for the haptoglobin 1 allele (1-1) showed any sign of diabetic nephropathy, as compared with 34% (19/55) of subjects homozygous for the haptoglobin 2 allele (2-2) and 27% (10/37) of heterozygous subjects (2-1) (p < 0.04). Of the subjects 29 showed macroalbuminuria. The risk of developing macroalbuminuria was found to be greater in subjects with two haptoglobin 2 alleles (22%) (12/55) as compared with one haptoglobin 2 allele (8%) (3/37) or no haptoglobin 2 alleles (0%) (0/18) (p < 0.03). Conclusion/interpretation. By showing a graded risk relation to the number of haptoglobin 2 alleles in Type I and Type II diabetic subjects, these studies further support our hypothesis that the haptoglobin phenotype is a major susceptibility gene for the development of diabetic nephropathy.
Bibliographical noteFunding Information:
Acknowledgements. This work was supported by grants from the National Institutes of Health (NIH) (RO1 58 510 and RO1 66 195), Israel Science Foundation, Israel Cancer Association and Israel Cancer Research Fund all to APL.
- Diabetic nephropathy
- Oxidative stress
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism