Correspondence
Haptoglobin Phenotype and Vascular Complications in Patients with Diabetes
N Engl J Med 2000; 343:969-970September 28, 2000
- Article
To the Editor:
Vascular complications cause serious morbidity in patients with diabetes mellitus. Two such complications are diabetic nephropathy and restenosis after percutaneous transluminal coronary angioplasty. There is currently scant evidence of a genetic marker that predicts which patients will have these complications.
Oxidative stress plays an important part in the development of diabetic vascular complications.1 Haptoglobin is a hemoglobin-binding protein that has a major role in providing protection against heme-driven oxidative stress.2 There are two common alleles for haptoglobin (1 and 2), and the three phenotypes, haptoglobin 1/1, haptoglobin 2/1, and haptoglobin 2/2, differ in their ability to function as antioxidants.2 We determined whether there was a relation between the haptoglobin phenotype, as determined by gel electrophoresis,3 and the development of diabetic nephropathy or coronary restenosis in patients with diabetes.
For the analysis of diabetic nephropathy, we determined the level of urinary albumin excretion in 53 consecutive patients (22 women and 31 men) who had had type 1 diabetes for at least 10 years, who did not have hypertension, and in whom the serum creatinine concentration was less than 1.5 mg per deciliter (133 μmol per liter). The mean (±SD) age of the patients was 35±14 years, the mean duration of diabetes was 18±8 years, and the mean glycosylated hemoglobin value was 7.9±1.6 percent. Urinary albumin excretion exceeded 30 mg per day in 14 of the 41 patients with the haptoglobin 2/1 or 2/2 phenotype (34 percent) but in none of the 12 patients with the haptoglobin 1/1 phenotype (P=0.02). There were no significant differences in age, sex, metabolic control, or duration of diabetes between these two groups.
For the analysis of restenosis, we studied 45 patients (11 women and 34 men) with type 2 diabetes who presented at least four months after undergoing angioplasty. The mean age of the patients was 60±9 years, the mean time since angioplasty was 23±24 months, the mean diameter of the coronary-artery lesion was 3.0±0.5 mm, and the mean length of the lesion was 14.7±7.7 mm. Restenosis was present in 33 of the 40 patients with the haptoglobin 2/1 or 2/2 (82 percent) but in none of the 5 patients with haptoglobin 1/1 (P<0.001). There were no significant differences in age, sex, or lesion characteristics between these two groups.
The haptoglobin 1/1 phenotype thus appears to provide protection against the development of two important vascular complications of diabetes: diabetic nephropathy and restenosis after percutaneous transluminal coronary angioplasty.
3 ReferencesAndrew P. Levy, M.D., Ph.D.
Rappaport Research Institute, 31096 Haifa, IsraelAriel Roguin, M.D.
Irit Hochberg, B.S.
Paula Herer, M.Sc.
Technion–Israel Institute of Technology, 31096 Haifa, IsraelStuart Marsh, M.D.
Farid M. Nakhoul, M.D.
Karl Skorecki, M.D.
Rambam Medical Center, 31096 Haifa, Israel1
Suzuki D ,Miyata T ,Saotome N , et al. Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. J Am Soc Nephrol 1999;10:822-832
Web of Science | Medline2
Langlois MR ,Delanghe JR . Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 1996;42:1589-1600
Web of Science | Medline3
Wassell J ,Keevil B . A new method for haptoglobin phenotyping. Ann Clin Biochem 1999;36:609-612
Web of Science | Medline
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