Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus — natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature

BackgroundDiabetes mellitus carries a high risk for vascular events. Diabetics with different haptoglobin (Hp) types may carry different risk profiles, and may respond differently to vitamin E treatment. We aim to summarize the evidence about cardiovascular risk in diabetic patients, according to their Hp type, and the effect of vitamin E treatment on these sub-groups.MethodsWe searched MEDLINE and on-going trials' databases until February 2011; gray literature; reference lists of identified articles; and experts. Two investigators screened and selected studies that prospectively followed cardiovascular outcomes in diabetic patients with different Hp types (natural history analysis), and randomized controlled trials reporting the effect of vitamin E on cardiovascular outcomes in diabetics, in which Hp typing was performed (interventional analysis).ResultsFive and three studies, comprising 1829 and 2110 patients, were eligible for the natural history and the interventional analyses, respectively. The percentage of diabetic patients experiencing non-fatal MI, stroke, or cardiovascular death was significantly higher in the Hp 2–2 population (odds ratio (OR) 2.03 (95% confidence interval (CI) 1.46 to 2.81)). In patients with Hp 2–2 genotype, the OR for a combined endpoint was 0.66 in favor of the vitamin E treated group (95% CI 0.48 to 0.9). This effect was not shown in other Hp types.ConclusionHp type 2–2 carries a high risk of cardiovascular events in diabetic patients. A pharmacogenomic approach towards treatment of diabetic patients with vitamin E may be warranted.