Haptoglobin genotype and endothelial function in diabetes mellitus: a pilot study

Endothelial function (EnF) is impaired in patients with diabetes mellitus (DM) due in large part to an increase in oxidative stress. Haptoglobin (Hp) is a potent antioxidant protein which is encoded by two different alleles (1 and 2) with the Hp 1 protein being a superior antioxidant to the Hp 2 protein. We hypothesized that DM individuals with the Hp 2-2 genotype would have greater endothelial dysfunction as compared to DM individuals with the Hp 1-1 genotype. We studied EnF in 16 Hp 2-2, 14 Hp 1-1 DM individuals and 14 healthy subjects. DM patients’ groups were matched in terms of age, cardiovascular risk factors and metabolic characteristics. EnF was assessed using post-ischemic reactive hyperemia and strain gauge plethysmography and expressed either as the maximal flow after the ischemic period or as the area under the flow–time curve (AUC). We showed that EnF indices, AUC and maximal flow, were also higher in the healthy and Hp 1-1 groups compared with Hp 2-2 genotype group (615 ± 60 and 600 ± 40 vs. 450 ± 50 ml dl⁻¹, 29 ± 2.6 and 25 ± 3 vs. 14 ± 1.8 ml min⁻¹ dl⁻¹, P < 0.003 and P < 0.05, for AUC and maximal flow, one-way ANOVA, respectively). We concluded that Hp 2-2 diabetic patients had a worse EnF than controls and Hp 1-1 diabetic subjects.