The increased oxidative stress associated with diabetic patients is partly due to increased reactivity of the iron within the heme pocket of hemoglobin. Haptoglobin, a plasma protein, functions as an antioxidant by binding to hemoglobin and preventing it from initiating oxidative chain reactions. Haptoglobin has two alleles, 1 and 2, which form three different phenotypes that differ in their antioxidant capabilities. Haptoglobin 2-2 is inferior to Haptoglobin 1-1 as an antioxidant. Due to the decreased antioxidant function of Haptoglobin 2-2, diabetic individuals carrying this phenotype suffer from increased rates of oxidative stress and increased incidence of cardiovascular complications. In several epidemiological studies, oral supplementation with vitamin E proved therapeutic for this group, with a decrease in cardiovascular complications and improved high-density lipoprotein (HDL) function. Those findings led to the conclusion that vitamin E should be given to Haptoglobin 2-2 diabetic individuals as a preventive therapy against cardiovascular complications of diabetes.

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