The Role of Haptoglobin Polymorphism in Cardiovascular Disease in the Setting of Diabetes

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in individuals with diabetes mellitus (DM). Preclinical models have suggested that excessive oxidative stress and hyperglycemia are directly responsible for this pathological association. However, numerous clinical trials involving the administration of high doses of the antioxidant vitamin E or attempts at strict glycemic control have failed to show a significant reduction of CVD in DM patients. We describe here a possible explanation for the failure of these trials, that being their lack of proper patient selection. The haptoglobin (Hp) genotype is a major determinant of the risk of CVD in the setting of DM. Treatment of individuals with the high-risk Hp genotype with antioxidants or aggressive glycemic control has shown benefit in several small studies. These studies suggest a precision medicine-based approach to preventing diabetes complications. This approach would have a profound effect on the costs of diabetes care and could dramatically reduce morbidity from diabetes.

Automated summary

Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality in individuals with diabetes mellitus, likely due to oxidative stress and hyperglycemia. Clinical trials involving high doses of vitamin E or strict glycemic control in DM patients have not shown significant reduction of CVD. Proper patient selection based on haptoglobin genotype may be crucial in achieving better outcomes in preventing complications in diabetes.