Cardiovascular disorders (CVD) are the leading cause of death among diabetes patients. Reduction in diseases associated with cardiovascular system is one of the main goals in the treatment of diabetes mellitus (DM).

The obvious reasons for increased risk of CVD in DM is the triggering of oxidative stress by generation of Reactive Oxygen Species (ROS) due to hyperglycaemia. Apart from the obvious reasons, there could be a genetic susceptibility in DM patients leading to increased CV risk. Haptoglobin (Hp), a protein produced by the genetic biomarker haplotype, protects blood vessels and kidneys from adverse oxidative effects and tissue injury induced by extracorpuscular free hemoglobin (Hb). However, the Hp 2-2 genotype is an inferior antioxidant which may result in oxidative modifications, HDL dysfunction, increased macrophage inflammation and apoptosis finally resulting in increased lipid accumulation in blood vessels or atherosclerosis, especially in DM patients. Some studies also found an association in HP 2-2 genotype in DM with ischemic stroke in general population.¹

A majority of DM patients have type 2 DM and approximately a high 36% of them have the Hp 2-2 genotype. This makes them highly susceptible to an increased cardiovascular risk.¹

Selective potential of Vitamin E in Cardiovascular Risk reduction in Diabetes patients with Hp 2-2 genotype: -

Vitamin E acts as an antioxidant by scavenging free radicals thereby decreasing oxidative stress.¹ It also offers cardioprotection in DM patients with Hp 2-2 genotype by improving HDL functionality. (Figure) 

In a meta-analysis study including a large study population of 6,161 patients without Hp 2-2 and 4,684 patients with Hp 2-2, Vitamin E supplementation in Hp 2-2 genotype cohort with diabetes mellitus patients showed a significant decrease in CV mortality. The trial also reported that the Vitamin E supplementation resulted in significantly lower rates of CV death among patients with Hp 2-2 and DM.¹

Clinical trial data from numerous studies (HOPE, ICARE and WHS) has shown that supplementation with Vitamin E is associated with approximately a 35% risk reduction in CVD. 

Another study indicated the effect of antioxidant treatment with Vitamin E on vascular health in DM patients with Hp 2-2 genotype. Diabetes negatively affects vascular functions in both arteries and small vessels resulting in increased risk of cardiovascular events. In this study, it was seen that there was significant improvement in the parameters of vascular health following 8 weeks of treatment with Vitamin E. Also, it was observed the effect continued even after discontinuation of treatment.³

In another trial observing the long term effects of lifelong supplementation with Vitamin E predicated a cumulative gain of 3 years in life expectancy in Hp 2-2 individuals with DM treated with vitamin E as compared with Hp 2-2 individuals who were not treated with vitamin E.⁴

Abbreviations: HDL, High Density Lipoprotein; LDL, Low Density Lipoprotein, Hb, Haemoglobin; HOPE, Heart Outcomes Prevention Evaluation; Israel Cardiovascular Events Reduction with vitamin E (ICARE); WHS, Womens Health Study

References

1. Asleh R, Briasoulis A, Berinstein EM, et al. Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation. Pharmgenomics Pers Med. 2018; 11:71-82.
2. Hochberg I, Berinstein EM, Milman U, Shapira C, Levy AP. Interaction Between the Haptoglobin Genotype and Vitamin E on Cardiovascular Disease in Diabetes. Curr Diab Rep. 2017 Jun;17(6):42.
3. Alshiek JA, Dayan L, Asleh R, Blum S, Levy AP, Jacob G. Anti-oxidative treatment with vitamin E improves peripheral vascular function in patients with diabetes mellitus and Haptoglobin 2-2 genotype: A double-blinded cross-over study. Diabetes Res Clin Pract. 2017 Sep; 131:200-207.
4. Blum S, Vardi M, Brown JB, et al. Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics. 2010;11(5):675-684