M.Sc Thesis

M.Sc StudentAmer-Alshiek Jonia
SubjectVitamin E Treatment Effect on Endothelial Function and
Reverse Cholesterol Transport in Type 2 Diabetic
Patients with Hp 2-2 Genotype
DepartmentDepartment of Medicine
Supervisors MR Giris Jacob
PROF. Andrew Peter Levy
Full Thesis textFull thesis text - English Version


Background. Pharmacogenomics and Pharmacogenetics are key components of personalized medicine. Clinical trials investigating vitamin E have failed to demonstrate cardio-protective effect. Inadequate nature of patient selection could be responsible for this failure, regarding oxidative stress level and inherited antioxidative capability. Haptoglobin is a major antioxidant protein. The haptoglobin 2 allelic protein provides inferior antioxidant protection compared with the Hp 1 allelic protein. In our recent ICARE study we have demonstrated that vitamin E provides cardiovascular benefit to diabetic individuals with the Hp 2-2 genotype.  This pharmacogenetic approach demonstrated that vitamin E has a significant benefit in these genetically selected patients. However, the mechanism behind this selective benefit still unknown. In this study we sought to provide a mechanistic explanation based on the hypothesis that the Hp 2‐2 genotype and DM interact to promote both endothelial and HDL dysfunction.

Methods. Endothelial function (Enf) was assessed by the veno-occlusive plethesmography method. HDL function was assessed based on its ability to promote reverse cholesterol transport (RCT). A crossover, double blinded, placebo controlled study in Hp 2-2 DM type II individuals assessed the ability of vitamin E to favorably modify these functional parameters.

Results. The indices of Enf, maximal blood flow (Max BF) and area under the curve (AUC) were similar at baseline in both groups, placebo and vitamin E. Administration of vitamin E for two months, caused significant improvement in both, Max BF and AUC compared with placebo in both groups (p value < 0.001). After the crossing over from vitamin E to placebo, the effect of vitamin E was preserved despite the placebo treatment. Similarly, the reverse cholesterol process (RCT), indicated HDL function, was improved under the effect of vitamin E compared with placebo in both groups (p value < 0.005).

Conclusions. Vitamin E, given to a genetically selected diabetic patient, Hp 2-2 DM individuals, significantly improves both the endothelial function and quality of HDL.