By: DSM Nutritional Products
Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at an increased risk of developing cardiovascular disease (CVD). As antioxidant function is impaired in those with the genotype, it has been suggested that vitamin E in therapeutic applications could provide additional cardiovascular protection.1
CVD is the leading cause of death in individuals with DM. This is attributable to the increased production of reactive oxygen species – or oxidative stress – that produce structural changes in lipoproteins, increasing atherogenic potential.
Previous studies have suggested that vitamin E does not provide any cardiovascular protection in genetically unselected populations with DM.2 However, high-dose antioxidant therapy may be more effective with populations that have higher levels of oxidative stress, such as those with gene mutations. One particular variant, the Hp genetic locus, prevents extracorpuscular haemoglobin (Hb) from oxidative injury. In fact, five longitudinal studies have shown that Hp 2-2 DM individuals have a significantly increased risk of CVD, compared with non-Hp 2-2 individuals.3
A meta-analysis published in Pharmacogenomics investigated the relationship between Hp type, vitamin E and cardiovascular end points in DM participants from two clinical trials: the Heart Outcomes Prevention Evaluation (HOPE) and the Israel Cardiovascular Events Reduction with Vitamin E (ICARE) trial.4
By combining data from both studies, pre-defined clinical end points of non-fatal myocardial infarction (MI), stroke and CVD death were assessed. The studies both administered the same 400 IU vitamin E dosage to all participants daily, as well as assessing only type 2 DM. All individuals were aged 55 years and above.
The data from both studies was analysed using a fixed-effect model. The meta-analysis found that for participants who did not receive vitamin E or the double placebo, the composite end point was significantly increased in Hp 2-2 DM, compared with non-Hp 2-2 DM. Further, the meta-analysis of the Hp 2-2 DM individuals revealed a significant overall reduction in the composite end point in those who received vitamin E.
Following the meta-analysis, figures were interpreted to determine the potential long-term effects. In fact, simulating the findings over the course of 50 years predicted that treating Hp 2-2 DM individuals with vitamin E would prolong life by approximately three years in each person. In addition, it is estimated that for every 1,000 Hp 2-2 DM individuals, treatment would prevent 75 MI hospital admissions, 31 cardiac surgical procedures and 19 percutaneous coronary interventions.
To summarize, there is strong evidence that vitamin E holds potential clinical benefits to DM individuals with the Hp 2-2 genotype. As such, there is an opportunity for vitamin E to present an inexpensive option for public healthcare strategies. Although larger, prospective clinical trials are still required, the results could nonetheless provide improvements in life expectancy, together with addressing other modifiable risk factors through smoking cessation, statin therapy and blood pressure and glucose control.
Contact us for more information on the applications for vitamins and pharmaceutical lipids within disease management or read our whitepaper, ‘Scientific evidence on vitamins and lipids for pharmaceutical applications'.
24 October 2017
5 min read
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