Type 1 Diabetes: Coronary Artery Disease and Oxidative Stress Response

MedicalResearch.com Interview with: Tina Costacou, Ph.D.

Assistant Professor of Epidemiology
University of Pittsburgh

MedicalResearch.com: What are the main findings of the study?

Answer: The generation of reactive oxygen species is a natural and essential feature of human physiology, although excess production of free radicals has been related to the development and progression of diabetes complications. Simply put, a “balance” is required between the pro- and the anti-oxidant forces to maintain good health. Our aim in this study of people with type 1 diabetes was to evaluate whether an individual’s antioxidant vitamin levels in blood can modify the heart disease risk conferred by increased oxidative stress.

Indeed, we observed that higher concentrations of α-tocopherol (a form of vitamin E) in blood overtime were related to lower risk of developing coronary heart disease, whereas greater oxidative stress (as measured by urinary 15-isoprostane F2t) was related to greater risk of disease. Interestingly, the ratio of α-tocopherol to urinary 15-isoprostane F2t, which we used as a measure of an individual’s ability to respond to / counteract oxidative stress, also was a strong predictor of subsequent coronary heart disease development.

Our findings thus point to a different way of assessing a person’s risk for developing disease. Currently in clinical practice, physicians assess an individual’s risk factors (e.g. oxidative stress) for a pathologic condition (e.g. heart disease) to make inferences about the person’s risk to develop this condition and take preventive measures if needed (e.g. assign a treatment regimen). Our findings, however, suggest that an individual’s risk for disease may be better evaluated by simultaneously assessing factors representing the risk and those representing protection from or resistance to the risk. Thus, though two individuals may have similarly high levels of oxidative stress, there may be differences in the concentration of antioxidant vitamins between the two (and vice versa), which may put them at different risk categories, with one person potentially requiring vitamin supplementation while the second not needing to use supplements.

MedicalResearch.com: Were any of the findings unexpected?

Answer: There has been controversy on whether vitamin E protects against the development of coronary heart disease and clinical trials have largely not shown a protective effect of supplementation with antioxidant vitamins. In our study of people with type 1 diabetes, however, we observed that those with higher blood levels of vitamin E overtime had a lower risk of developing coronary heart disease. Of course, the experimental nature of the design of a clinical trial renders it less susceptible to bias (errors) compared to our observational study design, where we simply evaluated the association between observed vitamin E levels in blood and heart disease risk without actively assigning study participants to take vitamin supplements or a sugar pill.

Thus, it is possible that the protective effect of vitamin E against heart disease in our study may reflect that those with higher vitamin levels engage in other beneficial practices that contribute to the reduced risk; however, we did control for a number of such factors (e.g. smoking) in the analysis. Alternatively, our results may simply reflect that specific population subgroups that may be susceptible to disease (e.g. individuals with type 1 diabetes) are the ones benefiting from supplementation with antioxidant vitamins while the general population receives no benefit.

MedicalResearch.com: What should clinicians and patients take away from your report?

Answer: If further data are published supporting our findings it may one day become possible to better classify a person’s disease risk and individualize treatment regimen. At present, though, we can’t make any inferences on where the “balance” between oxidative stress and antioxidant levels lies or what type or dosage of vitamin supplementation may best to reduce risk or prevent disease.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Answer: However difficult it may be, given that we don’t always know which markers represent protection or resistance to a specific stress, the concurrent evaluation of markers representing insult with those representing protection from or resistance to insults appears to have great implications and should be attempted more often in research studies. Findings obtained may surprise us, but could also open up new horizons for understanding and treating disease.


Oxidative Stress and Response in Relation to Coronary Artery Disease in Type 1 Diabetes

Costacou T, Evans RW, Schafer GL, Orchard TJ.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
Diabetes Care. 2013 Aug 6. [Epub ahead of print]