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Bernal-Mizrachi, Carlos , MD

    Washington University in St. Louis, St. Louis, Missouri

Effects of Vitamin D on Markers of Vascular Disease in Diabetic African Americans

General Research Subject: Type 2 Diabetes

Focus: Clinical Therapeutics/New Technology, Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications, Complications, Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Immunology

Type of Grant: Clinical Translational Research

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

Racial differences in diabetes have been well documented in the United States. African Americans have twice the risk of developing type 2 diabetes mellitus and increased risk of complications and death from heart disease compared to Caucasians. Together, heart disease and type 2 diabetes account for over one third of racial and ethnic differences in death. Vitamin D deficiency is more frequent in diabetics and in African Americans, and vitamin D deficiency is associated with excess risk of heart death in both groups. However, it is unclear whether vitamin D treatment decreases heart disease progression in African Americans.

To test this hypothesis, we will be studying 86 diabetic African Americans with low vitamin D levels, who are assigned to take vitamin D, either 4,000 or 600 units per day, for 12 months. At the beginning of the study, using ultrasound techniques, the thickness of the carotid arteries in the neck, as well as the blood flow in the brachial artery of the arm, will be measured, both of which are valid surrogate measurements of heart disease. At the end of the study, these tests will be repeated to determine changes in these measurements resulting from treatment. Additionally, changes in immune cell function are tested before and after treatment to determine the effects of both vitamin D treatments and assess predictive value for heart disease progression. This information could provide insight into mechanisms of heart disease in African Americans and a possible new target for therapy to reduce cardiac risk.

Research Profile

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes?

Racial differences in diabetes have been well documented in the United States. African Americans have twice the risk of developing type 2 diabetes mellitus and increased risk of complications and death from heart disease compared to Caucasians. Together, heart disease and type 2 diabetes account for over one third of racial and ethnic differences in death. Vitamin D deficiency is more frequent in diabetics and in African Americans, and vitamin D deficiency is associated with excess risk of heart death in both groups. However, it is unclear whether vitamin D treatment decreases heart disease progression in African Americans. This study will evaluate whether vitamin D supplementation in diabetic African Americans with low vitamin D levels will slow the progression of early cardiovascular disease and improve vascular inflammation.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

This information could provide novel insights regarding the mechanisms of heart disease in diabetic African Americans and a possible new target for therapy to reduce cardiac risk. In addition, this trial may offer critical information that will establish the need for widespread screening for vitamin D deficiency or routine supplementation in this high-risk population.

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts?

Millions of Americans with diabetes struggle to achieve blood glucose control and to prevent vascular complications, issues which are accentuated in the African American population. Despite my efforts as a physician using current establish therapeutic interventions to improve patient health, I have frequently observed  progression of their cardiovascular complications. This funding will provide our laboratory with an opportunity to translate the observations from many investigators into a human interventional trial testing a novel mechanistic link between vitamin D and vascular disease in African American diabetic patients. Given the worldwide high prevalence of vitamin D deficiency in patients with diabetes and related cardiovascular disease, the implications of this research may be significant.

In what direction do you see the future of diabetes research going?

Recent advances have occurred that illustrate the complexity of the interactions between multiple tissues involved in type 2 diabetes. However, the current evidence of the association between increased inflammation in critical tissues and the development of diabetes and its vascular complications opens the possibility of a unifying mechanism. Future research to determine the mechanism(s) causing this immune dysregulation will provide the basis for therapeutic interventions.

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