Low vitamin D status is endemic due to 21st century lifestyle and low dietary intake. An increasing body of data relates low vitamin D status to increased risk for non-musculoskeletal morbidities;including, most notably, cardiovascular disease and type II diabetes mellitus. Cardiovascular disease, for which type 2 diabetes mellitus is a major risk factor, causes over one-third of all deaths in the US. American Indians are more likely to develop cardiovascular disease and diabetes mellitus than non-Hispanic whites. In fact, American Indians of the Great Lakes Region have the third highest diabetes mellitus rate in the nation, an age-adjusted diabetes mellitus mortality rate almost three-fold higher than the all-race mortality and the highest rates of cardiovascular disease among American Indians nationally. In this population, where cardiovascular disease and diabetes mellitus are two of the top four causes of death, our preliminary work finds low vitamin D status commonplace. Our fundamental hypothesis is that low vitamin D status is causally related to cardiovascular disease by producing a cytokine mediated pro-inflammatory milieu that leads to endothelial dysfunction and ultimately to atherosclerotic disease. We further hypothesize that this pro-inflammatory state leads to a variety of other adverse health outcomes including impaired insulin sensitivity and ultimately type 2 diabetes mellitus. It follows that that vitamin D supplementation should reduce inflammation, thus restoring endothelial function and glucose homeostasis, thereby reducing cardiovascular disease and diabetes mellitus risk.
The specific aims of this study are: to evaluate the relationships between vitamin D status and endothelial function;to assess if vitamin D effects on endothelial dysfunction are related to a proinflammatory milieu and to explore relationships of vitamin D status with parameters of glucose homeostasis. In this study, 100 postmenopausal Al women up to age 70 years without diabetes mellitus or known cardiovascular disease will be randomly assigned to receive vitamin D3, either the current standard intake of 400 ID or a dose estimated to achieve optimal status, 2,500 ID, daily for six months. We will define the effects of vitamin D status, and subsequent response to supplementation, on endothelial function, arterial stiffness, plasma markers of inflammation and glucose homeostasis.

Public Health Relevance

Cardiovascular disease is common among American Indians, and the population worldwide. Diabetes mellitus is also endemic, causing substantial morbidity and mortality in itself, and is also associated with cardiovascular disease development. Endemic low vitamin D status, by creating a pro-inflammatory milieu, likely contributes to the pathogenesis of cardiovascular disease and type 2 diabetes mellitus. If so, non-toxic, inexpensive interventions to optimize vitamin D status will lead to profound beneficial health consequences.

National Institute of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)
Comprehensive Center (P60)
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Special Emphasis Panel (ZMD1-PA)
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University of Wisconsin Madison
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