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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Comprehensive Center (P60)
Project #
5P60MD003428-05
Application #
8473100
Study Section
Special Emphasis Panel (ZMD1-PA)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$106,029
Indirect Cost
$26,039
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Santiago-Torres, Margarita; Cui, Yuchen; Adams, Alexandra K et al. (2016) Structural equation modeling of the associations between the home environment and obesity-related cardiovascular fitness and insulin resistance among Hispanic children. Appetite 101:23-30
Tomayko, Emily J; Prince, Ronald J; Cronin, Kate A et al. (2016) The Healthy Children, Strong Families intervention promotes improvements in nutrition, activity and body weight in American Indian families with young children. Public Health Nutr 19:2850-9
Steffens, Nicole M; Tucholka, Jennifer L; Nabozny, Michael J et al. (2016) Engaging Patients, Health Care Professionals, and Community Members to Improve Preoperative Decision Making for Older Adults Facing High-Risk Surgery. JAMA Surg 151:938-945
Nabozny, Michael J; Kruser, Jacqueline M; Steffens, Nicole M et al. (2016) Constructing High-stakes Surgical Decisions: It's Better to Die Trying. Ann Surg 263:64-70
Krueger, Diane; Libber, Jessie; Sanfilippo, Jennifer et al. (2016) A DXA Whole Body Composition Cross-Calibration Experience: Evaluation With Humans, Spine, and Whole Body Phantoms. J Clin Densitom 19:220-5
Santiago-Torres, M; Cui, Y; Adams, A K et al. (2016) Familial and individual predictors of obesity and insulin resistance in urban Hispanic children. Pediatr Obes 11:54-60
Keller, Abiola O; Valdez, Carmen R; Schwei, Rebecca J et al. (2016) Disclosure of Depression in Primary Care: A Qualitative Study of Women's Perceptions. Womens Health Issues 26:529-36
Cui, Y; Guo, J; Santiago-Torres, M et al. (2015) Assessing Children's Time-Use in Relation to Physical Fitness and Risks of Obesity and Diabetes: Development of a New Physical Activity Self-Report Instrument. BAOJ Obes Weight Loss Manag 1:
Doherty, M; Santiago-Torres, M; Cui, Y et al. (2015) The Association between Screen Time and Weight Status in Hispanic Children. BAOJ Obes Weight Loss Manag 1:
Kruser, Jacqueline M; Nabozny, Michael J; Steffens, Nicole M et al. (2015) "Best Case/Worst Case": Qualitative Evaluation of a Novel Communication Tool for Difficult in-the-Moment Surgical Decisions. J Am Geriatr Soc 63:1805-11

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