The long term objective of the African American-Diabetes Heart Study is to identify the causes of the markedly lower amounts of calcified atherosclerotic plaque in African American (AA) subjects with type 2 diabetes mellitus (T2DM), relative to European Americans (EA). Additional goals are to evaluate the impacts of lifestyle, environment and inherited factors on the development of subclinical cardiovascular disease (CVD), and to identify genomic regions contributing to the inherited component of subclinical CVD in AAs with T2DM. These goals will be achieved by the concerted efforts of clinicians, epidemiologists, biostatisticians, biochemists, and molecular geneticists, building on work that was previously performed in the parent Diabetes Heart Study (DHS). Specifically, we will ascertain, phenotype, and collect DMA from an additional 566 unrelated AAs with T2DM, combining their information with 90 unrelated AA diabetic subjects previously recruited into the DHS (656 subjects total). Clinical risk factor profiles will be created for each participant and we will assess subclinical and clinical CVD using Multi-Detector Row Computed Tomography of the coronary and carotid arteries and infra-renal aorta. We will next examine the impact of conventional CVD risk factors (smoking, lipids and lipoproteins, hypertension and glycemic control) and novel risk factors (sex hormones and other endocrine measures, calcium regulating hormones, calcification inhibitors and inflammatory biomarkers) on the development of calcified atherosclerotic plaque in AAs with T2DM. We will investigate ethnic differences in calcified atheromatous plaque by comparing the above results with those obtained in a matched cohort of EA subjects with T2DM from the parent DHS. In years 4 and 5, we will screen the genome using Mapping by Admixture Linkage Disequilibrium (MALD) in an expanded sample of 1,100 unrelated AA subjects with T2DM (444 previously recruited in existing studies and 656 locally recruited) to locate genomic regions that harbor calcified atherosclerotic plaque susceptibility genes in the diabetic AA population. These strategies will provide novel information on causes of the marked ethnic disparity in subclinical CVD, will assist in identifying genes that predispose to CVD in AA subjects with T2DM, and may lead to the development of novel treatment strategies to prevent hardening of the arteries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK071891-03
Application #
7636852
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Mckeon, Catherine T
Project Start
2007-08-15
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2009
Total Cost
$645,731
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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Freedman, Barry I; Sink, Kaycee M; Hugenschmidt, Christina E et al. (2017) Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus. Am J Kidney Dis 70:627-637
McLean, Nicholas O; Robinson, Todd W; Freedman, Barry I (2017) APOL1 Gene Kidney Risk Variants and Cardiovascular Disease: Getting to the Heart of the Matter. Am J Kidney Dis 70:281-289
Divers, Jasmin; Palmer, Nicholette D; Langefeld, Carl D et al. (2017) Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes. BMC Genet 18:105

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