Review

Review of the Diabetes Heart Study (DHS) Family of Studies: A Comprehensively Examined Sample for Genetic and Epidemiological Studies of Type 2 Diabetes and its Complications

Donald W. Bowden^1,2,3, Amanda J. Cox^1,2,3, Barry I. Freedman⁴, Christina E. Hugenschimdt^1,2,3, Lynne E. Wagenknecht⁵, David Herrington⁴, Subhashish Agarwal⁴, Thomas C. Register⁶, Joseph A. Maldjian⁷, Maggie C.-Y. Ng^1,2,3, Fang-Chi Hsu⁸, Carl D. Langefeld⁸, Jeff D. Williamson⁴, J. Jeffrey Carr⁷

Manuscript submitted September 21, 2010; resubmitted October 14, 2010; accepted October 29, 2010.

Keywords: type 2 diabetes, adiposity, bone, cardiovascular disease, cerebrovascular disease, coronary calcium, genetics

Abstract

The Diabetes Heart Study (DHS) is a genetic and epidemiological study of 1443 European American and African American participants from 564 families with multiple cases of type 2 diabetes. Initially, participants were comprehensively examined for measures of subclinical cardiovascular disease (CVD) including computed tomography measurement of vascular calcified plaque, ultrasound imaging of carotid artery wall thickness, and electrocardiographic intervals. Subsequent studies have investigated the relationship between bone mineral density and vascular calcification, measures of adiposity, and biomarkers. Ongoing studies are carrying out an extensive evaluation of cerebrovascular disease using magnetic resonance imaging and cognitive assessment. A second, parallel study, the African American DHS, has expanded the sample of African Americans to investigate marked racial differences in subclinical CVD between European Americans and African Americans. Studies in development will evaluate the impact of social stress during the lifecourse on CVD risk, and the prevalence of gastroparesis in this diabetes enriched sample. In addition, the ongoing high mortality rate in DHS participants provides novel insights into the increased risks for type 2 diabetes affected individuals. A comprehensive genetic analysis of the sample is underway using the genome-wide association study (GWAS) approach. Data from this GWAS survey will complement prior family-based linkage data in the analysis of genetic contributors to the wide range of traits in the sample. To our knowledge the DHS family of studies has created the most comprehensively examined sample of individuals with type 2 diabetes yet available, and represents a unique resource for the study people with type 2 diabetes. The aim of this review is to provide a collective overview of the major results from the DHS family of studies, and relate them to the larger body of biomedical investigations of diabetes and its complications.

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