This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 2 diabetes mellitus (T2DM) and obesity are associated with a 5-7 fold increase in the risk of death from coronary heart disease (Laing et al, 2003). Factors associated with increased risk of developing coronary vascular disease include long duration of T2DM, poor metabolic control, hypertension, and dyslipidemia (Daniels, 2001). These factors are postulated to contribute to the development of atherosclerotic plaque by inducing oxidative stress, thus causing endothelial dysfunction, over-expression of inflammatory molecules, and subsequent recruitment and accumulation of lymphocytes, monocytes and smooth muscle cells in the intima of the vessel wall (Huo and Ley, 2001). Endothelial dysfunction is a major promoter of atherogenesis and has been established as a precursor of cardiovascular disease (Russo et al, 2002). Decreased arterial compliance is a consequence of endothelial vasomotor dysfunction and has been shown to be an early diagnostic marker of cardiovascular risk (Fathi and Marwick, 2001). Several non-invasive techniques have been developed to evaluate arterial compliance and endothelial dysfunction as a risk factor for the development of atherosclerosis and cardiovascular disease. One such technique, radial artery tonometry, can be used to assess the cumulative effect of multiple risk factors on the degree of endothelial dysfunction. We recently demonstrated that children with T1DM have increased arterial stiffness when compared to controls (Haller 2004). This study will compare the degree of arterial stiffness and endothelial dysfunction in children with T2DM, children with obesity, and healthy lean controls. Radial artery tonometry and reactive hyperemia will be performed in children with T2DM, obese children without T2DM, and age, sex, and race matched controls. In addition, blood will be drawn to compare degree of metabolic control, lipid profile, and serum inflammatory markers with degree of endothelial dysfunction.
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