Brachial artery reactivity in asymptomatic patients with type 2 diabetes mellitus and microalbuminuria (from the Detection of Ischemia in Asymptomatic Diabetics–Brachial Artery Reactivity study)

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Abstract

Microalbuminuria is a novel atherosclerotic risk factor in patients with type 2 diabetes mellitus (DM) and predicts future cardiovascular events. Endothelial dysfunction and systemic inflammation have been proposed as common links between microalbuminuria and cardiovascular disease. However, no study has assessed the relation between microalbuminuria and vascular dysfunction as measured by brachial artery reactivity (BAR) in DM. We evaluated 143 patients (85 men; mean age 60.0 ± 6.7 years) with DM (mean duration 8.2 ± 7.4 years) enrolled in the Detection of Ischemia in Asymptomatic Diabetics study. Subjects were categorized as those with microalbuminuria (ratio of urinary albumin to creatinine 30 to 299 μg/mg creatinine, n = 28) and those with normoalbuminuria (ratio of urinary albumin to creatinine 0 to 29.9 μg/mg creatinine, n = 115). High-resolution ultrasound BAR testing was used to measure endothelium-dependent and endothelium-independent vasodilations. C-reactive protein was measured as a marker of systemic inflammation. Patients with microalbuminuria and normoalbuminuria had similar baseline characteristics, with the exception that those with microalbuminuria had a longer duration of DM (p = 0.03). Endothelium-dependent vasodilation at 1 minute (p = 0.01) and endothelium-independent vasodilation at 3 minutes (p = 0.007) were significantly less in patients with microalbuminuria. In addition, 96% of patients with microalbuminuria and 76% of those with normoalbuminuria had impaired endothelium-dependent vasodilation (<8%, p = 0.01). Microalbuminuria was an independent predictor of endothelium-dependent vasodilation in the entire cohort (p = 0.045) and after excluding patients on hormone replacement therapy (p = 0.01). Levels of C-reactive protein were significantly higher in patients with microalbuminuria than in those with normoalbuminuria (p = 0.02). We conclude that in DM the presence of microalbuminuria is associated with impaired endothelium-dependent and endothelium-independent vasodilations of the brachial artery and a higher degree of systemic inflammation. In addition, microalbuminuria is an independent predictor of endothelial dysfunction in asymptomatic patients with DM, especially in the absence of hormone replacement therapy.

Section snippets

Patient population

The patient cohort consisted of subjects enrolled in the DIAD study who underwent assessment of BAR (DIAD-BAR substudy). The DIAD study is a prospective, multicenter, randomized trial that evaluates the prevalence of adenosine technetium-99m sestamibi myocardial perfusion imaging abnormalities in asymptomatic patients with type 2 DM and its association with adverse clinical outcomes. Eligible patients had asymptomatic type 2 DM, were 50 to 75 years old, and had no known coronary artery disease.

Baseline characteristics

The baseline clinical and biochemical characteristics of the entire study population are listed in Table 1. There were no significant differences between groups regarding use of medications (Table 2) with the exceptions of thiazolidinediones being used more frequently in patients with microalbuminuria (p = 0.05), and hormone replacement therapy was less prevalent in patients with microalbuminuria than in those with normoalbuminuria (p = 0.04).

Relation between microalbuminuria and brachial artery reactivity

There was a trend for larger baseline brachial

Discussion

The aim of this study was to investigate the relation between microalbuminuria and BAR in asymptomatic patients with DM. Our results demonstrated that patients with microalbuminuria have significant impairment of EDV and EIV compared with those with normoalbuminuria and a higher degree of systemic inflammation. These data associated the presence of microalbuminuria in patients with DM with impaired vascular reactivity secondary to smooth muscle dysfunction rather than to endothelial dysfunction

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    This study was supported by grants from the Hartford Hospital Research Administration, Hartford, Connecticut, and Bristol-Myers Squibb Medical Imaging, North Billerica, Massachusetts.

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