Endothelial dysfunction in Type 1 diabetic subjects with and without microalbuminuria

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Abstract
Aims The primary aim of this study was to determine whether micro- albuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported bio- chemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. Methods Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. Results There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0–3.8%) and 2.3% (95% CI 0.7–3.9%) respectively vs. 6.3% (95% CI 5.1–7.5%), P < 0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7–18.7%) and 15.2% (95% CI 11.2–19.2%) vs. 18.7% (95% CI 16.1–21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P = 0.45). FMD was not significantly associated with urinary albumin–creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-β concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r = 0.36, P < 0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-β concentration). Active TGF-β concentration was not associated with degree of microalbuminuria or other biochemical parameters. Conclusions These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-β are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.