Endothelial dysfunction in Type 1 diabetic subjects with and without microalbuminuria

Aims The primary aim of this study was to determine whether microalbuminuri a is associated with endothelial dysfunction in Type 1 diabetes mellitus. T he secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. Methods Measurements were made of the vasodilatory responses of the brachia l 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 di abetic patients with microalbuminuria, 18 age and sex-matched normoalbuminu ric Type 1 diabetic patients and 18 non-diabetic control subjects. Results There was a significant reduction in flow-mediated dilation (FMD) i n microalbuminuric and normoalbuminuric diabetic patients compared with con trol subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% C I 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P < 0.0001) but no dif ference 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 signi ficant difference in FMD, however, between the microalbuminuric group and n ormoalbuminuric 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 pos itive correlation between active transforming growth factor (TGF)-beta conc entration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r = 0.36, P < 0.05). GTN-mediated dilation was positivel y associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but n ot with other biochemical variables (including active TGF-beta concentratio n). Active TGF-beta concentration was not associated with degree of microal buminuria or other biochemical parameters; Conclusions These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunc tion 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-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Typ e 1 diabetic patients at a greater risk of coronary artery disease.