Evidence is increasing for small-vessel disease and disturbance of endothelium-dependent vasodilation in diabetic patients. The aim of this study was to compare coronary circulation in 11 diabetic patients (6 type I and 5 type II) and 7 control subjects. All patients had normal left ventricular systolic function and angiographically normal coronary arteries. To evaluate the maximal area of coronary microcirculation, coronary vascular reserve was determined by intracoronary Doppler and a maximally vasodilating dose of intracoronary papaverine (peak-to-resting coronary flow velocity ratio). To assess coronary endothelial function responses to stepwise intracoronary infusion of acetylcholine (10−8 to 10−5) M coronary estimated concentrations) were analyzed on four different segments in each patient by quantitative angiography. Peak-to-resting coronary flow velocity ratio was lower in diabetic patients than in control subjects (3.9 ± 0.9 and 5.0 ± 0.7, respectively, P < 0.02). Acetylcholine did not produce any diameter change at 10−8 and 10−7 M, but a progressive diameter reduction was observed at 10−6 and 10−5 M (−8.0 ± 15.2%, P < 0.02 and −24.0 ± 13.6%, P < 0.001, respectively). In control subjects, a progressive diameter dilation was produced from 10−8 to 10−6 M acetylcholine (5.1 ± 3.4, 12.1 ± 7.0, and 16.4 ± 7.3%, respectively, all P < 0.001), and a moderate reduction was observed at 10−5 M (−4.9 ± 7.5%, P < 0.02). In the two groups, all segments dilated similarly after intracoronary isosorbide dinitrate. In conclusion, these results provide evidence that diabetes mellitus may be responsible for both structural and functional alterations of the coronary circulation in patients with angiographically normal coronary arteries. These alterations of the coronary circulation in diabetic patients may contribute to the progressive deterioration of the myocardium and to the pathogenesis of diabetic cardiomyopathy.

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