Vascular Defect Beyond the Endothelium in Type II Diabetic Patients with Overt Nephropathy and Moderate Renal Insufficiency

There is a paucity of data on the effects of overt nephropathy and moderate renal impairment on endothelial function in diabetic patients. A total of 26 type II diabetic (DM) patients with nephropathy (DMN+) (mean +/- s.d. age: 63.7 +/- 6.3 years), 32 diabetic patients without nephropathy (DMN-) (59.4 +/- 10.1 years), and 52 non-diabetic subjects (54.9 +/- 8.2 years) were recruited. High-resolution ultrasound scan was used to measure carotid intima media thickness (IMT) and flow-mediated dilation (FMD) of the brachial artery. Endothelium-independent dilation was determined by maximal vascular dilation after sublingual nitroglycerine (glyceryl trinitrate (GTN)-induced dilation). The mean carotid IMT increased progressively from non-DM to DMN- to DMN+ groups (0.74 +/- 0.23 vs 0.80 +/- 0.25 vs 1.03 +/- 0.38 mm; P=0.001 for trend) whereas FMD- (4.3 +/- 2.5 vs 3.9 +/- 1.7 vs 1.9 +/- 2.0%, P<0.001 for trend) and GTN-induced dilation (14.7 +/- 4.0 vs 14.5 +/- 3.9 vs 10.3 +/- 3.2%; P<0.001 for trend) declined in an opposite manner. On multivariate analysis, age (beta=0.257, P=0.009), glomerular filtration rate (beta=-0.364, P<0.001), and smoking (beta=0.25, P=0.013) were independently associated with carotid IMT (F=15.76, R(2)=0.340, P<0.001). After adjustment for baseline brachial arterial diameter, history of smoking (beta=-0.039, P<0.001), fasting plasma glucose (beta=-0.033, P=0.002), and total cholesterol (beta=-0.023, P=0.024) were independently associated with vessel diameter after FMD (F=2446.5, R(2)=0.992, P<0.001); whereas age (beta=-0.069, P=0.001) and urinary albumin excretion (beta=-0.048, P=0.018) were independently associated with vessel diameter after GTN (F=851.6, R(2)=0.967, P<0.001). Type II diabetic patients with overt nephropathy and moderate renal impairment had both structural and functional vascular abnormalities beyond the endothelium.