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, beta = 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.