Vascular defect beyond the endothelium in type II diabetic patients with overt nephropathy and moderate renal insufficiency

• Published in: Kidney international Vol. 70; no. 4; pp. 711 - 716
• Main Authors: Chan, W.B., Chan, N.N., Lai, C.W.K., So, W.Y., Lo, M.K.W., Lee, K.F., Chow, C.C., Metreweli, C., Chan, J.C.N.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2006; Nature Publishing; Elsevier Limited
• Subjects: Aged; Biological and medical sciences; Brachial Artery - diagnostic imaging; Brachial Artery - pathology; Carotid Arteries - diagnostic imaging; Carotid Arteries - pathology; Case-Control Studies; Chinese; diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - etiology; Diabetic Angiopathies - pathology; Diabetic Nephropathies - etiology; Diabetic Nephropathies - pathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; endothelial function; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Kidney - blood supply; Kidney - pathology; Kidney - physiopathology; Male; Medical sciences; Middle Aged; Multivariate Analysis; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; nephropathy; Nitroglycerin - pharmacology; Renal failure; Renal Insufficiency - etiology; Renal Insufficiency - pathology; Risk Factors; Tunica Intima - pathology; Tunica Intima - physiopathology; Tunica Media - parasitology; Tunica Media - pathology; Ultrasonography; Vasodilation - drug effects; Vasodilation - physiology; Asia; China; endothelial function; nephropathy; Chinese; diabetes; Endocrinopathy; Kidney disease; Type 2 diabetes; Human; Endothelial cell; Nephrology; Urinary system disease; Metabolic diseases; Urology; Endothelium; Nephropathy; Blood vessel; Renal failure; Defect; Circulatory system
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/sj.ki.5001652

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±0.38mm; 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 (β=0.257, P=0.009), glomerular filtration rate (β=-0.364, P<0.001), and smoking (β=0.25, P=0.013) were independently associated with carotid IMT (F=15.76, R2=0.340, P<0.001). After adjustment for baseline brachial arterial diameter, history of smoking (β=-0.039, P<0.001), fasting plasma glucose (β=-0.033, P=0.002), and total cholesterol (β=-0.023, P=0.024) were independently associated with vessel diameter after FMD (F=2446.5, R2=0.992, P<0.001); whereas age (β=-0.069, P=0.001) and urinary albumin excretion (β=-0.048, P=0.018) were independently associated with vessel diameter after GTN (F=851.6, R2=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.