Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes.
Recent studies have suggested that hypercholesterolemia is associated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipidemia is mainly characterized by hypertriglyceridemia, low high density lipoprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the relationships among LDL subfractions, the susceptibility of LDL to oxidation in vitro, and endothelial function in type 2 diabetes mellitus. LDL subfractions were measured by density gradient ultracentrifugation. The susceptibility of LDL to oxidation was determined by measuring the kinetics of conjugated dienes formation during copper-mediated oxidation of LDL. Endothelium-dependent and independent vasodilation of the brachial artery were assessed by high resolution vascular ultrasound. Diabetic patients had a higher concentration of small dense LDL-III than matched controls (P < 0.01). The lag phase of conjugated dienes formation was shorter in the diabetic patients (P < 0.05), and the rate of LDL oxidation was faster (P < 0.05). Both endothelium-dependent (P < 0.01) and independent dilation of the brachial artery (P < 0.01) were impaired in the diabetic patients. On multivariate analysis, the rate of oxidation and LDL-III concentration accounted for 12% and 6%, respectively, of the variation in endothelium-dependent vasodilation (adjusted r2 = 0.18; P < 0.05), whereas LDL-III concentration and the maximum amount of conjugated dienes formed accounted for 27% and 5%, respectively, of the variation in endothelium-independent vasodilation (adjusted r2 = 0.32; P < 0.01) in the diabetic patients. In conclusion, endothelial and smooth muscle cell dysfunction in type 2 diabetes were related to abnormalities in LDL subfractions and in LDL oxidation.
Tan
K C
KC
Department of Medicine, University of Hong Kong, Hong Kong.
Ai
V H
VH
Chow
W S
WS
Chau
M T
MT
Leong
L
L
Lam
K S
KS
D000328:Adult; D001916:Brachial Artery / Q000503:physiopathology; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood; D003300:Copper / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D002784:Cholesterol; D003300:Copper; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; D005996:Nitroglycerin; D014665:Vasodilator Agents