Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes

J Clin Endocrinol Metab. 1999 Sep;84(9):3212-6. doi: 10.1210/jcem.84.9.5959.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brachial Artery / physiopathology
  • Centrifugation, Density Gradient
  • Cholesterol / blood
  • Copper / chemistry
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Kinetics
  • Lipid Peroxidation*
  • Lipoproteins, LDL / blood*
  • Male
  • Middle Aged
  • Nitroglycerin / pharmacology
  • Vasodilation*
  • Vasodilator Agents / pharmacology

Substances

  • Glycated Hemoglobin A
  • Lipoproteins, LDL
  • Vasodilator Agents
  • Copper
  • Cholesterol
  • Nitroglycerin