title: Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation.
abstract: BACKGROUND
  Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects. Thus, we tested whether (1) postsecretory modifications of LDL (glycation and oxidation), monocyte proatherogenic activity, and circulating levels of soluble cell adhesion molecules (sCAMs) are more pronounced in DM2-MV than in DM2 and control subjects and (2) RRR-alpha-tocopherol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group).
  
  
  RESULTS
  Although LDL glycation was increased in both diabetic groups compared with control subjects, AT therapy had no significant effect on glycation. AT therapy significantly decreased LDL oxidizability in all 3 groups. Diabetic monocytes released significantly more superoxide anion (O(2)(-)) and interleukin-1beta (IL-1beta) and exhibited greater adhesion to endothelium than control subjects. AT therapy significantly decreased the release of O(2)(-), IL-1beta, tumor necrosis factor-alpha, and monocyte-endothelium adhesion in all 3 groups. There was no significant difference between the 2 diabetic groups for any of the above parameters. sICAM levels were significantly elevated in both diabetic groups compared with controls. AT therapy resulted in a significant decrease in sCAMs.
  
  
  CONCLUSIONS
  This is the first demonstration of increased IL-1beta secretion and increased adhesion of monocytes to endothelium from normotriglyceridemic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.
authors.affiliation: Division of Clinical Biochemistry and Human Metabolism, Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9073, USA.
authors.forename: S
authors.initials: S
authors.lastname: Devaraj
authors.forename: I
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000368:Aged; D015815:Cell Adhesion Molecules / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D019040:E-Selectin / Q000097:blood; D005260:Female; D006031:Glycosylation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007375:Interleukin-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E