Low-Density Lipoprotein Postsecretory Modification, Monocyte Function, and Circulating Adhesion Molecules in Type 2 Diabetic Patients With and Without Macrovascular Complications The Effect of α-Tocopherol Supplementation

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-α-tocopherol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group). Methods and 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 (O2−) and interleukin-1β (IL-1β) and exhibited greater adhesion to endothelium than control subjects. AT...

[1]  P. Demacker,et al.  Plasma levels of lipid and cholesterol oxidation products and cytokines in diabetes mellitus and cigarette smoking: effects of vitamin E treatment. , 1997, Atherosclerosis.

[2]  S. Grundy,et al.  RRR-alpha-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus. , 1996, The American journal of clinical nutrition.

[3]  A. Blann,et al.  Increased Levels of Soluble Adhesion Molecules in Type 2 (Non-Insulin Dependent) Diabetes mellitus Are Independent of Glycaemic Control , 1994, Thrombosis and Haemostasis.

[4]  A. Proietti,et al.  Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes , 1998, Diabetologia.

[5]  M. Brownlee Advanced glycation end products in diabetic complications , 1996 .

[6]  E. Boerwinkle,et al.  Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. , 1997, Circulation.

[7]  B. Davis,et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. , 1996, The New England journal of medicine.

[8]  N. Hoogerbrugge,et al.  Hypertriglyceridemia Enhances Monocyte Binding to Endothelial Cells in NIDDM , 1996, Diabetes Care.

[9]  R. Collins,et al.  Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. , 1998, The New England journal of medicine.

[10]  S. Devaraj,et al.  Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[11]  P. Tsao,et al.  Adherence of Mononuclear Cells to Endothelium In Vitro Is Increased in Patients With NIDDM , 1997, Diabetes Care.

[12]  A. Desfaits,et al.  Normalization of Plasma Lipid Peroxides, Monocyte Adhesion, and Tumor Necrosis Factor-α Production in NIDDM Patients After Gliclazide Treatment , 1998, Diabetes Care.

[13]  P. Valensi,et al.  Elevated Concentrations of Soluble E-Selectin and Vascular Cell Adhesion Molecule-1 in NIDDM: Effect of intensive insulin treatment , 1998, Diabetes Care.

[14]  K. Kobayashi,et al.  Agarose gel electrophoresis with nitroblue tetrazolium coloration for determination of glycated lipoproteins in serum from diabetics. , 1990, Clinical chemistry.

[15]  T. Nicotera,et al.  Oxidative damage to DNA in diabetes mellitus , 1996, The Lancet.

[16]  A. Chait,et al.  Superoxide initiates oxidation of low density lipoprotein by human monocytes. , 1987, Arteriosclerosis.

[17]  R. Mcvie,et al.  Relationship of Blood Thromboxane-B2 (TxB2) With Lipid Peroxides and Effect of Vitamin E and Placebo Supplementation on TxB2 and Lipid Peroxide Levels in Type 1 Diabetic Patients , 1998, Diabetes Care.

[18]  Joël Ménard,et al.  Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial , 1998, The Lancet.

[19]  I. Jialal,et al.  The effect of alpha-tocopherol supplementation on LDL oxidation. A dose-response study. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[20]  A. Gotto,et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. , 1998, JAMA.

[21]  D. Giugliano,et al.  Vitamin E Reduction of Protein Glycosylation in Diabetes: New Prospect for Prevention of Diabetic Complications? , 1991, Diabetes Care.

[22]  B. Davis,et al.  Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. , 1998, Circulation.

[23]  R. Bucala,et al.  Effect of a-tocopherol on LDL oxidation and glycation : in vitro and in vivo studies , 2002 .

[24]  H. Eyre,et al.  Metabolic Activity of Diabetic Monocytes , 1980, Diabetes.

[25]  Terje R Pedersen,et al.  Cholesterol Lowering With Simvastatin Improves Prognosis of Diabetic Patients With Coronary Heart Disease: A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S) , 1997, Diabetes Care.

[26]  D. Steinberg,et al.  Role of oxidized low density lipoprotein in atherogenesis. , 1991, The Journal of clinical investigation.

[27]  S. Devaraj,et al.  The effects of alpha tocopherol supplementation on monocyte function. Decreased lipid oxidation, interleukin 1 beta secretion, and monocyte adhesion to endothelium. , 1996, The Journal of clinical investigation.

[28]  S. Devaraj,et al.  Oxidized low-density lipoprotein and atherosclerosis , 1996, International journal of clinical & laboratory research.

[29]  M. Laakso,et al.  Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. , 1998, The New England journal of medicine.

[30]  P. Libby,et al.  Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. , 1991, Laboratory investigation; a journal of technical methods and pathology.

[31]  R. Natarajan,et al.  Evidence That Glucose Increases Monocyte Binding to Human Aortic Endothelial Cells , 1994, Diabetes.

[32]  S. Devaraj,et al.  α-Tocopherol Enrichment of Monocytes Decreases Agonist-Induced Adhesion to Human Endothelial Cells , 1998 .

[33]  T. Lehtimäki,et al.  Susceptibility of LDL to oxidation is not associated with the presence of coronary heart disease or renal dysfunction in NIDDM patients. , 1998, Clinica chimica acta; international journal of clinical chemistry.

[34]  L. Aiello,et al.  High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. , 1999, Diabetes care.

[35]  I. Jialal,et al.  GISSI-Prevenzione trial , 1999, The Lancet.

[36]  M. Steiner,et al.  Vitamin E plus aspirin compared with aspirin alone in patients with transient ischemic attacks. , 1995, The American journal of clinical nutrition.

[37]  D. Herold,et al.  Effects of Vitamin E on Susceptibility of Low-Density Lipoprotein and Low-Density Lipoprotein Subfractions to Oxidation and on Protein Glycation in NIDDM , 1995, Diabetes Care.

[38]  F. Kelly,et al.  Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS) , 1996, The Lancet.

[39]  S. Jain,et al.  Effect of modest vitamin E supplementation on blood glycated hemoglobin and triglyceride levels and red cell indices in type I diabetic patients. , 1996, Journal of the American College of Nutrition.

[40]  J. Baynes,et al.  The role of oxidative stress in diabetic complications , 1996 .

[41]  E. Bierman George Lyman Duff Memorial Lecture. Atherogenesis in diabetes. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[42]  E. Bierman Atherogenesis in diabetes , 1992 .

[43]  D. Mikhailidis,et al.  Effect of Vitamin E Supplementation on Platelet Thromboxane A2 Production in Type I Diabetic Patients: Double-Blind Crossover Trial , 1988, Diabetes.

[44]  B. Wolffenbuttel,et al.  Lipid peroxidation and atherosclerosis in type II diabetes. , 1999, The Journal of laboratory and clinical medicine.

[45]  M. Laakso,et al.  Diabetes and atherosclerosis: an epidemiologic view. , 1987, Diabetes/metabolism reviews.

[46]  H. Hill,et al.  Functional and metabolic abnormalities of diabetic monocytes. , 1982, Advances in experimental medicine and biology.

[47]  E. Ferrannini,et al.  Troglitazone Reduces LDL Oxidation and Lowers Plasma E-selectin Concentration in NIDDM Patients , 1998, Diabetes.

[48]  R. Bucala,et al.  Effect of alpha-tocopherol on LDL oxidation and glycation: in vitro and in vivo studies. , 1996, Journal of lipid research.

[49]  T. Lyons,et al.  Glycation and oxidation: a role in the pathogenesis of atherosclerosis. , 1993, The American journal of cardiology.

[50]  T. Özben,et al.  Serum Glycated Lipoproteins in Type II Diabetic Patients with and without Complications , 1995, Annals of clinical biochemistry.