In Vivo Evidence for Increased Oxidation of Circulating LDL in Impaired Glucose Tolerance

Abstract

Oxidized LDL (oxLDL) is a key mediator in atherogenesis and a marker of coronary artery disease (CAD).Type 2 diabetes is associated with excessive cardiovascular morbidity and mortality. Because atherogenesis starts before diabetes is diagnosed, we investigated whether circulating oxLDL levels are increased in impaired glucose tolerance (IGT). OxLDL levels were measured in 376 subjects with normal glucose tolerance (NGT), 113 patients with IGT, and 54 patients with newly diagnosed type 2 diabetes. After correction for age and BMI, serum levels of oxLDL were significantly increased in IGT versus NGT subjects (P ‫؍‬ 0.002). OxLDL levels were not associated with the following parameters of the oxidative/antioxidative balance in the blood: total antioxidant capacity, urate-to-allantoin ratio, and circulating phagocyte oxygenation activity. In stepwise multivariate analysis, LDL cholesterol (P < 0.0005) and triglycerides (P < 0.0005) were the strongest predictors of circulating oxLDL levels, followed by HDL cholesterol (P ‫؍‬ 0.003), 2-h postchallenge C-peptide (P ‫؍‬ 0.011), fasting free fatty acids (P ‫؍‬ 0.013), and serum paraoxonase activity (P ‫؍‬ 0.035). The strong correlation of oxLDL with LDL cholesterol and triglycerides indicates that LDL oxidation in IGT is preferentially associated with dyslipidemia. OxLDL increase may explain the high atherogenic potency of dyslipidemia in the prediabetic state. Diabetes 51:3102-3106, 2002

Glycosylated Hemoglobin and Mortality in Patients with Nondiabetic Chronic Kidney Disease

“…Chronic hyperglycemia has also been associated with increased circulating levels of oxidized LDL, a highly atherogenic form of LDL cholesterol (26). In a population-based study, moderate elevations in glucose levels were associated with abnormalities of cellular antioxidant mechanisms (27).…”

Glycoxidised LDL isolated from subjects with impaired glucose tolerance increases CD36 and peroxisome proliferator–activator receptor γ gene expression in macrophages

“…Since atherosclerosis starts in prediabetic states, such as IGT [1,14], the aim of the present study was to determine whether LDL obtained from IGT subjects is modified by glycoxidation, and to investigate the potential proatherogenic effects of the LDL samples on CD36, SCARB1 and PPARG mRNA expression in macrophages.…”

“…Recent evidence suggests that vascular complications are triggered prior to overt manifestation of disease, and may occur in conjunction with IGT. The oxidation of LDL observed in prediabetic states [1] has been identified as a crucial step in atherosclerotic lesion formation [2]. The seemingly unregulated uptake of modified LDL by monocytes/macrophages, with subsequent foam cell formation, is mediated by a variety of scavenger receptors, including macrophage scavenger receptor types I and II (MSRI/II, also known as SR-AI/II), CD36, scavenger receptor class B type 1 (SCARB1, also known as SR-BI), CD68 and lectin-type oxidised LDL receptor 1 (LOX-1).…”

Oxidised LDL modulate adipogenesis in 3T3‐L1 preadipocytes by affecting the balance between cell proliferation and differentiation

“…Oxidised low density lipoproteins (oxLDL) have been found in arteriosclerosis, type 2 diabetes and recently in the plasma of obese patients [1][2][3]. OxLDL modulate growth and transcription factors and cytokine production, influencing cell proliferation, apoptosis and differentiation [4][5][6][7].…”