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Rocha M.,University of Valencia | Rocha M.,Found For The Promotion Of Healthcare And Biomedical Research In The Valencian Community Fisabio | Rocha M.,Institute of Health Research INCLIVA | Banuls C.,University of Valencia | And 18 more authors.
PLoS ONE | Year: 2013

Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m2) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9±14.6; 42.3±17.0 and 37.4±11.7 μg/ml, respectively) and correlated with triglycerides but not with those of HOMA-IR in the whole population. The multivariate regression model revealed that triglycerides were the strongest predictor of systemic RBP4 levels. Analysis of lipoprotein subfractions in a subpopulation of 80 subjects showed an altered profile of insulin resistant states characterized by higher VLDL, sdLDL and small HDL percentages and lower large HDL percentage. Although RBP4 levels correlated significantly with LDL particle size and small HDL percentage, the latter parameter was independently associated only with RBP4. Our study reveals that systemic RBP4 levels could play an important role in lipid metabolism in morbid obesity, increasing triglyceride levels and contributing to the formation of small HDL. © 2013 Rocha et al.

Hernandez-Mijares A.,University of Valencia | Hernandez-Mijares A.,Found For The Promotion Of Healthcare And Biomedical Research In The Valencian Community Fisabio | Hernandez-Mijares A.,INCLIVA Foundation | Rocha M.,University of Valencia | And 18 more authors.
Diabetes Care | Year: 2013

OBJECTIVE - Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed. RESEARCH DESIGN AND METHODS - Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition-and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed. RESULTS - Waist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), HbA1c, high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial O2 consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist. CONCLUSIONS - Oxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte- endothelium interactions are features of type 2 diabetes and correlate with SMI. © 2013 by the American Diabetes Association.

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