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      Subcutaneous adipose tissue plays a beneficial effect on subclinical atherosclerosis in young survivors of acute lymphocytic leukemia

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          Abstract

          Purpose

          The aim of this study was to evaluate the relationship between body composition, metabolic profile, adipokines, and carotid intima-media thickness (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL).

          Patients and methods

          This cross-sectional study compared 55 ALL survivors, of chronological age between 15 years and 24 years, assigned into two groups according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30 nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual-energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple regression analysis.

          Results

          Treatment with CRT had an effect on all of the variables derived from the computed tomography scan: visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) ( P<0.050). In a multiple linear regression model, cIMT positively correlated with exposure to CRT ( P=0.029), diastolic BP ( P=0.016), and leptin-to-adiponectin ratio ( P=0.048), while negatively related to SAT ( P=0.007).

          Conclusion

          In young survivors of childhood ALL, CRT modified the distribution of fat and played a critical role in determining cIMT. Leptin-to-adiponectin ratio, a biomarker of abdominal obesity and metabolic syndrome, and diastolic BP also influenced cIMT, a marker of subclinical atherosclerosis. Nonetheless, adiposity-associated vascular disease might be attenuated by SAT. Changes in body fat must be evaluated in this group of patients in the early course of survivorship in order to avoid premature cardiovascular disease associated with atherosclerosis. Yet, further research as regards the possible protective effect of SAT on vascular disease is warranted.

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          Most cited references23

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          Neck circumference as a simple tool for identifying the metabolic syndrome and insulin resistance: results from the Brazilian Metabolic Syndrome Study.

          To investigate the relationship of the neck circumference (NC) with the metabolic syndrome (MetS) and insulin resistance (IR) in a large Brazilian population-based sample, within a wide range of adiposity and glucose tolerance, and to establish cut-off values of the NC for MetS and IR. The NC correlates with cardiovascular risk factors, IR and components of MetS. Upper-body subcutaneous (sc) fat, as estimated by the NC, is associated with cardiovascular risk factors as much as abdominal fat, which is usually estimated by the waist circumference (WC). There are few epidemiological population-based studies on the clinical significance of the NC to MetS and IR. This is a cross-sectional study. About 1053 Brazilian adults (18-60 years). Patients with BMI 18.5-40.0 kg/m(2), with normal glucose tolerance or type 2 diabetes (T2DM), were submitted to anthropometric measurements including waist circumference (WC), NC and BMI. Abdominal visceral fat (VF) was assessed by ultrasound. Insulin sensitivity (IS) was assessed by euglycaemic-hyperinsulinaemic clamp (10% of total sample) and HOMA-IR. Spearman correlations were used to evaluate the association between NC and IR and MetS risk factors. Receiver operating characteristic (ROC) curves were used for gender-specific cut-off values for the prediction of IR and MetS. Binary logistic regression analysis was used to assess the chance of developing IR or MetS according to the enlargement of NC and WC. The sample consisted of 28.6% men, with a mean age of 39.4 (12 years). T2DM diagnosis was present in 306 individuals, of whom 34% were men. NC correlated with WC and BMI in both men and women (P < 0.001). In both genders, NC showed a positive correlation with triglycerides, fasting glucose, fasting insulin and HOMA-IR, and NC had a negative association with high-density lipoprotein (HDL). NC and IS showed a moderate negative correlation. A significant correlation was demonstrated between VF and NC. In the ROC curves, NC presented the largest AUC for IR in women (P < 0.001), while NC presented a large AUC for MetS in both genders. Neck circumference measurements are an alternative and innovative approach for determining body fat distribution. The NC is positively associated with MetS risk factors, IR and VF, with established cut-off values for the prediction of MetS and IR. © 2012 John Wiley & Sons Ltd.
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            Insulin resistance and the endothelium.

            There is increasing evidence of a parallel progression between insulin resistance and endothelial dysfunction, suggesting a close association between insulin action and the endothelium. Numerous studies have demonstrated that endothelial dysfunction occurs early in the insulin-resistant state and is predictive of future cardiovascular events. Similarly, insulin resistance has been associated with the metabolic syndrome, which also increases the risk of adverse cardiovascular outcomes. Approaches that improve endothelial dysfunction, such as treatment with statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or peroxisome proliferator-activated receptor gamma ligands, have been shown to prevent both diabetes and cardiovascular disease. This article reviews the relation between endothelial dysfunction and cardiovascular disease, assesses the endothelium in the spectrum of insulin resistance, and examines the effect of the thiazolidinediones on endothelial function.
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              Leptin:adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery.

              The evaluation of the leptin:adiponectin ratio (L:A) has been suggested as an atherosclerotic index in patients with type 2 diabetes and a useful parameter to assess insulin resistance in patients with and without diabetes. We investigated, therefore, the relationship between L:A ratio and intima media thickness (IMT), an independent predictor of cardiovascular disease, in 110 healthy males. L:A ratio was significantly correlated to body mass index, waist, hip, waist-to-hip ratio, systolic blood pressure, IMT, high-density lipoprotein, apolipoprotein A-I, glucose, and the homeostasis model of insulin resistance-revised. No significant correlation was observed with age, diastolic blood pressure, low-density lipoprotein, triglycerides, apolipoprotein B, ApoB/ApoA-I ratio, insulin, alanine transaminase, gamma-glutamyl-transferase, and resistin. In addition, when the relationship between IMT and adiponectin or leptin alone was analyzed, only leptin plasma levels significantly associated with IMT (r=0.301, P 30 kg/m(2)) showed a significantly higher L:A ratio compared with nonobese subjects (1.20 versus 0.42, respectively, P<0.001); in addition, subjects with the metabolic syndrome showed a significantly higher L:A ratio level (0.79) compared with subjects without (0.52) (P<0.01). We show here that the L:A ratio is a powerful independent predictor of IMT in healthy subjects and correlates with several anthropometric, metabolic, and clinical parameters better than each single adipokine.
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                Author and article information

                Journal
                Vasc Health Risk Manag
                Vasc Health Risk Manag
                Vascular Health and Risk Management
                Vascular Health and Risk Management
                Dove Medical Press
                1176-6344
                1178-2048
                2015
                18 August 2015
                : 11
                : 479-488
                Affiliations
                [1 ]Division of Pediatric Endocrinology, Department of Pediatrics, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo, Brazil
                [2 ]Pediatric Oncology Institute – IOP/GRAACC, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo, Brazil
                [3 ]Private Office, Castro Monteiro, Sao Paulo, Brazil
                [4 ]Division of Cardiology, Federal University of Sao Paulo (UNIFESP/EPM), Brazil
                [5 ]Laboratory of Investigation on Metabolism and Diabetes (LIMED), Faculty of Medical Sciences, State University of Campinas (UNICAMP), Brazil
                [6 ]Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Brazil
                Author notes
                Correspondence: Angela Maria Spinola-Castro, 307 Doutor Diogo de Faria Street, 04037-000 Sao Paulo, Brazil, Tel +55 11 5579 9409, Fax +55 11 5579 9409, Email aspinola.dped@ 123456epm.br
                Article
                vhrm-11-479
                10.2147/VHRM.S86883
                4547649
                fd04a351-71d9-4c55-89f7-15249348f6e8
                © 2015 Siviero-Miachon et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Cardiovascular Medicine
                precursor cell lymphoblastic leukemia–lymphoma/radiotherapy,abdominal fat,metabolic syndrome x,adipokines,endothelium,atherosclerosis

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