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      Non-Alcoholic Fatty Liver Disease (NAFLD) in children and adolescents with Prader-Willi Syndrome (PWS) : NAFLD in PWS children

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          The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index.

          Insulin sensitivity is higher in patients with Prader-Willi syndrome (PWS) than in body mass index-matched obese controls (OCs). Factors contributing to the heightened insulin sensitivity of PWS remain obscure. We compared the fasting levels of various hormones, cytokines, lipids, and liver function tests in 14 PWS patients and 14 OCs with those in 14 age- and gender-matched lean children (LC). We hypothesized that metabolic profiles of children with PWS are comparable with those of LC, but different from those of OCs. Leptin levels were comparable in PWS patients and OCs, suggesting comparable degrees of adiposity. Glucose levels were comparable among groups. However, fasting insulin concentrations and homeostasis model assessment insulin resistance index were lower in PWS patients than in OCs (P < 0.05) and similar to LC. Moreover, high-density lipoprotein levels were lower and triglycerides higher in OCs (P < 0.05) but not PWS patients. Total adiponectin, high-molecular-weight (HMW) adiponectin and the HMW to total adiponectin ratio were higher in PWS patients (P < 0.05) than in OCs and similar to LC. High-sensitivity C-reactive protein and IL-6 levels were higher in OCs than in PWS patients or LC (P < 0.05). Nevertheless, PAI-1 levels were elevated in both OC and PWS patients. There were no group differences in glucagon-like peptide-1, macrophage chemoattractant protein-1, TNFα, IL-2, IL-8, IL-10, IL-12p40, IL-18, resistin, total or low-density lipoprotein cholesterol, aspartate aminotransferase, or alanine aminotransferase. The heightened insulin sensitivity of PWS patients relative to OCs is associated with higher levels of adiponectin and lower levels of high-sensitivity C-reactive protein and IL-6. Future studies will determine whether PWS children are protected from obesity comorbidities such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease.
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            The obesity epidemic and nonalcoholic fatty liver disease in children.

            Childhood obesity is a worldwide health problem associated with an increase in the prevalence and severity of nonalcoholic fatty liver disease (NAFLD). This review covers the progress made between 2005 and 2007 in understanding the epidemiology, histology, and treatment of pediatric NAFLD. The number of children with NAFLD presents a major public health crisis. Noninvasive diagnostic tools offer future promise, but currently are unable to grade and stage disease. Therefore, pediatric NAFLD remains a clinico-pathological diagnosis requiring direct demonstration of liver steatosis and the exclusion of other causes of fatty liver and/or hepatitis. There are currently no proven therapies for NAFLD in children; however, TONIC (Treatment of Nonalcoholic Fatty Liver Disease in Children), the first multicenter clinical trial of pediatric NAFLD, is currently in progress. Such studies are imperative to address fundamental questions regarding cause and cure.
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              Is Non-Alcoholic Fatty Liver Disease Less Frequent among Women with Prader-Willi Syndrome?

              Objective: Patients with Prader-Willi syndrome (PWS) have been hypothesized to be at lower risk of non-alcoholic fatty liver disease (NAFLD) because of higher insulin sensitivity. However, PWS patients have a peculiar body composition, i.e. higher fat mass and lower fat-free mass, which may confound such associations. We evaluated whether NAFLD is less frequent in PWS than in non-PWS women matched on percent body fat (PBF). Methods: PBF was measured by dual-energy X-ray absorptiometry. Liver fat was assessed by ultrasonography. Insulin sensitivity and beta-cell function were evaluated by oral glucose tolerance testing. Coarsened exact matching (CEM) was used to match PWS and non-PWS women on PBF. General and generalized linear models taking CEM into account were used to perform comparisons between PWS and non-PWS women. Results: 20 women with PWS were matched to 27 women without PWS on the basis of PBF (mean 53 vs. 54%, p = 0.6). Insulin sensitivity and beta-cell function were similar in the two groups. However, the prevalence of NAFLD was 25% in PWS versus 59% in non-PWS women (p = 0.04). Conclusion: NAFLD is less frequent in PWS than in non-PWS women but this finding is not associated with higher insulin sensitivity.
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                Author and article information

                Journal
                Pediatric Obesity
                Pediatric Obesity
                Wiley
                20476302
                June 2016
                June 2016
                July 01 2015
                : 11
                : 3
                : 235-238
                Affiliations
                [1 ]Autoimmune Endocrine Diseases Unit; Bambino Gesù Children's Hospital; Research Institute; Palidoro Rome Italy
                [2 ]Endocrinology and Diabetic Unit; Bambino Gesù Children's Hospital; Research Institute; Palidoro Rome Italy
                [3 ]D.P.U.O. ‘Bambino Gesù’ Children's Hospital; ‘Tor Vergata’ University; Rome Italy
                [4 ]Radiology Dept.; Bambino Gesù Children's Hospital; Research Institute; Palidoro Rome Italy
                [5 ]Italian Auxological Institute Foundation; Piancavallo Verbania Italy
                [6 ]Hepato-Metabolic Unit; Bambino Gesù Children's Hospital; Research Institute; Palidoro Rome Italy
                [7 ]Department of Women's and Children's Health; Karolinska Institutet; Stockholm Sweden
                Article
                10.1111/ijpo.12052
                26132376
                8ba849f1-cf78-467c-ad2e-20fe9f768eb2
                © 2015

                http://doi.wiley.com/10.1002/tdm_license_1

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