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Alisi A.,Liver Research Unit | Cianfarani S.,Molecular Endocrinology Unit | Cianfarani S.,University of Rome Tor Vergata | Manco M.,Liver Research Unit | And 2 more authors.
Annals of Medicine

In the last three decades the incidence of metabolic syndrome (MetS) has been growing worldwide along with an increase of obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). In children and adolescents such epidemics are particularly worrisome, since the metabolic consequences in adulthood will significantly burden the health care system. Although the definition of MetS in childhood is still controversial, there is agreement with respect to NAFLD being the hepatic manifestation of MetS. However, the molecular pathogenesis of MetS and its contribution to NAFLD is complex and closely related to the pre-and postnatal environment as well as to genetic predisposing factors. The analysis of the possible relationships between NAFLD and MetS is particularly interesting, not only from an epidemiological point of view, but also to better understand the genetic and environmental factors contributing to the development of both diseases. We here summarize the most recent epidemiological data on the incidence of both diseases in adolescents, and several aspects linking MetS with NAFLD, discussing the possible role played by genetics and intrauterine environment. © 2012 Informa UK, Ltd. Source

Nobili V.,Metabolic and Autoimmune Liver Disease Unit | Nobili V.,A+ Network | Bedogni G.,Clinical Epidemiology Unit | Bedogni G.,University of Milan | And 13 more authors.
Pediatric Obesity

Background: The prevalence of obesity and its metabolic consequences has dramatically increased in the last two decades urging physicians to find a reliable definition for early detection, treatment and possibly prevention of metabolic syndrome (MS). MS could be diagnosed in adult patients in the presence of a large waist circumference and ≥2 of the following features: high serum triglycerides, low serum high-density lipoprotein cholesterol, high blood pressure and high fasting glucose. The definition of MS in children is more problematic, and the potential role of its single components on metabolic risk remains largely undefined. Recent evidence strongly suggests not only a relationship between non-alcoholic fatty liver disease (NAFLD) and MS in obese children, adolescents and adults, but also the key role exerted by liver fat deposition in the pathogenesis of MS. Conclusion: We propose that NAFLD should be routinely checked in obese subjects because early lifestyle changes may be effective in reducing the overall risk of MS. © 2012 The Authors. Source

Wit J.M.,Leiden University | Ranke M.B.,University of Tubingen | Albertsson-Wikland K.,Gothenburg University | Carrascosa A.,Autonomous University of Barcelona | And 20 more authors.
Hormone Research in Paediatrics

The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic. Copyright © 2013 S. Karger AG, Basel. Source

Cianfarani S.,TorV ergata University | Cianfarani S.,Molecular Endocrinology Unit
Frontiers in Endocrinology

Insulin-like growth factor-II (IGF-II), traditionally considered as a growth factor implicated in growth of fetal tissues and cancer cells, is now emerging as a potential metabolic regulator. The aim of this overview is to provide the available evidence, obtained in both experimen- tal conditions and in humans, for a role of IGF-II in the fine-tuning of metabolism and body composition. The underlying mechanisms and the potential clinical implications are discussed. © 2012 Cianfarani. Source

Benevento D.,Unit of Endocrinology and Diabetes | Bizzarri C.,Unit of Endocrinology and Diabetes | Patera I.P.,Unit of Endocrinology and Diabetes | Rava L.,Epidemiology Unit | And 5 more authors.
Diabetes/Metabolism Research and Reviews

Background: High birth weight has been related to an increased risk of type 1 diabetes (T1D), while suboptimal birth weight (both high and low) has been related to obesity, insulin resistance and type 2 diabetes. Insulin resistance, as a consequence of poor metabolic control, has been described in T1D patients. The aims of the study were to analyse the distribution of birth size for gestational age in a large group of T1D patients and to investigate the effect of birth weight on clinical phenotype. Methods: Six-hundred two Caucasian T1D patients were evaluated. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birth weight at <3rd percentile and >97th percentile for gestational age, respectively. Birth weights between the 3rd and 97th percentiles were defined as appropriate for gestational age. The clinical characteristics of small, appropriate for gestational age and large were compared. Multivariable linear regression models were fitted to evaluate the independent effects of birth weight and other covariates (age at T1D onset, gender and T1D duration) on different clinical outcomes (body mass index, HbA1c, insulin requirement, high-density lipoprotein cholesterol and triglycerides). Results: Thirteen subjects (2.16%) were small (SGA), and 39 (6.48%) were large (LGA). Daily insulin requirement (U/kg/day) was significantly higher in SGA, while body mass index and HbA1c were increased in LGA. Multivariable linear regression showed a significant negative effect of birth weight on daily insulin requirement (p<0.001). Conclusions: Suboptimal birth weight (both high and low) in T1D patients seems to be associated with clinical characteristics suggestive of insulin resistance. © 2012 John Wiley & Sons, Ltd. Source

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