D. Fintini - Academia.edu (original) (raw)

Papers by D. Fintini

Research paper thumbnail of MKRN3 circulating levels in Prader–Willi syndrome: a pilot study

Journal of Endocrinological Investigation

Research paper thumbnail of Impaired energy expenditure and physical activity in children affected by GH deficiency measured by SenseWear Armband: preliminary results

Background: Influence of growth hormone on energy expenditure and physical performance is clearly... more Background: Influence of growth hormone on energy expenditure and physical performance is clearly known. Objective and hypotheses: The aim of our study is to evaluate the energy expenditure (EE) during physical (PA) and sedentary activities (SA), in a group of children/adolescents affected by growth hormone deficiency (GHD) compared to healthy subjects, using an objective measure as SenseWear Armband (SWA-BodyMedia). Patients, methods and results: These preliminary data included 13 untreated, consecutive GHD children and adolescents (6 males) (GH peak <10 ng/ml; IGF1 SDS -2.0\ub10.3) and 10 controls (6 males), age and sex matched. As expected, the GHD group showed statistically lower height (-2.7\ub10.9 vs 0.4\ub10.5 SDS), weight (-1.5\ub11.2 vs 1.1\ub10.6 SDS) and Body Mass Index (BMI) (-0.1\ub11.2 vs 0.6\ub10.2 SDS). The use of SWA demonstrated that the GHD children showed lower Energy expenditure, total (1007\ub1458 vs 1337\ub1125 cal/d;1.7\ub10.2 vs 1.9 \ub10.2 Mets/d) and active (214\ub1136 vs 435\ub188 cal/d;7\ub13 vs 13\ub14 cal/Kg/d) and spent statistically less time in physical activity (>3 Mets) (1.5 \ub10.8 vs 2.3\ub11 h/d), especially moderate (3-6 Mets)(1.4\ub10.8 vs 2.2\ub10.9 h/d; 5.8\ub13.1 vs 9.2\ub13.9% of daily hours) compared with healthy subjects. A tendency to spend more time in sedentary activities was found in GHD group (16\ub14 vs 14\ub13 h/d), although not statistically significant. In multivariate regression IGF1 and BMISD resulted positive predictors of EE/daily (cal/daily) in GHD children. Conclusions: In conclusion our preliminary results seem to confirm that children affected by growth hormone deficiency showed lower energy expenditure as calories/daily and spent less time in physical activities compared to normal children. This result seems correlate to IGF1 values indicating a possible role of GH in physical performance. Further evaluations on greater number of patients, before and after GH therapy, are ongoing to confirm our findings

Research paper thumbnail of Uniparental disomy and pretreatment IGF-1 may predict elevated IGF-1 levels in Prader-Willi patients on GH treatment

Growth Hormone & IGF Research, 2019

Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhG... more Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhGH). These patients are highly sensitive to rhGH and the standard doses suggested by the international guidelines often result in IGF-1 above the normal range. We aimed to evaluate 1 the proper rhGH dose to optimize auxological outcomes and to avoid potential overtreatment, and 2 which patients are more sensitive to rhGH. In this multicenter real-life study, we recruited 215 patients with PWS older than 1 year, on rhGH at least for 6 months, from Italian Centers for PWS care. We collected auxological parameters, rhGH dose, IGF-1 at recruitment and (when available) at start of treatment. The rhGH dose was 4.3 (0.7/8.4) mg/m 2 /week. At recruitment, IGF-1 was normal in 72.1% and elevated in 27.9% of the patients. In the group of 115 patients with IGF-1 available at start of rhGH, normal pretreatment IGF-1 and uniparental disomy were associated with elevated IGF-1 during the therapy. No difference in height and growth velocity was found between patients treated with the highest and the lowest range dose. The rhGH dose prescribed in Italy seems lower than the recommended one. Normal pretreatment IGF-1 and uniparental disomy are risk factors for elevated IGF-1. The latter seems to be associated

Research paper thumbnail of The genetic background and vitamin D supplementation can affect irisin levels in Prader–Willi syndrome

Journal of Endocrinological Investigation, 2021

Background Prader–Willi syndrome (PWS) is associated to distinctive clinical symptoms, including ... more Background Prader–Willi syndrome (PWS) is associated to distinctive clinical symptoms, including obesity, cognitive and behavioral disorders, and bone impairment. Irisin is a myokine that acts on several target organs including brain adipose tissue and bone. The present study was finalized to explore circulating levels of irisin in children and adult PWS patients. Methods Seventy-eight subjects with PWS, 26 children (15 females, mean age 9.48 ± 3.6 years) and 52 adults (30 females, mean age 30.6 ± 10.7) were enrolled. Irisin serum levels were measured in patients and controls. Its levels were related with anthropometric and metabolic parameters, cognitive performance and bone mineral density either in pediatric or adult PWS. Multiple regression analysis was also performed. Results Irisin serum levels in PWS patients did not show different compared with controls. A more in-depth analysis showed that both pediatric and adult PWS with DEL15 displayed significantly reduced irisin levels...

Research paper thumbnail of Le cardiopatie congenite semplici e l'idoneità all'attività fisica agonistica

Medicina Dello Sport, 2010

Research paper thumbnail of Metabolic Syndrome in Italian Obese Children and Adolescents: Stronger Association with Central Fat Depot than with Insulin Sensitivity and Birth Weight

International Journal of Hypertension, 2011

Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FH... more Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FHD) were associated with metabolic syndrome (MetS) in children and adolescents.Methods. A total of 439 Italian obese children and adolescents (5–18 years) were enrolled. Subjects were divided into 2 groups: prepubertal and pubertal. MetS was diagnosed according to the adapted National Cholesterol Education Program criteria. Birth weight percentile, central obesity index (measured by dual-energy X-ray absorptiometry), insulin sensitivity (ISI), and disposition index were evaluated. Multivariate logistic regression models were used to determine variables associated with MetS.Results. The prevalence of MetS was 17%, with higher percentage in adolescents than in children (21 versus 12%). In the overall population, central obesity index was a stronger predictor of MetS than insulin sensitivity and low birth weight. When the two groups were considered, central fat depot remained the strongest p...

Research paper thumbnail of Physical activity, fitness, and dyspnea perception in children with congenital diaphragmatic hernia

Pediatric Pulmonology, 2011

Research paper thumbnail of Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

Research paper thumbnail of Obese Children with Low Birth Weight Demonstrate Impaired β-Cell Function during Oral Glucose Tolerance Test

The Journal of Clinical Endocrinology & Metabolism, 2009

Objective: Epidemiological studies have shown an association between birth weight and future risk... more Objective: Epidemiological studies have shown an association between birth weight and future risk of type 2 diabetes, with individuals born either small or large for gestational age at increased risk. We sought to investigate the influence of birth weight on the relation between insulin sensitivity and β-cell function in obese children. Subjects and Methods: A total of 257 obese/overweight children (mean body mass index-sd score, 2.2 ± 0.3), aged 11.6 ± 2.3 yr were divided into three groups according to birth weight percentile: 44 were small for gestational age (SGA), 161 were appropriate for gestational age (AGA), and 52 were large for gestational age (LGA). Participants underwent a 3-h oral glucose tolerance test with glucose, insulin, and C-peptide measurements. Homeostasis model of assessment for insulin resistance, insulinogenic index, and disposition index were calculated to evaluate insulin sensitivity and β-cell function. Glucose and insulin area under the curve (AUC) were a...

Research paper thumbnail of Association between Nocturnal Blood Pressure Reduction and Progression of Visual Field Defect in Patients with Primary Open-Angle Glaucoma or Normal-Tension Glaucoma

Japanese Journal of Ophthalmology, 2004

Objective: The purpose of this study was to analyze the relationship between insulin-glucose meta... more Objective: The purpose of this study was to analyze the relationship between insulin-glucose metabolism, nocturnal blood pressure (BP) dipping and cardiac left ventricular mass (LVM) in obese adolescents without diabetes. Methods: A cohort of 206 obese adolescents (mean age 15.4 years (s.d. 1.6), mean body mass index (BMI) 38 kg m-2 (s.d. 5.8), 53% girls) under clinical care were included in the study. Body fat was assessed by dual X-ray absorptiometry (DEXA). Blood samples were drawn for analyses of fasting insulin (fS-insulin), fasting glucose and glycosylated hemoglobin Alc. Homeostatic model assessment index (HOMA index) was calculated. Insulin sensitivity and acute insulin response (AIR) were calculated from the performed frequently sampled intravenous glucose tolerance test. An ambulatory BP measurement was performed and 24 h daytime and nighttime values were calculated. Non-dipping was defined as a nocturnal BP reduction of o10%. Ultrasound was used to measure heart LVM and LVM index (LVMI) was calculated (LVM Â height À2.7). Results: Systolic non-dipping was present in 50% (n ¼ 103) of the subjects. Systolic and diastolic dipping was negatively associated with measures of insulin metabolism (HOMA index, fS-insulin and AIR). These associations were present independently of gender, age, daytime BP or body mass index standard deviation score. Dipping (P ¼ 0.7-0.9) or measures of insulin-glucose metabolism (P ¼ 0.3-1.0) were not associated with LVMI in this population. Conclusion: Non-dipping is common among obese adolescents. We found a negative association between nocturnal BP fall (dipping) and measures of insulin metabolism independently of the degree of obesity or daytime BP level among severely obese, non-diabetic adolescents without diagnosed hypertension. Our findings suggest the importance of keeping the insulin levels under observation even in allegedly healthy obese adolescents in clinical care, as a part of the prevention of morbidity associated with obesity.

Research paper thumbnail of Thyroid Function Tests in Obese Prepubertal Children: Correlations with Insulin Sensitivity and Body Fat Distribution

Hormone Research in Paediatrics, 2012

Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly ele... more Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly elevated free triiodothyronine (fT(3)) and/or free thyroxine (fT(4)) have been consistently found in obese children. To examine relationships between adiposity, insulin sensitivity, and TSH, fT(3) and fT(4). 240 overweight/obese prepubertal children were studied. Fasting TSH, fT(3), fT(4), glucose, insulin, C-peptide, lipids, leptin and adiponectin were evaluated. Insulin sensitivity and resistance were estimated [quantitative insulin check index (QUICKI), insulin sensitivity index (ISI), and hepatic insulin resistance index]. Body fat was measured by dual-energy X-ray absorptiometry. The central obesity index was calculated as the ratio of fat tissue in the trunk region to fat tissue in the leg region. The multiple regression analysis with age, gender and measures of fatness as covariates showed that QUICKI was the only significant negative predictor of TSH and central obesity index the strongest positive predictor of fT(3), in association with either age or hepatic insulin resistance index, and that the only positive determinant of fT(4) was hepatic insulin resistance index. Reduced insulin sensitivity is associated with augmented TSH and fT(4), while progressive central fat accumulation is strictly related to a parallel increase in fT(3) levels, independently from total body fat. Further studies are needed to understand mechanisms linking thyroid function to insulin sensitivity and body composition in obese children.

Research paper thumbnail of Cardiovascular Fitness, Insulin Resistance and Metabolic Syndrome in Severely Obese Prepubertal Italian Children

Hormone Research, 2008

To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor card... more To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor cardiovascular fitness in very obese prepubertal Italian subjects. Children referred to the Endocrinology and Diabetes Unit of Bambino Gesù Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital underwent an OGTT with glucose and insulin assays. QUICKI, ISI and HOMA-IR were calculated. Total and HDL cholesterol, triglycerides and percentage of body fat (DEXA) were determined. Cardiovascular fitness (maximal treadmill time) was evaluated using a treadmill protocol. The MS was defined as having 3 or more of following risk factors: obesity, impaired glucose tolerance, high blood pressure, low HDL-cholesterol, high triglycerides. Fifty-five very obese prepubertal Italian children were enrolled in the study. Unadjusted correlation revealed maximal treadmill time negatively related to fasting insulin (r = -0.53, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and HOMA-IR (r = -0.57, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and positively to QUICKI (r = 0.51, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and ISI (r = 0.46, p = 0.0035). These relationships remained significant when in multivariate analysis age, gender, BMI SD and body composition were accounted for (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). The presence of the MS was independently associated with maximal treadmill time. Poorcardiovascular fitness, IR and MS were independently related, suggesting that the relationship between fitness and insulin action develops early in life.

Research paper thumbnail of Abnormal glucose tolerance in children with cystic fibrosis: the predictive role of continuous glucose monitoring system

European Journal of Endocrinology, 2010

A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibr... more A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibrosis (CF) since childhood.ObjectiveThe aims of the study were to compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in the diagnosis of altered glucose metabolism, and to longitudinally evaluate the role of CGMS in predicting glucose metabolism deterioration in children with CF.MethodsSeventeen children with CF and 14 controls were enrolled (mean age 13.3±3.0 years). All subjects underwent OGTT and CGMS registration. On the basis of OGTT, children were classified as normal glucose tolerance, impaired glucose tolerance (IGT), IGT plus at least one glucose value above 200 mg/dl at intermediate OGTT points (IGT+200) and CF-related diabetes (CFRD). HbA1c, glucose area under the curve, insulin sensitivity, and insulinogenic and disposition indexes were also considered. Subjects with CF underwent another OGTT after 2.5 years.ResultsBaseline OGTT revealed...

Research paper thumbnail of Fatty liver and insulin resistance in children with hypobetalipoproteinemia: the importance of aetiology

Clinical Endocrinology, 2013

Research paper thumbnail of Cardiovascular fitness is impaired in children born small for gestational age

Acta Paediatrica, 2014

Small for gestational age (SGA) refers to a child whose weight and, or, length at birth is less t... more Small for gestational age (SGA) refers to a child whose weight and, or, length at birth is less than a 2 standard deviation score (SDS) (1). Subjects born SGA have an increased risk of developing permanent metabolic changes as a result of intrauterine programming, leading to increased cardiometabolic risk in adulthood, including hypertension, excess abdominal fat deposition and type 2 diabetes (2). An appropriate lifestyle, based on a balanced diet and adequate physical activity, is the primary preventive intervention for reducing long-term cardiometabolic risk. To our knowledge, while physical activity and aerobic capacity have been extensively investigated in adolescents or adults born preterm (3), no data on cardiovascular fitness in children born SGA have so far been reported. The aim of this prospective study was to evaluate cardiovascular fitness capacity in a group of 22 consecutive children born SGA at term, defined as a gestational age of between 37 and 42 weeks, and referred to the Endocrinology and Diabetes Unit of the Bambino Ges u Children’s Hospital between January 2012 and September 2012. The SGA children were compared to 21 healthy children born at an appropriate for gestational age, with a birth weight of > 2 SDS and <+2 SDS at term, matched for age, gender and body mass index. Children with a birth weight of < 2 SDS were diagnosed as SGA (1). All the SGA children showed catch-up growth that was defined as having attained a height centile within the midparental height range (4). Children with intrauterine growth restriction (IUGR) defined as a weight below the 10th percentile for its gestational age by ultrasound measurements were excluded (5). The control group was recruited on a voluntary basis in the outpatient clinic and comprised children referred to our hospital for minor surgery or electrocardiographic screening. None of the children in either of the groups took part in organised physical activities. Subjects with chronic diseases, genetic syndromes or on chronic therapies were excluded from this study. All children underwent assessment of their anthropometric and physical activity parameters. Puberty development was clinically assessed on the basis of secondary sex characteristics (6). Only subjects with stage I or II gonadal or breast development were considered for the analysis. Maximal cardiovascular fitness capacity was assessed using the standard Bruce treadmill test (7) with increasing belt speed and per cent grade (Tecnogym Runrace, Tecnogym Gambettola, Italy). The parameters measured during the cardio pulmonary exercise test were as follows: time of exercise, maximal oxygen uptake (VO2 max) (L/min and mL/kg/min), maximum heart rate and maximum blood pressure. The cardiopulmonary exercise test was considered adequate if one or more of the following conditions were achieved: at least 80% of the maximum predicted heart rate (determined as 220 b/m minus age), a respiratory exchange ratio of 1.0 for a period of at least one minute or exhaustion of the subject (7). Time of exercise, maximal oxygen uptake and maximum heart rate and blood pressure were also calculated as a percentage of predicted values, as previously reported (8,9). The same physician performed all the examinations. Metabolic profile was analysed in the SGA patients by routine laboratory analyses, including the oral glucose tolerance test (10). The homoeostasis model assessments of fasting insulin resistance (HOMA-IR) (11) were calculated as the index of insulin resistance derived from basal values of glucose and insulin. The whole-body insulin

Research paper thumbnail of Sexual dimorphism of body composition and insulin sensitivity across pubertal development in obese Caucasian subjects

European Journal of Endocrinology, 2009

BackgroundPuberty is a period of rapid growth associated with metabolic, hormonal, and body compo... more BackgroundPuberty is a period of rapid growth associated with metabolic, hormonal, and body composition changes that can influence risk factors for chronic diseases such as type 2 diabetes.ObjectiveTo evaluate body composition and insulin sensitivity (IS) modifications throughout puberty in a large group of obese Caucasian subjects.MethodsFive hundred and nineteen obese subjects (4–19 years), grouped according to gender and Tanner stage (T), underwent oral glucose tolerance test. Quantitative insulin check index (QUICKI) and ISI were calculated as indexes of IS. In 309 subjects, body composition by dual-energy X-ray absorptiometry, IGF1, adiponectin, and leptin were also evaluated.ResultsBody composition modifications were sexually dimorphic, with girls not modifying fat and lean percentage and fat distribution (P>0.15), and boys decreasing fat percentage and increasing lean percentage and central fat depot…

Research paper thumbnail of Caratterizzazione ultrasonografica dei lipomi dei tessuti molli. 127 casi

Research paper thumbnail of Mechanisms of acute hypercalcemia in pediatric patients following the interruption of Denosumab

Journal of Endocrinological Investigation

Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract ... more Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract the bone loss induced by exacerbated osteoclast activity. Indeed, its binding to RANK-L prevents the interaction RANK-L/receptor RANK that is essential for osteoclastogenesis and bone resorbing activity. Although there are many medications available to treat bone loss diseases, including bisphosphonates, Denosumab is highly effective since it reduces the bone erosion. The use in pediatric patients is safe. However, some concerns are related to the interruption of the treatment. Indeed, in this study, we reported hypercalcemia in two pediatric patients and alterations of circulating osteoclast precursors. Peripheral Blood Mononuclear Cells (PBMC) were isolated from two pediatric patients with hypercalcemia after Denosumab interruption and from 10 controls. Cytofluorimetric analysis and in vitro osteoclastogenesis experiments were performed. Increase of CD16−CD14+CD11b+ cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis. Our data suggest that precautions must be taken when Denosumab therapy is interrupted and gradual decrease of dose and/or timing of treatment should be performed. To prevent the onset of hypercalcemia that could be in the discontinuation phase, cytofluorimetric analysis of PBMC should be performed to evaluate osteoclast precursors.

Research paper thumbnail of Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome

Journal of Endocrinological Investigation

Purpose Angiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predic... more Purpose Angiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predicts non-alcoholic fatty liver disease (NAFLD) and altered metabolic homeostasis in the general population as well as in persons with common and genetic obesity, including the Prader–Willi syndrome (PWS). However, its metabolic correlate in paediatric patients with respect to PWS is unknown. Methods This cross-sectional study investigated circulating ANGPTL8 and adipocytokines levels in 28 PWS and 28 age-, sex- and BMI-matched children and adolescents (age, 7.0–17.8y) in relation to NAFLD and metabolic homeostasis assessed by OGTT, paediatric metabolic index (PMI) and fatty liver index (FLI), liver ultrasonography (US), as well as dual-energy X-ray absorptiometry (DEXA) for analysis of fat (FM) and fat-free mass (FFM). Results At the set level of significance, PWS children showed lower values of FFM (p

Research paper thumbnail of Possible role of vitamin D in Covid-19 infection in pediatric population

Journal of Endocrinological Investigation

Purpose Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is... more Purpose Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. Methods: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. Results Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and β-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. Conclusions In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.

Research paper thumbnail of MKRN3 circulating levels in Prader–Willi syndrome: a pilot study

Journal of Endocrinological Investigation

Research paper thumbnail of Impaired energy expenditure and physical activity in children affected by GH deficiency measured by SenseWear Armband: preliminary results

Background: Influence of growth hormone on energy expenditure and physical performance is clearly... more Background: Influence of growth hormone on energy expenditure and physical performance is clearly known. Objective and hypotheses: The aim of our study is to evaluate the energy expenditure (EE) during physical (PA) and sedentary activities (SA), in a group of children/adolescents affected by growth hormone deficiency (GHD) compared to healthy subjects, using an objective measure as SenseWear Armband (SWA-BodyMedia). Patients, methods and results: These preliminary data included 13 untreated, consecutive GHD children and adolescents (6 males) (GH peak <10 ng/ml; IGF1 SDS -2.0\ub10.3) and 10 controls (6 males), age and sex matched. As expected, the GHD group showed statistically lower height (-2.7\ub10.9 vs 0.4\ub10.5 SDS), weight (-1.5\ub11.2 vs 1.1\ub10.6 SDS) and Body Mass Index (BMI) (-0.1\ub11.2 vs 0.6\ub10.2 SDS). The use of SWA demonstrated that the GHD children showed lower Energy expenditure, total (1007\ub1458 vs 1337\ub1125 cal/d;1.7\ub10.2 vs 1.9 \ub10.2 Mets/d) and active (214\ub1136 vs 435\ub188 cal/d;7\ub13 vs 13\ub14 cal/Kg/d) and spent statistically less time in physical activity (>3 Mets) (1.5 \ub10.8 vs 2.3\ub11 h/d), especially moderate (3-6 Mets)(1.4\ub10.8 vs 2.2\ub10.9 h/d; 5.8\ub13.1 vs 9.2\ub13.9% of daily hours) compared with healthy subjects. A tendency to spend more time in sedentary activities was found in GHD group (16\ub14 vs 14\ub13 h/d), although not statistically significant. In multivariate regression IGF1 and BMISD resulted positive predictors of EE/daily (cal/daily) in GHD children. Conclusions: In conclusion our preliminary results seem to confirm that children affected by growth hormone deficiency showed lower energy expenditure as calories/daily and spent less time in physical activities compared to normal children. This result seems correlate to IGF1 values indicating a possible role of GH in physical performance. Further evaluations on greater number of patients, before and after GH therapy, are ongoing to confirm our findings

Research paper thumbnail of Uniparental disomy and pretreatment IGF-1 may predict elevated IGF-1 levels in Prader-Willi patients on GH treatment

Growth Hormone & IGF Research, 2019

Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhG... more Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhGH). These patients are highly sensitive to rhGH and the standard doses suggested by the international guidelines often result in IGF-1 above the normal range. We aimed to evaluate 1 the proper rhGH dose to optimize auxological outcomes and to avoid potential overtreatment, and 2 which patients are more sensitive to rhGH. In this multicenter real-life study, we recruited 215 patients with PWS older than 1 year, on rhGH at least for 6 months, from Italian Centers for PWS care. We collected auxological parameters, rhGH dose, IGF-1 at recruitment and (when available) at start of treatment. The rhGH dose was 4.3 (0.7/8.4) mg/m 2 /week. At recruitment, IGF-1 was normal in 72.1% and elevated in 27.9% of the patients. In the group of 115 patients with IGF-1 available at start of rhGH, normal pretreatment IGF-1 and uniparental disomy were associated with elevated IGF-1 during the therapy. No difference in height and growth velocity was found between patients treated with the highest and the lowest range dose. The rhGH dose prescribed in Italy seems lower than the recommended one. Normal pretreatment IGF-1 and uniparental disomy are risk factors for elevated IGF-1. The latter seems to be associated

Research paper thumbnail of The genetic background and vitamin D supplementation can affect irisin levels in Prader–Willi syndrome

Journal of Endocrinological Investigation, 2021

Background Prader–Willi syndrome (PWS) is associated to distinctive clinical symptoms, including ... more Background Prader–Willi syndrome (PWS) is associated to distinctive clinical symptoms, including obesity, cognitive and behavioral disorders, and bone impairment. Irisin is a myokine that acts on several target organs including brain adipose tissue and bone. The present study was finalized to explore circulating levels of irisin in children and adult PWS patients. Methods Seventy-eight subjects with PWS, 26 children (15 females, mean age 9.48 ± 3.6 years) and 52 adults (30 females, mean age 30.6 ± 10.7) were enrolled. Irisin serum levels were measured in patients and controls. Its levels were related with anthropometric and metabolic parameters, cognitive performance and bone mineral density either in pediatric or adult PWS. Multiple regression analysis was also performed. Results Irisin serum levels in PWS patients did not show different compared with controls. A more in-depth analysis showed that both pediatric and adult PWS with DEL15 displayed significantly reduced irisin levels...

Research paper thumbnail of Le cardiopatie congenite semplici e l'idoneità all'attività fisica agonistica

Medicina Dello Sport, 2010

Research paper thumbnail of Metabolic Syndrome in Italian Obese Children and Adolescents: Stronger Association with Central Fat Depot than with Insulin Sensitivity and Birth Weight

International Journal of Hypertension, 2011

Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FH... more Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FHD) were associated with metabolic syndrome (MetS) in children and adolescents.Methods. A total of 439 Italian obese children and adolescents (5–18 years) were enrolled. Subjects were divided into 2 groups: prepubertal and pubertal. MetS was diagnosed according to the adapted National Cholesterol Education Program criteria. Birth weight percentile, central obesity index (measured by dual-energy X-ray absorptiometry), insulin sensitivity (ISI), and disposition index were evaluated. Multivariate logistic regression models were used to determine variables associated with MetS.Results. The prevalence of MetS was 17%, with higher percentage in adolescents than in children (21 versus 12%). In the overall population, central obesity index was a stronger predictor of MetS than insulin sensitivity and low birth weight. When the two groups were considered, central fat depot remained the strongest p...

Research paper thumbnail of Physical activity, fitness, and dyspnea perception in children with congenital diaphragmatic hernia

Pediatric Pulmonology, 2011

Research paper thumbnail of Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

Research paper thumbnail of Obese Children with Low Birth Weight Demonstrate Impaired β-Cell Function during Oral Glucose Tolerance Test

The Journal of Clinical Endocrinology & Metabolism, 2009

Objective: Epidemiological studies have shown an association between birth weight and future risk... more Objective: Epidemiological studies have shown an association between birth weight and future risk of type 2 diabetes, with individuals born either small or large for gestational age at increased risk. We sought to investigate the influence of birth weight on the relation between insulin sensitivity and β-cell function in obese children. Subjects and Methods: A total of 257 obese/overweight children (mean body mass index-sd score, 2.2 ± 0.3), aged 11.6 ± 2.3 yr were divided into three groups according to birth weight percentile: 44 were small for gestational age (SGA), 161 were appropriate for gestational age (AGA), and 52 were large for gestational age (LGA). Participants underwent a 3-h oral glucose tolerance test with glucose, insulin, and C-peptide measurements. Homeostasis model of assessment for insulin resistance, insulinogenic index, and disposition index were calculated to evaluate insulin sensitivity and β-cell function. Glucose and insulin area under the curve (AUC) were a...

Research paper thumbnail of Association between Nocturnal Blood Pressure Reduction and Progression of Visual Field Defect in Patients with Primary Open-Angle Glaucoma or Normal-Tension Glaucoma

Japanese Journal of Ophthalmology, 2004

Objective: The purpose of this study was to analyze the relationship between insulin-glucose meta... more Objective: The purpose of this study was to analyze the relationship between insulin-glucose metabolism, nocturnal blood pressure (BP) dipping and cardiac left ventricular mass (LVM) in obese adolescents without diabetes. Methods: A cohort of 206 obese adolescents (mean age 15.4 years (s.d. 1.6), mean body mass index (BMI) 38 kg m-2 (s.d. 5.8), 53% girls) under clinical care were included in the study. Body fat was assessed by dual X-ray absorptiometry (DEXA). Blood samples were drawn for analyses of fasting insulin (fS-insulin), fasting glucose and glycosylated hemoglobin Alc. Homeostatic model assessment index (HOMA index) was calculated. Insulin sensitivity and acute insulin response (AIR) were calculated from the performed frequently sampled intravenous glucose tolerance test. An ambulatory BP measurement was performed and 24 h daytime and nighttime values were calculated. Non-dipping was defined as a nocturnal BP reduction of o10%. Ultrasound was used to measure heart LVM and LVM index (LVMI) was calculated (LVM Â height À2.7). Results: Systolic non-dipping was present in 50% (n ¼ 103) of the subjects. Systolic and diastolic dipping was negatively associated with measures of insulin metabolism (HOMA index, fS-insulin and AIR). These associations were present independently of gender, age, daytime BP or body mass index standard deviation score. Dipping (P ¼ 0.7-0.9) or measures of insulin-glucose metabolism (P ¼ 0.3-1.0) were not associated with LVMI in this population. Conclusion: Non-dipping is common among obese adolescents. We found a negative association between nocturnal BP fall (dipping) and measures of insulin metabolism independently of the degree of obesity or daytime BP level among severely obese, non-diabetic adolescents without diagnosed hypertension. Our findings suggest the importance of keeping the insulin levels under observation even in allegedly healthy obese adolescents in clinical care, as a part of the prevention of morbidity associated with obesity.

Research paper thumbnail of Thyroid Function Tests in Obese Prepubertal Children: Correlations with Insulin Sensitivity and Body Fat Distribution

Hormone Research in Paediatrics, 2012

Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly ele... more Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly elevated free triiodothyronine (fT(3)) and/or free thyroxine (fT(4)) have been consistently found in obese children. To examine relationships between adiposity, insulin sensitivity, and TSH, fT(3) and fT(4). 240 overweight/obese prepubertal children were studied. Fasting TSH, fT(3), fT(4), glucose, insulin, C-peptide, lipids, leptin and adiponectin were evaluated. Insulin sensitivity and resistance were estimated [quantitative insulin check index (QUICKI), insulin sensitivity index (ISI), and hepatic insulin resistance index]. Body fat was measured by dual-energy X-ray absorptiometry. The central obesity index was calculated as the ratio of fat tissue in the trunk region to fat tissue in the leg region. The multiple regression analysis with age, gender and measures of fatness as covariates showed that QUICKI was the only significant negative predictor of TSH and central obesity index the strongest positive predictor of fT(3), in association with either age or hepatic insulin resistance index, and that the only positive determinant of fT(4) was hepatic insulin resistance index. Reduced insulin sensitivity is associated with augmented TSH and fT(4), while progressive central fat accumulation is strictly related to a parallel increase in fT(3) levels, independently from total body fat. Further studies are needed to understand mechanisms linking thyroid function to insulin sensitivity and body composition in obese children.

Research paper thumbnail of Cardiovascular Fitness, Insulin Resistance and Metabolic Syndrome in Severely Obese Prepubertal Italian Children

Hormone Research, 2008

To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor card... more To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor cardiovascular fitness in very obese prepubertal Italian subjects. Children referred to the Endocrinology and Diabetes Unit of Bambino Gesù Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital underwent an OGTT with glucose and insulin assays. QUICKI, ISI and HOMA-IR were calculated. Total and HDL cholesterol, triglycerides and percentage of body fat (DEXA) were determined. Cardiovascular fitness (maximal treadmill time) was evaluated using a treadmill protocol. The MS was defined as having 3 or more of following risk factors: obesity, impaired glucose tolerance, high blood pressure, low HDL-cholesterol, high triglycerides. Fifty-five very obese prepubertal Italian children were enrolled in the study. Unadjusted correlation revealed maximal treadmill time negatively related to fasting insulin (r = -0.53, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and HOMA-IR (r = -0.57, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and positively to QUICKI (r = 0.51, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and ISI (r = 0.46, p = 0.0035). These relationships remained significant when in multivariate analysis age, gender, BMI SD and body composition were accounted for (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). The presence of the MS was independently associated with maximal treadmill time. Poorcardiovascular fitness, IR and MS were independently related, suggesting that the relationship between fitness and insulin action develops early in life.

Research paper thumbnail of Abnormal glucose tolerance in children with cystic fibrosis: the predictive role of continuous glucose monitoring system

European Journal of Endocrinology, 2010

A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibr... more A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibrosis (CF) since childhood.ObjectiveThe aims of the study were to compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in the diagnosis of altered glucose metabolism, and to longitudinally evaluate the role of CGMS in predicting glucose metabolism deterioration in children with CF.MethodsSeventeen children with CF and 14 controls were enrolled (mean age 13.3±3.0 years). All subjects underwent OGTT and CGMS registration. On the basis of OGTT, children were classified as normal glucose tolerance, impaired glucose tolerance (IGT), IGT plus at least one glucose value above 200 mg/dl at intermediate OGTT points (IGT+200) and CF-related diabetes (CFRD). HbA1c, glucose area under the curve, insulin sensitivity, and insulinogenic and disposition indexes were also considered. Subjects with CF underwent another OGTT after 2.5 years.ResultsBaseline OGTT revealed...

Research paper thumbnail of Fatty liver and insulin resistance in children with hypobetalipoproteinemia: the importance of aetiology

Clinical Endocrinology, 2013

Research paper thumbnail of Cardiovascular fitness is impaired in children born small for gestational age

Acta Paediatrica, 2014

Small for gestational age (SGA) refers to a child whose weight and, or, length at birth is less t... more Small for gestational age (SGA) refers to a child whose weight and, or, length at birth is less than a 2 standard deviation score (SDS) (1). Subjects born SGA have an increased risk of developing permanent metabolic changes as a result of intrauterine programming, leading to increased cardiometabolic risk in adulthood, including hypertension, excess abdominal fat deposition and type 2 diabetes (2). An appropriate lifestyle, based on a balanced diet and adequate physical activity, is the primary preventive intervention for reducing long-term cardiometabolic risk. To our knowledge, while physical activity and aerobic capacity have been extensively investigated in adolescents or adults born preterm (3), no data on cardiovascular fitness in children born SGA have so far been reported. The aim of this prospective study was to evaluate cardiovascular fitness capacity in a group of 22 consecutive children born SGA at term, defined as a gestational age of between 37 and 42 weeks, and referred to the Endocrinology and Diabetes Unit of the Bambino Ges u Children’s Hospital between January 2012 and September 2012. The SGA children were compared to 21 healthy children born at an appropriate for gestational age, with a birth weight of > 2 SDS and <+2 SDS at term, matched for age, gender and body mass index. Children with a birth weight of < 2 SDS were diagnosed as SGA (1). All the SGA children showed catch-up growth that was defined as having attained a height centile within the midparental height range (4). Children with intrauterine growth restriction (IUGR) defined as a weight below the 10th percentile for its gestational age by ultrasound measurements were excluded (5). The control group was recruited on a voluntary basis in the outpatient clinic and comprised children referred to our hospital for minor surgery or electrocardiographic screening. None of the children in either of the groups took part in organised physical activities. Subjects with chronic diseases, genetic syndromes or on chronic therapies were excluded from this study. All children underwent assessment of their anthropometric and physical activity parameters. Puberty development was clinically assessed on the basis of secondary sex characteristics (6). Only subjects with stage I or II gonadal or breast development were considered for the analysis. Maximal cardiovascular fitness capacity was assessed using the standard Bruce treadmill test (7) with increasing belt speed and per cent grade (Tecnogym Runrace, Tecnogym Gambettola, Italy). The parameters measured during the cardio pulmonary exercise test were as follows: time of exercise, maximal oxygen uptake (VO2 max) (L/min and mL/kg/min), maximum heart rate and maximum blood pressure. The cardiopulmonary exercise test was considered adequate if one or more of the following conditions were achieved: at least 80% of the maximum predicted heart rate (determined as 220 b/m minus age), a respiratory exchange ratio of 1.0 for a period of at least one minute or exhaustion of the subject (7). Time of exercise, maximal oxygen uptake and maximum heart rate and blood pressure were also calculated as a percentage of predicted values, as previously reported (8,9). The same physician performed all the examinations. Metabolic profile was analysed in the SGA patients by routine laboratory analyses, including the oral glucose tolerance test (10). The homoeostasis model assessments of fasting insulin resistance (HOMA-IR) (11) were calculated as the index of insulin resistance derived from basal values of glucose and insulin. The whole-body insulin

Research paper thumbnail of Sexual dimorphism of body composition and insulin sensitivity across pubertal development in obese Caucasian subjects

European Journal of Endocrinology, 2009

BackgroundPuberty is a period of rapid growth associated with metabolic, hormonal, and body compo... more BackgroundPuberty is a period of rapid growth associated with metabolic, hormonal, and body composition changes that can influence risk factors for chronic diseases such as type 2 diabetes.ObjectiveTo evaluate body composition and insulin sensitivity (IS) modifications throughout puberty in a large group of obese Caucasian subjects.MethodsFive hundred and nineteen obese subjects (4–19 years), grouped according to gender and Tanner stage (T), underwent oral glucose tolerance test. Quantitative insulin check index (QUICKI) and ISI were calculated as indexes of IS. In 309 subjects, body composition by dual-energy X-ray absorptiometry, IGF1, adiponectin, and leptin were also evaluated.ResultsBody composition modifications were sexually dimorphic, with girls not modifying fat and lean percentage and fat distribution (P>0.15), and boys decreasing fat percentage and increasing lean percentage and central fat depot…

Research paper thumbnail of Caratterizzazione ultrasonografica dei lipomi dei tessuti molli. 127 casi

Research paper thumbnail of Mechanisms of acute hypercalcemia in pediatric patients following the interruption of Denosumab

Journal of Endocrinological Investigation

Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract ... more Denosumab is a fully human monoclonal anti-RANK-L antibody that is clinically used to counteract the bone loss induced by exacerbated osteoclast activity. Indeed, its binding to RANK-L prevents the interaction RANK-L/receptor RANK that is essential for osteoclastogenesis and bone resorbing activity. Although there are many medications available to treat bone loss diseases, including bisphosphonates, Denosumab is highly effective since it reduces the bone erosion. The use in pediatric patients is safe. However, some concerns are related to the interruption of the treatment. Indeed, in this study, we reported hypercalcemia in two pediatric patients and alterations of circulating osteoclast precursors. Peripheral Blood Mononuclear Cells (PBMC) were isolated from two pediatric patients with hypercalcemia after Denosumab interruption and from 10 controls. Cytofluorimetric analysis and in vitro osteoclastogenesis experiments were performed. Increase of CD16−CD14+CD11b+ cells was revealed in PBMC from patients reflecting the enhanced in vitro osteoclastogenesis. Our data suggest that precautions must be taken when Denosumab therapy is interrupted and gradual decrease of dose and/or timing of treatment should be performed. To prevent the onset of hypercalcemia that could be in the discontinuation phase, cytofluorimetric analysis of PBMC should be performed to evaluate osteoclast precursors.

Research paper thumbnail of Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome

Journal of Endocrinological Investigation

Purpose Angiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predic... more Purpose Angiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predicts non-alcoholic fatty liver disease (NAFLD) and altered metabolic homeostasis in the general population as well as in persons with common and genetic obesity, including the Prader–Willi syndrome (PWS). However, its metabolic correlate in paediatric patients with respect to PWS is unknown. Methods This cross-sectional study investigated circulating ANGPTL8 and adipocytokines levels in 28 PWS and 28 age-, sex- and BMI-matched children and adolescents (age, 7.0–17.8y) in relation to NAFLD and metabolic homeostasis assessed by OGTT, paediatric metabolic index (PMI) and fatty liver index (FLI), liver ultrasonography (US), as well as dual-energy X-ray absorptiometry (DEXA) for analysis of fat (FM) and fat-free mass (FFM). Results At the set level of significance, PWS children showed lower values of FFM (p

Research paper thumbnail of Possible role of vitamin D in Covid-19 infection in pediatric population

Journal of Endocrinological Investigation

Purpose Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is... more Purpose Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. Methods: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. Results Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and β-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. Conclusions In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.