Pediatric Obesity and GH/IGF-1 Axis: A New Insight

L'obesità pediatrica rappresenta problema allarmante, caratterizzato da molteplici implicazioni sulla salute del bambino e, in particolare, sul pattern secretivo ormonale del soggetto in crescita: una delle relazioni più interessanti riguarda l'obesità e l'asse GH/IGF-1 (GH: ormone della crescita, IGF-1: insulin like growth factor 1). Scopo dello studio: analizzare la relazione tra le caratteristiche fenotipiche-cliniche e metaboliche dell'obesità pediatrica e l'asse GH/IGF-1. Metodi Sono stati raccolti dati clinici, laboratoristici e strumentali di bambini-adolescenti affetti da obesità primitiva. I dati includevano: indici del metabolismo glucidico, profilo lipidico, valutazione dell'asse IGH/IGF-1 in condizioni basali e durante il test orale di tolleranza al glucosio (OGTT). Il rischio metabolico è stato definito in base al cardiometabolic risk score. La presenza di steatosi epatica (HS) è stata valutata mediante ecografia. È stato anche analizzato il polimorfismo del recettore IGF-1. Risultati Quarantotto bambini e adolescenti (età media 11,8 ± 2,8 anni): 80% del nostro campione presentava valori di IGF-1 Standard Deviation (SD) <0, cioè IGF-1<50°pc. IGF-1SD e BMI z-score hanno mostrato un’associazione inversa statisticamente significativa (r: -0.362, p= 0.033), anche dopo l'aggiustamento per stadio puberale. I bambini affetti da HS avevano inoltre livelli più bassi di IGF- 1SD (-0.811±0.56 vs -0.18±0.7; p=0.012). È stata osservata un'interessante relazione diretta tra IGF- 1SD e l’area sottesa dalla curva della secrezione insulinica durante l'OGTT (p<0.05). L'analisi di correlazione ha mostrato una forte associazione inversa tra cardiometabolic risk score e l'IGF-1 SD, anche dopo l'aggiustamento dei dati per età, sesso e stadio puberale (r:-0.629, p=0.029). L’analisi di regressione ha inoltre evidenziato IGF-1SD come unico predittore significativo sulla diagnosi ecografica HS (p=0.04). Tutti i bambini analizzati erano wild type per il recettore IGF-1. Conclusioni L'obesità è caratterizzata da influenze metaboliche e ormonali, soprattutto in età pediatrica. Per quanto ci siano molte incertezze sul ruolo dell’asse GH/IGF-1 in questo scenario, i nostri risultati hanno mostrato una forte interazione tra secrezione di GH, IGF-1 e stato metabolico dei bambini obesi. In particolare, ulteriori studi sono necessari per chiarire il ruolo dell'IGF-1 come potenziale “target” terapeutico nei pazienti obesi con aumentato rischio cardiometabolico o quale indicatore di disordini metabolici.Background Pediatric obesity is an alarming problem, characterized by many influences on child’s health and many hormonal implications: one of the most interesting relationship concerns obesity and GH/IGF- 1 axis (GH: growth hormone, IGF-1: insulin like growth factor 1). Aim of the Study: to analyze the relation between phenotypic-clinical and metabolic features of Pediatric Obesity and GH/IGF-1 axis. Methods Clinical, laboratory and instrumental data of children-adolescents affected by essential obesity were collected. Data included: glucose metabolism indexes, lipid profile, GH/IGF-1 axis evaluation in basal condition and during oral glucose tolerance test (OGTT) and metabolic risk definition according cardiometabolic risk score. Hepatic steatosis (HS) was assessed using ultrasonography. IGF-1 receptor polymorphism was also analyzed. Results Forty eight children and adolescents, (mean age 11.8 ±2.8 yrs): 80% of our sample had values of IGF- 1 Standard Deviation (SD) <0, i.e. IGF-1<50°pc. IGF-1SD and BMI z-score were associated (r: - 0.362, p= 0.033), even after adjustment for pubertal stage. Children affected by HS had lowest levels of IGF-1SD (-0.811±0.56 vs -0.18±0.7; p=0.012). An interesting direct relation was observed between IGF-1SD and Area Under the Curve for insulin secretion during OGTT (p<0.05). Correlation analysis showed a strong inverse correlation between cardio-metabolic risk score and IGF-1 SD after adjustment of data for age, sex and pubertal stage (r:-0.629, p=0.029). Multiple Linear regression analyses was adopted to assess the role of clinical and metabolic parameters on prediction of HS: IGF-1SD was the only predictor on HS prevision with statistical significance (p=0.04). All children analyzed were wild type for IGF-1 receptor. Conclusions Obesity is characterized by many metabolic and hormonal changes. There are many doubts concerning the role of the GH/IGF-1 axis in this scenario, but our results showed a strong interaction between GH secretion, IGF-1 function and metabolic state of obese children. In particular, the role of IGF-1 needs further examination whether it is a potential therapeutic target in obese patients of increased cardio-metabolic risk or only an indicator of metabolic disorders

Nutrition in preschool children and later risk of obesity: a systematic review and meta analysis

Objectives and study: Nutrition in infants and preschool children has been suggested to influence the risk of later obesity. However, the evidence for this association is conflicting and few studies have investigated this prospectively or considered the role of energy and specific macronutrients. Here we report a systematic review and meta-analyis of studies that tested the hypothesis that nutrition in the preschool period, between the ages of 6 months and 3 years, is associated with later obesity risk. Methods: MEDLINE, EMBASE and CENTRAL databases were searched from January 1988 to June 2015 for studies reporting nutritional intake in infants and preschool children aged 6-36 months and later measures of obesity. Bibliographies of included studies were hand searched and authors and other experts consulted to identify omissions. We included all studies that investigated dietary energy and/or macronutrient intake during 6-36 months in relation to later measures of obesity. Methodological quality was assessed using the Downs and Black checklist designed specifically to appraise both randomised and non-randomised studies. The checklist was adapted to include aspects of particular relevance to studies investigating nutritional exposures. Two reviewers independently scored studies against the 28 item checklist which included questions on study reporting, external validity, internal validity (bias and confounding), and statistical power. A statistician independently scored questions relating to statistical methods and their decision was final. Data from studies amenable to meta-analysis were analysed using STATA (StataCrop 12, Texas). For continuous outcomes, results were expressed as standardised mean difference (SMD) between the high and low protein intake groups. For dichotomous outcomes, results for each study were expressed as relative risk (RR). Both dichotomous and continuous outcomes were presented with 95% confidence intervals (CI). Between-study heterogeneity was assessed by the Q and I2 statistics. Results: 24 eligible articles (comprising 16 primary studies) were included in a narrative synthesis, and 13 studies in a random-effects meta-analysis. A higher protein intake was associated with later risk of obesity in 15 studies. In 13 studies included in the meta-analysis protein in the preschool period was associated with higher BMI z-score later in childhood (pooled effect size: 0.28 z-scores, 95% CI 0.20 to 0.35)(Figure 1). There was no significant hererogeneity between studies (I2 0.0%, p = 0.932). Associations of energy, fat and carbohydrate were inconclusive. Conclusion: Our findings suggest that nutrition and particularly high protein intake in infants and preschool children is important for risk of later obesity. Although further experimental data are required to establish causality, these findings suggest that optimising the protein intake of these children could be important for their long term health

Seventh Cranial Nerve Palsy: The First Sign of Multiple Sclerosis in A Young Children

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system characterized pathologically by demyelination and subsequent axonal degeneration..

The Italian registry for patients with Prader-Willi syndrome

Background: Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients' care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. Materials and methods: The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. Results: A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019-2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. Conclusions: The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Has COVID-19 Delayed the Diagnosis and Worsened the Presentation of Type 1 Diabetes in Children?

Objective: To evaluate whether the diagnosis of pediatric type 1 diabetes or its acute complications changed during the early phase of the coronavirus disease 2019 (COVID-19) pandemic in Italy. Research design and methods: This was a cross-sectional, Web-based survey of all Italian pediatric diabetes centers to collect diabetes, diabetic ketoacidosis (DKA), and COVID-19 data in patients presenting with new-onset or established type 1 diabetes between 20 February and 14 April in 2019 and 2020. Results: Fifty-three of 68 centers (77.9%) responded. There was a 23% reduction in new diabetes cases in 2020 compared with 2019. Among those newly diagnosed patient who presented in a state of DKA, the proportion with severe DKA was 44.3% in 2020 vs. 36.1% in 2019 (P = 0.03). There were no differences in acute complications. Eight patients with asymptomatic or mild COVID-19 had laboratory-confirmed severe acute respiratory syndrome coronavirus 2. Conclusions: The COVID-19 pandemic might have altered diabetes presentation and DKA severity. Preparing for any "second wave" requires strategies to educate and reassure parents about timely emergency department attendance for non-COVID-19 symptoms

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Diabetic ketoacidosis at the onset of disease during a national awareness campaign: a 2-year observational study in children aged 0-18 years

After a previous survey on the incidence of diabetic ketoacidosis (DKA) at onset of type 1 diabetes in children in 2013-2014 in Italy, we aimed to verify a possible decline in the incidence of DKA at onset during a national prevention campaign