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Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zucchini, Tumini, Scaramuzza, Bonfanti, Delvecchio, Franceschi, Iafusco, Lenzi, Mozzillo, Passanisi, Piona, Rabbone, Rapini, Rigamonti, Ripoli, Salzano, Savastio, Schiaffini, Zanfardino, Cherubini and Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetes.)

Competing Interests: No potential conflicts of interest relevant to this article were reported.

Objective: To evaluate (i) the prevalence and association of euthyroid sick syndrome (ESS) [decreased FT3 and/or FT4 and normal/decreased TSH] with severity indexes of type 1 diabetes mellitus (T1DM) onset such as diabetic ketoacidosis (DKA) and kidney damage [acute kidney injury (AKI) based on KDIGO criteria, acute tubular necrosis (ATN), renal tubular damage (RTD)], (ii) relationship between clinical/metabolic parameters at T1DM onset and thyroid hormones, and (iii) ESS as a prognostic indicator of delayed recovery from kidney damage., Methods: A total of 161 children with T1DM onset were included. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin (NGAL) and/or tubular reabsorption of phosphate <85% and/or fractional excretion of Na>2%. ATN was defined by RTD+AKI., Results: Of 161 participants, 60 (37.3%) presented ESS. It was more prevalent in case of more severe T1DM presentation both in terms of metabolic derangement (DKA) and kidney function impairment (AKI, RTD and ATN). Only ATN, however, was associated with ESS at adjusted analysis. FT3 inversely correlated with serum triglycerides and creatinine, and urinary calcium/creatinine ratio and NGAL. Participants with euthyroidism showed earlier recovery from AKI than those with ESS. ESS spontaneously disappeared., Conclusions: ESS is associated with T1DM onset severity and spontaneously disappears. ESS delayed the recovery from AKI., Impact: This is the first longitudinal study describing in detail the relationship between clinical/metabolic factors at type 1 diabetes mellitus (T1DM) onset and thyroid hormones, with particular attention to the relationship between diabetic ketoacidosis (DKA)-related kidney function impairment and euthyroid sick syndrome (ESS). Participants with more severe T1DM onset presentation both in terms of metabolic derangement and kidney function impairment had an increased prevalence of ESS. Children with ESS had a slower recovery from acute kidney injury compared with those without ESS. ESS spontaneously disappeared in all participants., (© 2023. The Author(s).)

This Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder., (© 2023. The Author(s).)

In the frame of metabolic syndrome, type 2 diabetes emerges along a continuum of the risk from the clustering of all its components, namely visceral obesity, high blood pressure and lipids, and impaired glucose homeostasis. Insulin resistance is the hallmark common to all the components and, in theory, is a reversible condition. Nevertheless, the load that this condition can exert on the β-cell function at the pubertal transition is such as to determine its rapid and irreversible deterioration leading to plain diabetes. The aim of this review is to highlight, in the context of metabolic syndrome, age-specific risk factors that lead to type 2 diabetes onset in youth; resume age specific screening and diagnostic criteria; and anticipate potential for treatment. Visceral obesity and altered lipid metabolism are robust grounds for the development of the disease. Genetic differences in susceptibility to hampered β-cell function in the setting of obesity and insulin resistance largely explain why some adolescents with obesity do develop diabetes at a young age and some others do not. Lifestyle intervention with a healthy diet and physical activity remains the pillar of the type 2 diabetes treatment in youth. As to the pharmacological management, metformin and insulin have failed to rescue β-cell function and to ensure long-lasting glycemic control in youth. A new era might start with the approval for use in pediatric age of drugs largely prescribed in adults, such as dipeptidyl peptidase-4 and sodium-dependent glucose transport inhibitors, and of new weight-lowering drugs in the pipeline such as single and multiple agonists of the glucagon-like peptide 1 receptor. The latter drugs can have tremendous impact on the natural history of the disease. By treating diabetes, they will reduce the burden of all the metabolic abnormalities belonging to the syndrome while causing a tremendous weight loss hitherto never seen before.

In pediatric diabetology, a precise diagnosis is very important because it allows early and correct clinical management of the patient. Monogenic diabetes (MD), which accounts for 1-6% of all pediatric-adolescent diabetes cases, is the most relevant example of precision medicine. The definitive diagnosis of MD, possible only by genetic testing, allows us to direct patients to more appropriate therapy in relation to the identified mutation. In some cases, MD patients can avoid insulin and be treated with oral hypoglycemic drugs with a perceptible impact on both the quality of life and the healthcare costs. However, the genetic and phenotypic heterogeneity of MD and the overlapping clinical characteristics between different forms, can complicate the diagnostic process. In recent years, the development of Next-Generation Sequencing (NGS) methodology, which allows the simultaneous analysis of multiple genes, has revolutionized molecular diagnostics, becoming the cornerstone of MD precision diagnosis. We report two cases of patients with clinical suspects of MD in which a genetic test was carried out, using a NGS multigenic panel, and it clarified the correct pathogenesis of diabetes, allowing us to better manage the disease both in probands and other affected family members.

Background: The association between Type 1 Diabetes Mellitus (T1DM) and obesity (Ob) is no longer unexpected due to unhealthy lifestyle mostly in adolescents. We compared clinical-biochemical characteristics, adherence to the Mediterranean Diet (MD), lifestyle habits and physical fitness across different weight categories of T1DM adolescents from Campania Region. As second aim, we assessed the relationship among lifestyle and physical fitness in these patients., Methods: 74 adolescents (35M; 39F; 13-18 y), with T1DM diagnosed at least 6 mo before the study, were enrolled at the Regional Center for Pediatric Diabetology of Vanvitelli University of Naples. Height, weight, Body Mass Index (BMI), BMI z-score, and Clinical Biochemical health-related parameters were determined. MD adherence, physical activity (PA) amount and sedentary habits were assessed by questionnaires. Handgrip strength, 2-Min Step test (2-MST) cardiorespiratory endurance and Timed up and go test (TUG) for agility and balance were used for physical fitness evaluation., Results: Our sample included 22 normal weight (NW), 37 overweight (OW) and 15 with Obese (Ob) adolescents. Across the three groups, adolescents showed similar Clinical-Biochemical parameters, MD adherence, PA amount, mostly walking (9.3 h/w), daily video exposure (8.5 h/d) and similar handgrip or 2-MST performance. Better performance was observed in NW compared to OW or Ob for TUG (7 vs 8 vs 9 s; p < 0.05). A positive correlation was found between TUG test and BMI, while no correlation was found between HbA1c (glycated haemoglobin) and BMI z score or 2-MST., Conclusions: T1DM adolescents did not meet the recommendations for active lifestyle, despite a medium/good adherence to MD, in particular in NW and OW youths. Sedentary habits correlated with a poor HbA1c. Further, reduced agility and balance were observed in adolescents with obesity compared to NW participants.Future research should be aimed to examine wider samples and to design health promotion interventions for T1DM adolescents., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)

[This corrects the article .]., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

The aim of this study was to investigate the association between uric acid (UA) and cardiometabolic risk factors (CMRFs) by sex in youth with type 1 diabetes (T1D). Retrospective data collected from 1323 children and adolescents (5-18 years; 716 boys) with T1D recruited in 9 Italian Pediatric Diabetes Centers were analyzed. CMRFs included UA, HbA 1c , blood pressure (BP), cholesterol (TC), HDL, triglycerides (TG), neutrophils (N) and lymphocytes (L) count, glomerular filtration rate (eGFR) (calculated using Schwartz-Lyon equation). In boys, we found a higher age, daily insulin dose, TG, TG/HDL ratio, TC/HDL ratio, systolic BP, N/L ratio and lower HDL, and eGFR across UA tertiles (p = 0.01-0.0001). Similar results were found in girls but not for TG and systolic BP. In boys, the odds ratio (OR) of high levels of TG/HDL ratio, TC/HDL ratio, BP and mildly reduced eGFR (MRGFR) increased for 0.5 mg/dL of UA. Instead, in girls an increased levels of 0.5 mg/dL of UA were associated with high OR of TC/HDL ratio, N/L ratio and MRGFR. Uric acid may represent a useful marker for identifying youth with T1D at high cardiometabolic risk, and this association appears to vary by sex., (© 2022. The Author(s).)

Aim/hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019., Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019., Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively)., Conclusions/interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks., Competing Interests: No author reported any conflict of interest as regards this study. The following conflicts of interest pointed out are referred to a period from January 2020 to the submission of this manuscript. VCh’s institution has received research grants from AstraZeneca, Novonordisk, Eli Lilly, Movi, Dompè, and Menarini, and VCh received honoraria from Eli Lilly, Tandem, and Insulet for participating on speakers’ bureaus and scientific advisory boards. CR, DT, IRa, BPr, BPi, SZ, ST, and AR has received support Eli Lilly. In addition, SZ’s institution has received support from Pfeizer, ST, BPi, and DT have received support from Abbott and Theras. MM and AR have received support from Menarini. BPr and PB received honoraria for participating on speakers’ bureaus and scientific advisory boards for Sandoz. Lastly, RS has received research grants by Sanofi and received honoraria for participating on speakers’ bureaus and scientific advisory boards for Movi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

Background: Although type 1 diabetes (T1D) represents one of the most common chronic diseases in pediatric age, few studies on the epidemiology of T1D exist globally and the exact prevalence and incidence rates of the disease are unknown. In many countries, including Italy, national registries are missing., Methods: This study aims to assess T1D incidence in the pediatric population of the Calabria region (southern Italy) in the period 2019-2021. The secondary objective was to describe the main demographical, clinical and immunological features of incident cases. Case ascertainment and all clinical data were assessed by retrospectively reviewing the electronic medical records of children and adolescents diagnosed with diabetes at any Pediatric Diabetes Center belonging to the Rete Diabetologica Calabrese (Calabria Region Diabetes Network), from January 2019 to December 2021. The incidence of T1D was estimated for the entire region and was stratified according to age group (0-4 years, 5-9 years, and 10-14 years) and gender. Standardized incidence ratios for each province in the region were also calculated., Results: The crude incidence of T1D was 20.6/100,000 person/years. Incidence rates were higher among females and children aged 5-9 years. The crude incidence of T1D was higher in the province of Reggio Calabria (26.5/100,000 person-years). The provinces of Crotone, Catanzaro, and Vibo Valentia showed significantly lower standardized incidence ratios. The annual incidence in the region progressively increased by 43% during the study period., Conclusions: Our study revealed a relatively high incidence in the Calabria region. The marked increasing incidence trend over the past two years could be related to the global impact of the COVID-19 pandemic, but further long-scale population-based studies are needed to confirm these findings., (© 2022. The Author(s).)

Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms that occur from childhood to adulthood. Usually, the first clinical sign is non-autoimmune diabetes even if other clinical features (optic subatrophy, neurosensorial deafness, diabetes insipidus) may be present in an early state and may be diagnosed after diabetes' onset. Prognosis is poor, and the death occurs at the median age of 39 years as a consequence of progressive respiratory impairment, secondary to brain atrophy and neurological failure. The aim of this paper is the description of the metabolic treatment of the WS. We reported the experience of long treatment in patients with this syndrome diagnosed in pediatric age and followed also in adult age. It is known that there is a correlation between metabolic control of diabetes, the onset of other associated symptoms, and the progression of the neurodegenerative alterations. Therefore, a multidisciplinary approach is necessary in order to prevent, treat and carefully monitor all the comorbidities that may occur. An extensive understanding of WS from pathophysiology to novel possible therapy is fundamental and further studies are needed to better manage this devastating disease and to guarantee to patients a better quality of life and a longer life expectancy.

Adequate and balanced nutrition is essential to promote optimal child growth and a long and healthy life. After breastfeeding, the second step is the introduction of complementary feeding (CF), a process that typically covers the period from 6 to 24 months of age. This process is, however, still highly controversial, as it is heavily influenced by socio-cultural choices, as well as by the availability of specific local foods, by family traditions, and pediatrician beliefs. The Società Italiana di Pediatria Preventiva e Sociale (SIPPS) together with the Federazione Italiana Medici Pediatri (FIMP), the Società Italiana per lo Sviluppo e le Origine della Salute e delle Malattie (SIDOHaD), and the Società Italiana di Nutrizione Pediatrica (SINUPE) have developed evidence-based recommendations for CF, given the importance of nutrition in the first 1000 days of life in influencing even long-term health outcomes. This paper includes 38 recommendations, all of them strictly evidence-based and overall addressed to developed countries. The recommendations in question cover several topics such as the appropriate age for the introduction of CF, the most appropriate quantitative and qualitative modalities to be chosen, and the relationship between CF and the development of Non-Communicable Diseases (NCDs) later in life.

The aim of this study was to evaluate the association between macronutrient intake and time in range (TIR) of 70-180 mg/dL in children and adolescents with type 1 diabetes (T1D). A multi-center study recruited patients with T1D using continuous glucose monitoring (CGM) between January 2019 and January 2020 from centers across Italy. Diet intake was recorded using three-day weighed food diaries. Nutrients were evaluated as percentages of total intake. TIR was considered at target if the percentage of readings was higher than 70%. Clinical and nutritional factors associated with TIR at target were analyzed using multiple correspondence analysis and multiple logistic regression. Data from 197 participants (53% male, median age 11.6 years, median HbA1c 55.2 mmol/mol, median TIR 60%) were analyzed. Macronutrient intake was 45.9% carbohydrates, 16.9% protein, 37.3% fat, and 13.1 g/day fiber (median values). TIR > 70% was observed in 28% of participants; their diet contained more protein (17.6%, p = 0.015) and fiber (14.4 g/day, p = 0.031) than those not at target. The probability of having a TIR > 70% was significantly higher with 40-44% consumption of carbohydrates compared with 45-50% consumption of carbohydrates and with the use of a carbohydrate counting system. Based on these results, a five percent reduction in the percentage of carbohydrate intake can help children and adolescents with T1D achieve the goal of a TIR > 70%. Both a lower and higher percentage of carbohydrate intake appears to reduce the probability of reaching the target TIR > 70%. These results require validation in other populations before being used in clinical practice.

Type 2 Diabetes Mellitus (T2DM) is a main cause of chronic kidney disease (CKD) in adulthood. No studies have examined the occurrence of acute kidney injury (AKI)-that enhances the risk of later CKD-and renal tubular damage (RTD)-that can evolve to AKI-in children with onset of T2DM. We aimed to evaluate the prevalence and possible features of AKI and RTD in a prospectively enrolled population of children with onset of T2DM. We consecutively enrolled 10 children aged 12.9 ± 2.3 years with newly diagnosed T2DM. AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or tubular reabsorption of phosphate (TRP) <85% and/or fractional excretion of Na >2%. None of the patients developed AKI, whereas 3/10 developed RTD with high beta-2-microglobulin levels (range: 0.6-1.06 mg/L). One of these three patients also presented with reduced TRP levels (TRP = 70%). Proteinuria was observed in two out of three patients with RTD, while none of patients without RTD had proteinuria. Patients with RTD presented higher beta-2-microglobulin, acute creatinine/estimated basal creatinine ratio, and serum ketones levels compared with patients without RTD. In conclusion, in our pilot observation, we found that none of the 10 children with T2DM onset developed AKI, whereas three of them developed RTD.

Aim: We explored the physical activity (PA) level and the variation in glycaemic control in children with type 1 diabetes (T1D) before and during the lockdown. Then, we proposed an online training program supported by sport-science specialists., Methods: Parents of children with T1D (<18 years) filled out an online survey. Anthropometric characteristics, PA, play, sport and sedentary time and the medical related outcomes were recorded. An adapted online program "Covidentary" was proposed through full-training (FT) and active breaks (AB) modality., Results: 280 youth (11.8 ± 3.3 years) were included in the analysis. We reported a decline in sport (-2.1 ± 2.1 h/week) and outdoor-plays (-73.9 ± 93.6 min/day). Moreover, we found an increase in sedentary time (+144.7 ± 147.8 min/day), in mean glycaemic values (+25.4 ± 33.4 mg/dL) and insulin delivery (71.8% of patients). 37% of invited patients attended the training program, 46% took part in AB and 54% in FT. The AB was carried out for 90% of the total duration, while the FT for 31%. Both types of training were perceived as moderate intensity effort., Conclusion: A decline of participation in sport activities and a subsequent increase of sedentary time influence the management of T1D of children, increasing the risk of acute/long-term complications. Online exercise program may contrast the pandemic's sedentary lifestyle., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

Background: Type 1 diabetes mellitus could be associated with other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, but the association with Familial Mediterranean Fever is rare, we describe a case of a boy with type 1 Diabetes Mellitus associated with Familial Mediterranean Fever (FMF)., Case Presentation: A 13 year old boy already suffering from Diabetes Mellitus type 1 since the age of 4 years, came to our attention because of periodic fever associated with abdominal pain, chest pain and arthralgia. The fever appeared every 15-30 days with peaks that reached 40 °C and lasted 24-48 h. Laboratory investigation, were normal between febrile episodes, but during the attacks revealed an increase in inflammatory markers. Suspecting Familial Mediterranean Fever molecular analysis of MEFV gene, was performed. The genetic analysis showed homozygous E148Q mutation. So Familial Mediterranean Fever was diagnosed and colchicine treatment was started with good response., Conclusion: Familial Mediterranean Fever could be associated with other autoimmune diseases such as Ankylosing Spondylitis, Rheumatoid Arthritis, Polyarteritis Nodosa, Behcet disease, Systemic Lupus, Henoch-Schönlein Purpura, and Hashimoto's Thyroiditis. Association of type 1 Diabetes Mellitus and Familial Mediterranean Fever has been newly reported in the medical literature, this is the third association of these two diseases described in the medical literature so far.

Objective: The aim of this study was to assess general psychosocial adjustment to diabetes and perceived disease management among patients with type 1 diabetes (T1D) and their parents before and after patients' participation in a diabetes summer camp. Methods: In this follow-up study, 20 children and adolescents with T1D (eight boys; mean age = 11.01 ± 0.94 years; mean diabetes duration = 3.02 ± 2.27) attending a southern Italian diabetic center, along with their parents, were assessed prior to and 3 months after the youths participated in a 1 week camp-based intervention involving didactic and interactive child-centered education and recreational activities. Patients and their parents completed measures assessing patients' quality of life and strategies employed by patients to cope with pain. Patients also completed measures evaluating their diabetes psychosocial adjustment, diabetes self-efficacy management, and illness perception; also, their parents completed measures of caregivers' perceived diabetes burden and treatment satisfaction. Youths' glycated hemoglobin (HbA1c) and standardized body mass index (z-BMI) values were also assessed. Within-subjects repeated-measures analyses of variance evaluated pre- and post-camp changes. Results: Camp attendance showed no beneficial effects on glycemic control, as indicated by HbA1c values both before (7.02%) and after (7.28%) camp being lower than 7.5%. HbA1c values were found to have increased after camp (pre-camp = 7.02%, post-camp = 7.28%; p = 0.010), but since they still fell within an acceptable range, they did not reveal clinically relevant changes in glycemic control. No substantial significant improvement in psychosocial measures was observed in children or parents (all p > 0.05). According to the parents' evaluation, social support-seeking as a patient pain-coping strategy was slightly increased ( p = 0.044) after attending the camp. Conclusions: This study does not provide empirical evidence of benefits of participating in a diabetes camp for either patients or their parents. These findings suggest that healthcare providers rethink such camps as an experience for youths with T1D that actively involves parents and that includes both youth- and parent-focused psychological interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with the authors DI and AZ., (Copyright © 2021 Troncone, Chianese, Cascella, Zanfardino and Iafusco.)

Rationale: Henoch-Schönlein Purpura (HSP) is an acute small vessel vasculitis. It is the most common vasculitis in children. In majority of the cases, the disease is self-limited. Relapses can occur, in particular during the first year of the disease. There is no consensus on a specific treatment. The efficacy and safety of steroidal treatment in treating HSP is still controversial. Immunosuppressive treatment of HSP nephritis is used in patients with severe renal involvement (nephrotic range proteinuria and/or progressive renal impairment). The literature on immunosuppressive treatment of severe HSP without kidney involvement is scanty., Patients Concerns: We report 2 case reports of 2 adolescents affected from Henoch-Schönlein Purpura and severe gastrointestinal involvement. Both patients presented a poor response to steroids treatment., Diagnoses: The diagnosis of HSP was made according to the diagnostic criteria published by European League against Rheumatism and Pediatric Rheumatology European Society in 2006., Interventions: In consideration of the recurrence of the Henoch Schönlein Purpura and the gastrointestinal involvement, we decided to start Mycophenolate Mofetil treatment., Outcomes: In both patients all clinical manifestations resolved in few days., Lessons: In our cases of HSP with gastrointestinal involvement Mycophenolate Mofetil treatment has been very effective. This experience teaches us that immunosuppressive agents may be very useful to induce and maintain remission not only in renal involvement, but in all cases of persistent, recurrent, or complicated Henoch Schönlein Purpura in children., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Recent research indicates that patients with type 1 diabetes (T1D) are at higher risk for disordered eating behaviors (DEBs) than their peers without diabetes. The present study aimed to explore the prevalence of DEBs in a sample of Italian children and adolescents with T1D and in matched-pair healthy controls during the COVID-19 lockdown., Methods: In a cross-sectional study, 138 children and adolescents with T1D (aged 8.01-19.11 years, 65 boys) attending a Southern Italian diabetic service and 276 age- and gender-matched healthy peers voluntarily completed an online survey about eating behaviors (ChEAT and EAT-26), anthropometric characteristics, and clinical characteristics., Results: 8.69% (N = 12) of participants with T1D and 13.4% (N = 37) of controls had ChEAT/EAT-26 scores indicating presence of DEBs, with no differences between patients-whether children (total ChEAT score F(1, 157) = .104, p = .748) or adolescents (total EAT-26 score F(1, 255) = .135, p = .731)-and healthy peers. zBMI values were lower than those measured in the latest diabetes visit (p < .0001), while HbA1c values remained unchanged (p = .110). In both groups, adolescents had lower Oral Control scores than children (T1D: F(1, 138) = 20.411, p < .0001, η 2  = .132, controls: F(1, 276) = 18.271, p < .0001, η 2  = .063); additionally, gender (female) and age were found to be significant predictors of several ChEAT/EAT-26 scores., Conclusions: This exploratory study suggested that children and adolescents with T1D did not experience more DEB symptoms during the COVID-19 lockdown compared to healthy controls. Results revealed DEBs as more of a female adolescent developmental issue rather than a result of the challenges of living with a chronic illness under quarantine measures. Possible effects of parental pressure on their children's eating behaviors in the context of home confinement and of using a non-diabetes-specific measure to assess DEBs are discussed.

This study aims to compare the frequency of Diabetic Ketoacidosis (DKA) at diagnosis in 2014-2016 with the one previously reported in 2004-2013; and to assess the association between family socioeconomic status and DKA at type 1 diabetes (T1D) diagnosis in children <15 years of age from 2014 to 2016. Methods: This nationwide, population-based, observational study included 2,679 children diagnosed with T1D from 54 Italian centers for pediatric diabetes during 2014-2016. The ISPAD criteria for DKA were used as a standard reference. The overall and by age frequency of DKA between the two time periods were compared. The association between family socioeconomic status and DKA was assessed using multiple logistic regression analysis. Results: Nine hundred and eighty nine children had DKA (36.9, 95% CI: 35.1-38.8). The frequency of DKA was significantly lower in 2014-2016 in comparison to 2004-2013 (40.3, 95% CI: 39.3-41.4, p = 0.002). The probability of having DKA at diagnosis was lower in mothers with a high level of education (OR = 0.69, 95% CI: 0.51-0.93) or a high level of occupation (OR = 0.76, 95% CI: 0.58 0.99), and in fathers with a high level of occupation (OR = 0.72, 95% CI: 0.55-0.94). Children living in Southern Italy had a higher probability of diagnosis with severe DKA than children living in Central Italy. Conclusion: There was a decrease in the frequency of DKA in children diagnosed with T1D under 15 years of age during 2014-2016. However, DKA frequency remains unacceptably high. This study demonstrated that socioeconomic inequalities, measured as low education and occupational levels, were associated with an increased probability of DKA at T1D diagnosis., (Copyright © 2020 Gesuita, Maffeis, Bonfanti, Cardella, Citriniti, D'Annunzio, Franzese, Iafusco, Iannilli, Lombardo, Maltoni, Patera, Piccinno, Predieri, Rabbone, Ripoli, Toni, Schiaffini, Bowers, Cherubini and Network of the Italian Society of Pediatric Endocrinology and Diabetes (ISPED) for DKA Study and Prevention.)

Objective: To examine body image problems and their associations with disordered eating behavior in adolescents with type 1 diabetes and well-matched healthy peers., Methods: Using a cross-sectional design, 183 adolescents with type 1 diabetes (13.02-18.05 years) were recruited from diabetes centers in southern Italy and compared to healthy peers matched for age and gender. Participants completed self-report measures of disordered eating behaviors (DEPS-r and EDI-3RF) and a gender-specific body image problem questionnaire (SATAQ-4R). Socio-demographic and clinical data (zBMI, HbA1c, and disease duration) were also collected. Hierarchical multiple linear regression analyses were computed to determine the relative importance of diabetes variables and body image problems on participants' disordered eating behaviors after controlling for demographic variables., Results: Adolescents with type 1 diabetes showed diabetes-specific eating problems in 37.7% of cases and had more eating problem symptoms (assessed as drive for thinness and bulimia) than healthy peers. Male adolescents with type 1 diabetes did not display more body image problems ( p > 0.05); females with type 1 diabetes compared to females in the control group were found to be more pressured by family ( p = 0.025) but less by media ( p = 0.022) to improve their appearance and attain a thin body. zBMI and body image problems contributed to a significant increase in disordered eating behavior risk both in male and female adolescents with diabetes and in healthy peers (zBMI 0.213 < β < 0.426, p < 0.05; body image 0.243 < β < 0.572, p < 0.05). None of the variables analyzed were found to significantly predict male bulimic symptoms (all β < 0.296, p > 0.05)., Conclusion: Since in adolescence type 1 diabetes and insulin therapy may increase the risk of weight gain and promote focus and attention on the body and thus contribute to the development of body image problems and disordered eating behaviors, continuity of medical, nutritional, and psychological care is needed., (Copyright © 2020 Troncone, Cascella, Chianese, Zanfardino, Piscopo, Borriello, Casaburo, del Giudice and Iafusco.)

Background: The relation between glucose homeostasis and outcome in hypoxic-ischemic encephalopathy (HIE) is unclear. To investigate whether glucose abnormalities assessed by using continuous interstitial glucose monitoring (CGM) correlate with later neurological outcomes in HIE., Methods: Prospective cohort study recruiting full-term neonates who received therapeutic hypothermia for HIE. CGM devices were placed soon after birth and recorded glucose profile for 3 days. The association between hypoglycemia (≤50 mg/dL), hyperglycemia (>144 mg/dL) and primary outcome defined as death or moderate or severe disability was examined with generalized estimating equations adjusted for Apgar scores, umbilical artery pH and base deficit. Neurodevelopmental outcome was assessed between 18 and 24 months., Results: Fifty-four neonates had outcome data available for the analysis; 19 of them (35%) had adverse outcome. Longer duration of hypoglycemia (OR 7.1, 95% CI 1.8-20.3, P < 0.001) and hyperglycemia (OR 5.4, 95% CI 1.6-15.7, P < 0.001), a greater area under the hypoglycemic (OR 2.6, 95% CI 1.4-4.6, P = 0.04) and hyperglycemic (OR 6.4, 95% CI 1.9-16.3, P < 0.001) curve were significantly associated with adverse outcomes., Conclusion: Both hyper and hypoglycemia may be associated with adverse outcome in neonates with HIE. Future studies are needed to assess their prognostic association with neurological outcome., Impact: Glucose abnormalities during therapeutic hypothermia are associated with later neurological outcomes.Increased glucose variability correlates to the neurological outcome between 18 and 24 months.This study provides the first data on the continuous glucose profile in a group of HIE infants followed up to 2 years of age.Glucose homeostasis represents a key point in the management of HIE patients.Further research is needed to find the appropriate glycemic target in this population.

We present the case of a 45-year-old man with atrial fibrillation and morbid obesity (weight 128 kg, height 168 cm, BMI 45.4) who was switched from Warfarin 5 mg once daily to Apixaban 5 mg twice daily because he did not achieve at least 60% of the time in therapeutic range. We performed serial determinations of apixaban plasma concentration (at 2, 6, 12, 24 hrs after intake) showing drug levels within reference range, even when the patient lose weight., Competing Interests: The authors declare no conflicts of interest in this work., (© 2020 Russo et al.)

Type 1 diabetes mellitus (DM) is characterized by irreversible, autoimmune, pancreatic β -cell destruction. During the disease, some patients experience a phase of Partial Clinical Remission (PCR) known as " honeymoon ." This is a transitory period that is characterized by insulin production by residual β cells following DM diagnosis and initiating the insulin therapy. In this study, we aimed to evaluate the influence of insulin production on immune system after the onset of diabetes, and we showed that the duration of honeymoon period could be related to the onset of other autoimmune conditions. For this retrospective study, 159 children aged between 11 and 18 years with type 1 DM were eligible. They have been diagnosed diabetes at least 10 years ago and use exogenous insulin. Our results showed that younger age at the onset of Type 1 DM in children, predicts Celiac Disease. Female sex and low HCO 3 levels at the onset of DM had a high predictive value on patients who did not experience longer Partial Clinical Remission phase. Patients with higher BMI at the diagnosis of DM experienced shorter honeymoon period than the average. Smaller of our patients who diagnosed just DM have more than 297 days honeymoon period with respect to patients with one associated autoimmune disease. This may be due to a continuous and prolonged stimulation of immune system during the period of honeymoon that predispose the patient to develop other TH1 diseases. The patients who experienced more than 297 days Partial Clinical Remission seem under risk of developing one other autoimmune disease more than the patients who experienced less than 297 days Partial Clinical Remission. We have to consider that this observation is very intriguing because many protocols spring-up to try prolonging the honeymoon period in patients with autoimmune DM. If this aim is important from a metabolic point of view, long follow-ups are needed to be sure that the risk of other autoimmune diseases does not increase., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2020 Gulsum Ozen et al.)

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.

Background: Patients with diabetes, especially pediatric ones, sometimes use continuous glucose monitoring (CGM) sensor in different positions from the approved ones. Here we compare the accuracy of Dexcom® G5 CGM sensor in three different sites: abdomen, gluteus (both approved) and arm (off-label)., Method: Thirty youths, 5-9 years old, with type 1 diabetes (T1D) wore the sensor during a clinical trial where frequent self-monitoring of blood glucose (SMBG) measurements were obtained. Sensor was inserted in different sites according to the patient habit. Accuracy metrics include absolute relative difference (ARD) and absolute difference (AD) of CGM with respect to SMBG. The three sites were compared with ANOVA. If the test detected a difference, an additional pair-wise comparison was performed., Results: Overall, no accuracy difference was detected: the mean ARD was 13.3% (SD = 13.5%) for abdomen, 13.4% (12.9%) for arm and 12.9% (20.2%) for gluteus ( P value = .83); the mean AD was 17.0 mg/dl (17.2 mg/dl) for abdomen, 17.2 mg/dl (17.1 mg/dl) for arm and 18.3 mg/dl (18.5 mg/dl) for gluteus ( P value = .30). In hypo- and euglycemia ARD ( P value = .87 and .15, respectively), and AD ( P value = .68 and .37, respectively) were not statistically different. At variance, in hyperglycemia, a significant difference was detected between the two approved sites, abdomen and gluteus (ΔARD = -2.2% [CI = -4.2%, -0.1%], P value = .04), whereas the comparisons with the off-label location, arm-abdomen, and arm-gluteus were not significant., Conclusions: These results suggest that the accuracy of the sensor placed on the arm was not significantly different with respect to the two approved insertion sites (abdomen and gluteus). Larger, randomized trials are needed to draw final conclusions.

This longitudinal population-based study analyses the frequency of diabetic ketoacidosis (DKA) at type 1 diabetes diagnosis in Italian children under 15 years of age, during 2004-2013. DKA was defined as absent (pH ≥ 7.30), mild/moderate (7.1 ≤ pH < 7.30) and severe (pH < 7.1). Two multiple logistic regression models were used to evaluate the time trend of DKA frequency considered as present versus absent and severe versus absent, adjusted for gender, age group and geographical area of residence at diagnosis. Overall, 9,040 cases were ascertained. DKA frequency was 40.3% (95%CI: 39.3-41.4%), with 29.1% and 11.2% for mild/moderate and severe DKA, respectively. Severe DKA increased significantly during the period (OR = 1.03, 95%CI: 1.003-1.05). Younger-age children and children living in Southern Italy compared to Central Italy were at significantly higher risk of DKA and severe DKA. Family history of type 1 diabetes and residence in Sardinia compared to Central Italy were significantly associated with a lower probability of DKA and severe DKA. The high frequency of ketoacidosis in Italy over time and high variability among age groups and geographical area of residence, strongly suggests a continuing need for nationwide healthcare strategies to increase awareness of early detection of diabetes.

Objective: To explore the experiences of children with type 1 diabetes and their parents taking part in an artificial pancreas (AP) clinical trial during a 7-day summer camp., Research Design and Methods: A semistructured interview, composed of 14 questions based on the Technology Acceptance Model, was conducted at the end of the clinical trial. Participants also completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ, parent version) and the AP Acceptance Questionnaire., Results: Thirty children, aged 5-9 years, and their parents completed the study. A content analysis of the interviews showed that parents were focused on understanding the mechanisms, risks, and benefits of the new device, whereas the children were focused on the novelty of the new system. The parents' main concerns about adopting the new system seemed related to the quality of glucose control. The mean scores of DTSQ subscales indicated general parents' satisfaction (44.24 ± 5.99, range 32-53) and trustful views of diabetes control provided by the new system (7.8 ± 2.2, range 3-12). The AP Acceptance Questionnaire revealed that most parents considered the AP easy to use (70.5%), intended to use it long term (94.0%), and felt that it was apt to improve glucose control (67.0%)., Conclusions: Participants manifested a positive attitude toward the AP. Further studies are required to explore participants' perceptions early in the AP development to individualize the new treatment as much as possible, and to tailor it to respond to their needs and values., (© 2016 by the American Diabetes Association.)