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Introduction: Acromegaly is a rare disease that results from growth hormone (GH) excess. Diabetes mellitus, hypertension,cardiomyopathy, and obstructive sleep apnoea syndrome( OSAS) are frequent complications. Aim of the study: Identify a useful system to obtain a reliable remote monitoring of glucose and the most important vital parameters in the acromegalic subjects. Patients and Methods: Sixteen acromegalic patients (from 30 to 73 years old) were enrolled. We provided health monitor devices to the patients for continuous acquisition of physiological signals including twelve-lead electrocardiography (EKG) and nocturnal SpO2. At the same time, we applied on the same patients the blinded continuous glucose monitoring system(CGMS). Results: The lowest saturation peaks at night ( Conclusion: The health monitor device associated with CGM may be a new useful and versatile tool for fragile patients who can self-manage remote monitoring, and for physicians who can obtain real-time information for the clinical and therapeutic management of patients. It is also a useful tool for the follow-up of patients with OSAS. Moreover, once the interference of the OSAS is excluded, the CGM allows us to obtain a more reliable and accurate diagnosis of DM.

Background: An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic. Methods: For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006–19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker. Findings: 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27·3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1·6% (95% CI 1·3 to 1·9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39·4% (95% CI 34·0 to 45·6) in 2020 and 38·9% (33·6 to 45·0) in 2021, significantly higher than the predicted prevalence of 32·5% (27·8 to 37·9) for 2020 and 33·0% (28·3 to 38·5) for 2021 (p

Background/Aims: Mutations in KCNJ11, the gene encoding the Kir6.2 subunit of pancreatic and neuronal KATP channels, are associated with a spectrum of neonatal diabetes diseases. Methods: Variant screening was used to identify the cause of neonatal diabetes, and continuous glucose monitoring was used to assess effectiveness of sulfonylurea treatment. Electrophysiological analysis of variant KATP channel function was used to determine molecular basis. Results: We identified a previously uncharacterized KCNJ11 mutation, c.988T>C [p.Tyr330His], in an Italian child diagnosed with sulfonylurea-resistant permanent neonatal diabetes and developmental delay (intermediate DEND). Functional analysis of recombinant KATP channels reveals that this mutation causes a drastic gain-of-function, due to a reduction in ATP inhibition. Further, we demonstrate that the Tyr330His substitution causes a significant decrease in sensitivity to the sulfonylurea, glibenclamide. Conclusions: In this subject, the KCNJ11 (c.988T>C) mutation provoked neonatal diabetes, with mild developmental delay, which was insensitive to correction by sulfonylurea therapy. This is explained by the molecular loss of sulfonylurea sensitivity conferred by the Tyr330His substitution and highlights the need for molecular analysis of such mutations.

Introduction The Post-traumatic Stress Disorder (PTSD) is a group of persistent psychological and physiological symptoms due to a traumatic, severe, event. Only few studies focused on the effects of Covid-19 on psychosocial outcomes in children with Type 1 Diabetes (T1D) and their parents. Aim of the study The aim of this study was to evaluate the presence PTSD in parents of children with T1D during COVID-19 pandemic lockdown. Patients and methods In the period between March and May 2020 we submitted the “Impact of Event Scale – Revised” (IES-R) questionnaire to the parents of 34 children with Type 1 Diabetes, asking them to express their emotions about the ongoing Covid-19 pandemic. Results A total of thirty mothers (mean age 43.0 ± 4.2 years) and 25 fathers (mean age 45.6 ± 5.9 years) participated in the survey and completed the questionnaires. 29.1% of parents had a score that allows to define a clinically relevant level of PTSD; ten mothers and 6 fathers had a PTSD clinically relevant score, corresponding, respectively, to 28.4 and 24% of total mothers and fathers. Finally, mothers and fathers, both express PTSD symptoms mainly in the form of intrusion and hyperarousal. Conclusions The present study confirms a high prevalence symptoms related to PTSD in mothers and fathers of children with Type 1 Diabetes. We believe that psychosocial outcomes of the COVID-19 pandemic should be taken into account in the planning of the next future assistance for children with T1D.

The immunological events leading to type 1 diabetes (T1D) are complex and heterogeneous, underscoring the necessity to study rare cases to improve our understanding. Here, we report the case of a 16-year-old patient who showed glycosuria during a regular checkup. Upon further evaluation, stage 2 T1D, autoimmune thrombocytopenic purpura (AITP), and common variable immunodeficiency (CVID) were diagnosed. The patient underwent low carb diet, losing > 8 kg, and was placed on Ig replacement therapy. Anti-CD20 monoclonal antibody (Rituximab, RTX) was administered 2 years after diagnosis to treat peripheral polyneuropathy, whereas an atypical mycobacteriosis manifested 4 years after diagnosis and was managed with prolonged antibiotic treatment. In the fifth year of monitoring, the patient progressed to insulin dependency despite ZnT8A autoantibody resolution and IA-2A and GADA autoantibody decline. The patient had low T1D genetic risk score (GRS = 0.22817) and absence of human leukocyte antigen (HLA) DR3/DR4-DQ8. Genetic analysis identified the monoallelic mutation H159Y in TNFRSF13C, a gene encoding B-cell activating factor receptor (BAFFR). Significant reduced blood B-cell numbers and BAFFR levels were observed in line with a dysregulation in BAFF–BAFFR signaling. The elevated frequency of PD-1+ dysfunctional Tfh cells composed predominantly by Th1 phenotype was observed at disease onset and during follow-up. This case report describes a patient progressing to T1D on a BAFFR-mediated immunodysregulatory background, suggesting a role of BAFF–BAFFR signaling in islet-specific tolerance and T1D progression.

Background SARS-CoV-2 causes lesions, in addition to lung, in endocrine organs such as the pancreas through ACE2 receptor. Recently the relationship between SARS-CoV-2 exposition and the incidence or evolution of clinical autoimmune diabetes has attracted the attention of diabetologists. Case presentation We report the analysis of the clinical history of a child diagnosed for insulin-dependent diabetes mellitus (Type 1 diabetes) at the time a paucisymptomatic COVID-19 infection occurred, followed by well-controlled metabolic status. As opposite to previous findings SARS-CoV2 did not cause ketosis and ketoacidosis. Polydipsia was reported a few months and weight loss 4 weeks before SARS- CoV-2 infection suggesting that SARS-CoV-2 could not be the trigger of Type 1 diabetes in this patient. Conclusions SARS-CoV-2 in this patient was an unexpected event in the course of disease. We advance the hypothesis that the SARS-CoV-2 infection, even if paucisymptomatic could have acted in the present case report as a hypothetical downstream precipitating factor; whilst the inciting triggering event of the autoimmune disease, as confirmed by the presence of circulating autoantibodies, could have occurred even before, as generally assumed for this category of disorders. The precipitating mechanism could have been the acute interaction between virus and the ACE receptor on the beta cells, at the time that hyperglycemia and glycosuria were ascertained, and HbA1c levels confirmed a metabolic dysregulation over the previous 3 months in absence of ketoacidosis.

Aim/HypothesisTo 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.MethodsForty-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.ResultsOverall, 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, pConclusions/InterpretationThere 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.

Monogenic diabetes, a form of diabetes mellitus, is caused by a mutation in a single gene and may account for 1-2% of all clinical forms of diabetes. To date, more than 40 loci have been associated with either isolated or syndromic monogenic diabetes.While the request of a genetic test is mandatory for cases with diabetes onset in the first 6 months of life, a decision may be difficult for childhood or adolescent diabetes. In an effort to assist the clinician in this task, we have grouped monogenic diabetes genes according to the age of onset (or incidental discovery) of hyperglycemia and described the additional clinical features found in syndromic diabetes. The therapeutic options available are reviewed.Technical improvements in DNA sequencing allow for rapid, simultaneous analysis of all genes involved in monogenic diabetes, progressively shrinking the area of unsolved cases. However, the complexity of the analysis of genetic data requires close cooperation between the geneticist and the diabetologist, who should play a proactive role by providing a detailed clinical phenotype that might match a specific disease gene.

The C1858T variant of the protein tyrosine phosphatase N22 (

Autoimmune endocrine disorders, such as type 1 diabetes (T1D) and thyroiditis, at present are treated with only hormone replacement therapy. This emphasizes the need to identify personalized effective immunotherapeutic strategies targeting T and B lymphocytes. Among the genetic variants associated with several autoimmune disorders, the C1858T polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, encoding for Lyp variant R620W, affects the innate and adaptive immunity. We previously exploited a novel personalized immunotherapeutic approach based on siRNA delivered by liposomes (lipoplexes) that selectively inhibit variant allele expression. In this manuscript, we improved lipoplexes carrying siRNA for variant C1858T by functionalizing them with Fab of Rituximab antibody (RituxFab-Lipoplex) to specifically target B lymphocytes in autoimmune conditions, such as T1D. RituxFab-Lipoplexes specifically bind to B lymphocytes of the human Raji cell line and of human PBMC of healthy donors. RituxFab-Lipoplexes have impact on the function of B lymphocytes of T1D patients upon CpG stimulation showing a higher inhibitory effect on total cell proliferation and IgM+ plasma cell differentiation than the not functionalized ones. These results might open new pathways of applicability of RituxFab-Lipoplexes, such as personalized immunotherapy, to other autoimmune disorders, where B lymphocytes are the prevalent pathogenic immunocytes.

Aims: To evaluate access to screening tools for monogenic diabetes in paediatric diabetes centres across the world and its impact on diagnosis and clinical outcomes of children and youth with genetic forms of diabetes. Methods: 79 centres from the SWEET diabetes registry including 53,207 children with diabetes participated in a survey on accessibility and use of diabetes related antibodies, c-peptide and genetic testing. Results: 73, 63 and 62 participating centres had access to c-peptide, antibody and genetic testing, respectively. Access to antibody testing was associated with higher proportion of patients with rare forms of diabetes identified with monogenic diabetes (54 % versus 17 %, p = 0.01), lower average whole clinic HbA1c (7.7[Q1,Q2: 7.3-8.0]%/61[56-64]mmol/mol versus 9.2[8.6-10.0]%/77[70-86]mmol/mol, p < 0.001) and younger age at onset (8.3 [7.3-8.8] versus 9.7 [8.6-12.7] years p < 0.001). Additional access to c-peptide or genetic testing was not related to differences in age at onset or HbA1c outcome. Conclusions: Clinical suspicion and antibody testing are related to identification of different types of diabetes. Implementing access to comprehensive antibody screening may provide important information for selecting individuals for further genetic evaluation. In addition, worse overall clinical outcomes in centers with limited diagnostic capabilities indicate they may also need support for individualized diabetes management. info:eu-repo/semantics/publishedVersion

Aims: In March and April 2020, at the start of the COVID-19 pandemic, our previous survey of Italian pediatric diabetes centers showed that 75% of telemedicine use was voluntary. We hypothesized that the COVID-19 pandemic has acted as a picklock to overcome barriers to telemedicine regulation, use, and reimbursement. Methods: Between March 22nd and April 12th, 2021, the same survey administered in 2020 was sent to all 68 Italian pediatric diabetes centers belonging to the Italian Society for Pediatric Endocrinology and Diabetes (ISPED) to collect data on the demographic variables of respondents; information about the center; the use, codification, and reimbursement of telemedicine; and used tools. Descriptive data were evaluated to establish how the COVID-19 pandemic has changed telemedicine practice. Results: Eighty-two percent of responder centers reported an increase in the use of telemedicine, with televisits by video calling implemented in over half of centers. There was a significant increase in the number of centers formally tracking telemedicine use and obtaining reimbursement from the national health service (42% vs. 29% and 62% vs. 32%; p < 0.001, respectively). No reimbursement was provided to centers not using televisits. Conclusions: From a voluntary procedure with a lack of traceability, telemedicine has become a new structured reality that may help our pediatric patients beyond this pandemic.

Over the last years significant advances have been achieved in the development of technologies for diabetes management. Continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring (CGM), predictive low glucose management (PLGM), hybrid closed loop (HCL) and advanced hybrid closed loop (AHCL) systems allow better diabetes management, thus reducing the burden of the disease and the risk of chronic complications. This review summarizes the main characteristics of the currently available HCL and AHCL systems and their primary effects in children and adolescents with type 1 diabetes (T1D). The findings of trials assessing the glucose control (time in range, HbA1c values, hypoglycemic events), the health-related quality of life and the existing limits of the use of these technologies are reported. The most recent data clearly confirm the ability of the HCL and AHCL insulin delivery systems to safely achieve a significant improvement of glucose control and quality of life in the pediatric population with T1D. Further studies are underway to overcame current barriers and future improvements in the usability of these technologies are awaited to facilitate their use in the routine clinical practice. The HCL and AHCL algorithms are the key features of today's insulin delivery systems that mark a crucial step towards fully automated closed loop systems.

Background and aim: Albuminuria and reduced eGFR are hallmarks of Diabetic Kidney Disease in adults. Our aim was to analyze factors associated with albuminuric and non-albuminuric mildly reduced eGFR phenotypes in youths with type 1 diabetes. Methods and results: This multicenter cross-sectional study included 1549 youths (age 5–17 years) with type 1 diabetes enrolled at 14 Italian Pediatric Diabetes Centers. Albuminuria, creatinine, glycosylated hemoglobin (HbA1c), lipids, blood pressure (BP), neutrophils (N) and lymphocytes (L) count were analyzed. Uric acid (UA) was available in 848 individuals. Estimated GFR (eGFR) was calculated using bedside Schwartz's equation. The sample was divided in three phenotypes: 1) normoalbuminuria and eGFR ≥90 mL/min/1.73 m2 (reference category, n = 1204), 2) albuminuric and normal GFR phenotype (n = 106), 3) non-albuminuric mildly reduced GFR (MRGFR) phenotype (eGFR 60–89 mL/min/1.73 m2, n = 239). Albuminuric and non-albuminuric reduced eGFR phenotypes were significantly associated with autoimmune thyroiditis (P =0.028 and P=0.044, respectively). Albuminuric phenotype showed high risk of high HbA1c (P=0.029), high BP (P < 0.001), and low HDL-C (P =0.045) vs reference category. Non-albuminuric MRGFR phenotype showed high risk of high BP (P < 0.0001), low HDL-C (P =0.042), high Triglycerides/HDL-C ratio (P =0.019), and high UA (P < 0.0001) vs reference category. Conclusion: Non albuminuric MRGFR phenotype is more prevalent than albuminuric phenotype and shows a worst cardiometabolic risk (CMR) profile). Both phenotypes are associated with autoimmune thyroiditis. Our data suggest to evaluate both albuminuria and eGFR earlier in type 1 diabetes to timely identify young people with altered CMR profile.

Aim To compare nasal glucagon (NG) with intramuscular glucagon (IMG) for the treatment of insulin‐induced hypoglycaemia in Japanese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). Materials and methods This phase 3, randomized, open‐label, two‐treatment, two‐period crossover non‐inferiority study enrolled Japanese adults with T1DM or T2DM on insulin therapy, with glycated haemoglobin levels ≤86 mmol/mol (≤10%). After ≥8 hours of fasting, hypoglycaemia was induced with human regular insulin (intravenous infusion). Patients received NG 3 mg or IMG 1 mg approximately 5 minutes after insulin termination. The primary endpoint was the proportion of patients achieving treatment success [plasma glucose (PG) increase to ≥3.9 mmol/L (≥70 mg/dL) or ≥1.1 mmol/L (≥20 mg/dL) increase from the PG nadir within 30 minutes of receiving glucagon]. Non‐inferiority was declared if the upper limit of the two‐sided 95% confidence interval (CI) of the mean difference in the percentage of patients achieving treatment success (IMG minus NG) was 2 patients were rhinalgia, increased blood pressure, nausea, ear pain and vomiting in the NG group, and nausea and vomiting in the IMG group. Conclusion Nasal glucagon was non‐inferior to IMG for successful treatment of insulin‐induced hypoglycaemia in Japanese patients with T1DM/T2DM, supporting use of NG as a rescue treatment for severe hypoglycaemia.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

AIM To ascertain whether the prevalence of retinopathy has declined over the last 2 decades in individuals with childhood-onset type 1 diabetes and whether this might be explained by changes in lifetime HbA1c. MATERIALS AND METHODS A multicentre, retrospective, observational study, comparing 128 subjects with diabetes onset in 2000-2003 assessed for retinopathy in 2016-2019, with a previous cohort of 115 individuals diagnosed in 1990-1993 and assessed for retinopathy in 2007-2009, was conducted. The two cohorts had both a similar diabetes duration and age at diagnosis. Retinal photographs were centrally graded. Lifetime HbA1c and its variability, estimated as the ratio between intrapersonal mean and standard deviation of HbA1c, were evaluated. RESULTS The prevalence of any retinopathy in the new and old cohort was 24.2% and 43.5% (P

Cystic fibrosis related diabetes (CFRD) is a comorbidity of cystic fibrosis (CF) that negatively impacts on its clinical course. Prediabetes is an important predictor of either CFRD development and unfavorable prognosis of CF in both pediatric and adult patients. International guidelines recommend insulin only in case of CFRD diagnosis. Whether early detection and treatment of prediabetes may contribute to improve the clinical course of CF is still debated. A subgroup of pediatric diabetologists of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) performed a systematic review of the literature based on predefined outcomes: impact of pre-diabetes on clinical outcomes and on the risk of developing CFRD; diagnosis of diabetes and pre-diabetes under 10 years of age; effectiveness of therapy on glycemic control, impact of therapy on pulmonary function and nutritional status. Thirty-one papers were selected for the analysis data presented in these papers were reported in tables sorted by outcomes, including comprehensive evidence grading according to the GRADE approach. Following the grading of the quality of the evidence, the entire ISPED diabetes study group achieved consensus for the Italian recommendations based on both evidence and clinical experience. We concluded that in patients with CF, prediabetes should be carefully considered as it can evolve into CFRD. In patients with CF and prediabetic conditions, after complete evaluation of the OGTT trend, glucometrics, glycemic values measured during pulmonary exacerbations and/or steroid therapy, early initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with CF and prediabetes.

Aim: To evaluate the impact of a virtual educational camp (vEC) on glucose control in children and adolescents with type 1 diabetes using a closed-loop control (CLC) system. Materials and Methods: This was a prospective multicentre study of children and adolescents with type 1 diabetes using the Tandem Basal-IQ system. Insulin pumps were upgraded to Control-IQ, and children and their parents participated in a 3-day multidisciplinary vEC. Clinical data, glucose metrics and HbA1c were evaluated over the 12 weeks prior to the Control-IQ update and over the 12 weeks after the vEC. Results: Forty-three children and adolescents (aged 7-16 years) with type 1 diabetes and their families participated in the vEC. The median percentage of time in target range (70-180 mg/dL; TIR) increased from 64% (interquartile range [IQR] 56%-73%) with Basal-IQ to 76% (IQR 71%-81%) with Control-IQ (P&nbsp

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), responsible for the coronavirus disease COVID-19, was first identified in Wuhan, China in December 2019. Diabetes, as well as other cardiovascular comorbidities, has been recognized as a major risk factor for outcomes and mortality in adults with COVID19, particularly in the elderly with type 2 diabetes. Based on these conclusions, COVID-19 data on adults have been generalizedto youth with diabetes. Nevertheless, experience from Pediatric Diabetes practices in China (Wuhan), Italy, Spain (Catalonia) and the US (San Francisco Bay Area) consistently report only a single severe case of COVID-19 in a 20-year-old female youth with type 1 diabetes (T1D) that was hospitalized for bilateral pneumonia and was subsequently discharged without complications. In Italy, information on COVID-19 in all children with diabetes is collected on a weekly basis andthose with positive swab test or infection-related symptoms reported to a dedicated national registry. Of a total of 15,500 children tested,11subjects with T1D (age 8-17y) tested positive for COVID-19; 6/11 were asymptomatic and the rest presented with mild symptoms. In the rest of locations, youth with T1D diagnosed with COVID-19 were based on clinical suspicion and a confirmatory PCR test(Wuhan:0; Catalonia-HSJD:3; California-Stanford:2) and all of them were asymptomatic or had a mild course.We suggest that COVID-19 data from adults should not be generalizedto children, adolescents and youth with diabetes as their outcomes and prognosis seem to be similar to their non-diabetic-peers and consistently milder than adults with diabetes. This article is protected by copyright. All rights reserved.

Introduction Management of Type 1 Diabetes (T1D) poses numerous challenges, especially for young children and their families. Parental care positively influences the outcomes of children with T1D, while there are often criticisms in school environment. The COVID-19 pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents. Aim of the study To evaluate the effectiveness of exclusive return to parental care in pre-school and school children with T1D treated with Tandem Basal IQ system during the COVID-19 pandemic. Patients and methods 22 children (M:F = 14:8) with T1D have been evaluated. We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. Results During the IN-COV period a significantly (p < 0.001) higher median value of TIR (66,41%) was observed as compared to PRE-COV period (61,45%). Patients also showed a statistically significant difference (p < 0.002) between the IN-COV period and the PRE-COV period as concerning the TAR metric: respectively 29,86 ± 10,6 % vs 34,73 ± 12,8 %. The difference between the bolus insulin doses was statistically significant (PRE-COV 5,3 IU/day, IN-COV 7,9 IU/day – p

Background: Glucose sensors consist of real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM). Their clinical use has been widely increasing during the past 5 years. The aim of this study is to evaluate percentage of time in range (TIR) in a large group of children with type 1 diabetes (T1D) using glucose sensors with nonautomated insulin delivery systems, in a real-world setting. Methods: An 11-center cross-sectional study was conducted during January-May 2019. Children with T1D 1 year, treated with multiple daily injections (MDI) or nonautomated insulin pump (IP), were recruited consecutively. Clinical data, HbA1c measurement, and CGM downloaded data were collected by each center and included in a centralized database for the analysis. Glucose metrics of four treatment strategies were analyzed: isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP. Results: Data from 666 children with T1D (51% male and 49% female), median age 12 years, diabetes duration 5 years, were analyzed. An rtCGM was used by 51% of the participants, and a nonautomated IP by 46%. For isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP, the median TIR 70-180 mg/dL values were 49%, 56%, 56%, and 61% (P < 0.001), respectively; HbA1c 7.6%, 7.5%, 7.3%, and 7.3% (P < 0.001), respectively. Use of rtCGM was associated with significant lower time below target range 180 mg/dL and lower HbA1c. If there are no barriers, an upgrade of the treatment strategy with a higher performing technology should be offered to all children who do not achieve blood glucose metrics within the suggested range.

Background: Acromegaly is characterized by an insulin resistance condition. There is a significant difference between the different types of therapy in relation to the glycometabolic framework. The blinded continuous glucose monitoring system (CGMS), throughout a period of maximum 6 days for a total of 288 glycemic registrations per day, identifies glycemic excursions and could constitute a valid device to understand the 24-hour glycemic profiles. Aim of the study: To compare the oral glucose tolerance test (OGTT) and CGMS methods in acromegalic patients to evaluate their glycemic profiles, in relation to different treatments for acromegaly. Methods: Thirty-five acromegalic patients were divided into 18 somatostatin analogs (SSA), 9 pegvisomant, and 8 successfully surgically treated. A 72-hour CGM was performed and, immediately after, an OGTT. Results: Results obtained from OGTT: 11/35 impaired fasting glucose, 6/35 impaired glucose tolerance, and 4/35 diabetes mellitus. A positive significant correlation was demonstrated between the OGTT peak and CGM peak in all of the patients, CGM peak of patients treated with SSA and those surgically treated, OGTT average and CGM area under concentration–time curve (AUC) for hyperglycemia of patients treated with SSA and those surgically treated, and CGM AUC for hyperglycemia of patients treated with SSA and those surgically treated. Conclusions: Our results show a significantly higher response in terms of mean and peak OGTT in patients treated with SSA, both compared to the CGM study, and compared to the group of patients receiving pegvisomant. The CGM system could represent an instrument for the evaluation of the glycemic trend of acromegalic patients.

OBJECTIVE To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally. RESEARCH DESIGN AND METHODS We analyzed data on 17,280 cases of T1D diagnosed during 2018–2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models. RESULTS The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1–12.2) in 2018 to 21.7 (20.6–22.8) in 2021 for the youngest age-group, CONCLUSIONS The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent.

Objectives To assess the optimal setting of the predictive low glucose management (PLGM) algorithm for preventing exercise-induced hypoglycemia in adolescents with type 1 diabetes. Methods Thirty-four adolescents, 15 to 20 years, wearing PLGM system, were followed during 3 days exercise during a diabetes camp. PLGM threshold was set at 70 mg/dL between 8 am and 10 pm and 90 mg/dL during 10 pm and 8 am Adolescents were divided into group A and B, with PLGM threshold at 90 and 70 mg/dL, respectively, during exercise. Time spent in hypoglycemia and AUC for time slots 8 am to 1 pm, 1 to 4 pm, 4 to 11 pm, 11 pm to 3 am, 3 to 8 am, in 3 days were compared between groups by Wilcoxon rank sum test. Results We analyzed 31 patients (median age 15.0 years, 58.1% males, median diabetes duration 7.0 years, hemoglobin A1c [HbA1c] 7.1%). No significant difference has been observed in time spent in hypoglycemia between groups using threshold 70 or 90. Time spent in target was similar in both groups, as well as time spent in hypo or hyperglycemia. The trends of blood glucose over the 3 days in the 2 groups over-lapped without significant differences. Conclusions A PLGM threshold of 90 mg/dL during the night was associated with reduced time in hypoglycemia in adolescents doing frequent physical exercise, while maintaining 65.1% time in range during the day. However, a threshold of 70 mg/dL seems to be safe in the duration of the physical exercise. PLGM system in adolescents with type 1 diabetes was effective to prevent hypoglycemia during and after exercise, irrespective of the PLGM thresholds used.

Type 1 diabetes mellitus is a heterogeneous disorder characterized by destruction of pancreatic β cells, culminating in absolute insulin deficiency. The goals of Type 1 diabetes care, established by the Diabetes Control and Complications Trial (DCCT), are to achieve good glycemic control, to prevent hyperglycaemia (which is associated with long-term microvascular and macrovascular complications) and to avoid recurrent episodes of hypoglycaemia (which may have adverse effects on cognitive function). However, despite continuing optimization of insulin therapy regimes, the actual hormonal substitutive administration acts only to treat the symptoms without an effect on disease pathology and etiopathogenesis. In recent decades, a great deal of interest has been focused on prevention approaches in high-risk individuals, based on the hypothesis that a therapeutic intervention, if applied at the early stage of disease, might contribute to maintaining endogenous β cell function by preserving the residual β cell reservoir from autoimmune attack. This manuscript provides an overview of the most important immunotherapeutic interventions established so far for Type 1 diabetes treatment at different stages of disease that have reached an advanced stage of assessment.

Background: Transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is benign and self-limited, with neurologic deficits including sensory disturbance of one body side, aphasia, nausea/vomiting, weakness, decreased vision, homonymous hemianopsia, photophobia. Acute confusional state can rarely occur. Papilledema and intracranial hypertension have also been described. It is a rare entity mainly affecting adults; however, it has been sporadically described in children and adolescents. Main findings: In this clinical observational study, we describe a clinical series of three consecutive pediatric patients being diagnosed with HaNDL after presenting with altered consciousness, papilledema, and increased intracranial pressure. They all recovered without relapses. Conclusion: Presentation during childhood and adolescence is rare; the majority of pediatric cases presented with altered consciousness, which is infrequent in HaNDL. This may suggest that in childhood this symptom might be more common than in adults. All three patients presented with increased intracranial pressure and papilledema, thus suggesting that these aspects should be investigated in all patients presenting with this clinical pattern. Finally, all our patients began to suffer from migraine. This feature, together with the benign course of the disease, could favor the hypothesis of a migrainous pathophysiology of this syndrome, although this remains a speculative.

Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Introduction In the past years, we developed a telemonitoring service for young patients affected by Type 1 Diabetes. The service provides data to the clinical staff and offers an important tool to the parents, that are able to oversee in real time their children. The aim of this work was to analyze the parents’ perceived usefulness of the service. Methods The service was tested by the parents of 31 children enrolled in a seven-day clinical trial during a summer camp. To study the parents’ perception we proposed and analyzed two questionnaires. A baseline questionnaire focused on the daily management and implications of their children’s diabetes, while a post-study one measured the perceived benefits of telemonitoring. Questionnaires also included free text comment spaces. Results Analysis of the baseline questionnaires underlined the parents’ suffering and fatigue: 51% of total responses showed a negative tendency and the mean value of the perceived quality of life was 64.13 in a 0–100 scale. In the post-study questionnaires about half of the parents believed in a possible improvement adopting telemonitoring. Moreover, the foreseen improvement in quality of life was significant, increasing from 64.13 to 78.39 ( p-value = 0.0001). The analysis of free text comments highlighted an improvement in mood, and parents’ commitment was also proved by their willingness to pay for the service (median = 200 euro/year). Discussion A high number of parents appreciated the telemonitoring service and were confident that it could improve communication with physicians as well as the family’s own peace of mind.

Aim: To evaluate the incidence of insulin pump and infusion set failures in a cohort of children and adolescents with type 1 diabetes during a 1-year follow-up. Materials and Methods: Insulin pump breakdown and infusion set failures were prospectively registered in a cohort of 1046 children and adolescents from 25 tertiary pediatric diabetes centres (50% male, mean age 12.2 ± 4.1 years), with type 1 diabetes from the age of 6.7 ± 3.6 years, and using an insulin pump from the age of 3.3 ± 2.2 years. Results: An average rate of 4.5 failures/person-year was registered; the incidences (events per person-year) for each failure were 8.4 for hyperglycaemia episodes solved with infusion set change, 7 for bubbles, 2.8 for kinking, 2.4 for bleeding, 2 for set dislodge, 2 for pump blockage, 1.9 for tunnelling, 1.8 for lipohypertrophy, and 0.3 for infection. At multivariate analysis significant association between HbA1c and lipohypertrophy (P < 0.0028) was shown. Analysis by age group (11 years) showed a higher frequency of bubbles, hyperglycaemia episodes and lipohypertrophy in preschoolers; tunnelling and pump blockage were more frequent in adolescents. Aspart was associated with a lower risk of bubbles and hyperglycaemia whereas glulisine was associated with a higher risk of lipohypertrophy and pump blockage. The usage of oblique cannula was associated with a low risk of all failures except infections. Conclusions: This prospective 1-year study on a large cohort of Italian children and adolescents with type 1 diabetes using insulin pump therapy showed a low total failure rate, highlighting the importance of continuous education to reduce failures. Lipohypertrophy was the only issue associated with a worsening of metabolic control.

Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4+CD25+ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of CD4+CD25high T cells in autoimmunity and their molecular mechanisms remain the subject of investigation. We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. Percentages of total PD-1+, PD-1low and PD-1high expressing T regulatory cells did not change in patients and in controls. After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1+, PD-1low and PD-1high expressing cells were lower in patients. Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface.

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). 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.

SummaryObjectives To evaluate the usefulness of continuous glucose monitoring (CGM) to identify nocturnal hypoglycaemia in children affected by combined ACTH and GH deficiency and to optimize the hydrocortisone replacement therapy in these patients. Study design Eleven patients with ACTH and GH deficiency (five boys and six girls, age 1·6–16·8 years) underwent CGM for 36 h, including two nights. At least two consecutive glucose levels

The incidence of type 1 diabetes in childhood is increasing by 3 % per year, placing growing demands on healthcare professionals and medical expenditures. Aim of this study wars to assess the organization of care to children with diabetes in Italy.During 2012 a structured questionnaire was sent to all of the members of Italian Society of Paediatric Endocrinology and Diabetology (ISPED). Questions examined organizational structure of Centers, personnel dedicated to the care of children with diabetes, number of subjects followed, local legal legislation supporting centres.A total of 68 centers taking care to 15,563 children and adolescents with diabetes under 18 years of age were identified with a prevalence of 1.4 per 1,000 people. A wide variation in the organizational background was also reported. Fourty-four centers were organized as outpatient departments, 17 as simple units, 5 as complex units and 2 as simple departmental structures. Most centers had a multidisciplinary team. Ten out of twenty Italian regions had introduced supportive regional legislation, but it was fully applied only in six of them.Great differences between regions were found in organizational structures, staffing levels and supportive legislation. The national legislation on diabetes was broadly implemented throughout the country regions. Further efforts are needed to improve standards and consistency of pediatric diabetes care in Italy.

We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0–18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records(n=2453)of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n=1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05–0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers.

Aims: The aim of the study was to evaluate and compare continuous subcutaneous insulin infusion (CSII) use in pediatric and adult age groups. Methods: Data were collected with a questionnaire sent by e-mail to CSII-experienced Diabetes Centers. The questionnaire assessed: (1) number of CSII-treated patients; (2) patient demographic data and characteristics; (3) structure and organization of Diabetes Centers providing CSII therapy; (4) pump characteristics (conventional pump, sensor-augmented pump); and (5) CSII dropouts. Results: A total of 217 out of 1093 Italian centers participated: 51 pediatric (23.5%) and 166 (76.5%) adult centers (AP). Compared to a survey performed in 2005, there was a significant increase in the number of pediatric units when compared to adult units (112 vs 37%, respectively, p&nbsp

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.

OBJECTIVE The Pediatric Artificial Pancreas (PedArPan) project tested a children-specific version of the modular model predictive control (MMPC) algorithm in 5- to 9-year-old children during a camp. RESEARCH DESIGN AND METHODS A total of 30 children, 5- to 9-years old, with type 1 diabetes completed an outpatient, open-label, randomized, crossover trial. Three days with an artificial pancreas (AP) were compared with three days of parent-managed sensor-augmented pump (SAP). RESULTS Overnight time-in-hypoglycemia was reduced with the AP versus SAP, median (25th–75th percentiles): 0.0% (0.0–2.2) vs. 2.2% (0.0–12.3) (P = 0.002), without a significant change of time-in-target, mean: 56.0% (SD 22.5) vs. 59.7% (21.2) (P = 0.430), but with increased mean glucose 173 mg/dL (36) vs. 150 mg/dL (39) (P = 0.002). Overall, the AP granted a threefold reduction of time-in-hypoglycemia (P < 0.001) at the cost of decreased time-in-target, 56.8% (13.5) vs. 63.1% (11.0) (P = 0.022) and increased mean glucose 169 mg/dL (23) vs. 147 mg/dL (23) (P < 0.001). CONCLUSIONS This trial, the first outpatient single-hormone AP trial in a population of this age, shows feasibility and safety of MMPC in young children. Algorithm retuning will be performed to improve efficacy.

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 3/17 (7.6%) children with CF with at least one glucose value above 200 mg/dl (1 CFRD and 2 IGT+200), while CGMS revealed 6/17 (35.3%) children with glucose excursions above 200 mg/dl (P=0.010). None of the controls showed glucose over 200 mg/dl either at OGTT or at CGMS. At the 2.5-year follow-up OGTT, all the six subjects who had diabetic glucose excursion (i.e. >200 mg/dl) at baseline CGMS presented IGT+200 or CFRD. In logistic regression analysis, CGMS diabetic excursion was the strongest predictor of IGT+200 and CFRD (PConclusionsCGMS could be a useful tool to predict glucose metabolism derangements in children affected by CF.

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 (PPPPConclusionsIn obese Caucasian subjects, further decrease of IS observed during puberty is a transient phenomenon. Factors that independently from T or age influence IS are central fat depot in girls, lean amount in boys, and total fat mass in both sexes.

Aims To investigate on the relationship between severity of ketoacidosis, an important risk factor for C-peptide preservation, and long-term microvascular complications in childhood-onset type 1 diabetes mellitus (T1DM). Methods 230 childhood-onset diabetic patients (177 pre-pubertal), aged 7.0 ± 3.8 years followed for at least 15 years after their diagnosis, were enrolled. Clinical and laboratory data at diagnosis, and C-peptide levels in a subset of patients, were compared with the severity of retinopathy and nephropathy, after a mean of 19.6 ± 3.8 years of disease. Digital retinal photographs were taken in all patients, and centrally graded. Repeated measurements of HbA1c and microalbuminuria for the whole duration of diabetes were collected in over half of the cases. Results Out of 230 patients, those with the lowest age at diagnosis had the most severe DKA and clinical conditions (p < 0.05), and lower C-peptide levels (p < 0.0001) at diagnosis. There was a significant relationship between pH and clinical severity (r = - 0.783, p < 0.0001), and between pH and C-peptide levels (r = 0.278, p < 0.05). The severity of ketoacidosis had no relationship with subsequent lifetime HbA1c values and long-term microvascular complications. In logistic regression analysis, the only variables that independently influenced severity of retinopathy were lifetime HbA1c (B = 0.838, p < 0.001), duration of disease (B = 0.208, p < 0.005) and age at diagnosis (B = 0.116, p < 0.05). Conclusions The degree of metabolic derangement at diagnosis is not associated with retinopathy and nephropathy in childhood-onset T1DM. Age at diagnosis seems to be an important variable to be considered when evaluating the long-term effects of residual beta-cell function.

Background: Glucose derangement has been reported to increase oxidative stress, one of the most important factors underlying the progression of hepatic fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). To date, careful evaluation of the glucose profile in pediatric NAFLD has not been performed. Methods: A total of 30 severely obese children (15 males; mean age 12.87 ± 2.19 years) with biopsy-proven NAFLD were enrolled in this study from September to December 2013. All patients underwent anthropometric and laboratory evaluation, including the oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM). Results: Our study reveals some differences between OGTT and CGM in detecting NAFLD children with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). OGTT showed 2 (6.67%) patients with IFG and 1 (3.34%) with IGT, while CGM showed 5 (16.67%) patients with IFG and 6 (20%) with IGT. The daily blood glucose profile positively correlated with the baseline blood glucose (r = 0.39, p = 0.04) and the homeostatic model assessment (r = 0.56, p = 0.05). A positive correlation between hyperglycemia and liver fibrosis was found (r = 0.65, p < 0.05). Mean glucose values (F3-F4 group: 163.2 ± 35.92 mg/dl vs. F1 group: 136.58 ± 46.83 mg/dl and F2 group: 154.12 ± 22.51 mg/dl) and the difference between the minimum and maximum blood glucose levels (F3-F4 group: 110.21 ± 25.26 mg/dl vs. F1 group: 91.67 ± 15.97 mg/dl and F2 group: 92 ± 15.48 mg/dl) were significantly (p < 0.05) higher in the F3-F4 group compared to the F1 and F2 groups. Conclusion: Glucose profile derangement as detected by CGM is associated with the severity of hepatic fibrosis in children with NAFLD.

Telemedicine in diabetes includes telemonitoring and transmission of important data (self monitoring of blood glucose data, insulin therapy, pump setting, etc.) from the patient s home to the diabetic unit, with a real-time health feedback. Moreover, an eHealth approach is thought to facilitate diabetes management and to improve compliance to CSII/SAP treatment in adolescents, but to date, limited literature related to this topic is available and long-term studies are still lacking. The main aim of this study was to compare the long-term effect on glycometabolic control of eHealth intervention and traditional care in T1DM SAP-treated adolescents. In our study we demonstrated a favorable impact of monthly teleassistance on treatment compliance. Adolescents receiving frequent feedback provided by the medicalmultidisciplinary team, due to the telemonitoring, resulted more compliant in self-management of diabetes. In particular, the medical team feedback resulted in interventions on behavioral errors and insulin therapy adjustments, leading to an improved glycometabolic control.

Objective The advantages of continuous subcutaneous insulin infusion (CSII) or insulin glargine have been demonstrated both in adult and paediatric diabetic patients; however, as no data comparing these two approaches during childhood are available, we have examined the efficacy of these two intensive approaches. Research Design and Methods We retrospectively evaluated data from 36 diabetic children, who had changed their previous insulin regimen [with isophane insulin (NPH) at bedtime] because of HbA1c levels >8.0%. Twenty patients underwent CSII, while the other 16 (significantly younger for age) started insulin glargine at bedtime. Results At 6 and 12 months, CSII-treated patients showed a significant reduction in HbA1c values from 8.5 ± 1.8 to 7.4 ± 1.1% and to 7.6 ± 1.2%, respectively. The insulin requirement significantly decreased from 0.93 ± 0.2 IU/kg to 0.73 ± 0.2 IU/kg of body weight and to 0.74 ± 0.15 IU/kg of body weight, respectively, while no significant differences were observed for BMI SDS, fructosamine and severe hypoglycaemic events. The patients treated with glargine showed a small decline in HbA1c values from 8.9 ± 1.7 to 8.3 ± 0.9% (not significant) in the first 6 months of treatment and to 8.2 ± 0.9% after 12 months. Conclusion The basal insulin supplementation can be supplied effectively in children with type 1 diabetes by either CSII or insulin glargine. As previously reported for adults, it is confirmed that CSII is the best current intensive approach aimed to the improvement of glycaemic control. Copyright © 2004 John Wiley & Sons, Ltd.

AIMS—To investigate whether diabetic retinopathy (DR), already associated with microvascular alterations, ischaemia, and endothelial dysfunction, was also characterised by abnormal modulation of coagulation pathways. METHODS—Plasma samples, collected from 67 type 1 diabetics comparable for age, duration of disease (DD), and metabolic control (MC), were processed for prothrombin degradation products (F1+2) and factor VII coagulant activity (FVII:c). 50 normal subjects served as a control group. The ETDRS-Airlie House Classification of DR was used. RESULTS—A significant correlation between FVII:c and F1+2 plasma concentrations was observed (p 0.05). CONCLUSIONS—These findings pointed out the presence of a hypercoagulable state associated with endothelial dysfunction in patients with insulin dependent diabetes mellitus (IDDM), demonstrated both by increased FVII:c and F1+2 plasma levels. Moreover, the observation of different DR related degrees of procoagulant activity, despite comparable DD and MC, strengthens the hypothesis of multiple risk factors in the pathogenesis of DR.

High birth weight has been related to an increased risk of type 1 diabetes (T1D), while suboptimal birth weight (both high and low) has been related to obesity, insulin resistance and type 2 diabetes. Insulin resistance, as a consequence of poor metabolic control, has been described in T1D patients. The aims of the study were to analyse the distribution of birth size for gestational age in a large group of T1D patients and to investigate the effect of birth weight on clinical phenotype.Six-hundred two Caucasian T1D patients were evaluated. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birth weight at3rd percentile and97th percentile for gestational age, respectively. Birth weights between the 3rd and 97th percentiles were defined as appropriate for gestational age. The clinical characteristics of small, appropriate for gestational age and large were compared. Multivariable linear regression models were fitted to evaluate the independent effects of birth weight and other covariates (age at T1D onset, gender and T1D duration) on different clinical outcomes (body mass index, HbA(1c), insulin requirement, high-density lipoprotein cholesterol and triglycerides).Thirteen subjects (2.16%) were small (SGA), and 39 (6.48%) were large (LGA). Daily insulin requirement (U/kg/day) was significantly higher in SGA, while body mass index and HbA(1c) were increased in LGA. Multivariable linear regression showed a significant negative effect of birth weight on daily insulin requirement (p 0.001).Suboptimal birth weight (both high and low) in T1D patients seems to be associated with clinical characteristics suggestive of insulin resistance.

Objective To clarify the effects of insulin therapy on ovarian androgen production, hyperandrogenism and polycystic ovary syndrome (PCOS) in adolescents and young women with type 1 diabetes (T1D). Design Case-control study. Setting Children's research hospital. Patient(s) Fifty-four consecutive T1D subjects (age, 15–25 years), without residual endogenous insulin secretion, treated by intensive insulin therapy (multiple injection therapy [MI] or continuous SC insulin infusion [CSII]); and one-hundred fifty age-matched healthy women. Intervention(s) Analysis of the prevalence and risk factors of ovarian hyperandrogenism and PCOS in T1D adolescents and young women. Main Outcome Measure(s) Biometric, glycemic, and metabolic parameters. Evaluation of androgen levels and ovary ultrasound during the early follicular phase of the menstrual cycle. Result(s) Androgen levels were significantly higher in T1D subjects than in the control group (T, 68.8 ± 23.4 vs. 46.1 ± 20.8 ng/dL). Four subjects (7.4%) were affected by PCOS according to the Rotterdam criteria. No correlation was evident between HbA1c% and androgen levels. No significant differences were evident between subjects on MI or CSII therapy. Multivariable linear regression analysis showed a direct and independent effect of age and body mass index on T levels. T levels were also negatively affected by birth weight. Conclusion(s) Androgen levels are significantly increased in T1D adolescents and young women treated by intensive insulin therapy. The presence and severity of ovarian hyperandrogenism seem to be primarily related to common risk factors such as age, low birth weight, overweight, and obesity.

The aim of our study was to identify factors that are related to a more aggressive beta-cell destruction in children at presentation of type 1 diabetes mellitus (T1D). We analyzed age, HbAlc, pH, bicarbonate, IAA, IA2, GADA, C peptide of 290 consecutive patients with T1D at onset. Seventy-three (25.2%) were younger than 4 years; 217 (74.8%) were aged 4-18 years. Younger patients had lower C peptide, pH and bicarbonate than older ones. Age at T1D onset was negatively related to IAA titers (r: -0.3404, p < 0.001), positively related to IA2 titers (r: 0.1249, p: 0.03) and to C peptide (r: 0.42, p: < 0.001). Multivariable linear regression showed that C peptide was negatively related to HbA1c and positively related to age, pH at admission and IAA titers. T1D in very young children is characterized by a more extensive beta-cell destruction, and younger age at onset is related to a more severe decompensation.

Summary A strong association between type 1 insulin-dependent diabetes mellitus (IDDM1) and coeliac disease (CD) is well documented, but it is known that prevalence values are underestimated. Serum anti-endomysial antibodies (EMA), considered diagnostic for CD because of their high sensitivity and specificity, belong to the IgA class, but the existence of EMA of IgG1 isotype in the presence or absence of IgA deficiency was reported. In order to re-evaluate the occurrence of CD in IDDM1 patients we performed a screening in IDDM1 patients using EMA of both isotypes. Ninety-four adults affected by IDDM1 (unaffected by CD before enrolling) were enrolled and 83 blood donors as controls. All subjects were on a gluten-containing diet. Histology and biopsy culture were performed. EMA IgA and IgG1 in sera and culture supernatants were detected. Serum EMA were positive in 13 of 94 IDDM1 patients (13·8%). Six of 13 presented IgA-EMA, seven of 13 presented IgG1-EMA. No EMA were found in the control population. Total intestinal atrophy was found in all six patients with serum IgA-EMA and in five of seven with serum IgG1-EMA. Diagnosis of CD was confirmed by histology and organ culture in all 13 patients with serum EMA. The prevalence of CD in the patients affected by IDDM1 was 6·4% for IgA-EMA-positive and 7·4% for IgG1-EMA-positive patients. We confirmed the prevalence of CD in the IDDM1 population obtained with IgA-EMA screening only (6·4%). This prevalence value increases dramatically to 13·8% when IgG1-EMA are also used in the screening. We conclude that IgG1-EMA should also be sought whenever an IDDM1 patient undergoes screening for CD.