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Context Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective This work aimed to identify patients’ characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. Methods A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Results Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. Conclusion CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime.

Lockdown due to COVID-19 pandemic has forced a decrease in physical activity (PA), an increase in sedentary behavior (SB) and a possibly worsening of fat accumulation in already obese subjects. The aim of this study was to investigate how social restriction may have contributed to weight changes in adolescents with obesity. Secondary aim was to evaluate possible parameters influencing weight changes.Parameters of 51 obese adolescents were compared between two visits: within 2 months before 8 March, start of lockdown, and within 40 days after the end of it.Mean weight gain during lockdown was 2.8 ± 3.7 kg (p 0.001). Weight increase was higher in males than in females (3.8 ± 3.4 kg vs 1.2 ± 3.7 kg, p = 0.02). The hours dedicated to SB increased (+2.9 ± 2.8 h/day; p 0.001) while the hours of PA decreased (-1.0 ± 1.6 h/week; p 0.001). Males spent more hours in SB than females (+3.8 ± 2.7 h/day vs +1.5 ± 2.5 h/day; p = 0.003). There were minor changes in diet during lockdown. The most significant variables influencing both delta BMI and waist/height ratio increase were hours devoted to SB during lockdown and differences in mild and moderate PA before and after lockdown.Obese adolescents showed a worsening of obesity during lockdown, with males mainly affected, mainly due to a reduced mild PA and increased hours spent in SB.

Purpose: To investigate the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the somatropin biosimilar Omnitrope®. Methods: PATRO Children is an ongoing, multicenter, observational, post-marketing surveillance study. Children who received Omnitrope® for any indication were included. Adverse events (AEs) were evaluated in all study participants. Auxological data, including height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), were used to assess effectiveness. In this snapshot analysis, data from the Italian subpopulation up to August 2017 were reported. Results: A total of 291 patients (mean age 10.0 years, 56.0% male) were enrolled at 19 sites in Italy. The mean duration of Omnitrope® treatment was 33.1 ± 21.7 months. There were 48 AEs with a suspected relationship to the study drug (as reported by the investigator) that occurred in 35 (12.0%) patients, most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal range, abdominal pain, pain in extremity and acute gastroenteritis. There were no confirmed cases of type 1 or type 2 diabetes; however, two patients (0.7%) had impaired glucose tolerance that was considered Omnitrope® related. The mean HSDS increased from − 2.41 ± 0.73 at baseline (n = 238) to − 0.91 ± 0.68 at 6.5 years (n = 10). The mean HVSDS increased from − 1.77 ± 1.38 at baseline (n = 136) to 0.96 ± 1.13 at 6.5 years (n = 10). Conclusions: In this sub-analysis of PATRO Children, Omnitrope® appeared to have acceptable safety and effectiveness in the treatment of in Italian children, which was consistent with the earlier findings from controlled clinical trials.

Type 1 diabetes (T1D) and obesity are strongly associated with cardiovascular (CV) risk and can start in the paediatric age. The CV risk profile of two groups of adolescents was compared through the evaluation of sAGE, IMT and known variables associated with CV risk. The first group was affected by T1D with duration of disease of at least 5 years or 3 years since puberty onset, and the second by severe obesity for more than 3 years. A total of 116 patients were prospectively enrolled in the study (71 T1D, 33 males and 38 females; 45 obese, 18 males and 27 females), and their sAGE, IMT, waist/height ratio, LDL cholesterol, triglycerides/cholesterol HDL ratio, BMI, HbA1c and blood pressure were measured. An IMT value > 0.7 mm, cut-off value to define CV risk, was present in 28% of the obese patients and in no T1D patients. Age-adjusted sAGE and HbA1c levels were higher T1D patients, whereas a higher percentage of pathological values was present in most of the remaining studied variables. In T1D patients, there was a higher percentage of females with waist/height ratio > 0.5, LDL cholesterol > 100 mg/dL, triglycerides/HDL cholesterol ratio > 2 and BMI > 99° centile and a higher percentage of males with HbA1c > 7%. On the contrary, in obese patients there were no differences between males and females. Multiple analysis is identified BMI SDS as the only variable with a significant influence on IMT in both groups. Furthermore, it showed that HbA1c and gender affected sAGE in T1D patients, whereas only age and gender in the obese patients. Our study demonstrates that our adolescents with severe obesity carry a much higher CV risk than adolescents with T1D unless in bad metabolic control. Apart from lower sAGE levels, most of the variables considered to define CV risk were higher in the obese group than in the T1D group. Gender seems to have a significant impact on sAGE levels but not on IMT.

Xarxes reguladores de gens; Marcadors predictius Redes reguladoras de genes; Marcadores predictivos Gene regulatory networks; Predictive markers Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855. This work was supported by Merck KGaA, Darmstadt, Germany.

Objective Recently, we observed some cases of Precocious Puberty (PP) with a partial central activation of hypothalamic-pituitary-gonadal (HPG) axis that tended to normalized in 6–12 months. To evaluate the frequency of this form within the spectrum of forms of PP, we retrospectively assessed the clinical, hormonal and ultrasound characteristics of patients attending to our Center for signs of PP, between 2007 and 2017. To hypothesize some causes of this “pubertal poussée” a questionnaire about environmental data was provided to patients. Methods 96 girls were recruited for the study and divided into three Groups. Group 1: 56 subjects with Central PP (CPP) requiring treatment with GnRH analogue; Group 2: 22 subjects with transient activation of pubertal axis, that tended to normalize, “Transient CPP”(T-CPP); Group 3: 18 subjects with Isolated Thelarche (IT). Results Mean age at diagnosis was 6.8 ± 1.0 years in Group 1, 5.9 ± 1.3 years in Group 2 and 5.6 ± 1.5 years in Group 3. A significant increase of diagnosis of T-CPP was observed over the study period. Significantly higher use of some homeopathic medicines and potential exposure to pesticides was reported in Group 2 vs Group 1. Conclusions To our knowledge, we first reported a form defined as T-CPP, characterized by partial activation in the HPG axis normalizing over time. An increased use of homeopathic medicines and exposure to environmental pollutants in these patients was evidenced.

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

Aims: To evaluate the relationships between HbA1c and Continuous Glucose Monitoring (CGM) metrics in children/adolescents with Type 1 Diabetes (T1D). Methods: HbA1c and real-life CGM data of the 12 weeks preceding its measurement were retrospectively collected from 654 children/adolescents with T1D. The relationships between HbA1c and CGM metrics were assessed by Spearman correlation coefficient. Participants were categorized into groups based on HbA1c and CGM metrics values. ANOVA was run across HbA1c and CGM metrics groups in the entire study population and in subjects stratified by CGM type, insulin therapy, age and puberty. Results: HbA1c was positively correlated with mean glucose, SD, %TAR > 180 mg/dL, %TAR > 250 mg/dL, HBGI and negatively with %TIR, %TBR and %time < 54 mg/dL. HbA1c-based groups were significantly associated with these metrics, but for each group their value widely ranged with a substantial overlap between them. HbA1c and HbA1c-based groups were not associated with %CV and LBGI, as well as %CV and LBGI-based groups had not significantly different HbA1c. Comparable results were found analysing subjects according to age, type of CGM, insulin therapy and puberty. Conclusions: The relationships between HbA1c and CGM metrics described in this cohort of paediatric subjects with T1D support the importance of the evaluation of these metrics, in particular %CV and LBGI, independently of HbA1c value.

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: No studies have assessed if 2-week of continuous glucose monitoring (CGM) data provide good estimation of long-term glycemic control and glucose variability (GV) in pediatric patients with type 1 diabetes (T1D) as in adults. Methods: Six hundred fifty-four T1D pediatric patients were enrolled and 12-weeks of CGM data, before HbA1c measurement, were collected. Metrics of glycemic control and GV in incremental sampling periods were calculated. The agreement between metrics calculated in the sampling periods and the full 12-week period was assessed with correlation analysis (R2), median relative absolute difference (RAD) or absolute difference in the entire study populations and subjects stratified by age, pubertal status, insulin therapy (MDI,CSII), type of CGM (intermittently scanned [isCGM], real-time [rtCGM]), and HbA1c level. Results: Correlations with metrics of the full 12-week period improved by extending the sampling periods. R2 values close to 0.90 using 4-week period were significantly higher than 2-week period, particularly for coefficient of variation, mean glucose SD, percentage of time below the range

Aims to assess the prevalence of cardiovascular risk factors (CVRFs) and to identify the variables associated with CVRFs in a cohort of children and adolescents with Type 1 Diabetes. Methods 2,021 subjects, 2-18 year-old, were recruited in 17 Italian Pediatric Diabetes Centers. Anthropometric, blood pressure, biochemical (HbA1c, lipid profile, ACR), insulin therapy, physical activity level, smoking and family socio-economic status data were collected. CVRFs prevalence and their distribution were analyzed according to age and binary logistic regression was performed with positivity for at least one major CVRF (BMI-SDS>+2SD, blood pressure>90th percentile, LDL cholesterol>100 mg/dl) as dependent variable and age, duration of illness, gender, HbA1c and physical activity, as independent variables. Results The prevalence of CVFRs not at the recommended target was respectively: 32.5% one CVRF, 6.7% two CVRFs and 0.6% three CVRFs, with no significant differences across the 3 age groups (2-10, 10-15, 15-18 years). In the total sample, HbA1c and inadequate physical activity were associated with a higher probability of having at least one major CVRF. This probability was associated with physical activity in the 2-10-year-old group, with physical activity and HbA1c in the 10-15-year-old group and with HbA1c only in subjects older than 15 years. Conclusions More than 30% of subjects had at least a major CVRF. Early detection of CVRFs may be useful to enforce the therapeutic intervention in this subgroup, in order to reduce the risk to develop cardiovascular complications. This article is protected by copyright. All rights reserved.

Diabetes mellitus is a chronic disease affecting millions of people worldwide. Type 2 diabetes is the most frequent form, involving more than 10% of the population over the age of 50 in some developed countries and it is mainly associated with sedentary habits and obesity. Type 1 diabetes (T1D) represents 5–10% of the cases of diabetes and affected individuals need insulin therapy right from diagnosis. Type 1 diabetes most commonly affects children and young people as it is diagnosed before the age of 18 in over 50% of cases, thus exposing the subjects to hyperglycemia for several decades. Chronic hyperglycemia, whatever the cause is, inevitably leads to the typical diabetes complications affecting both the microvascular circulation mainly of the retina, the kidneys and peripheral nervous system, and the big vessels, therefore accelerating atherosclerotic processes. Myocardial infarction is the first cause of death in patients suffering from any types of diabetes.

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Aim To assess the association between alcohol consumption and/or cigarette smoking with other unhealthy behaviors and clinical cardiovascular risk factors in youth with type 1 diabetes. Methods Two hundred and twenty-eight youth with type 1 diabetes (age 13–19 years) were consecutively enrolled in three Regional Pediatric Diabetes Centers in Italy. Demographic, anthropometric, lifestyle (adherence to the Mediterranean diet pattern and sports participation) and laboratory parameters were compared among youth reporting isolated or combined alcohol consumption and/or cigarette smoking. Results Ten percent of the youth reported alcohol consumption, 10% cigarette smoking and 6% both alcohol and cigarette use; 74% did not report alcohol or cigarette use. Compared to non-drinker non-smoker youth, smokers showed significantly higher percentages of each of the behavioral and clinical cardiovascular risk factors. Drinkers showed a significantly higher proportion of abdominal adiposity, dyslipidemia and poor adherence to the Mediterranean diet. Alcohol consumption was independently associated with both dyslipidemia and high glycosylated hemoglobin. Conclusions Our findings emphasize the need to increase the awareness of youth with T1D about the negative impact of alcohol drinking on cardiovascular risk, since the effects of alcohol might be underestimated with respect to the well-known detrimental effects of smoking. Clustering of unhealthy lifestyle should be discouraged in type 1 diabetes youth in order to promote cardiovascular protection.

IntroductionThe COVID-19 pandemic forced the Italian government to issue extremely restrictive measures on daily activities since 11 March 2020 (‘lockdown’), which may have influenced the metabolic control of type 1 diabetes mellitus (T1D). The aims of the study were to investigate continuous glucose monitoring (CGM) metrics in children and adults with T1D during lockdown and to identify their potentially related factors.Research design and methodsWe enrolled 130 consecutive patients with T1D (30 children (≤12 years), 24 teenagers (13–17 years), and 76 adults (≥18 years)) using either Dexcom or FreeStyle LibreCGM>70% during the study period, without hybrid closed-loop insulin pump. CGM metrics during the 20 days before and the 20 days after lockdown were calculated. By telephonic contact, we performed validated physical activity and perceived stress questionnaires.ResultsIn children, significantly lower glucose SD (SDglu) (p=0.029) and time below range (TBR)ConclusionIn patients with T1D during lockdown, CGM metrics mostly improved in children and adults, whereas it was unchanged in teenagers. In adults, age, physical activity, and perceived stress may be relevant contributing factors.

Background/Objective: Insulin degludec (IDeg) is an ultra-long-acting analog with less daily variability compared to other basal insulins. In this retrospective study we examined 1-year efficacy and safety of IDeg in youth with type 1 diabetes (T1D).Subjects/Methods: Thirty-seven patients [11.7 ± 4.22 years; T1D duration 4.97 ± 3.63 years; once-daily glargine (IGlar) by at least 1 year] were switched to once-daily IDeg because of glycosylated hemoglobin (HbA1c) >7.5% and/or reported physical pain at IGlar injection. Changes in HbA1c, 30-day mean fasting plasma glucose (mean FPG), daily insulin dose, and severe hypoglycemia rates were collected at basal insulin switch (T0), 3-months (T1), 6-months (T2), and 12-months (T3) after IDeg was started.Results: In patients with HbA1c >7.5% at T0 we found a decrease in HbA1c values (%) from 8.46 ± 0.53 to 7.89 ± 0.72 at T1 (p = 0.008) and 7.97 ± 0.89 at T2 (p = 0.035). At T3, 38.9% of patients had HbA1c ≤ 7.5%. Mean FPG levels significantly decreased at T2 (p = 0.043). In the overall study population, we documented an increase in IDeg dose (+12.5% at T3; p < 0.001) and a decrease in mealtime insulin dose (−11.6% at T3; p = 0.001) after switch. HbA1c levels were unchanged. No episode of severe hypoglycemia was reported.Conclusions: Our data in children and adolescents with T1D suggest that IDeg dose should be increased by 12% and mealtime insulin doses should be lowered by 11% for patients who previously received IGlar. IDeg might be considered useful and well tolerated and it seems to improve the glycemic control compared to IGlar, mainly in patients with poor glycemic control.

WS diagnosis is often delayed since misdiagnosed as autoimmune diabetes. The rarity of the condition and the absence of other diseases at diabetes diagnosis might make extremely challenging the recognition of WS. However the novel compound heterozygosity for the here reported mutations, seems to confer a mild phenotype among the spectrum of WS manifestations.

Aims Management of type 1 diabetes mellitus (T1DM) influences several aspects of life, such as adherence to healthy lifestyle habits and health-related quality of life (HRQoL). Our aim was to evaluate the association between unhealthy lifestyle habits and HRQoL in adolescents and young adults with T1DM. Methods Two hundred and forty-two Caucasian patients (13–19 years) consecutively enrolled over a 12-month period in three Regional Pediatric Diabetes Centers in Italy. Demographics, clinical, and laboratory parameters, adherence to lifestyle habits (Mediterranean Diet assessed by KIDMED, Physical Activity levels and sedentary behavior by questionnaire) considered either separately or in cluster, and HRQoL by Pediatric Quality of Life Inventory Diabetes Module (PedsQL 3.0 DM) were collected. Metabolic control was determined by HbA1cmean of previous year. Results Only 15 (6.2%) patients fulfilled the cluster of three healthy lifestyle habits without gender differences (p = 0.353); 62 (25.6%) had 1 unhealthy lifestyle habit, and 165 (68.2%) had ≥2. Adolescents meeting physical activity recommendations had better PedsQL scores than those who did not meet. PedsQL total score and specific sub-scales decreased in patients with unhealthy lifestyle habits. High PedsQL was significantly associated with being male, living in South Italy, having lower HbA1c mean levels, and reporting lower adherence to unhealthy lifestyle habits. Conclusions The clustering of unhealthy lifestyle habits is associated with reduced HRQoL in adolescents and young adults with T1DM. Promoting multiple behavior changes may be a useful approach to improve the health status and the HRQoL in youths with T1DM.

BACKGROUND: Transition from pediatric to adult care is a critical process in the life of patients with diabetes. AIM: Primary aim of the study was to compare the metabolic control between pediatric care and adult care at least 5 years in a group of patients with type 1 diabetes mellitus (T1DM). Secondary aim was to evaluate the presence of complications, associated diseases and psychological-psychiatric disorders. SUBJECTS AND METHODS: We obtained data from 73 % (69/94) patients (current mean age 34 years) transferred to local adult centers between 1985 and 2005 at a mean age of 23.8 years. Data were collected for HbA1c, diabetic complications and associated diseases. RESULTS: Mean HbA1c did not change during the pediatric, transition and adult period [8.4 ± 1.8 % (68 ± 18 mmol/mol), 8.3 ± 1.4 % (67 ± 15 mmol/mol) and 8.4 ± 1.3 % (68 ± 14 mmol/mol), respectively]. 13 patients dropped out, after 2-12 years since transition, and their HbA1c mean value at transition was 10.4 %. After a mean of 25.9 years of disease, 35/69 patients (50.7 %) showed retinopathy, and 12/69 patients (17.3 %) nephropathy. Thyroid diseases were the most frequent associated diseases (18.3 %), followed by depression (11.2 %) and benign neoplasms (9.8 %). Drug or alcohol addictions were present in four cases (5.6 %). CONCLUSIONS: After a mean follow-up of 8 years metabolic control after transition did not change significantly in patients constantly attending to adult care centre. Patients with diabetes onset between 20 and 40 years ago were free from complications in 50 % of cases when considering retinopathy and in more than 80 % considering nephropathy. Thyroid problems were the most common associated diseases. Poor metabolic control at transition is associated with higher risk of drop-out and psychosocial morbidity. Background: Transition from pediatric to adult care is a critical process in the life of patients with diabetes. Aim: Primary aim of the study was to compare the metabolic control between pediatric care and adult care at least 5 years in a group of patients with type 1 diabetes mellitus (T1DM). Secondary aim was to evaluate the presence of complications, associated diseases and psychological-psychiatric disorders. Subjects and methods: We obtained data from 73 % (69/94) patients (current mean age 34 years) transferred to local adult centers between 1985 and 2005 at a mean age of 23.8 years. Data were collected for HbA1c, diabetic complications and associated diseases. Results: Mean HbA1c did not change during the pediatric, transition and adult period [8.4 ± 1.8 % (68 ± 18 mmol/mol), 8.3 ± 1.4 % (67 ± 15 mmol/mol) and 8.4 ± 1.3 % (68 ± 14 mmol/mol), respectively]. 13 patients dropped out, after 2-12 years since transition, and their HbA1c mean value at transition was 10.4 %. After a mean of 25.9 years of disease, 35/69 patients (50.7 %) showed retinopathy, and 12/69 patients (17.3 %) nephropathy. Thyroid diseases were the most frequent associated diseases (18.3 %), followed by depression (11.2 %) and benign neoplasms (9.8 %). Drug or alcohol addictions were present in four cases (5.6 %). Conclusions: After a mean follow-up of 8 years metabolic control after transition did not change significantly in patients constantly attending to adult care centre. Patients with diabetes onset between 20 and 40 years ago were free from complications in 50 % of cases when considering retinopathy and in more than 80 % considering nephropathy. Thyroid problems were the most common associated diseases. Poor metabolic control at transition is associated with higher risk of drop-out and psychosocial morbidity. © 2014 Italian Society of Endocrinology (SIE).

Type 1 insulin-dependent diabetes mellitus (IDDM 1) is a chronic disease with a sudden onset often during childhood and adolescence. The onset of diabetes implies a radical change in personal and family habits. The right insulin therapy accompanied by a correct diet and physical activity is required in order to reduce hypoglycaemic and hyperglycaemic episodes, and the outcome of long-term diabetic complications is first and foremost a medical problem. It is well known, however, that despite many medical and technical developments, metabolic control in children and adolescents with IDDM 1 has not improved as much as it had been expected. It is only in recent years that clinicians have focused on other factors that may be involved in the process of treating diabetes. The sudden onset of this chronic illness often has the features of a traumatic emotional experience that exceeds the subject's resilience and capacity to deal with it and elaborate it in psychic terms. This paper explores some of the anxieties ...

Background PATRO Children is an ongoing observational, longitudinal, non-interventional, global post-marketing surveillance study, which is investigating the long-term safety and effectiveness of Omnitrope®, a somatropin biosimilar to Genotropin®, in children with growth disturbances. The primary endpoint of PATRO Children is long-term safety and the secondary endpoint is effectiveness, which is assessed by analysing auxological data such as height (HSDS) and height velocity (HVSDS) standard deviation scores. Here, we report the data from the Italian interim analysis of PATRO Children data up to August 2015. Methods PATRO Children is enrolling children who are diagnosed with conditions of short stature requiring GH treatment and are receiving Omnitrope®. Adverse events (AEs) are assessed in all Omnitrope®-treated patients. Height is evaluated yearly to near-adult (final) height, and is herein reported as HSDS; height velocity is also assessed and reported as a standard deviation score (HVSDS). Results Up to August 2015, a total of 186 patients (mean age 10.2 years, 57.5 % males) were enrolled :156 [84 %] had growth hormone deficiency, 12 [6.5 %] were born small for gestational age, seven [3.8 %] had Prader-Willi syndrome, one [0.5 %] had Turner syndrome and one [0.5 %] had chronic renal insufficiency; seven [3.8 %] patients had other indication profiles. The mean treatment duration with Omnitrope® was 28.1 ± 19.1 months. AEs were reported in 35.6 % of patients and included headache, pyrexia, arthralgia, abdominal pain, leg and/or arm pain and increased blood creatine phosphokinase. Two serious AEs in two patients were thought to be drug-related; one patient experienced a minimal increase in a known residual craniopharyngioma, and another a gait disturbance with worsening of walking difficulties. Similar to investigational studies, Omnitrope® treatment was associated with improvements in both HSDS and HVSDS. Conclusions Omnitrope® appears to be well tolerated and effective for the treatment of a wide range of paediatric indications, which is consistent with the outcomes from controlled clinical trials. These results need to be interpreted with caution until the data from the global PATRO Children study are available.

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.

ObjectiveThe diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents.DesignRetrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests.MethodsSeventy four patients with organic GHD (GH peak 10μg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS.ResultsThe optimal GH cut-off for arginine resulted 6.5μg/L, 5.1μg/L for ITT and 6.8μg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC=0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity.ConclusionsThe results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

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.

The association between low HDL cholesterol (HDL-C) concentrations and increased cardiovascular risk is well established. Low HDL-C levels were found in subjects with type 1 diabetes (T1D) who presented complications (1) and in untreated subjects with celiac disease (CD). The association between TID and CD might therefore enhance this lipid abnormality and accelerate the atherosclerotic process. We collected data from 13 centers belonging to the Italian Society of Pediatric Endocrinology and Diabetology (ISPED) of a large number of children with both T1D and concurrent biopsy-proven CD, at the exact time point a gluten-free diet (GFD) was initiated and after 1 year of a GFD, verified by means of CD-related antibodies. A total of 201 children with T1D diagnosed at age of 5.8 ± 3.8 years and CD diagnosed at age of 7.5 ± 4.5 years were enrolled. …

OBJECTIVE To evaluate the frequency of normalization, the persistence of remission, and the impact on normalization of glycemic control and lipid profile, we analyzed data from a retrospective observational cohort study of type 1 diabetic children and adolescents with abnormal urinary albumin excretion (UAE). RESEARCH DESIGN AND METHODS All diabetic children and adolescents (n = 41) who had persistent abnormal UAE in the period of 1984 to 2008 and followed up until 2009 (follow-up duration = 13.1 ± 6.2 years) were included in the study. Nine patients progressed to macroalbuminuria; 24 patients were administered ACE inhibitor treatment. RESULTS The cumulative prevalence of abnormal UAE was 9%. During follow-up, 14 of 17 untreated and 19 of 24 treated patients reverted to normoalbuminuria. In the remission group compared with the nonremission group, A1C levels during follow-up decreased (7.5 ± 1.0 vs. 9.4 ± 1.2%, P < 0.0001) and serum HDL cholesterol increased (52.7 ± 11.3 vs. 42.7 ± 8.6 mg/dL, P < 0.05). The micro-macroalbuminuric patients had lower HDL cholesterol (51.0 ± 11.4 vs. 62.4 ± 13.6 mg/dL, P < 0.0001) than 134 normoalbuminuric diabetic patients. CONCLUSIONS Microalbuminuria and macroalbuminuria were not permanent in most of our diabetic children and adolescents. If abnormal UAE values are high and persist for >1 year, only long-lasting treatment with ACE inhibitors seems able to induce persistent remission, especially when associated with good metabolic control and high HDL cholesterol levels.

Nardi L, Zucchini S, D’Alberton F, Salardi S, Maltoni G, Bisacchi N,Elleri D, Cicognani A. Quality of life, psychological adjustment andmetabolic control in youths with type 1 diabetes: a study with self- andparent-report questionnaires.Pediatric Diabetes 2008: 9: 496–503.Objective: To evaluate self and parent reports on quality of life (QoL)and psychological adjustment of youths with type 1 diabetes, incomparison to a general paediatric population, and identify relationshipsbetween disease duration, metabolic control and psychologicalparameters.Research design and methods: Participants included 70 youths with type1 diabetes and their parents. They were compared with 70 non-diabeticsubjects. Data were analyzed in the whole group and in subgroups aged6–10, 11–13 and 14–18 yr. All cases performed pediatric QoL, ChildBehaviour Checklist, filled in by parents, and Youth Self-Report, filled inby youths. Data were compared with haemoglobin A1c (HbA1c) valuesand disease duration.Results: Self-reports showed a psychological adjustment of youths withtype 1 diabetes similar to that of controls. Parent reports showed thatparents of children with type 1 diabetes were more worried than those ofcontrols (p , 0.01). Adolescents showed a worse QoL and more frequentpsychological disturbances. In this group, for youth and parent reports,HbA1c levels correlated positively with psychological problems(p , 0.05) and negatively with QoL (p , 0.05). Only for parent reports,in the whole group and in subgroups aged 6–10 and 11–13 yr, diseaseduration correlated positively with psychological adjustment (p , 0.05).Conclusions: Before adolescence, youths with type 1 diabetes showedonly slight problems in psychological adjustment and QoL, with anassociation with disease duration reported by parents. In adolescence,both youths and their parents reported more emotional and behaviouralproblems, independent of disease duration. Better metabolic control andpsychological well-being seemed directly related.

By retrospectively collecting data from nine Italian centres of pediatric endocrinology, we assessed the different management and final outcome of children with short stature and idiopathic delayed puberty. Data were obtained in 77 patients (54 males, 23 females) diagnosed and followed-up in the various centres during the last 15 years. Inclusion criteria were short stature at initial observation and idiopathic delayed puberty diagnosed during follow-up. At first observation, age was 13.8 +/- 1.0 years and height standard deviation score (SDS) was -2.6 +/- 0.6 in males. In females age was 13.1 +/- 0.9 years and height SDS -2.6 +/- 0.4. Local diagnostic and therapeutic protocols included testing for growth-hormone deficiency (six centres) and treatment in case of deficiency or, in the remaining centres, testosterone or no treatment in males, and no treatment in females. At diagnosis, both in males and in females, the auxological features (height SDS, target height SDS and bone age delay) were similar in the patients treated with growth hormone, testosterone or not treated. Overall 32 patients received growth hormone (25 males, 7 females), 33 no treatment (17 males, 16 females) and 12 testosterone. There was no difference in the adult height of males and females in the different treatment groups. In males there were no differences between adult and target height SDSs (growth hormone-treated 0.31 +/- 0.79, untreated 0.10 +/- 0.82, testosterone-treated 0.05 +/- 0.95), between adult and initial height SDSs (growth hormone-treated 1.70 +/- 0.93, untreated 1.55 +/- 0.92, testosterone-treated 1.53 +/- 1.43) and percentage of subjects with adult height above target height. In females, there were no differences between adult and target height SDSs (growth hormone-treated -0.49 +/- 1.13; untreated 0.10 +/- 0.97) and between adult and initial height SDSs (growth hormone-treated 1.76 +/- 0.92; untreated 1.77 +/- 0.98), whereas a significantly higher percentage of patients remained below target height in the growth hormone-treated group (6/7, 85.7% vs 5/11, 31.3%) (P = 0.02). In conclusion, the diagnostic and therapeutic management of the patients with short stature and delayed puberty is different among Italian pediatric endocrinologists. Our data do not support the usefulness of growth-hormone therapy in improving adult height in subjects with short stature and delayed puberty, particularly in the female sex.

We evaluated growth hormone (GH) secretion in 81 patients with Turner's syndrome (TS) (mean age 10.7+/-3.6 y) with respect to karyotype, auxological characteristics and growth response to GH treatment (1 IU/kg/wk). None of the patients had spontaneous puberty or had started replacement therapy with estrogens. Thirty-nine patients (48%) had monosomia 45X, 29 (36%) structural abnormalities of the X chromosome and 13 (16%) X mosaicism. Before the start of GH therapy, each patient underwent an evaluation of mean nocturnal GH concentration (MGHC) and 75 patients also underwent 2 pharmacological tests. MGHC of the TS patients did not differ from that of 29 prepubertal GH-deficient girls (GH peaks8 microg/l after pharmacological tests) and both groups were lower (p0.0001 and p0.0005, respectively) than MGHCs of 27 short normal girls (GH peak8 microg/l). MGHC of the patients with TS was negatively correlated (p0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE20% was significantly higher (p0.02) than that of the TS patients with BWE20%, but again did not differ from that of the GH-deficient patients and was lower (p0.001) than that of the short normal girls. MGHC did not significantly differ between the 3 groups subdivided according to karyotype. Forty-four percent of the TS patients showed GH responses to pharmacological tests8 microg/l. Height velocity SDS at first and second year of therapy was not influenced by MGHC levels, chronological or bone age, target height or BWE. In conclusion, spontaneous secretion in our patients with TS was lower than that of the short normal prepubertal girls and did not differ from that of GH-deficient subjects, even if we excluded overweight patients. The level of GH secretion was unable to predict GH response to treatment.

We read with interest the data reported by Castellaneta et al. (1) about the spontaneous normalization of autoantibody markers for celiac disease (CD) in a wide population of children and adolescents with type 1 diabetes mellitus (T1DM). The authors hypothesized that this phenomenon could be related to a state of temporary positivity of celiac serology in children with T1DM. They concluded that a gluten-free diet should be delayed in the absence of clinical signs of CD and that these subjects should be carefully followed up with serological and histological tests for a confirmation of the diagnosis. …

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: Type 1 diabetes (T1DM) is an autoimmune disease often associated with thyroid abnormalities. PURPOSE: We investigated the correlation between thyroid function and metabolic derangement at onset and the influence of autoimmunity on thyroid function at onset and subsequently. METHODS: We evaluated 152 patients diagnosed with T1DM between 2000 and 2012 at onset and during a mean follow-up of 5.45 ± 2.8 years. Thyroid function at onset was correlated with metabolic derangement (degree of acidosis, metabolic control and adrenal function) and compared with that of 78 healthy children. Follow-up consisted of regular evaluation of thyroid function and autoimmunity. RESULTS: Thyroid hormonal pattern was not influenced at onset by thyroid autoimmunity, but only by metabolic derangement: pH and base excess in fact were significantly lower in patients with impaired thyroid function (p < 0.0001). Patients presenting normal thyroid function at onset showed a reduced conversion from FT4 to FT3 compared to nondiabetic children (FT3/FT4 0.3 ± 0.4 in the control group, 0.24 ± 0.4 in diabetic patients, p < 0.0001). Multiple regression analysis showed the highest correlation (negative) between FT3 levels at onset and base excess (p < 0.005). Thyroid abnormalities related to metabolic derangement disappeared during follow-up. Patients with thyroid antibodies at T1DM onset were at higher risk to require levothyroxine treatment during follow-up (p < 0.05). CONCLUSIONS: Thyroid function at T1DM onset is mainly influenced by metabolic derangement, irrespective of thyroid autoimmunity. Antithyroid antibodies evaluation at T1DM onset may be helpful to define which patients are at higher risk of developing hypothyroidism.

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.

BACKGROUND: Sensor-augmented continuous subcutaneous insulin infusion (CSII) therapy is superior to CSII therapy alone, but little is known on the effectiveness of sensor-augmented multiple daily injections (MDI) therapy. METHODS: We compared during everyday life mean glucose control and several variability indexes recorded for 3 days by a real-time glucose sensor (Medtronic, Northridge, CA) in two groups of children treated with either CSII or MDI. Fifty-five consecutive subjects were examined: 17 receiving CSII and 38 receiving MDI basal-bolus therapy (age range, 7-22 years). All subjects wore the sensor for 4 days, and 3 days were used for statistical analysis. Mean glucose and SD, coefficient of variation (CV), mean amplitude of glucose excursion (MAGE), mean of daily differences (MODD), continuous overall net glycemic action (CONGA) at 2 and 4 h, blood glucose (BG) rate, area under the curve (AUC) above 180 mg/dL and below 70 mg/dL, Low BG Index (LBGI), and High BG Index (HBGI) were calculated. RESULTS: Patients receiving CSII administered more daily boluses than patients receiving MDI (5.2±1.5 vs. 3.2±0.3, respectively; P=0.001). Mean glucose was lower in the CSII group. AUC above 180 mg/dL and HBGI were higher in the MDI group. CV, CONGA at 2 h, CONGA at 2 h during the day, and HBGI were worse in the MDI group, whereas MODD, LBGI, BG rate, and MAGE were similar. A positive correlation (r=0.95; P

Aim: The purpose of the present study was to compare relationships between the clinical presentation of type 1 diabetes in children and residual β-cell secretion and long-term metabolic control. Methods: This retrospective study was conducted in 66 diabetic children with age at diagnosis ranging from 0.7 to 14.8 yr. The patients showed contrasting characteristics at diagnosis: either diabetic ketoacidosis (DKA) (group 1, n = 29) or absence of metabolic derangement (group 2, n = 37) associated with marked (group 2A, n = 12) or mild hyperglycemia (group 2B, n = 25). A regular follow-up was available for at least 10 yr (10–32 yr) in all cases and for 20 yr in 23 cases. C-peptide levels were measured from diagnosis and thereafter at intervals for the first years of disease until becoming permanently undetectable. Results: C-peptide levels at diagnosis were undetectable in about 20% of the cases both with and without DKA. C-peptide levels at diagnosis, the duration of measurable C-peptide levels and the maximum value found during follow-up were not significantly different in the three groups and were not correlated with glycated hemoglobin (GHb) calculated throughout the whole period. No differences were found between the groups of patients concerning GHb values and insulin dose at 10, 15 and 20 yr of disease. The patients of group 2A, characterized by an extremely high glycemic level without ketoacidosis, had a significantly higher prevalence of HLA DR3/4 heterozygosity. Conclusions: The severity of clinical presentation at diagnosis does not significantly influence residual β-cell function, and long-term metabolic control.

We read with interest the data by Craig et al. (1) about the prevalence of celiac disease (CD) in 52,721 youth with type 1 diabetes (T1D). The authors found a prevalence of 3.5% based on four national registries (range 1.9–7.7). We would like to share the experience of five centers of pediatric diabetes care of northern Italy (Bologna, Florence, Genoa, Trento, and Turin): we recently collected data on 2,164 children and adolescents with T1D and found 213 subjects affected by both CD and T1D (punctual prevalence 9.8% [range 6.8–12.8]). As in Italy there is no registry for pediatric diabetes, and in order to avoid a “hot spot effect” (big centers attract …

We report a peculiar case of a GCK/MODY2 family in whom monogenic and autoimmune diabetes coexist and exert different effects on clinical pictures, passing from mild hyperglycaemia not requiring any treatment through occasional insulin administration to complete insulin dependent type 1 diabetes.

Background/Aim: Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). Methods: A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Results: Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Conclusions: Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control.

AIM—To compare final height in two groups of low birth weight children examined for short stature: the first group untreated because of normal growth hormone (GH) secretion, the second treated with human growth hormone (hGH) because of abnormal secretion. METHODS—A total of 49 subjects born at term of birth weight below the 10th centile were consecutively examined for idiopathic short stature. The first group of subjects (n = 20) with normal GH peaks after pharmacological tests (>8 µg/l) spontaneously reached final height. The second group (n = 29) with abnormal secretion were treated with hGH (20 U/m2/week) for 36-84 months. At diagnosis the two groups were of similar height for chronological age and bone age, and had similar target height. RESULTS—In both groups final height was significantly lower than target height (−0.65 (SEM 0.20) in untreated cases, −0.61 (0.18) in treated cases). Fewer than one third of subjects had a final height above target height. Final height data of untreated and treated cases were not different. In the treated group the best results were obtained by those subjects who improved their height for bone age after three years of therapy. CONCLUSIONS—Our subjects with birth weight below the 10th centile remained as short adults with final height below target height. Treatment with hGH 20 U/m2/week in those diagnosed as deficient was not effective, with final results overlapping those of untreated subjects.

OBJECTIVE We describe a maturity-onset diabetes of the young (MODY) case with mutations involving both HNF4A and HNF1A genes. RESEARCH DESIGN AND METHODS A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both the parents (father at age 50 years, mother at age 54 years) and the sister (at age 32 years, during pregnancy). RESULTS The genetic screening showed a double heterozygosity for the mutation p.E508K in the HNF1A/MODY3 gene and the novel variant p.R80Q in the HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister, and her two children carried the MODY1 mutation. CONCLUSIONS MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation and early need of insulin therapy to control hyperglycemia).

OBJECTIVE Birth weight influences both postnatal growth and the initial response to GH therapy in GH-deficient subjects, but its relationship to final height is uncertain. Therefore, we examined final height results in a group of subjects treated for GH deficiency who were born small, appropriate or large for gestational age (GA). DESIGN Retrospective study. PATIENTS 108 GH-treated patients (age at diagnosis 11.1 ± 2.0 years) affected by idiopathic and isolated GH deficiency (peak

The aim of the present study was to evaluate retrospectively the influence of various auxological and laboratory parameters on final height in a group of GH-deficient children after replacement therapy and to compare their final height with that of a group of short children with normal GH secretion and hence not treated. The final height was evaluated of 83 patients (51 males and 32 females) affected by idiopathic isolated GH deficiency and treated with recombinant human GH (hGH) for 2-7 years. Inclusion criteria at the start of treatment were short stature (mean height for chronological age in standard deviation score (SDS) -2.21) due to idiopathic isolated GH deficiency (GH peak < 8 micrograms/l after two pharmacological tests and/or mean GH concentration < 3.3 micrograms/l during the night) and treatment with recombinant hGH for at least 2 years at a dose of 15-20 U/m2 per week by s.c. injection for 6 or 7 days/ week. Mean chronological age at diagnosis was 12.2 +/- 1.7 years; 35 were prepubertal and 48 pubertal. The final height of 51 untreated short stature (mean height for chronological age in SDS -2.13 at diagnosis) subjects (42 males and 9 females: 29 prepubertal and 22 pubertal at diagnosis with mean chronological age 11.6 +/- 2.4 years) with normal GH secretion was also evaluated. In the treated subjects final height SDS was higher than that of the untreated group (-1.3 vs -1.7 SDS; P = 0.01). Both treated and untreated subjects showed a final height lower than target height, but 39% of the treated subjects vs only 20% of the untreated group (P = 0.035) had a final height greater than target height. In the treated subjects this percentage was higher in the patients improving their height for bone age in the first years of therapy. While treated females showed a positive correlation only between target and final height (P = 0.0001), in treated males final height correlated with the Bayley-Pinneau prediction at diagnosis, height for chronological age and bone age at diagnosis and target height. Patients who started therapy before puberty also showed these correlations with data calculated at the onset of puberty, together with a correlation with chronological age at the onset of puberty. When considering the influence of GH response at tests on final height, the percentage of subjects exceeding target height increased progressively according to the severity of the GH deficiency. There was no difference in height gain between the patients starting therapy before or during puberty. The height gain, however modest, obtained by our treated patients, the number of patients with final height greater than target height and the favourable comparison with the untreated short-stature subjects represent a promising result, which could be improved by personalizing treatment.