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Background: Skin reactions due to technological devices pose a significant concern in the management of type 1 diabetes (T1D). This multicentric, comparative cross-sectional study aimed to assess the psychological impact of device-related skin issues on youths with T1D and their parents., Methods: Participants with skin reactions were matched in a 1:1 ratio with a control group. Diabetes-related emotional distress was evaluated using the Problem Areas in Diabetes-Teen version (PAID-T) for participants aged 11 to 19 years and the Problem Areas in Diabetes-Parent Revised version (PAID-PR) completed by parents. In addition, glucose control was assessed through glycated hemoglobin (HbA 1c ) values and continuous glucose monitoring (CGM) metrics., Results: A total of 102 children and adolescents were consecutively recruited. Adolescents with skin issues had higher PAID-T scores compared to those without (79.6 ± 21.1 vs 62 ± 16.8; P = .004). Parents of youths with skin reactions also reported higher PAID-PR scores than the control group (34.0 ± 11.0 vs 26.9 ± 12.3; P = .015). No differences were observed in HbA 1c levels (6.9 ± 0.8% vs 6.8 ± 0.8%, P = .555) or CGM glucose metrics between the two groups. Remarkably, 25.5% were forced to discontinue insulin pumps and/or glucose sensors (21.5% and 5.9%, respectively)., Conclusions: Our study highlighted the increased emotional burden experienced by youths with T1D and their parents due to device-related skin reactions, emphasizing the need for further research and interventions in this crucial aspect of diabetes management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SP received speaking honoraria from Roche and Movi SpA. NM received speaking honoraria from Movi SpA, Theras, and Novonordisk. MB received speaking honoraria from Movi SpA. All other authors declare no conflicts of interest.

Aim: To assess the incidence and the temporal trend of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) during the period 2014-2023 in youths aged 0-14 years in the Trentino-Alto Adige region, Italy., Methods: A retrospective review of all incident cases of T1D diagnosed at the two Pediatric Diabetes Centers of Bolzano and Trento was matched with diabetes exemptions (No. 344). Demographic, clinical, and socioeconomic status (SES) data at first hospitalization were collected from subjects who agreed to participate (No. 272)., Results: The incidence of T1D was 21.5/100,000 person/years, with a peak of 31.1 in 2021 during the COVID-19 pandemic. The mean age at the onset was 8.8 ± 3.9 years. Seventy-nine percent of the subjects were Italians, primarily residents in rural areas, and SES was equally represented. The mean incidence of DKA was 36.9%. The logistic regression analysis showed that the independent characteristics of the patients with DKA were of a younger age and displayed higher glycated hemoglobin (HbA1c) values. No relation of DKA with seasonality, ethnicity, or first-degree relative (FDR) with T1D or SES was detected., Conclusions: Our study revealed an incidence of T1D in the Trentino-Alto Adige region comparable to other areas in the North of Italy. The DKA rate negatively correlated with age; therefore, targeted prevention educational campaigns to increase awareness are needed.

Aims: While continuous glucose monitoring (CGM) and associated technologies have positive effects on metabolic control in young people with type 1 diabetes (T1D), less is known about their impact on quality of life (QoL). Here, we quantified CGM satisfaction and QoL in young people with T1D and their parents/caregivers to establish (i) the relationship between QoL and CGM satisfaction and (ii) the impact of the treatment regimen on QoL., Methods: This was a cross-sectional study of children and adolescents with T1D on different treatment regimens (multiple daily injections, sensor-augmented pumps and automated insulin delivery). QoL was assessed with the KINDL instrument, and CGM satisfaction with the CGM-SAT questionnaire was evaluated in both youths with T1D and their parents., Results: Two hundred and ten consecutively enrolled youths with T1D completed the KINDL and CGM-SAT questionnaires. The mean total KINDL score was greater than neutral in both subjects with T1D (3.99 ± 0.47) and parents (4.06 ± 0.40), and lower overall CGM-SAT scores (i.e., higher satisfaction) were significantly associated with higher QoL in all six KINDL subscales (p < 0.05). There were no differences in KINDL scores according to delivery technology or when participants were grouped according to optimal and sub-optimal glucose control., Conclusions: Higher satisfaction with recent CGMs was associated with better QoL in all dimensions. QoL was independent of both the insulin delivery technology and glycaemic control. CGM must be further disseminated. Attention on perceived satisfaction with CGM should be incorporated with the clinical practice to improve the well-being of children and adolescents with T1D and their families., (© 2024 Diabetes UK.)

Aims: In this study, we aimed to analyze the possible change in Time In Range (TIR) in subjects with type 1 diabetes (T1D) using the Ambulatory Glucose Profile (AGP) and to identify the main socio-demographic and clinical predictors of sustained use., Methods: 143 youths wearing instant-scanning CGM received structured counseling on the AGP report interpretation, and who were able to use AGP at least every 14 days were enrolled in group A (n = 100), whereas no users were considered as group B (n = 43). Socio-demographic data at the enrollment, clinical data, and glucose metrics were collected at baseline and during quarterly consultations. Metabolic outcomes were evaluated during follow-up, and a comparison between groups A and B was performed., Results: In group A compared to group B, at 12 months, the percentage of sensor usage and TIR were higher (p = 0.04 and p = 0.02), and Time Above Range and HbA1c were lower (p = 0.0004, p < 0.0001, respectively). Multiple logistic regression analysis did not show a significant relationship between sustained AGP software usage and the variables analyzed., Conclusions: Systematic use of the AGP software was feasible and showed improved metabolic control in youths with T1D. This may be related to increased sensor usage and more informed decisions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diet is an essential element of treating and managing type 1 diabetes (T1D). However, limited research has examined food behaviour in children and adolescents with T1D and their relationship to glycaemic control. This study evaluated food behaviour, metabolic characteristics and their impact on the glycaemic control of children and adolescents with T1D. Two hundred and fifty-eight participants with T1D (6-15 years, duration of diabetes >1 year) were recruited. Demographic, anthropometric and clinical data were collected. Questionnaires on food neophobia and food preferences were administered. The Child Food Questionnaire (CFQ) also assessed parental feeding practices. An analysis of food behaviour showed that food neophobia was inversely associated with the liking of vegetables, fruits, fish, sweets and carbohydrates. Moreover, by analysing parental feeding practices, an inverse association of "Pressure to eat", "Monitoring" and "Restriction" with liking for vegetables and carbohydrates emerged. Considering glycaemic control, increased food neophobia and the parent practices "Restriction", "Pressure to eat" and "Concern about weight" were found in participants with glycated haemoglobin (HbA1c) values >8.5%. Finally, higher body mass index (BMI) and total cholesterol values were observed in subjects with HbA1c values >8.5%. These findings contribute to a better understanding of eating behaviour, metabolic status and their complex relationship with glycaemic control.

Aims: Continuous glucose monitoring (CGM) can improve glucometrics in children with type 1 diabetes (T1D), and its efficacy is positively related to glucose sensor use for at least 60% of the time. We therefore investigated the relationship between CGM satisfaction as assessed by a robust questionnaire and glucose control in pediatric T1D patients., Methods: This was a cross-sectional study of children and adolescents with T1D using CGM. The CGM Satisfaction (CGM-SAT) questionnaire was administered to patients and demographic, clinical, and glucometrics data were recorded., Results: Two hundred and ten consecutively enrolled patients attending 14 Italian pediatric diabetes clinics completed the CGM-SAT questionnaire. CGM-SAT scores were not associated with age, gender, annual HbA1c, % of time with an active sensor, time above range (TAR), time below range (TBR), and coefficient of variation (CV). However, CGM satisfaction was positively correlated with time in range (TIR, p < 0.05) and negatively correlated with glycemia risk index (GRI, p < 0.05)., Conclusions: CGM seems to have a positive effect on glucose control in patients with T1D. CGM satisfaction is therefore an important patient-reported outcome to assess and it is associated with increased TIR and reduced GRI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Patient-reported outcomes (PROs) are increasingly important for assessing patient satisfaction with diabetes technologies. PROs must be assessed with validated questionnaires in clinical practice and research studies. Our aim was to translate and validate the Italian version of the continuous glucose monitoring (CGM) Satisfaction (CGM-SAT) scale questionnaire., Methods: Questionnaire validation followed MAPI Research Trust guidelines and included forward translation, reconciliation, backward translation, and cognitive debriefing., Results: The final version of the questionnaire was administered to 210 patients with type 1 diabetes (T1D) and 232 parents. The completion rate was excellent, with almost 100% of items answered. The overall Cronbach's coefficient was 0.71 and 0.85 for young people (patients) and parents indicating moderate and good internal consistency, respectively. Parent-young people agreement was 0.404 (95% confidence interval: 0.391-0.417), indicating moderate agreement between the two assessments. Factor analysis identified that factors assessing the "benefits" and "hassles" of CGM accounted for 33.9% and 12.9% of score variance in young people and 29.6% and 19.8% in parents, respectively., Discussion: We present the successful Italian translation and validation of the CGM-SAT scale questionnaire, which will be useful for assessing satisfaction with Italian T1D patients using CGM systems., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequencing (NGS) panels provide a highly sensitive method even for rare forms., Methods: We investigated 28 pediatric subjects suspected for MODY-X, utilizing a 15-gene NGS panel for monogenic diabetes (MD)., Results: NGS detected variants of uncertain significance (VUS), likely pathogenic or pathogenic for rarer subtypes of MODY, in six patients. We found variants in the wolframin gene ( WFS1 ), traditionally not considered in MD genetic screening panels, in three patients; KCNJ11 gene mutation, typically responsible for neonatal diabetes and rarely causing isolated diabetes in adolescents; INS gene mutation; a variant in the HNF1B gene in a young male with diabetes on sulfonylurea treatment., Conclusion: In our cohort, the availability of an NGS panel for MD was determined for the correct identification of MD subtypes in six patients with MODY-X. Our study underlines how a precise diagnosis utilizing NGS may have an impact on the management of different forms of MODY and, thus, lead to a tailored treatment and enable genetic counselling of other family members.

Background: Precision medicine in type 1 diabetes (T1D) treatment considers context and environmental data to subclassify patients. Parental Health Locus of Control PHLOC) could influence behavior, self-management, and metabolic control of children with T1D. Methods: No. 135 pediatric patients with T1D (No. 57 with HbA1c ≤ 7.0%, “optimal” group, and No. 78 with >7.0%, “sub-optimal” group) were enrolled in the study. History, anthropometric and diabetes management data were collected, as well as caregiver’s data about socioeconomic status (SES). The PHLOC scale questionnaire and a semi-structured interview were administered. Results: Access to technology was lower in the “sub-optimal” group and, in particular, in the ethnic minority subgroup, only 8% used them. In the “sub-optimal” group ethnic minority status was higher (24%), the caregiver had a lower SES and showed lower internal HLOC. Conclusions: New care models have to be implemented to ensure equity in diabetes care and precision treatment, particularly for ethnic minority groups, because SES and external PHLOC are still an important barrier to “optimal” diabetes control. In the “sub-optimal” group, we have to implement strategies aimed at increasing self-efficacy, while in the “optimal” one, a personalised approach should be considered to facilitate the shifting of responsibilities within the family, avoiding psychological distress.

Aims: To evaluate the impact of gluten free diet (GFD) on growth, metabolic control and quality of life in children and adolescents with type 1 diabetes (T1D) and celiac disease (CD)., Methods: A systematic search was performed including studies published in the last 15 years. PICOS framework was used in the selection process and evidence was assessed using the GRADE system., Results: Overall, studies comparing youth with T1D + CD on GFD to those with T1D only, showed no significant differences in growth parameters, HbA1c, number of episodes of hypoglycemia, total daily insulin doses. Studies assessing the effect of GFD introduction showed stable BMI and HbA1c. Only two studies assessed QoL of life, which was not different between T1D + CD vs T1D only youth, as well as pre- and post-CD diagnosis and introduction of GFD., Conclusion: This systematic review, including only studies of moderate-high evidence quality level and reporting data on objectively assessed adherence to GFD, highlights that adherence to GFD in youth with T1D + CD leads to regular growth, stable BMI, without any negative effect on HbA1c and insulin requirements. Although assessed in few studies, lipid profile and QoL improved with the introduction of GFD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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

Aims: Data about sleep quality and quantity are not available in patients with type 1 diabetes (T1D) using intermittently scanned continuous glucose monitoring (isCGM). We questioned whether the isCGM with alarms could fragment sleep in patients and parents, compared to isCGM without alarms., Methods: A prospective, observational study including 47 child-adolescents with T1D who had experience with isCGM without alarms (Freestyle Libre 1-FSL1). They were asked to wear the isCGM with alarms (Freestyle Libre 2-FSL2) for 14 days. Patients enrolled and their caregiver (s), during a 14 day period with FSL1 and the following 14 days with FSL2, completed psychosocial and sleep-related questionnaires. Furthermore they wore an actigraph that was downloaded to a web platform and processed by the validated and certified algorithm "Dormi ® .", Results: By the switch to the alarmed FSL2 we found about a 5% increase in Time In Range (from 62.5 to 67.8%), a reduction in time spent in hypoglycemia, number of weekly hypoglycemic events, and coefficient of variation. We did not find significant differences in sleep parameters in patients and their parents; therefore, alarms did not worsen the duration and quality of sleep. A significant improvement in the Quality of Life was perceived by parents using FSL2., Conclusions: Introduction of alarms in isCGM systems gives, in the short term, an improvement in metabolic control in terms of time in range and reduction in hypoglycemia, without worsening duration and quality of sleep, measured by actigraphy, in children-adolescent and their parents., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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

Background: Use of Continuous Glucose Monitoring (CGM) systems early in the course of diabetes has the potential to help glycemic management and to improve quality of life (QoL). No previous research has examined these outcomes in children-adolescents with type 1 diabetes (T1D) who use intermittently scanned CGM (isCGM) starting within the first month after diagnosis., Aim: To evaluate the impact of isCGM early after T1D diagnosis, on metabolic control and QoL, comparing a group who started the use of the device within one month from the onset with another one who started at least one year later., Subjects and Methods: Patients who used isCGM within 1 month from T1D diagnosis were enrolled in group A; those who didn't have the device during the first year were considered as control group (group B). HbA1c and total daily insulin were evaluated at 3 (T1), 6 (T2) and 12 (T3) months post-baseline (T0, diabetes onset), QoL after 1 year. In group A, isCGM glucose metrics were also recorded., Results: 85 patients were enrolled in group A and 67 patients in group B. In group A isCGM was well accepted during follow up: no patient dropped out; percentage of time with active sensor was in mean > 87%; number of scans/day remained stable. QoL was higher in group A than in group B both in children-adolescents (p<0.0001) and in parents (p 0.003). Group A presented lower HbA1c during the first year after diagnosis (p<0.001), and this data correlated with glucose management indicator (GMI), time in range (TIR) and mean glucose. The honeymoon period lasted more in group A than in B (p 0.028). Furthermore, the mean hypoglycemia duration decreased during follow-up (p 0.001) in group A., Conclusions: Early use of isCGM, starting within the first month after diagnosis, improves metabolic control and QoL in pediatric patients with T1D., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Franceschi, Cauvin, Stefani, Berchielli, Soffiati and Maines.)

Purpose: The aim was to verify in a pediatric population with Hashimoto's thyroiditis whether there is a relationship between antithyroid antibodies and inflammatory status on thyroid ultrasound and thyroid function., Subjects and Methods: A total of 154 children and adolescents, aged 4 to 18 years, diagnosed with Hashimoto's thyroiditis with normal body weight were followed up for 1 year., Results: Patients with only antiperoxidase antibodies presented with higher TSH levels than subjects with only antithyroglobulin antibodies (p 0.027) but with similar FT4 levels and thyroid score. Prevalence of seronegative Hashimoto's thyroiditis in this cohort was 12.3% (19/154). At diagnosis, the seronegative group presented with lower prevalence of overt hypothyroidism, symptoms of hypothyroidism, and thyroid score, meaning less severe thyroid involvement. In contrast, similar TSH and FT4 values were found at diagnosis and during follow-up in both the seronegative and seropositive groups. A comparison between patients with seronegative Hashimoto's thyroiditis and an overweight/obese antibody-negative population, who presented superimposable altered parenchymal pattern on thyroid ultrasound without circulating antithyroid antibodies, presented similar clinical data., Conclusion: We report for the first time in the literature that seronegative Hashimoto's thyroiditis in the pediatric age group has a less severe pattern. The seronegative group presents similar characteristics to those of overweight/obese children and adolescents with ultrasound changes, but, according to the established knowledge, the latter condition is reversible and does not need follow-up examinations., (© 2022. Hellenic Endocrine Society.)

Aims: We aimed to estimate the prevalence of Diabetic peripheral neuropathy (DPN) and Cardiac autonomic neuropathy (CAN) in youth with type 1 diabetes; identify key risk factors; identify the most useful tests for the diagnostic evaluation of DPN and CAN; identify key treatment options for DPN and CAN., Methods: A systematic search was performed including studies published in the last 15 years. PICO framework was used in the selection process and evidence was assessed using the GRADE system., Results: A total of 758 studies were identified and a final number of 49 studies were included in this systematic review. According to moderate-high level quality studies, the prevalence of probable DPN, ranged between 13.5 and 62%; subclinical DPN between 22 and 88%; confirmed DPN between 2.6 and 11%. The Michigan Neuropathy Screening Instrument was the tool with higher sensitivity and specificity for detecting DPN, which needs to be confirmed by nerve conduction velocity. The prevalence of CAN was 4-39%. Specific treatment options for DPN or CAN in patients younger than 25 years are not available. Key risk factors for DPN and CAN are hyperglycemia/HbA1c, age, diabetes duration, the presence of other microvascular complications, waist/height ratio, lipid profile and blood pressure. For CAN, additional risk factors were cigarette smoking, BMI and total daily insulin., Conclusions: Prevalence of neuropathy in youth with type 1 diabetes varies depending on different screening methods and characteristics of the study populations. However, the assessed studies confirmed a relatively high prevalence of subclinical neuropathy, reiterating the importance of early identification of risk factors to prevent this complication., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Past studies on altered taste function in individuals with type 1 diabetes have yielded inconsistent results. We therefore evaluated taste recognition and possible association with personal and diseases characteristics in young individuals with type 1 diabetes and healthy controls. Taste recognition and intensity for 6-n-propylthiouracil (PROP), quinine, citric acid, sucrose, and sodium chloride were assessed using a filter paper method in 276 participants with type 1 diabetes and 147 healthy controls. Personal and clinical data were recorded for all participants during a baseline visit. Regression analysis was adjusted for sex, age, and standardized BMI. Overall, 47% of participants with type 1 diabetes vs. 63.5% of healthy controls recognized all tastes ( p = 0.006). Moreover, a lower capacity for recognizing the bitter taste of PROP and the sour taste of citric acid was found in participants with type 1 diabetes compared to healthy controls ( p = 0.014 and p = 0.003, respectively). While no significant effect of glycemic control on taste recognition was found, an association with lower age at onset emerged. Our findings suggest an impaired taste perception in individuals with type 1 diabetes, possibly linked to age at onset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Catamo, Robino, Tinti, Dovc, Franceschi, Giangreco, Gasparini, Barbi, Cauvin, Rabbone, Battelino and Tornese.)

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 < .003), respectively, and that of severe retinopathy was 1.7% and 9.6% (P = .018). Lifetime HbA1c was lower in the new cohort (7.8% ± 0.8% vs. 8.1% ± 0.8%; P = .002) during all periods following the first 5 years after diagnosis. Patients without retinopathy in the two cohorts had similar levels of HbA1c. Compared with patients without retinopathy, those with retinopathy had higher lifetime HbA1c and long-term HbA1c variability. However, on multiple regression analysis, only lifetime HbA1c was independently associated with retinopathy (P = .0018)., Conclusions: The risk of developing retinopathy was nearly halved in children who developed type 1 diabetes in the new millennium compared with previous cohorts. These results confirm that maintaining the lowest possible levels of HbA1c throughout lifetime protects from diabetic retinopathy., (© 2021 John Wiley & Sons Ltd.)

Aim: To explore the impact of real-time continuous glucose monitoring (rtCGMs) or intermittently scanned/viewed CGM (isCGM) on psychological outcomes in children and caregivers, and to grade the level of evidence. Method: Systematic review of the literature from PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Nursing reference center, Up to date, Google Scholar, and PsycINFO databases. The studies selected used validated questionnaires for investigating the psychological outcomes. We applied GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rank the quality of a body of evidence. Results: A total of 192 studies were identified in the initial search and after the process of evaluation 25 studies were selected as appropriate to be included in this systematic review. We found in moderate quality studies that isCGM in adolescents can improve diabetes related distress, family conflicts, fear of hypoglycemia, and quality of life, while depression, anxiety, and quality of sleep have not yet been evaluated by validated questionnaires. In moderate-high quality studies, rtCGM technology does not impact on diabetes burden, diabetes specific family conflict, and depressive symptoms. The effect on fear of hypoglycemia, sleep quality, and anxiety is still debated and RCT studies powered to find significant results in psychological outcomes are lacking. RtCGM increases satisfaction and quality of life in parents and patients wearing rtCGM. Conclusion: these data present an interesting point to consider when families are deciding whether or not to start CGM use, choosing between rtCGM to reach a tighter metabolic control, or isCGM which allows greater benefits on psychological outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Franceschi, Micheli, Mozzillo, Cauvin, Liguori, Soffiati and Giani.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mozzillo, Franceschi, Piona, Passanisi, Casertano, Pjetraj, Maltoni, Calcaterra, Cauvin, Cherubini, D’Annunzio, Franzese, Frongia, Lombardo, Lo Presti, Matteoli, Piccinno, Predieri, Rabbone, Scaramuzza, Toni, Zucchini, Maffeis and Schiaffini.)

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: 2021 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., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: management of children with type 1 diabetes (T1DM) during physical activity includes intensive blood glucose monitoring and proper insulin and nutritional adjustments in order to prevent hypoglycemia. Regarding the treatment of hypoglycemia during physical activity, different types of rapid acting carbohydrate (CHO) can be used and recommendations are still debated., Aim of the Work: compare the response to three types of frequently used rapid acting CHO to correct hypoglycemia during prolonged aerobic exercise.  Subjects and Methods: 21 subjects with T1DM, aged 12-16 years, agreed to be recruited in the study. All participants took part in a trekking camp for 5 days, with 70 Km itinerary. A "flash monitoring" device was put on every participant and insulin and nutritional adjustments were done according to a protocol. Subjects have been randomized into three different groups: group 1 had to correct hypoglycemia with 0.3g/Kg of a glucose preparation; group 2 used sugar fondant candies; group 3 used fruit juice., Results: no significant differences were highlighted among the three treatments in terms of time spent in hypoglycemia, rise in blood glucose levels and number of hypoglycemic events after correction of hypoglycemia., Conclusions: our results suggest that 0.3g pro Kg of rapidly acting CHO in the form of glucose, sugar fondant or orange juice, effectively resolve hypoglycemia in children during aerobic prolonged physical activity.

Adults with Type 1 diabetes mellitus show a high risk of bone fracture, probably as a consequence of a decreased bone mass and microarchitectural bone alterations. The aim of the study was to investigate the potential negative effects of type 1 diabetes on bone geometry, quality, and bone markers in a group of children and adolescents. 96 children, mean age 10.5 ± 3.1 years, agreed to participate to the study. Bone geometry was evaluated on digitalized X-rays at the level of the 2nd metacarpal bone. The following parameters were investigated and expressed as SDS: outer diameter (D), inner diameter (d), cortical area (CA), and medullary area (MA). Bone strength was evaluated as Bending Breaking Resistance Index (BBRI) from the geometric data. Bone turnover markers (PINP, CTX-I, and BAP), sclerostin, Dkk-1, PTH, and 25OH-Vitamin D were also assessed. A group of healthy 40 subjects of normal body weight and height served as controls for the bone markers. D (- 0.99 ± 0.98), d (- 0.41 ± 0.88), CA (- 0.85 ± 0.78), and MA (- 0.46 ± 0.78) were all significantly smaller than in controls (p < 0.01). BBRI was significantly lower (- 2.61 ± 2.18; p < 0.0001). PTH, PINP, and BAP were higher in the diabetic children. Multiple regression analysis showed that CA and D were influenced by insulin/Kg/day and by BMI, while d was influenced by PINP only. Type 1 diabetic children show smaller and weaker bones. The increased bone turnover could play a key role since it might amplify the deficit in bone strength associated with the inadequate osteoblastic activity caused by the disease itself.

Aims: Low HDL cholesterol (HDL-C) levels have been described in patients with coexisting type 1 diabetes mellitus (T1DM) and celiac disease (CD). Data on other possible lipid abnormalities that could further increase cardiovascular risk in these patients are scarce and incomplete. Aim of this retrospective multicenter study was to evaluate whole lipid profiles, besides HDL-C, in children with T1DM associated with biopsy-proven CD, and to investigate the influence of age and degree of adherence to gluten-free diet (GFD) on lipid changes., Methods: A total of 261 children with both T1DM and CD were enrolled. Serum lipid profiles at CD diagnosis were compared with those after 1 year of GFD and with those of 224 matched children with T1DM alone. The adherence to GFD was judged by means of CD-related antibodies., Results: At CD diagnosis, children with T1DM + CD showed higher LDL cholesterol (LDL-C) compared to children with T1DM alone. Gluten withdrawal failed to normalize LDL-C levels, not even in completely adherent individuals. HbA1c values were not influenced by GFD. The youngest children were characterized at diagnosis by lower levels of total cholesterol and on treatment by a greater decrease in triglycerides levels., Conclusions: An unfavorable lipid profile, characterized not only by low HDL-C levels but also by high LDL-C values, may increase the risk of cardiovascular disease in children with T1DM and untreated CD. Therefore, a strict gluten-free diet is mandatory in these children, especially the youngest.

Context: An etiologic diagnosis of diabetes can affect the therapeutic strategy and prognosis of chronic complications., Objective: The aim of the present study was to establish the relative percentage of different diabetes subtypes in patients attending Italian pediatric diabetes centers and the influence of an etiologic diagnosis on therapy., Design, Setting, and Patients: This was a retrospective study. The clinical records of 3781 consecutive patients (age, 0 to 18 years) referred to 15 pediatric diabetes clinics with a diagnosis of diabetes or impaired fasting glucose from January 1, 2007 to December 31, 2012 were examined. The clinical characteristics of the patients at their first referral to the centers, type 1 diabetes-related autoantibodies, molecular genetics records, and C-peptide measurements, if requested for the etiologic diagnosis, were acquired., Main Outcome Measures: The primary outcome was to assess the percentage of each diabetes subtype in our sample., Results: Type 1 diabetes represented the main cause (92.4%) of diabetes in this group of patients, followed by monogenic diabetes, which accounted for 6.3% of cases [maturity onset diabetes of the young (MODY), 5.5%; neonatal diabetes mellitus, 0.6%, genetic syndromes, 0.2%]. A genetic diagnosis prompted the transfer from insulin to sulphonylureas in 12 patients bearing mutations in the HNF1A or KCNJ11 genes. Type 2 diabetes was diagnosed in 1% of the patients., Conclusions: Monogenic diabetes is highly prevalent in patients referred to Italian pediatric diabetes centers. A genetic diagnosis guided the therapeutic decisions, allowed the formulation of a prognosis regarding chronic diabetic complications for a relevant number of patients (i.e.,GCK/MODY), and helped to provide genetic counseling., (Copyright © 2017 Endocrine Society)

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

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: 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±3.8years followed for at least 15years 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±3.8years 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Iliopsoas abscesses have been reported in adult diabetic patients, but only one case has been so far reported in the pediatric diabetic literature. We report three cases of iliopsoas abscesses in three adolescents with type 1 diabetes mellitus, suggesting that an increased awareness of this condition is required for its early recognition and prompt treatment.

Objective: To compare the effect of the prepubertal duration of diabetes on the occurrence of complications in two groups of patients after the same number of years of the disease., Research Design and Methods: This multicenter study enrolled 105 patients aged 16-40.3 years; 53 were prepubertal at diagnosis (aged 0-3) and 52 were pubertal (Tanner stage) and aged 9-14.9. The mean duration of disease was 19.8 and 19.5 years for prepubertal and pubertal patients, respectively. In all patients, retinal photographs were taken and centrally graded. Urinary albumin excretion (UAE; 86 case subjects), blood pressure (BP; 89 case subjects), and lifetime HbA(1c) (72 case subjects) were also evaluated., Results: The prevalence of diabetic retinopathy (DR) was higher in pubertal than in prepubertal patients, both for any grade DR (71 vs. 40%, P = 0.002) and for mild or more severe DR (P = 0.005). The prevalence of abnormal UAE was not different in the two groups. Hypertension was found only in three patients, all pubertal at diagnosis. In the small group with moderate-to-severe DR, lifetime HbA(1c) levels, as percentages above the upper normal reference value, were higher (P < 0.01) in prepubertal than in pubertal patients., Conclusions: If diabetes is diagnosed in infants or toddlers and the prepubertal duration of diabetes is very long, the patients seem to be protected against DR. This protection disappears if lifetime metabolic control is bad. Instead, when onset is at puberty, the DR risk is higher and less dependent on metabolic control and may be influenced by age-related factors, such as BP.

We report the first published case of megapolycalicosis with prenatal ultrasound diagnosis. Pyeloureteral junction dysplasia was observed only after delivery. The etiopathogenesis of megapolycalicosis (MPC) and its hypothetical association with uretero-pelvic junction obstruction are discussed. Presence of polycalicosis, good glomerular filtration and absence of compensatory controlateral renal hypertrophy are determinant in the diagnosis.