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There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closedloop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Diabetic ketoacidosis (DKA) is a frequent manifestation at the onset of type 1 diabetes mellitus in children, possibly associated with a wide range of complications, often as a consequence of wrong or delayed treatment. Due to its complex and risky management, direct exposure to real situations alone is not sufficient to achieve adequate skills in pediatric DKA for residents. Simulation could be a valuable aid, allowing to practice a standardized scenario of a complex real-world situation. We aimed to test the effectiveness of a standardized scenario of pediatric DKA in teaching its recognition and treatment. Methods: We develop a standardized scenario able to guide step-by-step the learners through the flowchart of DKA management and considering alternative evolutions in the case of possible deviations from guidelines. It was a real-life simulation with the use of a high-fidelity pediatric simulator. It was played by 78 pediatrics 20 and emergency medicine residents. At the end of the simulation, a validated questionnaire was administered to collect feedback from participants regarding the impact of the simulation on learning. All materials to reproduce the DKA scenario are provided. Results: Overall, the scenario was rated as realistic (mean score 4.37 ± 0.68, from 1 to 5) and relevant to professional training (4.72 ± 0.47), useful in increasing confidence in interpreting laboratory tests (3.97 ± 0.65), group organization and communication strategies (3.49 ± 0.94), and managing the treatment of DKA (3.46 ± 0.92). Conclusions: The use of a standardized scenario of pediatric DKA may be a valid tool to reinforce theoretical knowledge in residents, both in pediatrics and in emergency medicine, and to directly and safely practice pediatric DKA management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The HNF1A transcription factor, implicated in the regulation of pancreatic beta cells, as well as in glucose and lipid metabolism, is responsible for type 3 maturity-onset diabetes of the young (MODY3). HNF1A is also involved in increased susceptibility to polygenic forms of diabetes, such as type 2 diabetes (T2D) and gestational diabetes (GD), while its possible role in type 1 diabetes (T1D) is not known. In this study, 277 children and adolescents with T1D and 140 healthy controls were recruited. The following SNPs in HNF1A gene were selected: rs1169286, rs1169288, rs7979478, and rs2259816. Through linear or logistic regression analysis, we analyzed their association with T1D susceptibility and related clinical traits, such as insulin dose-adjusted glycated hemoglobin A1c (IDAA1c) and glycated hemoglobin (HbA1c). We found that rs1169286 was associated with IDAA1c and HbA1c values (p-value = 0.0027 and p-value = 0.0075, respectively), while rs1169288 was associated with IDAA1c (p-value = 0.0081). No association between HNF1A SNPs and T1D development emerged. In conclusion, our findings suggest for the first time that HNF1A variants may be a risk factor for beta cell function and glycaemic control in T1D individuals. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate lipid profile and kidney function in children and adolescents with Type 1 Diabetes. Methods: This was a retrospective study including 324 children and adolescents with Type 1 Diabetes (48% females, mean age 13.1 ± 3.2 years). For all participants, demographic and clinical information were collected. The prevalence of dyslipidemia and kidney function markers were analyzed according to age. Multivariate linear regression analyses were performed to test the association of lipids or markers of renal function with demographic and clinical information (sex, age, disease duration, BMI SDS, HbA1c). Results: In our study the rate of dyslipidemia reached 32% in children <11 years and 18.5% in those ≥11 years. Children <11 years presented significantly higher triglyceride values. While the albumin-to-creatinine ratio was normal in all individuals, 17% had mildly reduced estimated glomerular filtration rate. Median of HbA1c was the most important determinant of lipids and kidney function, being associated with Total Cholesterol (p-value<0.001); LDL Cholesterol (pvalue= 0.009), HDL Cholesterol (p-value=0.045) and eGFR (p-value=0.001). Conclusion: Dyslipidemia could be present both in children and adolescents, suggesting that screening for markers of diabetic complications should be performed regardless of age, pubertal stage, or disease duration, to optimize glycemia and medical nutrition therapy and/or to start a specific medical treatment. [ABSTRACT FROM AUTHOR]

Aim: There is conflicting evidence about the impact of the COVID‐19 pandemic on the incidence of type 1 diabetes. Here, we analysed long‐term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID‐19 pandemic with that estimated from long‐term data. Materials and Methods: This was a population‐based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 to 31 December 2019 were estimated using Poisson and segmented regression models. Results: There was a significant increasing trend in the incidence of type 1 diabetes of 3.6% per year [95% confidence interval (CI): 2.4‐4.8] between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95% CI: ‐1.3 to 2.4). There was a significant 4‐year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95% CI: 23.0‐30.9) was significantly higher than expected (19.5, 95% CI: 17.6‐21.4; p =.010). Conclusion: Long‐term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to understand better the impact of COVID‐19 on new‐onset type 1 diabetes in children. [ABSTRACT FROM AUTHOR]

The aims of this study were to evaluate: (i) the chemical and nutritional composition of rice before and after cooking and (ii) postprandial glycemic impacts in children and adolescents with type 1 diabetes (T1D) after eating two different types of rice ("Gigante Vercelli" white rice and "Artemide" black rice) or white rice cooked "risotto" style or boiled using an advanced hybrid closed loop (AHCL) system (Tandem Control-IQTM). General composition and spectrophotometric analyses of raw and cooked rice were performed. Eight T1D subjects (four males and four females, aged 11 ± 1.4 years), two with celiac disease (CD), using an AHCL system were enrolled. "Gigante Vercelli" white rice cooked as risotto or boiled and boiled "Artemide" rice were prepared by the same cook on two evenings. Continuous glucose monitoring metrics were evaluated for 12 h after meal consumption. Total dietary fiber was higher for both rice types after cooking compared with raw rice. Cooking as risotto increased polyphenols and antioxidants (p < 0.05) in both rice varieties, and total starch decreased after boiling (p < 0.05) in white rice. There was a significant peak in glycemia after consuming risotto and boiled white rice (p < 0.05), while the mean glycemic peak remained <180 mg/dL in individuals eating boiled Artemide rice. There were no significant differences in automatic basal or auto-bolus insulin deliveries by the AHCL according to different types of rice or cooking method. Our findings suggest that glycemic trends are impacted by the different chemical and nutritional profiles of rice but are nevertheless well controlled by AHCL systems. [ABSTRACT FROM AUTHOR]

2 TABLE Raw incidence rates (IR) of type 1 diabetes in Piedmont (Italy) by 100 000 residents and rate ratios (RR), comparison between before and during the COVID pandemic years. Nevertheless, over the 3 years of the COVID-19 pandemic, the overall incidence of DM1 has remained ~17% higher than before the pandemic, suggesting further work to understand the link between coronaviruses and diabetes is a priority. Keywords: database research; observational; population study; study; type 1 diabetes EN database research observational population study study type 1 diabetes 3068 3070 3 09/06/23 20231001 NES 231001 BACKGROUND There have now been several reports that the incidence of type 1 diabetes (DM1) increased during the COVID-19 pandemic, particularly in young children,[[1], [3]] although some data are conflicting.[4] Overall, however, there is emerging evidence from diabetes registries that this observed increase is real. [Extracted from the article]

Our study aimed to show a relationship between metabolic control, vitamin D status (25OHD), and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in children with type 1 diabetes (T1D). The secondary aim was to evaluate dietary intake and the presence of ketoacidosis (DKA) at the onset of T1D. Methods: A cohort of 40 children with T1D was recruited, mean age 9.7 years (7.1; 13), with onset of T1D in the last 5 years: some at onset (n: 20, group A) and others after 18.0 ± 5 months (n: 20; group B). Twenty healthy children were compared as control subjects (CS). Dietary intakes were assessed through a diary food frequency questionnaire. Moreover, dried blood spots were used to test AA/EPA ratio by gas chromatography. Results: T1D children had a lower percentage of sugar intake (p < 0.02) than CS. Furthermore, group B introduced a greater amount of AA with the diet (g/day; p < 0.05) than CS (p < 0.01) and group A (p < 0.01). Children with an AA/EPA ratio ≤ 22.5 (1st quartile) required a lower insulin demand and had higher 25OHD levels than those who were in the higher quartiles (p < 0.05). Subjects with DKA (9/40) had levels of 25OHD (p < 0.05) and C-peptide (p < 0.05) lower than those without DKA. Moreover, analyzing the food questionnaire in group A, subjects with DKA showed a lower intake of proteins, sugars, fiber (g/day; p< 0.05), vitamin D, EPA, and DHA (g/day; p < 0.01) compared to subjects without DKA. Non-linear associations between vitamin D intake (p < 0.0001; r2:0.580) and linear between EPA intake and C-peptide (p < 0.05; r: 0.375) were found in all subjects. Conclusions: The study shows a relationship between vitamin D status, AA/EPA ratio, and metabolic state, probably due to their inflammatory and immune mechanisms. A different bromatological composition of the diet could impact the severity of the onset. [ABSTRACT FROM AUTHOR]

The pharmacokinetic and pharmacodynamic properties of the second-generation basal insulin glargine 300 Units/mL (Gla-300) may be of benefit in the treatment of type 1 diabetes mellitus (T1DM). Gla-300 provides a stable and sustained time-action profile, which is associated with glycaemic control and flexible dosing schedule. This review summarises the available evidence on the safety and efficacy of Gla-300 in children and adolescents with T1DM. Gla-300 is as effective as the first-generation basal insulin glargine 100 Units/mL (Gla-100), a standard of care for patients with diabetes in reducing HbA1c, and shows a lower risk of severe hypoglycaemia and hyperglycaemia in children and adolescents with T1DM. However, Gla-300 and Gla-100 are not bioequivalent and are not directly interchangeable. Real-world studies on patients aged 6–17 years are limited. To date, only one small study assessed the effectiveness and safety of Gla-300 versus Gla-100 in newly diagnosed T1DM paediatric patients, confirming the treatment safety and effectiveness of Gla-300 in clinical practice. Gla-300 is a longer-acting basal insulin alternative in the management of children (aged ≥ 6 years) and adolescents with T1DM. Plain Language Summary: The smooth and prolonged activity of insulin glargine 300 Units/mL (Gla-300), a second-generation basal insulin, results in a stable and sustained glycaemic control while allowing flexible dosing times. In children aged ≥ 6 years and adolescents with type 1 diabetes mellitus (T1DM), Gla-300 provides a glycaemic control comparable to that of glargine 100 Units/mL (Gla-100), a standard of care in patients with T1DM. Gla-300 and Gla-100 show similar safety profiles, with Gla-300 resulting in a clinically relevant trend towards a lower incidence of hyperglycaemia with ketosis and a lower incidence and event rate of severe hypoglycaemia in children and adolescents with T1DM. Overall, these two insulins are similar, but not interchangeable. To the best of our knowledge, only one real-world study has addressed the effectiveness and safety of Gla-300 compared to Gla-100 in newly diagnosed T1DM paediatric patients, and it has shown the therapeutic benefits of Gla-300 in clinical practice. [ABSTRACT FROM AUTHOR]

Incidence rate ratios (RRs) were calculated as the ratio between the incidence of each year with the appropriate incidences in 2017 (reference year). Increased incidence of type 1 diabetes in 2 years of COVID-19 pandemic Comparisons of pooled incidence between three non-COVID years (2017-2019) and the two COVID-19 years (2020-2021) confirm the above significant increase in the total population. [Extracted from the article]

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 <.001). After the vEC, more than 75% of participants achieved a TIR of more than 70%. The percentage of time between 180 and 250 mg/dL and above 250 mg/dL decreased by 5% (P <.01) and 6% (P <.01), respectively, while the time between 70 and 54 mg/dL and below 54 mg/dL remained low and unaltered. HbA1c decreased by 0.5% (P <.01). There were no episodes of diabetic ketoacidosis or severe hypoglycaemia. Conclusions: In this study of children managing their diabetes in a real‐world setting, more than 75% of children who participated in a vEC after starting a CLC system could obtain and maintain a TIR of more than 70%. The vEC was feasible and resulted in a significant and persistent improvement in TIR in children and adolescents with type 1 diabetes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Vitamin D plays an immunoregulatory activity. The aim of this study was to assess the correlation between blood serum 25(OH)D levels and Th17 and Treg circulating subsets, mainly Treg/inducible costimulatory-positive (ICOS+), which seems to have a protective role in autoimmunity, in children with type 1 diabetes mellitus (T1D) and their healthy siblings (S). The secondary aim was to evaluate the impact of vitamin D supplementation on these subsets.Patients and Methods: 22 T1D and 33 S were enrolled. Glucose, hemoglobin A1c, 25 OH vitamin D (25[OH]D), T helper type 17 (Th17; CD4+CCR6+), regulatory T cells (Treg; CD4+CD25+Foxp3+), and Treg/ICOS+ cells were evaluated. According to human leukocyte antigen (HLA) haplotypes, subjects were classified as "at risk" (HLA+), "protective haplotypes" (HLA-; "nested controls"), and "undetermined" (HLAUND). T1D and S subjects were supplemented with cholecalciferol 1000 IU/die and evaluated after 6 months.Results: Vitamin D insufficiency (74.4%) and deficiency (43%) were frequent. S subjects with 25(OH)D levels <25 nmol/L had Th17, Treg (p < 0.01), and Treg/ICOS+ (P < 0.05) percentages higher than subjects with 25(OH)D >75 nmol/L. Treg/ICOS+ percentages (P < 0.05) were higher in HLA- S subjects compared to percentages observed in S with T1D. At baseline, in S subjects, a decreasing trend in Th17 and Treg/ICOS+ values (P < 0.05) from vitamin D deficiency to sufficiency was observed; 25(OH)D levels were negative predictors of Treg/ICOS+ (R2 = 0.301) and Th17 percentages (R2 = 0.138). After 6 months, supplemented S subjects showed higher 25(OH)D levels (P < 0.0001), and lower Th17 (P < 0.0001) and Treg/ICOS+ (P < 0.05) percentages than at baseline; supplemented T1D patients only had a decrease in Th17 levels (P < 0.05).Conclusion: Serum 25(OH)D levels seem to affect Th17 and Treg cell subsets in S subjects, consistent with its immunomodulating role. HLA role should be investigated in a larger population. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a common autoimmune disease that is characterized by insufficient insulin production. The onset of T1D is the result of gene-environment interactions. Sociodemographic and behavioural factors may contribute to T1D, and the gut microbiota is proposed to be a driving factor of T1D. An integrated preventive strategy for T1D is not available at present. This case–control study attempted to estimate the exposure linked to T1D to identify significant risk factors for healthy children. Forty children with T1D and 56 healthy controls were included in this study. Anthropometric, socio-economic, nutritional, behavioural, and clinical data were collected. Faecal bacteria were investigated by molecular methods. The findings showed, in multivariable model, that the risk factors for T1D include higher Firmicutes levels (OR 7.30; IC 2.26–23.54) and higher carbohydrate intake (OR 1.03; IC 1.01–1.05), whereas having a greater amount of Bifidobacterium in the gut (OR 0.13; IC 0.05 – 0.34) was a protective factor for T1D. These findings may facilitate the development of preventive strategies for T1D, such as performing genetic screening, characterizing the gut microbiota, and managing nutritional and social factors. [ABSTRACT FROM AUTHOR]

A new technique for estimating postprandial glucose flux profiles without the use of glucose tracers is proposed. A sparse vector space representation is first found for the space of plausible glucose flux profiles using sparse encoding. A Lasso formulation is then used to estimate the glucose fluxes that combines (1) known patient model parameters; (2) the vector space of plausible glucose flux profiles; (3) continuous glucose monitor measurements taken during the meal; (4) amount of insulin injected; (5) amount of meal carbohydrates; and (6) an estimate of the initial conditions. Three glucose fluxes are then estimated, namely; glucose rate of appearance from the intestine; endogenous glucose production from the liver; insulin dependent glucose utilization; and other important state variables. The simulation results show that the technique is capable of estimating the glucose fluxes with high accuracy, even for complex meal scenarios. The experimental results indicate that the technique is capable of reproducing the triple tracer measurements for three T1DM undergoing the triple tracer protocol while estimating the missing measurements for a certain model parameter selection. [ABSTRACT FROM AUTHOR]

Human endogenous retroviruses (HERVs) have been studied and proposed as relevant cofactors in several autoimmune diseases, including type 1 diabetes (T1D), though with controversial results and no study at disease onset. In order to gather further information on the potential role of HERVs in the development of T1D we assessed the transcription levels of pol genes of HERV-H, HERV-K, and HERV-W in peripheral leucocytes from 37 children and adolescents with new-onset T1D and 50 age-matched control subjects. A PCR real time Taqman amplification assay was used to evaluate HERV transcripts with normalisation of the results to glyceraldehyde-3-phosphate dehydrogenase. The expression levels of HERV-H-pol gene and HERV-W-pol gene were significantly higher in diabetic patients than in control subjects. Conversely, no significant difference emerged in the expression levels of HERV-K-pol gene between diabetic patients and controls. The activation of HERV-H and HERV-W in new-onset T1D suggests their importance in the pathogenesis of the disease and supports targeted therapeutic attempts to hinder their activation. [ABSTRACT FROM AUTHOR]

Objective: After a previous survey on the incidence of diabetic ketoacidosis (DKA) at onset of type 1 diabetes in children in 2013-2014 in Italy, we aimed to verify a possible decline in the incidence of DKA at onset during a national prevention campaign.Design: Prospective observational study.Setting: Multicentre study throughout Italy.Intervention: National awareness campaign started in November 2015 and held until December 2017.Patients: During 2016 and 2017 we collected data on all patients aged 0-18 years with new-onset diabetes.Main Outcome Measures: DKA (pH <7.30), severe DKA (pH <7.1), DKA in children below 6 years and DKA treatment according to the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) protocol were evaluated.Results: Records (n=2361) of children with newly diagnosed type 1 diabetes were collected from 58 out of 68 (85.3%) centres of the original survey participants and 100% of the previously surveyed tertiary centres. Overall, DKA was observed in 1124 patients, with an increased rate when compared with the previous survey (47.6% vs 38.5%, p=0.002), and severe DKA in 15.3%. In children below 6 years, DKA was observed in 323 out of 617 (52.5%) and severe DKA in 16.7%; in this age group, occurrence of DKA reduced by 21.3% (p=0.009). DKA treatment according to the ISPED guidelines was adopted in 95% of the centres, with a 27% improvement (p=0.025).Conclusions: During a 2-year awareness campaign, DKA at onset of diabetes in children and adolescents 0-18 years is still common and increased when compared with the 2013-2014 survey. [ABSTRACT FROM AUTHOR]

Aims: Hypoglycemia in small children with type 1 diabetes is difficult to manage if nausea, vomit or food refusal occurs. If oral carbohydrate cannot be used, there is a hypothetical risk of severe hypoglycemia. The present article describes the effect on glucose of small doses of subcutaneous glucagon to revert hypoglycemia and prevent severe events in small children with type 1 diabetes using a continuous glucose monitoring. Methods: We analyzed 4 episodes of impending or mild hypoglycemia in 3 children with type 1 diabetes who refused to eat carbohydrates. Using a standard U-100 insulin syringe, children received one "unit" (10 μg) of glucagon subcutaneously for every year of age up to 15 units (150 μg). If the blood glucose did not increase within 30 min, the initial dosage was repeated at that time. Instructions were given by phone from the physician. At the following visit data from continuous glucose monitoring devices, insulin pump and glucometer were downloaded and reviewed retrospectively from the physician. Results: Blood glucose from continuous glucose monitoring after one and 2 h was 127 ± 80 mg/dl and 165 ± 78 mg/dl, respectively. After a glucagon injection, there was a single recurrence of hypoglycemia, requiring another shot. The glucagon was well tolerated, except for nausea, present before the injection. None of the children were taken to our hospital because of concerns for hypoglycemia. Conclusion: Mini-doses of glucagon given subcutaneously were effective and safe in preventing frank or impending hypoglycemia in type 1 diabetes children refusing food. [ABSTRACT FROM AUTHOR]

Background/Objective: In 1993, the Diabetes Control and Complications Trial (DCCT) found that intensive antihyperglycemic therapy was effective in the primary and secondary prevention of microvascular complications in patients with type 1 diabetes (T1D) but was associated with a 3‐fold greater rate of severe hypoglycemia (SH) than conventional therapy. The aim of this analysis was to determine whether, in the real‐world setting, the incidence of SH in pediatric patients with T1D has changed since 1993. Methods: A systematic literature search of PubMed for prospective or retrospective observational studies (≥250 participants) on SH epidemiology or related topics in pediatric patients with T1D, published between October 1993 and June 2016, identified 35 articles (involving >55 000 participants). SH incidence data were analyzed in approximate 5‐year blocks: 1993‐2000, 2001‐2005, 2006‐2010, and 2011‐2016. Information on factors that might influence the incidence of SH was also collected. Results: A trend for a marked reduction in the incidence of SH in the post‐DCCT setting (from 62.0 per 100 patient‐years to 1.21‐30 per 100 patient‐years) was apparent. Factors that could have influenced this temporal trend in SH incidence included the increased use of new types of, and methods of administering, insulin, in particular rapid‐acting insulin analogs and continuous subcutaneous insulin infusion. Conclusions: SH in pediatric patients with T1D has declined in incidence since the DCCT but remains a common problem. The optimal use of new insulin therapies/regimens/technologies, improved education, and dedicated specialized management teams are needed to help reduce the risk of SH in this population. [ABSTRACT FROM AUTHOR]

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

Aim: To evaluate the incidence of insulin pump and infusion set failures in a cohort of children and adolescents with type 1 diabetes during a 1‐year follow‐up. Materials and Methods: Insulin pump breakdown and infusion set failures were prospectively registered in a cohort of 1046 children and adolescents from 25 tertiary pediatric diabetes centres (50% male, mean age 12.2 ± 4.1 years), with type 1 diabetes from the age of 6.7 ± 3.6 years, and using an insulin pump from the age of 3.3 ± 2.2 years. Results: An average rate of 4.5 failures/person‐year was registered; the incidences (events per person‐year) for each failure were 8.4 for hyperglycaemia episodes solved with infusion set change, 7 for bubbles, 2.8 for kinking, 2.4 for bleeding, 2 for set dislodge, 2 for pump blockage, 1.9 for tunnelling, 1.8 for lipohypertrophy, and 0.3 for infection. At multivariate analysis significant association between HbA1c and lipohypertrophy (P < 0.0028) was shown. Analysis by age group (<6, 6–11, >11 years) showed a higher frequency of bubbles, hyperglycaemia episodes and lipohypertrophy in preschoolers; tunnelling and pump blockage were more frequent in adolescents. Aspart was associated with a lower risk of bubbles and hyperglycaemia whereas glulisine was associated with a higher risk of lipohypertrophy and pump blockage. The usage of oblique cannula was associated with a low risk of all failures except infections. Conclusions: This prospective 1‐year study on a large cohort of Italian children and adolescents with type 1 diabetes using insulin pump therapy showed a low total failure rate, highlighting the importance of continuous education to reduce failures. Lipohypertrophy was the only issue associated with a worsening of metabolic control. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Neonatal diabetes mellitus (NDM) is a rare disorder, and guidance is limited regarding its optimal management. We reviewed insulin usage in NDM, with a focus on continuous subcutaneous insulin infusion (CSII).Methods: A PubMed search identified 40 reports of patients with NDM treated with insulin published between 1994 and 2016.Results: Data concerning treatment of NDM are limited. CSII resolves some of the issues associated with insulin therapy in neonates. No clinical trials of CSII in NDM have been reported. Case reports suggest that CSII is a safe and effective means of treating NDM. CSII was initiated to improve glycaemic control, for practicality and convenience, and to overcome difficulties associated with the maintenance of long-term intravenous catheters. CSII can provide better glycaemic control than multiple daily injections, with few hypoglycaemic events. Continuous glucose monitoring integrated with the pump helps provide more precise control of blood glucose levels. CSII generally uses short-acting insulin or rapid-acting insulin analogues, and those that are approved for use in neonates appear to be appropriate for the treatment of NDM using an insulin pump.Conclusions: Information from case reports indicates that CSII is safe and effective for the management of NDM. [ABSTRACT FROM AUTHOR]

Objective To identify the role of the family's socio-economic and clinical characteristics on metabolic control in children and adolescents with type 1 diabetes. Methods In this cross-sectional, multicentre study, 768 subjects with type 1 diabetes under 18 years of age were consecutively recruited from January 2008 to February 2009. Target condition was considered for HbA1c values <7.5% (<58 mmol/mol). A multiple correspondence analysis ( MCA) was performed to analyze the association between the socio-economic and clinical characteristics of the participants. A logistic regression analysis was performed to identify factors associated with the subjects metabolic control. In both analyses, the family's socio-economic status was represented, measured by the Hollingshead Four-Factor Index of Social Status ( SES) or by parental years of education. Results A total of 28.1% of subjects reached target HbA1c values. The MCA identified a strong association between at-target condition and several factors: high levels of SES or high levels of parental education, the use of the carbohydrate counting system, the use of insulin pumps, the use of the insulin delivery system over a short period of time, a normal body mass index. The logistic regression analysis showed that SES and the mother's years of education were significantly associated with the target condition [odds ratio ( OR): 1.01, 95% confidence interval ( CI): 1.01-1.03, p = 0.029; OR: 1.05, 95% CI: 1.01-1.10, p = 0.027, respectively). Conclusions Personal, clinical, and family characteristics were found to be associated with HbA1c target. Their identification can be crucial in addressing strategies to optimize metabolic control and improve diabetes management. [ABSTRACT FROM AUTHOR]

Correction to: Increased incidence of type 1 diabetes in 2 years of COVID-19 pandemic B Correction to: Acta Diabetologica b https://doi.org/10.1007/s00592-022-01986-w The given name and family name of co-authors corrected in original publication. The original article can be found online at https://doi.org/10.1007/s00592-022-01986-w. [Extracted from the article]

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

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

Aims: To assess whether vitamin D levels at birth were associated with risk of having type 1 diabetes up to 10 years of age and the potential modifier effect of ethnic group. Methods: The Piedmont Diabetes Registry and the Newborn Screening Regional data were linked to identify cases ( n = 67 incident children aged ≤10 years at diabetes onset, 2002-2012) and up to five controls ( n = 236) matched for birthday and ethnic group. Cards with neonatal blood spot were used and 25-hydroxyvitamin D(3) assessed with tandem mass spectroscopy. Results: In conditional logistic regression, OR for unit increment of log vitamin D was 0.78 (95 % CI 0.56-1.10). Vitamin D was significantly lower in migrant than in Italian control newborn babies ( p < 0.0001), and interaction between vitamin D and migrant status was statistically significant ( p = 0.04). Compared to migrant newborns babies with vitamin D ≥ 2.14 ng/ml, migrants with lower levels had an OR of 14.02 (1.76-111.70), whereas no association was evident in Italians. Conclusions: Our case-control study within the Piedmont Diabetes Registry showed no association between vitamin D levels at birth and risk of having type 1 diabetes up to 10 years of age, apart from the subgroup of migrant babies, which might have clinical implications if confirmed. [ABSTRACT FROM AUTHOR]

Nasal glucagon is an easy-to-deliver, needle-free, single-use, drug-device combination containing 3 mg of dry glucagon,3,4 thereby overcoming reported patient resistance to using injectable preparations.5 In a recent meta-analysis of randomized controlled trials,6 nasal glucagon was as effective as injected glucagon for treating hypoglycaemia, and an open-label study of nasal glucagon showed that it was effective in treating moderate, symptomatic, hypoglycaemic events in children and adolescents with T1D.7 However, real-world data (i.e. outside study settings) on nasal glucagon knowledge, use and efficacy in children and adolescents with T1D are limited. This case is consistent with trial data showing that nasal glucagon is safe and effective.6 However, the survey showed that not all Italian paediatric patients know about nasal glucagon and, of those that do, only a few bought it, still preferring the injectable form, probably because nasal glucagon is not yet reimbursed and must be paid out of pocket (140 euros) rather than through the public health system. The single patient needing to use nasal glucagon mirrors the low incidence of severe hypoglycaemia in Italy,4 but without knowing why people were either unaware of nasal glucagon or aware of it but had not bought it makes it difficult to understand precisely what drives its use. [Extracted from the article]

The article presents the observational perspective anonymous data collection that aims to assess the effectiveness and safety of the predictive low glucose management (PLGM) system in free-living conditions. A group of young patients with type 1 diabetes took part of the study and used the system. Findings of the study confirm the efficacy of PLGM in adolescents suffering type 1 diabetes both in usual care conditions and in real-world setting.

Background The PedsQL™3.0 Diabetes Module is a widely used instrument to measure the diseasespecific health-related quality of life summary measures in children and adolescents with type 1 diabetes. After cultural adaptation, we confirmed reliability and validity of PedsQL™3.0 Diabetes Module in its Italian version. Methods Participants were 169 Italian children and adolescents with type 1 diabetes aged 5-18 years and 100 parents. Reliability was determined by internal consistency using Cronbach's coefficient alpha, and test-retest reliability by intra-class correlation coefficient (ICC). Validity was assessed through factor validity examined by exploratory factor analysis, and discriminant validity examined through multitrait/multi-item scaling analysis. Discriminant validity with respect to dichotomous patients' characteristics at baseline was also examined through a multivariate analysis on the summary measures using the Wilks' Lambda test. Results Data completeness was optimal. Item internal consistency was satisfied at 89% for the child self-report scales and at 100% for the parents' proxy-report scales. Most diabetes module scales was acceptable for group comparisons. Discriminant validity was satisfied for 71% of children and adolescents and for 82% of parents. A ≥70% Cronbach's a coefficient was found for the summary measures of both reports. For the test-retest reliability, the ICC coefficients ranged from 0.66 (i.e., the Worry scale) to 0.82 for the other scales of the child self-report. The ICC coefficients were ≥0.87 for all the parents' proxy-report scales. Factor analysis showed that the PedsQL™3.0 Diabetes Module for child self-report could be summarized in 10 components, which explained the 62% of the variance. For the parent proxy-report the statistical analysis selected 9 factors, which explained about 68% of variance. The external discriminant validity of the PedsQL™3.0 Diabetes Module summary measures were compared across gender, age, time since diagnosis and HbA1c mean cut off values. Significant differences in the "Treatment adherence" scale and in the "Communication" scale were observed across age, and by time since diagnosis. Conclusions The results show the reliability and validity of the Italian translation of the PedsQL™3.0 Diabetes Module, supporting therefore its use as an outcome measure for diabetes crossnational clinical trials and research. [ABSTRACT FROM AUTHOR]