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Objective: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales)., Subjects and Methods: Data on individuals aged 10-21 years with T1D for >1 year during the period 2000-2020 were analyzed. We used a cross-sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR., Results: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aOR per-1-year-increase  = 1.04, 95% CI: 1.03-1.04, p < 0.0001), and decreased over time (aOR per-1-year-increase  = 0.99, 95% CI: 0.98-1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aOR per-1-mmol/mol-increase-in-HbA1c  = 1.03, 95% CI: 1.03-1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11-1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17-1.44, p < 0.0001)., Conclusions: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Objective: The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success., Methods: All past attendees from 2000-2019 ISSP and 2004-2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities., Results: One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys. Most of ISSP attendees reported that the programs supported their career (82%) by helping to achieve a research position (59%), being engaged with diabetes care (68%) or research (63%) or starting a research fellowship (59%). Responders indicated that ISSP was effective in increasing interest in diabetes research (87%) and enhancing the number (66%) and quality (83%) of scientific productions, and promotion of international collaborations (86%). After the ISSP, 34% of responders received research grants. From the first round of the ISSHP survey (2004-2013), responders reported have improved knowledge (60%), gained more confidence in research (69%), undertaken a research project (63%), and achieved a higher academic degree (27%). From the second round (2014-2019), participants indicated that the program was valuable/useful in workplace (94%) through understanding (89%) and conducting (68%) research and establishing communication from other participants (64%) or from faculty (42%). After the ISSHP, 17% had received awards., Conclusions: From the participants' viewpoint, both programs were effective in improving engagement with diabetes research, supporting career opportunities, increasing scientific skills, and enhancing networking and research activities., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Telemedicine for routine care of people with diabetes (PwD) during the COVID-19 pandemic rapidly increased in many countries, helping to address the several barriers usually seen., Objective: This study aimed to describe healthcare professionals' (HCPs) experience on telemedicine use in diabetes care and investigate the changes and challenges associated with its implementation., Methods: A cross-sectional electronic survey was distributed through the global network of JENIOUS members of ISPAD. Respondents' professional and practice profiles, clinic sizes, their country of practice, and data regarding local telemedicine practices during COVID-19 pandemic were investigated., Results: Answers from 209 HCPs from 33 countries were analyzed. During the pandemic, the proportion of PwD receiving telemedicine visits increased from <10% (65.1% of responders) to >50% (66.5%). There was an increase in specific privacy requirements for remote visits (37.3% to 75.6%), data protection policies (42.6% to 74.2%) and reimbursement for remote care (from 41.1% to 76.6%). Overall, 83.3% HCPs reported to be satisfied with the use of telemedicine. Some concerns (17.5%) about the complexity and heterogeneity of the digital platforms to be managed in everyday practice remain, feeding the need for unifying and making interoperable the tools for remote care. Also, 45.5% of professionals reported to feel stressed by the need for extra-time for telemedicine consultations., Conclusions: Telemedicine was rapidly and broadly adopted during the pandemic globally. Some issues related to its use were promptly addressed by local institutions. Challenges with the use of different platforms and for the need of extra-time still remain to be solved., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We present the results of the pilot study of a multinational "Diabetes Know-Me" project investigating knowledge regarding diabetes of medical students. This is the first collaborative project of the ISPAD JENIOUS group., Methods: Students of the final year of medical studies from six countries answered a 25-question survey regarding basic knowledge concerning diabetes (1091 surveys handed out, response rate 86%)., Results: Among the responders (58% female) 90% confirmed attending diabetology classes; 11% planned to specialize in diabetology. There were significant differences between countries in the median score of correct answers ranging from 10/25 to 22/25. Attending diabetes classes (20 vs. 13/25, p < 0.0001) was the strongest factor associated with improved knowledge about diabetes (other factors analyzed were: gender, familiar/personal experience of diabetes, interest to specialize in diabetology)., Conclusions: Basic knowledge about diabetes remains a challenge. Participating in classes concerning diabetes contributed the most to the diabetes-related knowledge among students of the final year of medical faculties., (© 2021 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes., (© 2020 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Background: Coronavirus diasease (COVID-19) is an infectious disease that started in Wuhan, China in late 2019 and later spread around the world. Diabetes has been recognized as a possible risk factor for COVID-19 complications., Objective: International Society for Pediatric and Adolescent Diabetes (ISPAD) investigated perceptions, challenges and experience of health care professionals (HCP) taking care of children and young people with diabetes worldwide during COVID-19 pandemic., Methods: From 21st April to 17th May 2020, during COVID-19 pandemic, a web-based survey was sent to ISPAD members and former participants of ISPAD conferences by email., Results: Responders from 215 diabetes centers from 75 countries completed the survey. Majority were from UK (35; 16.3%), USA (20; 9.3%), and India (15; 7%). HCP were mostly pediatric endocrinologists (64%). During COVID-19 pandemic, 16.5% of responders continued face-to-face consultation while most changed to telephone (32%) or video (18%) consultations. 19% reported a shortage of medical supplies. 22% reported a delay in diagnosis of patients with new-onset diabetes, while 15% reported a higher incidence of DKA. 12% reported having one or more patients with COVID-19. Most of the 86 children and adolescents with diabetes and COVID-19 had only mild/moderate symptoms, while 5 required admission to an intensive care unit. No deaths were reported., Conclusions: This large global survey during COVID-19 pandemic showed that many HCP adapted to the pandemic by resorting to telemedicine. One fourth of HCP reported delays in diagnosis and an increased rate of DKA. The emergence of COVID-19 pandemic had an important impact on family's behavior that might have led to increase in diabetic ketoacidosis presentation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Visceral adipose tissue (VAT) accumulation is a major cardiometabolic risk factor, associated with increased inflammation. Oxidative stress (OS) is also associated with inflammation and cardiometabolic issues, yet mainly through general obesity. Both OS and obesity were linked to vitamin D deficiency., Objectives: To investigate whether OS increase is associated with VAT accumulation in youth, and whether in the presence of VAT accumulation, a higher vitamin D status is associated with lower OS., Methods: One hundred and fifty-eight youth with overweight/obesity, 7 to 17 years old, were recruited (Pediatric Clinic, Luxembourg). We assessed visceral and subcutaneous abdominal adipose tissues by magnetic resonance imaging, OS by DNA/RNA oxidative damage with ELISA and vitamin D by high-performance liquid chromatography., Results: VAT was the body fat compartment the most strongly associated with OS (R Pearson : 0.298; P < 10 -4 ). The general linear (GLM) models assessing the relationship between OS, VAT and vitamin D concentrations showed that "Log 10 OS = (0.003 × VAT) + 3.911 (R 2 adjusted : 0.083; P-value < 10 -4 )"; "Log 10 OS = (0.003 × VAT) - (0.156 × log 10 vitamin D) + 4.110 (R 2 adjusted : 0.101; P-value < 10 -4 )". After back-transformation of the log-values into normal values, the GLM showed that, for a person with an average value of VAT (40.7 cm 2 ), a 10 cm 2 increase in VAT would increase OS by approx. 771.833 pg/mL, after age, gender, Tanner stage and physical activity adjustment. An approximate increase of 9 ng/mL of vitamin D would counterbalance this negative effect of increased VAT., Conclusion: Dietary strategies improving vitamin D status should be investigated to tackle VAT and OS increase., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the experiences of families with very young children aged 1 to 7 years (inclusive) with type 1 diabetes using day-and-night hybrid closed-loop insulin delivery., Methods: Parents/caregivers of 20 children aged 1 to 7 years with type 1 diabetes completed a closed-loop experience survey following two 3-week periods of unrestricted day-and-night hybrid closed-loop insulin therapy using Cambridge FlorenceM system at home. Benefits, limitations, and improvements of closed-loop technology were explored., Results: Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed-loop. Ninety percent of the responders felt less worried about their child's glucose control using closed-loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets., Conclusions: Parents/caregivers of very young children reported important quality of life benefits associated with using closed-loop, supporting adoption of this technology in this population., (© 2019 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Objective: To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET)., Methods: Data were collected from 55 centers with documented patients' height. All subjects below 20 years of age, diabetes duration >1 year, and without celiac disease were included. World Health Organization growth charts were used to calculate height and body mass index z-scores. Multiple hierarchic regression models adjusting for known confounders were applied., Results: Data on 22 941 subjects (51.8% male) were analyzed with a median and interquartile range for age 14.8 years (11.2, 17.6), diabetes duration 5.6 years (3.1, 8.9), and height z-score 0.34 (-0.37, 1.03). Children were taller in the youngest age groups: adjusted height z-scores of 0.31 (±0.06) and 0.39 (±0.06), respectively; with shorter diabetes duration (<2 years: 0.36 [±0.06]; 2-<5 years: 0.34 [±0.06]; ≥5 years: 0.21 [±0.06]) and if they were pump users: 0.35 ± 0.05 vs 0.25 ± 0.05 (>three injections/day and 0.19 ± 0.06 [0-3 injections daily]), respectively. High hemoglobin A1c (HbA1c) and low to normal weight were associated with a lower height z-score. Trends were identical in all models except for gender. No gender differences were found except in the final height model where females exhibited higher z-score than males., Conclusion: For youths treated at centers offering modern diabetes management, major growth disturbances are virtually eliminated. For children with a young age at onset, high HbA1c, injections, and/or non-intensive diabetes, treatment still requires attention in order to attain normal growth., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To examine and compare the clinical characteristics and treatment of youth with type 2 diabetes (T2D) in two registries: one in Europe and one in the United States., Methods: Youth with onset of T2D at 10 to 18 years of age with current age <20 years and an office visit after diabetes duration >1 year were identified in the European (Prospective Diabetes Follow-up, DPV) and the United States (Pediatric Diabetes Consortium, PDC) databases. Demographic, physical and clinical characteristics and treatment at diagnosis as well as physical characteristics, treatment, laboratory data, and diabetes adverse events at most recent visit were analyzed from both registries., Results: At diagnosis, the majority were female and obese; 70% of DPV vs 34% of PDC youth were diagnosed by targeted diabetes testing. PDC youth were younger, 12 vs 13 years (P < 0.001), had a greater body mass index-SDS, 3.07 vs 2.74 (P < 0.001), a higher hemoglobin A1c (HbA1c), 9.9% vs 7.1% (P < 0.001), were more likely to present in DKA, 7.5% vs 1.3% (P < 0.001) and more likely to be treated with insulin, 62% vs 32% (P < 0.001); insulin treatment difference was not significant when adjusted for HbA1c. At follow-up, DPV youth had shorter diabetes duration, 2.1 vs 3.2 years (P < 0.001), lower HbA1c, 6.5% vs 7.8% (P < 0.001), were less likely to be treated with insulin, 36% vs 56%, (P < 0.001), and were more likely to have dyslipidemia and hypertension than PDC youth. PDC youth had a higher rate of microalbuminuria., Conclusions: Both DPV and PDC youth have multiple risks for diabetes complications. Understanding reasons for persistently higher HbA1c in PDC youth requires further study., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the prevalence of underweight (UW), overweight (OW), and obesity in children and adolescents with type 1 diabetes (T1D)., Methods: An international cross-sectional study including 23 026 T1D children (2-18 years, duration of diabetes ≥1 year) participating in the SWEET prospective, multicenter diabetes registry. Body mass index SD score (BMI-SDS) was calculated using the World Health Organization BMI charts. Children were categorized as UW (BMI-SDS < -2SD), OW (+1SD < BMI-SDS ≤ +2SD), and obese (OB) (BMI-SDS > +2SD). Hierarchic regression models were applied with adjustment for sex, age, and duration of diabetes., Results: The prevalence of UW, OW, and obesity was: 1.4%, 22.3%, and 7.3% in males and 0.6%, 27.2%, and 6.8% in females. Adjusted BMI-SDS was significantly higher in females than in males (mean ± SEM: 0.54 ± 0.05 vs 0.40 ± 0.05, P < 0.0001). In males, BMI-SDS significantly decreased by age (P < 0.0001) in the first three age categories 0.61 ± 0.06 (2 to <10 years), 0.47 ± 0.06 (10 to <13 years), 0.34 ± 0.05 (13 to <16 years). In females, BMI-SDS showed a U-shaped distribution by age (P < 0.0001): 0.54 ± 0.04 (2 to <10 years), 0.39 ± 0.04 (10 to <13 years), 0.55 ± 0.04 (13 to <16 years). BMI-SDS increased by diabetes duration (<2 years: 0.38 ± 0.05, 2 to <5 years: 0.44 ± 0.05, and ≥5 years: 0.50 ± 0.05, P < 0.0001). Treatment modality did not affect BMI-SDS. Adjusted HbA1c was significantly higher in females than in males (8.20% ± 0.10% vs 8.06% ± 0.10%, P < 0.0001). In both genders, the association between HbA1c and BMI-SDS was U-shaped with the highest HbA1c in the UW and obesity groups., Conclusions: The high rate of OW and obesity (31.8%) emphasize the need for developing further strategies to prevent and treat excess fat accumulation in T1D., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate differences in cardiovascular risk factors and metabolic control in girls with type 1 diabetes with or without use of oral contraceptives (OC) from the multicenter "diabetes prospective follow-up" (DPV) registry., Methods: Twenty-four thousand eleven adolescent girls (13 to < 18 years of age) from Germany, Austria or Luxembourg with type 1 diabetes from the DPV registry were included in this cross-sectional study. Multivariable regression models were applied to compare clinical characteristics (hemoglobin A1c [HbA1 C ], blood pressure, serum lipids, body mass index) and lifestyle factors (smoking, physical inactivity, alcohol consumption) between girls with or without OC use. Confounders: age, diabetes duration and migration background., Statistical Analysis: SAS 9.4., Results: In girls with type 1 diabetes and OC use, clinical characteristics and lifestyle factors were less favorable compared to non-users. Differences were most pronounced for the prevalence of dyslipidemia (OC-users: 40.0% vs non-users: 29.4; P < .0001) and the number of smokers (OC-users: 25.9% vs non-users: 12.5%; P < .0001). OC use, sociodemographic characteristics and lifestyle factors explained between 1 and 7% of the population variance in serum lipids and blood pressure. The use of OC explained a small additional proportion in all variables considered (<1%)., Conclusions: OC use in adolescent girls with type 1 diabetes was associated with a poorer cardiovascular risk profile. Biological risk factors were partly explained by a clustering of sociodemographic and lifestyle factors with a small additional contribution of OC use. Prescription of OC should therefore be combined with a screening for cardiovascular risk factors and targeted education., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The reason for center differences in metabolic control of childhood diabetes is still unknown. We sought to determine to what extent the targets, expectations, and goals that diabetes care professionals have for their patients is a determinant of center differences in metabolic outcomes., Research Design and Methods: Children, under the age of 11 with type 1 diabetes and their parents treated at the study centers participated. Clinical, medical, and demographic data were obtained, along with blood sample for centralized assay. Parents and all members of the diabetes care team completed questionnaires on treatment targets for hemoglobin A1c (HbA1c) and recommended frequency of blood glucose monitoring., Results: Totally 1113 (53% male) children (mean age 8.0 ± 2.1 years) from 18 centers in 17 countries, along with parents and 113 health-care professionals, participated. There were substantial differences in mean HbA1c between centers ranging from 7.3 ± 0.8% (53 mmol/mol ± 8.7) to 8.9 ± 1.1% (74 mmol/mol ± 12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health-care professionals that reported lower targets and more frequent testing, and (3) teams with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac., Conclusions: The diabetes care teams' cohesiveness and perspectives on treatment targets, expectations, and recommendations have an influence on parental targets, contributing to the differences in pediatric diabetes center outcomes., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Few diabetes-specific quality of life (QOL) tools are available for young children., Objectives: To design and evaluate, a new age-specific QOL questionnaire and its associations with treatment regimens and metabolic control., Methods: Clinical, demographic data and centrally analyzed HbA1c were collected on 1133 children <11 years (girls 48%; mean ± SD age 8.0 ± 2.1 years; diabetes duration ≥1 year) from 18 centers (Europe, Japan, North America and Australia). Children completed the 10-item Smiley Faces QOL questionnaire constructed for the study, and children ≥7 years also completed the KIDSCREEN-10 Index., Results: In total, 1035 children completed the new Smiley Faces questionnaire which was well understood by 993 (70% ≥4 years and 96% ≥5 years, respectively). Internal consistency and reliability were good (Cronbach's α = .73). Inter-item correlation ranged r = 0.047 to 0.451 indicating each item measures separate aspects of children's satisfaction construct. Convergent validity assessed by comparison to the HrQOL KIDSCREEN-10 Index showed moderate correlation coefficient 0.501. Factor analysis revealed 3 factors explaining 51% of the variance. Children reported good QOL with most items positive, mean values between 1 and 2 on a 5-point scale (lower scores indicating greater QOL). Diabetes satisfaction was unrelated to age, diabetes duration, HbA1c, or severe hypoglycemia. Girls were more satisfied than boys. Children on intensive regimens reported better QOL (P < .02). Main dissatisfaction related to insulin injections and blood sugar testing., Conclusions: The Smiley Faces questionnaire enables QOL assessment in young children and identification of areas of dissatisfaction and other clinically relevant items relating to diabetes management., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Glucocorticoid (referred to from here on as simply steroid) is used for effective treatment of various inflammatory disorders since its discovery in 1940s. However, these useful drugs cause important side effects, such as impairment of glucose tolerance. We sought to determine the prevalence of steroid-induced impairment of glucose tolerance in pediatric patients on long-term steroid use., Materials and Methods: A cross-sectional, descriptive and hospital-based study. Consenting subjects who met the inclusion criteria were screened with random glucometer measurements repeated twice. An average of both readings obtained from the initial measurement of their random blood glucose (RBG) and a repeat during the next clinic visit was taken as the RBG., Results: Hundred patients were studied, 66 males/34 females. Subjects with nephrotic syndrome were 61 while 39 had asthma. Mean age of 10.13 years (range: 0.5-18 years); mean body mass index (BMI): 18.2 kg/m 2 (range: 6.6 to 26.30 kg/m 2 ). The subjects with nephrotic syndrome were on oral prednisolone while the asthmatics were on inhaled fluticasone, budesonide and oral methylprednisolone. Mean (range) duration of steroid use was 9.74 (0.5-72) months. Mean (range) RBG was 3.49 (3.3-7.5) mmol/L. None of the subjects showed abnormal RBG. However, the RBG was further categorized into low, moderate and high normal RBG. A positive correlation between longer duration of steroid use as well as high doses of both oral and inhaled steroids, and high normal RBG existed (P = .015). No statistically significant relationship existed between body mass index (BMI) percentile and RBG (P = .437)., Conclusion: Low to moderate doses of oral and inhaled steroids should be used when indicated as they are associated with lesser risk of impairment of glucose tolerance in the pediatric population., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control., Objective: To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI., Methods: This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out., Results: Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47-1.55), P < .0001) and the diabetes-related expenditure per capita [odd ratio 1.55 (1.49-1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001)., Conclusions: Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although type 1 diabetes (T1D) remains the most frequent form of diabetes in individuals aged less than 20 years at onset, other forms of diabetes are being increasingly recognized., Objectives: To describe the population of children with other forms of diabetes (non-type 1) included in the multinational SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) database for children with diabetes., Methods: Cases entered in the SWEET database are identified by their physician as T1D, type 2 diabetes (T2D) and other types of diabetes according to the ISPAD classification. Etiologic subgroups are provided for other types of diabetes. Descriptive analyses were tabulated for age at onset, gender, daily insulin doses, and hemoglobin A1c (A1C) for each type and subtype of diabetes and when possible, values were compared., Results: Of the 27 104 patients included in this report, 95.5% have T1D, 1.3% T2D, and 3.2% other forms of diabetes. The two most frequent etiologies for other forms of diabetes were maturity onset diabetes of the young (MODY) (n = 351) and cystic fibrosis-related diabetes (CFRD) (n = 193). The cause was unknown or unreported in 10% of other forms of diabetes. Compared with T1D, children with T2D and CFRD were diagnosed at an older age, took less insulin and had lower A1C (all P < .0001)., Conclusion: In centers included in SWEET, forms of diabetes other than type 1 remain rare and at times difficult to characterize. Sharing clinical information and outcome between SWEET centers on those rare forms of diabetes has the potential to improve management and outcome., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Childhood obesity is associated with early cardiometabolic risk (CMR), increased risk of adulthood obesity, and worse health outcomes. Leg fat mass (LFM) is protective beyond total fat mass (TFM) in adults. However, the limited evidence in children remains controversial., Objective: We investigated the relationship between LFM and CMR factors in youth., Subjects: A total of 203 overweight/obese children, 7-17-yr-old, followed in the Pediatric Clinic, Luxembourg., Methods: TFM and LFM by dual energy x-ray absorptiometry and a detailed set of CMR markers were analyzed., Results: After TFM, age, sex, body mass index (BMI) Z-score, sexual maturity status, and physical activity adjustments, negative significant partial correlations were shown between LFM and homeostasis model assessment of insulin resistance (HOMA) (variance explained: 6.05% by LFM*; 7.18% by TFM**), fasting insulin (variance explained: 5.71% by LFM*; 6.97% by TFM**), triglycerides (variance explained: 3.96% by LFM*; 2.76% by TFM*), systolic blood pressure (variance explained: 2.68% by LFM*; 4.33% by TFM*), C-reactive protein (variance explained: 2.31% by LFM*; 4.28% by TFM*), and resistin (variance explained: 2.16% by LFM*; 3.57% by TFM*). Significant positive partial correlations were observed between LFM and high-density lipoprotein (HDL) cholesterol (variance explained: 4.16% by LFM*) and adiponectin (variance explained: 3.09% by LFM*) (*p-value < 0.05 and **p-value < 0.001). In order to adjust for multiple testing, Benjamini-Hochberg method was applied and the adjusted significance level was determined for each analysis. LFM remained significant in the aforementioned models predicting HOMA, fasting insulin, triglycerides, and HDL cholesterol (Benjamini and Hochberg corrected p-value < 0.01)., Conclusions: LFM is protective against CMR in children, at least in terms of insulin resistance and adverse blood lipid profiles., (© 2015 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Background: The Hvidoere Study Group (HSG) has demonstrated major differences in glycemic control between pediatric diabetes centers which remain largely unexplained. This study investigates whether these differences are partly attributable to healthy eating norms in the background population., Methods: The study involved adolescents from 18 countries from (i) the Health Behaviour in School-Aged Children study (HBSC) and (ii) the HSG. There were 94 387 participants from representative HBSC samples of 11-, 13- and 15-yr-olds and 1483 11- to 15-yr-old adolescents with diabetes from the HSG. The frequency of intake of fruit, vegetables, sweets, sugary soft drinks, and daily breakfast was compared between the two groups. The glycemic control of the adolescents in the HSG cohort was determined by measuring glycated hemoglobin (HbA1c)., Results: Across countries in the HSBC survey, there was substantial variation in prevalence of healthy eating behavior and even greater variation between adolescents from the HSG centers. In all countries more adolescents with diabetes reported healthy eating behavior compared to national norms. In individuals healthy eating behavior had a significant effect on the individual level HbA1c. There was no significant correlation between the frequencies of these healthy eating behaviors at (i) the national level and (ii) diabetes center level and the center mean HbA1c., Conclusions: Although individual healthy eating behavior is associated with better glycemic control at the individual level, such eating behavior does not explain the center differences in HbA1c. Similarly, the reported healthy eating norm of the background populations does not explain the variation in glycemic control among centers., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate whether center differences in glycemic control are present in prepubertal children <11 yr with type 1 diabetes mellitus., Research Design and Methods: This cross-sectional study involved 18 pediatric centers worldwide. All children, <11 y with a diabetes duration ≥12 months were invited to participate. Case Record Forms included information on clinical characteristics, insulin regimens, diabetic ketoacidosis (DKA), severe hypoglycemia, language difficulties, and comorbidities. Hemoglobin A1c (HbA1c) was measured centrally by liquid chromatography (DCCT aligned, range: 4.4-6.3%; IFFC: 25-45 mmol/mol)., Results: A total of 1133 children participated (mean age: 8.0 ± 2.1 y; females: 47.5%, mean diabetes duration: 3.8 ± 2.1 y). HbA1c (overall mean: 8.0 ± 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p < 0.001 resp. p = 0.179). Language difficulties showed a negative relationship with HbA1c (8.3 ± 1.2% vs. 8.0 ± 1.0%; p = 0.036). Frequency of blood glucose monitoring demonstrated a significant but weak association with HbA1c (r = -0.17; p < 0.0001). Although significant different HbA1c levels were obtained with diverse insulin regimens (range: 7.3-8.5%; p < 0.001), center differences remained after adjusting for insulin regimen (p < 0.001). Differences between insulin regimens were no longer significant after adjusting for center effect (p = 0.199)., Conclusions: Center differences in metabolic outcomes are present in children <11 yr, irrespective of diabetes duration, age, or gender. The incidence of severe hypoglycemia is lower than in adolescents despite achieving better glycemic control. Insulin regimens show a significant relationship with HbA1c but do not explain center differences. Each center's effectiveness in using specific treatment strategies remains the key factor for outcome., (© 2012 John Wiley & Sons A/S.)

Background: It is known that the systems of pediatric diabetes care differ across the member states of the European Union (EU). The aim of this project was to characterize some of the main differences among the national systems., Methods: Data were collected using two questionnaires. The first one was distributed among leading centers of pediatric diabetes (one per country) with the aim of establishing an overview of the systems, national policies, quality control (QC) and financing of pediatric diabetes care. Responses were received from all 27 EU countries. The second questionnaire was widely disseminated among all 354 International Society for Pediatric and Adolescent Diabetes members with a domicile in an EU country; it included questions related to individual pediatric diabetes centers. A total of 108 datasets were collected and processed from healthcare professionals who were treating more than 29 000 children and adolescents with diabetes. Data on the reimbursement policies were verified by representatives of the pharmaceutical and medical device companies., Results: The collected data reflect the situation in 2009. There was a notable heterogeneity among the systems for provision of pediatric diabetes care across the EU. Only 20/27 EU countries had a pediatric diabetes register. Nineteen countries had officially recognized centers for pediatric diabetes, but only nine of them had defined criteria for becoming such a center. A system for QC of pediatric diabetes at the national level was reported in 7/26 countries. Reimbursement for treatment varied significantly across the EU, potentially causing inequalities in access to modern technologies., Conclusions: The collected data help develop strategies toward improving equity and access to modern pediatric diabetes care across Europe., (© 2012 John Wiley & Sons A/S.)

Objective: Identify and evaluate current treatment recommendations in Europe for the care of children with diabetes in view of the European Union (EU) recommendations for Reference Centers., Methods: A questionnaire was sent in 2008 to representatives of all EU countries and Norway, all known to be actively involved in pediatric diabetes care. Participants were asked whether specific guidelines were recommended and applied in their countries; when possible, they were invited to forward their national guidelines. As a second step, we evaluated the guideline mostly used in relationship to the recommendations of the EU., Results: Information was obtained from all EU countries (including Scotland and Norway). National guidelines, as available, were forwarded for review. A 15/29 reported to use the International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines (CPCG), whereas 10 reported using national guidelines. These national guidelines were partly based on and/or compatible with ISPAD guidelines, but in most cases were far less detailed. The size and presentation differed (web based, booklet, page or chapter in adult guidelines). In four countries, no specific guidelines were used. As ISPAD CPCG were used most frequently, its content was evaluated within the EU Centres of Reference recommendations and minor changes were made in agreement with the ISPAD editor., Discussion: Differences between guidelines may influence surveillance and quality of care in pediatric diabetes within Europe. Although a majority of countries is using or at least mentioning the ISPAD CPCG, their implementation as EU standard needs further endorsement. As language difficulties may hamper its implementation on a wider scale, further translation of the ISPAD guidelines should be endorsed to render it accessible to all healthcare professionals. With respect to the content, some changes were then made in agreement with the editors, adjusting them to the European context. For European Reference Centers, some further guidance on research may be included. Once implemented on an EU wide level, benchmarking of carefully defined robust quality of care and quality of life indicators will allow us to improve these guidelines on a regular basis ensuring an evidence-based care for all children with diabetes., (© 2012 John Wiley & Sons A/S.)

Background: One of the most important tasks of the SWEET study is benchmarking the data collected. Information on the occurrence of the disease of diabetes, the treatment, and their outcomes in children from the different member states of European Union (EU) is crucial. How the collection of data is realized is essential, concerning both the technical issues and the results. The creation of SWEET Centers of Reference (CoR), all over Europe will be facilitated by the access to safe data collection, where legal aspects and privacy are ascertained., Objective: To describe the rationale for- and the technical procedure in the data collection implementation, in the SWEET study., Subjects: Selected data on all patients treated at SWEET CoR are collected., Methods: The SWEET project data collection and management system, consists of modular components for data collection, online data interchange, and a database for statistical analysis., Conclusion: The SWEET study and the organization of CoR aims for the goal of offering an updated, secure, and continuous evaluation of diabetes treatment regimens for all children with diabetes in Europe. To support this goal, an appropriate and secure data management system as described in this paper has been created., (© 2012 John Wiley & Sons A/S.)

Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes., Methods: Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C ≤ 9%. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA)., Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p < 0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p < 0.0001) and IA (p = 0.0024, p = 0.0068, p < 0.0001) at 1, 6, and 12 months. Glucagon (p < 0.0001 and p < 0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002)., Conclusions: In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function., (© 2011 John Wiley & Sons A/S.)

Type 1 diabetes is treated with insulin, which has traditionally been delivered by vial and syringe. However, for many patients, dosing inaccuracy, pain, anxiety, inconvenience, and social acceptability present barriers to this method of administration (1-5). This has contributed to the increased popularity of alternative insulin delivery systems, including pen delivery devices (4, 6). Evidence suggests that discreet devices, such as insulin pens, facilitate adherence to intensive insulin therapy regimens, help improve lifestyle flexibility, and reduce injection pain compared with the conventional syringe-based regimens, as shown in studies in adults and adolescents (7). In addition, compared with the vial and syringe method of insulin administration, pens may provide more accurate dosing - which is particularly important in children - thereby improving short-term blood glucose control and potentially improving long-term outcomes (5, 8). Children, in particular, may benefit from insulin pens that are simple to use as adherence issues may be more evident in this patient group (9). Pens for insulin delivery in children with type 1 diabetes have been used for a long time in Europe, and have recently gained in popularity in many other places around the world (4, 10). Furthermore, the conventional vial and syringe method of insulin delivery is beginning to be considered as obsolete (11). Moreover, there is a continued drive to improve insulin pen technology, to refine and enhance the functionality and usability of these pens. However, despite recent advances in pen design and function, the selection of pens available especially for children is limited., (© 2011 John Wiley & Sons A/S.)

Objective: To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D)., Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal-stimulated C-peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally., Results: Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta-cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C-peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C-peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C-peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non-white Caucasian ethnicity (p = 0.002)., Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta-cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month.

Objectives: The purpose of this study is to evaluate the practices of diabetes health care providers concerning the transition from pediatric to adult diabetes care. The information presented here may help increase awareness of the organization of transitional care for young people with diabetes and prevent the loss of follow-up during this vulnerable period in their lives., Methods: A questionnaire with an explanatory letter was sent to all members (n = 578) of the International Society for Pediatric and Adolescent Diabetes (ISPAD). A follow-up mailing was sent 4 months later., Results: In total, 92 questionnaires (16%) from members representing 36 countries were included in the analysis. In 76% of the centers, youth are seen until the age of 18 yr; 36% of the pediatric centers see adults > 25 yr; 30% report children under the age of 16 receive follow up from adult diabetologists or internists. About half of the programs already have a structured transition process usually targeting youth 16-25 yr of age. The majority of responders propose that preparation for transition starts at least 1 yr prior to leaving the pediatric center., Conclusion: Youth with type 1 diabetes often struggle to keep diabetes management a priority and find it challenging to maintain optimal metabolic control. When they graduate from pediatric care, some of these young people opt out of care altogether, only to resurface in the medical system when they develop complications which may have been prevented. Our survey of diabetes health care professionals in 36 countries worldwide shows that the actual transition practices in many places are far from optimal and require improvement. Transitional care should start early and strategies should promote uninterrupted, comprehensive, and accessible adult care.

Objective: To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90-d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel., Methods: Data of patients (1-18 yr) treated with CSII in 23 centers from nine European countries and Israel were recorded with the encapture software (PEC International, Frankfurt, Germany). The number of patients who participated was 377 (48% female; mean diabetes duration +/- SD: 6.8 +/- 3.7 yr; age: 12.9 +/- 3.8 yr, preschool n = 33; prepubertal n = 95; adolescent n = 249; CSII duration: 1.6 +/- 1.2 yr; local HbA1c: 8.1 +/- 1.2%)., Results: The total insulin dose was lower than previously reported for injection therapy (0.79 +/- 0.20 U/kg/d). Covariance coefficient of daily total insulin was high in all age groups (adolescents 19 +/- 9%, prepubertal 18 +/- 8 and preschool 17 +/- 8). The distribution of basal insulin infusion rates over 24 hr (48 +/- 12% of total dose) varied significantly between centers and age groups. The number of boluses per day (7 +/- 3) was not significantly different between the age groups (average daily bolus amount: 0.42 +/- 0.16 U/kg). The rate of severe hypoglycemia (coma/convulsions) was 12.4 episodes per 100 patient-years and the number of diabetes-related hospital days was 124 per 100 patient-years., Discussion: Pediatric CSII patients show a high variability in their insulin therapy. This relates both to age-dependent differences in the distribution of basal insulin as to the age-independent day-to-day variation in prandial insulin.