B Aschemeier

Criteria for Centers of Reference for pediatric diabetes – a European perspective

‘SWEET’ is an acronym standing for ‘Better control in pediatric and adolescent diabeteS: Working to crEate CEnTers of Reference (CORs)’ and is based on a partnership of established national and European diabetes organizations such as International Diabetes Federation, Federation of European Nurses in Diabetes, and Primary Care Diabetes Europe (PCDE, www.sweet-project.eu). A three‐level classification of centers has been put forward. In addition to centers for local care, SWEET collaborating centers on their way to being a COR have been defined. Peer‐audited CORs with a continuous electronic documentation of at least 150 pediatric patients with diabetes treated by a multidisciplinary team based on the International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice recommendations have been created in 12 European countries. In 2011, they cared for between 150 to more than 700 youth with diabetes with an average hemoglobin A1c between 7.6 and 9.2%. Although these clinics should not be regarded as representative for the whole country, the acknowledgment as COR includes a common objective of targets and guidelines as well as recognition of expertise in treatment and education at the center. In a first step, the SWEET Online platform allows 12 countries using 11 languages to connect to one unified diabetes database. Aggregate data are de‐identified and exported for longitudinal health and economic data analysis. Through their network, the CORs wish to obtain political influence on a national and international level and to facilitate dissemination of new approaches and techniques. The SWEET project hopes to extend from the initial group of centers within countries, throughout Europe, and beyond with the help of the ISPAD network.

Insulin degludec's ultra-long pharmacokinetic properties observed in adults are retained in children and adolescents with type 1 diabetes.

Insulin degludec (IDeg) is a basal insulin with an ultra‐long pharmacokinetic profile in adults that at steady‐state produces remarkably flat and stable insulin levels; however, no studies have yet reported on the pharmacokinetic properties of IDeg in subjects younger than 18 years of age. This was a single‐centre, randomised, single‐dose, double‐blind, two‐period crossover trial conducted in children (6–11 years), adolescents (12–17 years), and adults (18–65 years) with type 1 diabetes. Subjects received a single subcutaneous dose of 0.4 U/kg IDeg or insulin glargine (IGlar), respectively, on two separate dosing visits, with pharmacokinetic blood sampling up to 72‐h postdose. A total of 37 subjects (12 children, 13 adolescents, and 12 adults) completed the trial. Total exposure of IDeg after a single dose (AUCIDeg,0‐∞,SD) was higher in children compared to adults [estimated ratio children/adults 1.48 (95% confidence interval, CI: 0.98; 2.24)] and in adolescents compared to adults [estimated ratio adolescents/adults 1.33 (95% CI: 1.08; 1.64)]; however, the difference was only statistically significant for the latter comparison. No statistically significant difference in maximum concentration of IDeg (Cmax,IDeg,SD) was observed. Estimated ratios for Cmax,IDeg,SD were (children/adults) 1.20 (95% CI: 0.90; 1.60) and (adolescents/adults) 1.23 (95% CI: 1.00; 1.51). Simulated mean steady state pharmacokinetic profiles supported a flat and stable IDeg exposure across a 24‐h dosing interval. IDeg was detectable in serum for at least 72 h (end of blood sampling period) in all subjects following single dose. In conclusion, the ultra‐long pharmacokinetic properties of IDeg observed in adults are preserved in children and adolescents with type 1 diabetes.

SWEET – where are we heading with international type 1 diabetes registries?

In light of the technological advances in diabetes therapy becoming more widely available and with healthcare costs rising generally, economic data regarding health care are desperately needed to allocate resources appropriately. ‘SWEET’ is an acronym derived from ‘Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference’ and is based on a partnership of established national and European diabetes organizations (www.sweet-project.eu) led by the International Society for Pediatric and Adolescent Diabetes (ISPAD), with the initial participating pediatric centres being from the Czech Republic, France, Germany, Greece, Hungary, Italy, Luxembourg, the Netherlands, Poland, Portugal, Romania, Sweden, and the UK. In addition, the valuable contributions of the International Diabetes Federation (IDF) Europe, the Federation of European Nurses in Diabetes (FEND), and Primary Care Diabetes Europe (PCDE) need to be acknowledged. Co-funding for the initial project was granted by the European Public Health Executive Agency with additional funds from corporate partners and foundations (see acknowledgements for the complete list). The present Special Issue of Pediatric Diabetes summarizes the major findings of the project. Before SWEET, 17 out of 26 EU countries had officially recognized centers for pediatric diabetes, but only eight of them had defined criteria for becoming such a center. A system of quality control of pediatric diabetes at the national level was reported from 7/26 countries. Only 13/26 EU countries had a pediatric diabetes register. These SWEET results were based on 108 datasets from healthcare professionals caring for >29 000 children and adolescents with diabetes in Europe. Recommendations for diabetes care and treatment, as well as age-appropriate education for children and adolescents with diabetes and pediatric training programs for healthcare professionals have been developed by SWEET. The proposed Criteria for an European Pediatric Diabetes Reference Centre include a multidisciplinary approach, an ongoing electronic documentation of at least 150 pediatric diabetes patients ≤18 years (i.e., at least age, diabetes duration, gender, HbA1c, type of diabetes), and the readiness to participate in external peer-reviewed auditing process and quality control circles. An initial 12 centres were approved jointly by the ISPAD Executive Committee and IDF Europe. It has been our experience that this approval has helped to raise awareness for the efforts to achieve optimal diabetes care within the different local circumstances. There is reason to believe that the international comparison within the SWEET project will help to secure funding from payers to ensure quality delivery of care and to harmonize pediatric diabetes healthcare delivery on the highest achievable standard within the ramifications of the differing national health systems. Optimal functioning of a team requires clear identification of all team players, with the child and the family at the centre of care. So far, huge differences have been identified between the different multidisciplinary teams, not only in numbers of healthcare professionals, but as well their training and the services provided. Therefore, a Toolbox supporting the creation of Centres of Reference for pediatric and adolescent diabetes has been developed. For benchmarking and quality control, a platform was put in place that allows any participating centre to import and input data online using a standard diabetes data set for pediatric diabetes patients to monitor the long-term outcome after the conclusion of the initial SWEET project. This will allow adapting the current recommendations on the basis of the ongoing evaluations. Adolescents with type 1 and type 2 diabetes are particularly prone to poor metabolic and psychosocial outcomes due to the potentially long diabetes duration. At the same time, the study of the effect of diabetes in this age group provides an opportunity to study early vascular ageing without other concomitant diseases. Normal ageing with diabetes starts in childhood as many processes leading to debilitating complications later in life have their onset then. This offers a unique opportunity to identify potential factors that are important to delay accelerated biological ageing

A pediatric diabetes toolbox for creating centres of reference

ISPAD guidelines recommend age appropriate diabetes education concepts for young patients and their families as well as tools for nutritional management, psychosocial assessment, and psychological advice but their implementation in Europe is presently unknown.

Continuous rise of insulin resistance before and after the onset of puberty in children at increased risk for type 1 diabetes - a cross-sectional analysis.

Insulin resistance has been postulated to be linked to the frequent onset of type 1 diabetes (T1D) during puberty. Very few studies have investigated the time course of insulin resistance in childhood. To address the question of how insulin resistance develops with age and how this is related to puberty onset, we examined insulin resistance and pubertal development over time in children at increased risk for T1D.

Harmonize care to optimize outcome in children and adolescents with diabetes mellitus: treatment recommendations in Europe.

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.

Evaluating the diet of children at increased risk for type 1 diabetes: first results from the TEENDIAB study.

OBJECTIVE The development of type 1 diabetes (T1D) is potentially influenced by nutrition. The aim of our study was to assess food and nutrient intakes of children at increased risk of T1D. DESIGN Dietary intake of the last 4 weeks was assessed using a diet history interview. The daily nutrient and food intakes were compared with the German Dietary Reference Intakes, the Optimized Mixed Diet recommendations and those of a representative sample of children from the EsKiMo study. SETTING Children included in the analysis participated in the prospective TEENDIAB study. SUBJECTS First-degree relatives of people with T1D (n 268), aged 8-12 years. RESULTS The TEENDIAB children consumed 52·0 % of their total energy from carbohydrates, 32·6 % from fat and 14·3 % from protein. Compared with the reference values, their intake was lowest for folate at 61·3 % of the reference, for iodine at 58·1 % and for vitamin D at 8·9 %, and exceeded the reference for vitamin K about 5-fold, for Na about 3·5-fold and for protein about 1·5-fold. Their nutrient intakes were similar to those of a control cohort without increased T1D risk. The consumption of non-desirable food groups (meat products, sweets/snacks) was above the recommendations and the consumption of desirable food groups (fruits, vegetables, carbohydrate-rich foods) was below the recommendations. CONCLUSIONS The TEENDIAB children had intakes considerably below the recommendations for vitamin D, iodine, folate and plant-based foods, and intakes above for vitamin K, Na, protein, meat products and sweets/snacks. They showed similar dietary patterns to non-risk children.

Pharmacokinetic and prandial pharmacodynamic properties of insulin degludec/insulin aspart in children, adolescents, and adults with type 1 diabetes

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of long‐acting insulin degludec and short‐acting insulin aspart. This open‐label, Phase 1 study aimed to determine the pharmacodynamic and pharmacokinetic properties of IDegAsp in children (6–11 yr), adolescents (12–17 yr), and adults (18–65 yr) with type 1 diabetes mellitus (T1DM). Thirty‐eight subjects received single subcutaneous IDegAsp dosing (0.5 U/kg) immediately before a standardized liquid meal (17.3 g carbohydrates/100 mL; adjusted for body weight) followed by plasma glucose (PG) and pharmacokinetic blood sampling for 36 and 57 h, respectively. There were no apparent differences between age groups in PG lowering effect (AUCPG baseline,0–6 h,meal,SD), maximum PG excursion (ΔPGmax,meal,SD), or maximum PG concentration (PGmax,meal,SD) after the standardized meal. Estimated ratios (ERs) for total exposure (AUCIAsp,0–12 h,SD) and maximum concentration (Cmax,IAsp,SD) of IAsp in IDegAsp were children/adults, 1.69 (95% confidence interval, CI: 1.02; 2.80) and 1.66 (95% CI: 1.10; 2.51); adolescents/adults, 1.14 (95% CI: 0.76; 1.69) and 1.16 (95% CI: 0.84; 1.61). ERs for total exposure (AUCIDeg,0–∞,SD) and maximum concentration (Cmax,IDeg,SD) of IDeg in IDegAsp were children/adults, 1.42 (95% CI: 0.94; 2.16) and 1.38 (95% CI: 1.09; 1.76); adolescents/adults, 1.23 (95% CI: 0.96; 1.58) and 1.16 (95% CI: 0.95; 1.42). IDegAsp was well tolerated across age groups. The fast onset of prandial coverage of IAsp in IDegAsp and the ultra‐long pharmacokinetic properties of IDeg in IDegAsp were preserved in children and adolescents. Exposure to IAsp and IDeg seemed to be higher in children vs. adults, but no differences were observed in PG lowering effect. IDegAsp could be an alternative treatment option in children and adolescents with T1DM.

Technical solution for data collection, data safety and data privacy legislation: experiences from the SWEET study.

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.

Pediatric diabetes training for healthcare professionals in Europe: Time for change

Training for healthcare professionals (HCPs) in Europe who care for children and young people (CYP) with type 1 diabetes and their families is variable depending on the country. Building on the work of SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) and using the German Certified Diabetes Educators (CDEs) curriculum, a European collaboration of pediatric diabetes experts aimed to (1) establish current core elements that should be included in a pediatric diabetes education training course and (2) create a template for a European CDEs training curriculum.