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See detailThe genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus
Kaur, S.; Mirza, A. H.; Brorsson, C. A. et al

in Molecular and Cellular Endocrinology (2016), 419

The study aimed to explore the role of ERBB3 in type 1 diabetes (T1D). We examined whether genetic variation of ERBB3 (rs2292239) affects residual β-cell function in T1D cases. Furthermore, we examined ... [more ▼]

The study aimed to explore the role of ERBB3 in type 1 diabetes (T1D). We examined whether genetic variation of ERBB3 (rs2292239) affects residual β-cell function in T1D cases. Furthermore, we examined the expression of ERBB3 in human islets, the effect of ERBB3 knockdown on apoptosis in insulin-producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351) was found to be expressed in human islets. ERBB3 was expressed and down-regulated by pro-inflammatory cytokines in human islets and INS-1E cells; knockdown of ERBB3 in INS-1E cells decreased basal and cytokine-induced apoptosis. Our data suggests an important functional role of ERBB3 and its potential regulators in the β-cells and may constitute novel targets to prevent β-cell destruction in T1D. © 2015 Elsevier Ireland Ltd. [less ▲]

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See detailLessons from the Hvidoere International Study Group on childhood diabetes: Be dogmatic about outcome and flexible in approach
Cameron, F. J.; De Beaufort, Carine UL; Aanstoot, H.-J. et al

in Pediatric Diabetes (2013), 14(7), 473-480

[No abstract available]

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See detailMetabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009
De Beaufort, Carine UL; Lange, K.; Swift, P.G. et al

in Pediatric Diabetes (2012), 14(6), 422-428

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 ... [more ▼]

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. [less ▲]

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See detailHeterogeneity in the systems of pediatric diabetes care across the European Union
Cinek, O.; Šumník, Z.; De Beaufort, Carine UL et al

in Pediatric Diabetes (2012), 13(SUPPL. 16), 5-14

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 ... [more ▼]

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 29000 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. [less ▲]

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See detailCriteria for Centers of Reference for pediatric diabetes--a European perspective
Danne, T.; Lion, S.; Madaczy, L. et al

in Pediatric Diabetes (2012), 13(16), 62-75

' 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 ... [more ▼]

' 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. [less ▲]

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See detailRecommendations for age-appropriate education of children and adolescents with diabetes and their parents in the European Union
Martin, D.; Lange, K.; Sima, A. et al

in Pediatric Diabetes (2012), 13(16), 20-28

Education is the keystone of diabetes care, and structured self-management education is the key to a successful outcome. Existing guidelines provide comprehensive guidance on the various aspects of ... [more ▼]

Education is the keystone of diabetes care, and structured self-management education is the key to a successful outcome. Existing guidelines provide comprehensive guidance on the various aspects of education and offer general and organizational principles of education, detailed curricula at different ages and stages of diabetes, and recommendations on models, methods, and tools to attain educative objectives. The International Society for Pediatric and Adolescent Diabetes guidelines give the most elaborate and detailed descriptions and recommendations on the practice of education, which other national guidelines address on specific aspects of education and care. The aim of the work package on education developed by Better Control in Paediatric and Adolescent Diabetes in the European Union: Working to Create Centers of Reference ( SWEET) project was not to generate new guidelines but to evaluate how the existing guidelines were implemented in some pediatric diabetes reference centers. The SWEET members have completed a questionnaire that elaborates on the many aspects of delivery of education. This survey highlights a profound diversity of practices across centers in Europe, in terms of organization as well as the practices and the content of initial and continuing education. A toolbox is being developed within SWEET to facilitate exchanges on all aspects of education and to establish a process of validation of materials, tools, written structured age-adjusted programs, and evaluation procedures for the education of children and adolescents with diabetes. [less ▲]

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See detailSWEET--where are we heading with international type 1 diabetes registries?
Danne, T.; Aschemeier, B.; Perfetti, R. et al

in Pediatric Diabetes (2012), 13(16), 1-4

The authors discuss a project "Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference" (SWEET) led by the International Society for Pediatric and Adolescent Diabetes ... [more ▼]

The authors discuss a project "Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference" (SWEET) led by the International Society for Pediatric and Adolescent Diabetes (ISPAD). The project includes pediatric centres from countries such as Czech, Germany and Greece. They also discuss the European DIAMAP project which addresses clinical research issues for people with diabetes. They believe these initiatives will enable evaluation of invaluable data sets. [less ▲]

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See detailProinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes
Kaas, A.; Max Andersen, M. L.; Fredheim, S. et al

in Pediatric Diabetes (2012), 13(1), 51-58

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 ... [more ▼]

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. [less ▲]

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See detailUse of continuous glucose monitoring in children and adolescents
Phillip, M.; Danne, T.; Shalitin, S. et al

in Pediatric Diabetes (2012), 13(3), 215-228

[No abstract available]

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See detailTarget setting in intensive insulin management is associated with metabolic control: The Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005
Swift, P. G. F.; Skinner, T. C.; De Beaufort, Carine UL et al

in Pediatric Diabetes (2010), 11(4), 271-278

Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control.Methods: Clinical data and questionnaires were ... [more ▼]

Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control.Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally.Results: A total of 2062 adolescents completed questionnaires (age 14.4 ± 2.3 yr; diabetes duration 6.1 ± 3.5 yr). Mean HbA 1c = 8.2 ± 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001).Conclusions: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres. © 2009 John Wiley & Sons A/S. [less ▲]

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See detailNew definition for the partial remission period in children and adolescents with type 1 diabetes
Mortensen, H. B.; Hougaard, P.; Swift, P. et al

in Diabetes Care (2009), 32(8), 1384-1390

OBJECTIVE - To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS - A total of 275 ... [more ▼]

OBJECTIVE - To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS - A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function. RESULTS - By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient -0.21, P < 0.001) and insulin dose (-0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P < 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg-1 · 24 h-1 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS - A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions. © 2009 by the American Diabetes Association. [less ▲]

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See detailAssociations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: The Hvidoere Study Group on Childhood Diabetes
Åman, J.; Skinner, T. C.; De Beaufort, Carine UL et al

in Pediatric Diabetes (2009), 10(4), 234-239

Background: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by ... [more ▼]

Background: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by differences in demographic, medical, or treatment variables. Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers. Methods: An observational cross-sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants. Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory. All individuals with diabetes aged 11-18 yr (49.4% female), with duration of diabetes of at least 1 yr, were invited to participate. Individuals completed a self-reported measure of quality of life (Diabetes Quality of Life - Short Form [DQOL-SF]), with well-being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project. Results: Older participants (p < 0.001) and females (p < 0.001) reported less physical activity. Physical activity was associated with positive health perception (p < 0.001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis. The more time spent on the computer (r = 0.06; p < 0.05) and less time spent doing school homework (r = -0.09; p < 0.001) were associated with higher HbA1c. Between centers, there were significant differences in reported physical activity (p < 0.001) and sedentary behavior (p < 0.001), but these differences did not account for center differences in metabolic control. Conclusions: Physical activityis strongly associated with psychological well-being but has weak associations with metabolic control. Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences. © 2009 John Wiley & Sons A/S. [less ▲]

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See detailAre family factors universally related to metabolic outcomes in adolescents with type 1 diabetes?
Cameron, F. J.; Skinner, T. C.; De Beaufort, Carine UL et al

in Diabetic Medicine : A Journal of the British Diabetic Association (2008), 25(4), 463-468

Aims: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. Methods: Adolescents with Type 1 diabetes aged 11-18 years, from 21 ... [more ▼]

Aims: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. Methods: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth - Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA1c) was analysed centrally on capillary blood. Results: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. Conclusions: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres. © 2008 The Authors. [less ▲]

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See detailA cross-sectional international survey of continuous subcutaneous insulin infusion (CSII) in 377 children and adolescents with type 1 diabetes mellitus from 10 countries
Danne, T.; Battelino, T.; Kordonouri, O. et al

in Pediatric Diabetes (2005), 6

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 ... [more ▼]

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. [less ▲]

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