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 alpha = .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.

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.

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.

Peter Swift, retired, previously Consultant Paediatrician (Diabetes and Endocrinology), Leicester Royal Infirmary Children’s Hospital There have been considerable changes in the provision of services and standards of care for children and young people (CYP) with type 1 diabetes over the past 30 years. Although significant improvements have been made, services are inconsistent and the great majority of CYP with diabetes fail to meet the HbA1c target of <58 mmol/mol (<7.5%). Fundamental changes in attitudes and organisation, with the implementation of the best practice tariff in paediatric diabetes, should provide more equal access to quality care, improved transitional care, standardised, accredited education and consistent expert psychological and social support to significantly improve outcomes in CYP with type 1 diabetes.

Objective: To investigate whether center differences in glycemic control are present in prepubertal children <11yr 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 12months 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: 25-45mmol/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 <11yr, 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.

BACKGROUND:To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes.MATERIALS AND METHODS:In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation.RESULTS:Twenty-four patients (9.1%) tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual β-cell function (P = 0.002), lower blood glucose (P = 0.004), received less insulin (P = 0.05) and had lower HbA1c (P = 0.02) 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8) by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide.CONCLUSION:GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes.

Diabetes in childhood and adolescence is a difficult, lifelong, evolving disorder. Insulin treatment is essential for the establishment and maintenance of optimal metabolic control but it is only part of a comprehensive child-focused management strategy which must be initiated at the time of diagnosis. Attention must also be given to other vital aspects of the child's constantly changing circumstances such as food intake, exercise, the psychosocial environment and particularly the young person's individual motivation, attitude and behaviour. The insulin regime must fit the child's eating and exercise habits. Individual biochemical targets should be negotiated and encouragement given on self-care including insulin adjustments. Regular surveillance in specialist children's diabetic clinics is mandatory. Considerable human and financial resources are needed to organize successful paediatric diabetic services. The success of the service will be reflected in a significant reduction in long-term vascular complications in adulthood.

Department of Pediatrics, Uddevalla Hospital, Uddevalla,SwedenCorresponding author:Ragnar Hanas, MD, PhDDepartment of Pediatrics,Uddevalla Hospital,S-451 80 Uddevalla,Sweden.Tel: 146 522 92000;fax: 146 522 93149;e-mail: ragnar.hanas@vgregion.seConflicts of interest: SB is the owner of the New EnglandDiabetes and Endocrinology Center (NEDEC) and Presidentof New England Diabetes and Endocrinology ResearchFund, Incorporated (NEDERF, Inc.). He is a member of theadvisory panel, standing committee or board of directors:for American Diabetes Association (ADA), Juvenile DiabetesResearch Foundation (JDRF), International Diabetes Federation(IDF),International SocietyforPediatric andAdolescentDiabetes(ISPAD),AmericanAcademyofPediatrics(AAP),LawsonWilkinsPediatric Endocrine Society (LWPES); has received honorariaor speaker’s fees from Eli Lilly, Novo-Nordisk, Minimed,LifeScan, Genentech, Serono, Teva Pharmaceuticals; and hasreceived grants from Eli Lilly, Novo-Nordisk, NIH, SelfCare,InvernessMedical,MedicalFoods,Abbott-Medisense,LifeScan,Genentech, Pharmacia, Bristol-Squibb Myers, Pfizer, Serono,Johnson and Johnson. The remaining authors have declared noconflicts of interest.Editors of the ISPAD Clinical Practice Consensus Guidelines2009 comperdium: Ragnar Hanas, Kim Donaghue, GeorgeannaKlingensmith, Peter GF Swift.This article is a chapter in the

Proteomics analysis of serum from patients with type 1 diabetes (T1D) may lead to novel biomarkers for prediction of disease and for patient monitoring. However, the serum proteome is highly sensitive to sample processing and before proteomics biomarker research serum cohorts should preferably be examined for potential bias between sample groups. SELDI-TOF MS protein profiling was used for preliminary evaluation of a biological-bank with 766 serum samples from 270 patients with T1D, collected at 18 different paediatric centers representing 15 countries in Europe and Japan over 2 years (2000-2002). Samples collected 1 (n = 270), 6 (n = 248), and 12 (n = 248) months after T1D diagnosis were grouped across centers and compared. The serum protein profiles varied with collection site and day of analysis; however, markers of sample processing were not systematically different between samples collected at different times after diagnosis. Three members of the apolipoprotein family increased with time in patient serum collected 1, 6, and 12 months after diagnosis (ANOVA, p<0.001). These results support the use of this serum cohort for further proteomic studies and illustrate the potential of high-throughput MALDI/SELDI-TOF MS protein profiling for evaluation of serum cohorts before proteomics biomarker research.

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.

Pediatric DiabetesVolume 15, Issue S20 p. 77-85 ISPAD Clinical Practice Consensus Guidelines 2014 Compendium Diabetes education in children and adolescents Karin Lange, Corresponding Author Karin Lange Department of Medical Psychology, Hannover Medical School, OE 5430, 30625 Hannover, Germany Corresponding author: Karin S. Lange, PhD, Department of Medical Psychology, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Tel: +49511-532-4437; fax: +49511-532-4214; e-mail: [email protected]Search for more papers by this authorPeter Swift, Peter Swift Childrens Hospital, Leicester Royal Infirmary, Leicester, LE1 5WW UKSearch for more papers by this authorEwa Pańkowska, Ewa Pańkowska The Institute of Diabetology, ul. Żegańska 46a, 04-736 Warszawa, PolandSearch for more papers by this authorThomas Danne, Thomas Danne Diabetes Centre for Children and Adolescents at the Kinder- und Jugendkrankenhaus, Auf der Bult, Janusz-Korczak-Allee 12, 30173 Hannover, GermanySearch for more papers by this author Karin Lange, Corresponding Author Karin Lange Department of Medical Psychology, Hannover Medical School, OE 5430, 30625 Hannover, Germany Corresponding author: Karin S. Lange, PhD, Department of Medical Psychology, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Tel: +49511-532-4437; fax: +49511-532-4214; e-mail: [email protected]Search for more papers by this authorPeter Swift, Peter Swift Childrens Hospital, Leicester Royal Infirmary, Leicester, LE1 5WW UKSearch for more papers by this authorEwa Pańkowska, Ewa Pańkowska The Institute of Diabetology, ul. Żegańska 46a, 04-736 Warszawa, PolandSearch for more papers by this authorThomas Danne, Thomas Danne Diabetes Centre for Children and Adolescents at the Kinder- und Jugendkrankenhaus, Auf der Bult, Janusz-Korczak-Allee 12, 30173 Hannover, GermanySearch for more papers by this author First published: 03 September 2014 https://doi.org/10.1111/pedi.12187Citations: 92 Editors of the ISPAD Clinical Practice Consensus Guidelines 2014 Compendium: Carlo Acerini, Carine de Beaufort, Maria Craig, David Maahs, Ragnar Hanas. This article is a chapter in the ISPAD Clinical Practice Consensus Guidelines 2014 Compendium. The complete set of guidelines can be found for free download at www.ispad.org. The evidence grading system used in the ISPAD Guidelines is the same as that used by the American Diabetes Association. See page 3 (the Introduction in Pediatric Diabetes 2014; 15 (Suppl. 20): 1-3). Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 ISPAD Consensus Guidelines for the Management of Type 1 Diabetes Mellitus in Children and Adolescents. PGF Swift, ed. Zeist: Medforum, Brussels, 2000. 2Haas L, Maryniuk M, Beck J et al. Standards Revision Task Force. National standards for diabetes self-management education and support. Diabetes Care 2012: 37 (Suppl. 1): S144– S153. 3Silverstein J, Klingensmith G, Copeland K et al. American Diabetes Association. 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Citing Literature Volume15, IssueS20Supplement: International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines 2014. Wiley has published this supplement without financial support. Guest Editors: Carlo Acerini, Maria E Craig, Carine de Beaufort, David M Maahs and Ragnar HanasSeptember 2014Pages 77-85 ReferencesRelatedInformation

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.

1 Glostrup University Hospital, Department of Paediatrics, Glostrup, Denmark, 2 Department of Statistics, University of Southern Denmark, Denmark 3 Leicester Royal Infirmary Children’s Hospital, Leicester, United Kingdom 4 University of Ulm, Germany, 5 Trinity College , National Childrens Hospital, Dublin, Ireland 6 Ulleval University Hospital, Department of Pediatrics, Oslo, Norway 7 Clinique Pediatrique, Centre Hospitalier de Luxembourg 8 Clinica Pediatrica Universita, Chieti, Italy, 9 Kinderkrankenhaus auf der Bult, Department of Paediatrics, Hannover, Germany 10 University Children’s Hospital, Zurich, Switzerland, 11 Regionsjukhuset i Örebro, Örebro, Sweden

Communities all across the U.S. are concerned about the safety of their residential streets. Although this concern is nearly universal, the literature offers few precedents and little information on the relative safety of common residential street typologies. This study offers a method for analyzing the theory that the physical design of streets impacts safety. Through research, systematic observation, and statistical analysis, an attempt was made to identify the safest residential street form with respect to several physical characteristics. These findings expose issues that need to be addressed by practitioners and policy-makers and encourage further study of related topics. Approximately 20,000 police accident reports from the City of Longmont, Colorado, were reviewed and compared against five criteria for evaluating the probability that street design contributed to the accidents. Once catalogued and entered into a database, each accident location was mapped and described by several physical characteristics. To compare injury accidents per mile per year against other factors, several correlations were explored. The most significant relationship to injury accidents was found to be street width. AS street widths widen, accidents per mile per year increases exponentially, and the safest residential street width are the narrowest (curb face).

This supplement of Pediatric Diabetes is the compendium of guidelines chapters published 2006–2008 as individual articles in Pediatric Diabetes, which are available on ISPAD’s website www.ispad.org. The guidelines have been modified and updated to reflect major new evidence published since they were published previously. In 2007, the total child population of the world (0–14 years) was estimated to be 1.8 billion, of whom 0.02% have diabetes. This means that approximately 440,000 children around the world have diabetes with 70,000 new cases diagnosed each year (1). However, field data would suggest that some individual country estimates (especially in Africa) are over-estimated. This very large number of children need help to survive with injections of insulin to live a full life without restrictions or disabling complications and without being stigmatized for their diabetes. Even today, almost a century after the discovery of insulin, the most common cause of death in a child with diabetes from a global perspective is lack of access to insulin (2). Many children die before their diabetes is diagnosed. It is therefore of utmost importance that all forces unite to make it come true that no child should die from diabetes. A promising initiative has been taken by IDF/Life for a Child (www.lifeforachild.org) in collaboration with ISPAD and other organizations (Access to Essential Diabetes Medicines for Children in the Developing World). Several major companies that produce insulin and other diabetes supplies have pledged their support, and the numbers of children provided with insulin will according to plan increase to approximately 12,000 in 2010 and 30,000 by 2015. ISPAD has pledged structural support and assistance in the training of paediatricians and healthcare professionals in childhood and adolescent diabetes through its membership network. In 1993, members of the International Society for Pediatric and Adolescent Diabetes (ISPAD) formulated the Declaration of Kos, proclaiming their commitment to ‘‘promote optimal health, social welfare and quality of life for all children with diabetes around the world by the year 2000.’’ Although all the aims and ideals of the Declaration of Kos had not been reached by 2000, we feel that slowly, by small steps, the worldwide care of children is improving. ISPAD published its first set of guidelines in 1995 (3) and its second in 2000 (4). Since then, the acceptance of intensive therapy, also for very young children, has increased around the world. Insulin pump usage has risen in all age groups in countries where this treatment modality can be afforded. Intensive therapy requires better and more comprehensive education for it to be successful. The ISPAD Consensus Guidelines 2000 has been translated into 11 languages, indicating the need for a truly international document. In 2003–2005, national guidelines for childhood diabetes have been released: the Australian Clinical Practice Guidelines from the National Health and Medical Research Council, (Writing Committee Chair, Martin Silink) (5); in the United Kingdom, the National Institute for Clinical Excellence (NICE) Clinical Guideline (Group Leader Stephen Greene) (6). Both these publications are truly evidence-based in that they deal with the body of evidence with a systematic approach, grading each reference and building the case for each recommendation. In 2003 the Canadian Diabetes Association published Clinical Practice Guidelines with chapters both on type 1 and type 2 in children and adolescents (7). In 2005, the American Diabetes Association (ADA) published their statement on the care of children and adolescents with type 1 diabetes (8). This updated third edition of ISPAD’s Consensus Guidelines, now Clinical Practice Consensus Guidelines is much larger, and has been enriched by the above mentioned national guidelines. In the Introduction to the 2000 ISPAD Guidelines the acknowledged intention was for the next guidelines to be referenced. We have used the ADA grading system for grading evidences (9). Whenever possible, the reference for a statement or recommendation has been included, but as the reader will see, a vast majority of the recommendations and suggestions do have the grade E (Expert consensus or clinical experience). The updated 2009 guidelines are based on a wide consensus of clinical practice. They were drafted by international writing teams, modified by experts in different specialties from many countries, debated at the annual ISPAD meetings in 2005–2008 by the members, and were reviewed by members via the Internet and the

Objective: Evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents and their influence on metabolic control in a large international cohort of adolescents with type 1 diabetes. Methodology: Cross-sectional clinical data were collected and questionnaires completed by adolescents and parents/carers attending 21 international centres. Haemoglobin A1c (HbA1c) (DCCT adjusted) was measured centrally. Results: Questionnaires were completed by 2062 adolescents (age 14.4 ± 2.3 years; 50.6% male; diabetes duration 6.1 ± 3.5 years). Mean HbA1c was 8.2% ± 1.4 with significant difference between centres (F = 12.3; p 17.4; p 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.