Introduction : Trente-neuf programmes d’éducation thérapeutique ont été autorisés par l’Agence régionale de santé d’Île-de-France entre 2010 et 2012 à l’hôpital universitaire Necker – Enfants malades et ont donc dû conduire leur évaluation quadriennale pour demander leur renouvellement en 2014 et 2015.Objectifs : La réalisation d’une synthèse de ces évaluations avait pour objectifs de faire un état des lieux après quatre ans de mise en œuvre des programmes et de définir des pistes d’amélioration.Résultats : Trente-huit programmes sont destinés à des enfants/adolescents et 30 concernent des pathologies rares. L’offre initiale d’éducation est réalisée en hospitalisation (15/39), en ambulatoire (17/39), ou les deux selon le patient (7/39), et a le plus souvent des objectifs de compétences de soins et de sécurité. Trente-quatre programmes proposent une offre éducative de suivi, 24 des offres de reprise de l’éducation. Les équipes sont toutes pluridisciplinaires, 41 % des intervenants sont formés, et des parents-ressources interviennent dans deux programmes. L’évaluation des compétences acquises par le patient est formalisée dans 18 programmes. Six programmes ont des indicateurs clinico-biologiques de suivi, 25 utilisent des questionnaires de satisfaction et 18 font des auto-évaluations annuelles régulièrement. Le principal frein à la mise en œuvre des programmes est le manque de personnel, les leviers sont l’implication de l’équipe, l’amélioration de la coordination, la collaboration avec d’autres structures de soins et la valorisation des activités.Discussion : L’offre éducative proposée est spécifique et complète, même si elle est principalement axée sur les compétences de soins. Des évolutions sont nécessaires pour poursuivre la promotion d’une éducation thérapeutique de qualité, adapter l’offre aux besoins des patients et à leur contexte de vie, lever le principal frein à la mise en œuvre qu’est celui du temps et impliquer les patients.Conclusion : La conduite des évaluations quadriennales a permis de valoriser le travail des équipes, de montrer les spécificités de l’offre éducative, mais aussi de définir des pistes d’amélioration à mettre en œuvre à l’échelle des programmes et de l’établissement.

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.

Neonatal diabetes mellitus (NDM) is a rare form of non-autoimmune diabetes usually diagnosed in the first 6 months of life. Various genetic defects have been shown to cause NDM with diverse clinical presentations and variable severity. Among transcriptional factor genes associated with isolated or syndromic NDM, a few cases of homozygous mutations in the NEUROG3 gene have been reported, all mutated patients presenting with congenital malabsorptive diarrhea with or without diabetes at a variable age of onset from early life to childhood. Through a targeted next-generation sequencing assay for monogenic diabetes genes, we aimed to search for pathogenic deleterious mutation in a Turkish patient with NDM, severe malabsorptive diarrhea, neurointestinal dysplasia and other atypical features. In this patient, we identified a novel homozygous nonsense mutation (p.Q4*) in NEUROG3. The same biallelic mutation was found in another affected family member. Of note, the study proband presents with abnormalities of the intrahepatic biliary tract, thyroid gland and central nervous system, which has never been reported before in NEUROG3 mutation carriers. Our findings extend the usually described clinical features associated with NEUROG3 deficiency in humans, and question the extent to which a complete lack of NEUROG3 expression may affect pancreas endocrine function in humans.

Objectives:To further describe the changes in insulin therapy regimens and hemoglobin A1c (HbA1c) in children and adolescents with type 1 diabetes, and their associations with diabetes knowledge and quality of life.Research design and methods:The study included 4293 children and adolescents (12.92.6yr, diabetes >1yr) attending AJD (Aide aux Jeunes Diabetiques) summer camps between 2009 and 2014. The distribution of insulin regimens and associations between HbA1c, therapeutic regimens, diabetes knowledge (AJD questionnaire), and Quality of Life (Ingersoll et Marrero, Hvidoere Study Group short version) were assessed.Results:The percentage of youth treated with insulin pumps increased up to about 45%, basal bolus stabilized around 40%, and other regimens decreased majorly. HbA1c was higher with premixed insulins only regimens (9.05 +/- 2.43%), but there was no difference between pump (8.12 +/- 1.09%), basal bolus (8.32 +/- 1.33%) and two to three injections (8.18 +/- 1.28%). Mean HbA1c decreased by 0.014% per year. The percentage of HbA1c <7.5% increased by 1.5% per year, and the percentages of HbA1c >9% or >10% decreased by 4 and 5.5%, changes being greater with the pump. HbA1c was weakly associated with diabetes knowledge, and strongly with general health perception and perception about diabetes.Conclusion:The percentage of children and adolescents with the highest risk of complications decreased markedly. The distribution of HbA1c better depicts the glycemic control in a population than the mean or the percentage of patients reaching the target (7.5%). HbA1c was more strongly associated with general health perception than with therapeutic regimens and diabetes knowledge.

BACKGROUND:Polycystic ovary syndrome (PCOS) is more frequently observed in type 1 diabetes mellitus (T1DM) adult women than in nondiabetic women. No such prevalence has yet been studied in adolescent girls with T1DM.AIM:The aim of this study was to evaluate the prevalence of PCOS in adolescent girls with T1DM and to determine the clinical and hormonal features associated with the disorder.METHODS:A cross-sectional study of 53 adolescent girls (gynecological age >2 years) referred for routine evaluation for T1DM was conducted. We diagnosed PCOS using the National Institutes of Health (NIH) and Rotterdam criteria.RESULTS:26.4 and 47.9% of adolescents had PCOS according to NIH (NIH-PCOS) and Rotterdam (Rotterdam-PCOS) criteria. 66.7% of NIH-PCOS adolescents had a complete phenotype associated with hyperandrogenism, oligomenorrhea, and polycystic ovarian morphology, unlike only 33.3% of the Rotterdam-PCOS adolescents. A family history of type 2 diabetes mellitus (T2DM) was more frequent in PCOS than in non-PCOS girls, whichever criteria were used. Late pubertal development and a T1DM diagnosis close to puberty were factors associated with NIH-PCOS.CONCLUSION:Adolescents with T1DM had a high prevalence of PCOS. More differences between PCOS and non-PCOS patients were found using the NIH criteria, suggesting that clinical characteristics might be more accurate for diagnosing PCOS in girls with T1DM. A family history of T2DM is associated with a high risk of PCOS.

To evaluate diabetes knowledge and skills (DKS) in adolescents (>10 year) with type 1 diabetes (T1D) and their parents, and its effect on glycemic control.

Objectifs : Elaborer et valider un questionnaire de connaissance pour les enfants et les adolescents ayant un diabete de type 1 (DT1) et leurs parents. Patients et methodes : Le questionnaire a ete elabore a partir d’un outil publie pour l’education initiale du diabete de type 1, les Cahiers de l’AJD , avec la participation de 1 576 jeunes de 10–20 ans ayant un DT1, 466 parents, 33 services de pediatrie et huit maisons sanitaires de l’AJD (Aide aux jeunes diabetiques). A partir de 310 questions initiales de type Vrai-Faux, la selection de 50 questions a ete basee sur l’expertise de la commission pedagogique de l’AJD, la reproductibilite des questions (test-retest) et l’analyse statistique par methode de variance minimum de Ward. Le questionnaire final a ensuite ete administre a 2 933 jeunes de 10–20 ans (âge 14,1 + 2,5 ans, duree du diabete 5,5 ± 3,6 ans, HbA1c 8,25 ± 1,54 %) et 2 978 parents pour etablir des references avec l’âge et evaluer les associations avec l’equilibre glycemique. Resultats : Le questionnaire est un reflet fidele du programme d’education des Cahiers de l’AJD . Le questionnaire est faisable (temps de passage 5–15 min), reproductible et sensible : nombres moyens de bonnes reponses significativement differents entre filles et garcons (37,8 ± 5,7 vs 37,2 ± 6,0), entre meres et peres (40,3 ± 5,4 vs 38,5 ± 5,7) et pour des intervalles d’âge de un a deux ans. Le pourcentage de bons repondeurs est tres variable d’une question a l’autre : il augmente avec l’âge pour 39 questions, mais ne varie pas pour 7 et diminue meme pour 4. Les associations entre le nombre de bonnes reponses au questionnaire, l’equilibre glycemique et d’autres facteurs, font l’objet d’une autre publication. Conclusion : La publication du questionnaire de connaissance de l’AJD et des resultats pour chaque question en fonction de l’âge permet de disposer d’un outil et de references utilisables en clinique et en recherche pour l’evaluation des connaissances des jeunes de 10–20 ans ayant un DT1 et de leurs parents.

OBJECTIVE:To describe the bone imaging features of lipodystrophies in the largest cohort ever published.MATERIALS AND METHODS:We retrospectively examined bone imaging data in 24 patients with lipodystrophic syndromes. Twenty-two had genetic lipodystrophy: 12/22 familial partial lipodystrophy (FPLD) and 10/22 congenital generalized lipodystrophy (CGL), 8 with AGPAT2-linked CGL1 and 2 with seipin-linked CGL2. Two patients had acquired generalized lipodystrophy (AGL) in a context of non-specific autoimmune disorders. Skeletal radiographs were available for all patients, with radiographic follow-up for two. Four patients with CGL1 underwent MRI, and two of them also underwent CT.RESULTS:Patients with FPLD showed non-specific degenerative radiographic abnormalities. Conversely, CGL patients showed three types of specific radiographic alterations: diffuse osteosclerosis (in 7 patients, 6 with CGL1 and 1 with CGL2), well-defined osteolytic lesions sparing the axial skeleton (7 CGL1 and 1 CGL2), and pseudo-osteopoikilosis (4 CGL1). Pseudo-osteopoikilosis was the sole bone abnormality observed in one of the two patients with AGL. Osteolytic lesions showed homogeneous low signal intensity (SI) on T1-weighted and high SI on T2-weighted MR images. Most of them were asymptomatic, although one osteolytic lesion resulted in a spontaneous knee fracture and secondary osteoarthritis in a patient with CGL1. MRI also showed diffuse fatty bone marrow alterations in patients with CGL1, with intermediate T1 and high T2 SI, notably in radiographically normal areas.CONCLUSIONS:The three types of peculiar imaging bone abnormalities observed in generalized lipodystrophic syndromes (diffuse osteosclerosis, lytic lesions and/or pseudo-osteopoikilosis) may help clinicians with an early diagnosis in pauci-symptomatic patients.

Human type 1 diabetes results from a destructive auto-reactive immune response in which CD8(+) T lymphocytes play a critical role. Given the intense ongoing efforts to develop immune intervention to prevent and/or cure the disease, biomarkers suitable for prediction of disease risk and progress, as well as for monitoring of immunotherapy are required. We undertook separate multi-parameter analyses of single naïve and activated/memory CD8(+) T lymphocytes from pediatric and adult patients, with the objective of identifying cellular profiles associated with onset of type 1 diabetes. We observe global perturbations in gene and protein expression and in the abundance of T cell populations characterizing pediatric but not adult patients, relative to age-matched healthy individuals. Pediatric diabetes is associated with a unique population of CD8(+) T lymphocytes co-expressing effector (perforin, granzyme B) and regulatory (transforming growth factor β, interleukin-10 receptor) molecules. This population persists after metabolic normalization and is especially abundant in children with high titers of auto-antibodies to glutamic acid decarboxylase and with elevated HbA1c values. These findings highlight striking differences between pediatric and adult type 1 diabetes, indicate prolonged large-scale perturbations in the CD8(+) T cell compartment in the former, and suggest that CD8(+)CD45RA(-) T cells co-expressing effector and regulatory factors are of interest as biomarkers in pediatric type 1 diabetes.

Assess the frequency of anti‐H+/K+ adenosine triphosphatase (ATPase) autoantibodies (AAB) and symptoms of autoimmune gastritis in children and adolescents with type 1 diabetes (T1D).

Introduction: Congenital hyperinsulinism (CHI) is the term used for hyperinsulinemic hypoglycemia due to a primary defect of the pancreatic β-cell owing to genetic causes. Severe CHI is responsible for recurrent severe hypoglycemia in neonates. A delayed diagnosis or improper medical management is responsible for brain damage in approximately one-third of patients. Areas covered: From the experiences of the authors and an extensive review of the literature, this review aims to offer a precise overview of the current knowledge in the field of CHI, including the latest updates, and a description of the current medical and surgical management proposed in referral centers for CHI worldwide. Expert opinion: Despite satisfactory care of the focal form of CHI, severe diffuse CHI is a burden for patients and families, and a subtotal pancreatectomy only offers a short-term respite, since insulin requiring diabetes is the unavoidable outcome. A better understanding of the disease mechanisms (e.g., concerning spontaneous remission) and the development of new therapeutic tools should lead to a safe conservative approach for severe, focal and diffuse CHI.

To describe the changes in insulin therapy regimens of children and adolescents with type 1 diabetes over 10 yr and their correlation with hemoglobin A1c (HbA1c).

Aim To determine risk factors for neurological sequelae following hypoglycemia.Method We analysed the neurological outcome in 164 patients (mean age 10y 10mo, SD 5.9) following hypoglycemia due to three diseases with various metabolic contexts, different ages at onset, and combinations with comorbidity (fever/infection, hypoxia/ischemia): glycogen storage disease type I (GSDI) (21 patients, mean age at first hypoglycemic episode 3.8mo, SD 3.5); fatty acid β‐oxidation defects (FAOD) (29 patients, mean age at first hypoglycemic episode 14.8mo, SD 12.6); and hyperinsulinism (HIns) (114 patients, mean age at first hypoglycemic episode 2.3mo, SD 4.7).Results Risk factors of poor neurological outcome were aetiology (p<0.006), comorbidity (p<0.001), and prolonged convulsions (p<0.001). Ordinal logistic regression showed that comorbidity (p<0.001) and status epilepticus (p=0.002) were the main determinants of sequelae. Asymptomatic hypoglycemia did not lead to sequelae, whatever the aetiology. Age was not correlated to sequelae, whatever the aetiology. The highest prevalence of hypoglycemic sequelae was found in FAOD and HIns combined with comorbidity, the lowest in GSDI (p<0.001) in which hypoglycemia is often asymptomatic, associated with increased plasma lactate, and rarely combined with comorbidity.Interpretation Hypoglycemia is severely deleterious for the brain in the context of fever/infection and/or hypoxia/ischemia, and status epilepticus. The metabolic context providing alternative fuels may improve neurological outcome.

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.

BACKGROUND:The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS:We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS:The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS:Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).

OBJECTIVES:To compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM).METHODS:Data were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years.RESULTS:High prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls.CONCLUSIONS:Hirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.