Accuracy of Serological Screening for the Diagnosis of Celiac Disease in Type 1 Diabetes Children.

Background and Objectives: Patients with type 1 diabetes (T1D) are considered at high-risk for developing celiac disease (CD). The purpose of our study was to determine the prevalence of CD among children who were followed in our unit for T1D using the latest ESPGHAN guidelines, and avoiding intestinal biopsies in some of the children. Materials and Methods: We performed a prospective monocentric study, which included 663 T1D children between June 2014 and June 2016. We considered CD according to serological (tissue transglutaminase (TGAs) and endomysium antibodies) results. Children were included either at the time of T1D diagnosis or during their follow up. We looked for clinical and biochemical signs of CD, and for T1D characteristics. Results: The children's ages ranged from 11 months to 18 years. CD was confirmed in 32 out of 663 patients with T1D, with a prevalence of 4.8%. CD was excluded in 619 children and remained uncertain for 12 children, who had positive TGAs without the required criteria. We found that 95% of T1D children express HLA-DQ2 and/or -DQ8, which was 2.4 times higher than in the general population. Conclusions: An intestinal biopsy could be avoided to confirm CD in the majority of T1D children. Silent forms of CD are frequent and screening is recommended for all patients. Importantly, repeated TGA assessment is required in HLA genetically predisposed T1D patients, while it is unnecessary in the 5% who are HLA-DQ2 and -DQ8 negative.

Hybrid closed-loop insulin delivery versus sensor-augmented pump therapy in children aged 6-12 years: a randomised, controlled, cross-over, non-inferiority trial.

BACKGROUND: Time in range (TIR) goals are rarely met in children with type 1 diabetes, except at the cost of increased hypoglycaemia episodes. Our objective was to evaluate the safety and efficiency of the Diabeloop DBL4K (Diabeloop, Grenoble, France) hybrid closed-loop system in prepubescent children. METHODS: We did a multicentre, open-label, randomised, controlled, non-inferiority, two-session crossover study in the paediatric endocrinology departments of three university hospitals in France and Belgium. Eligible participants were aged 6-12 years with type 1 diabetes for at least 1 year, glycated haemoglobin A1C 9% (75 mmol/mol) or less, and insulin pump treatment for at least 3 months. Participants were randomly assigned (1:1) to a closed-loop device or sensor-augmented pump (open loop) therapy. Randomisation was by a permuted block randomisation scheme, using an interactive web-based response system, and was stratified on centre (block size 6). The assessed closed-loop device, the Diabeloop for Kids DBL4K hybrid closed-loop system, is an automated blood glucose regulation system composed of a handset, insulin pump, and continuous glucose monitor. The open-loop system is defined as a sensor-augmented pump therapy composed of the usual insulin pump used by the patient and a continuous glucose monitor. A 72-h in-patient period was followed by a 6-week home phase. After a 1-week washout period, the participants crossed over to the other device. The primary outcome, assessed in the intention-to-treat population, was the mean proportion of time spent in hypoglycaemia (3·9 mmol/L [<70 mg/dL]) during the hospital phase, with a non-inferiority margin of -2·5% (absolute value). Safety was assessed in the intention-to-treat population on a per-protocol basis. This study was registered with ClinicalTrials.gov, NCT03671915. FINDINGS: Between May 6 and Dec 23, 2019, we included 21 participants (closed loop then open loop, n=10; open loop then closed loop, n=11). The proportion of time spent in hypoglycaemia was significantly lower with the closed-loop system than the open-loop system in both groups (2·04% [95% CI 0·44 to 3·64] vs 7·06% [5·46 to 8·66]; non-inferiority one-sided p<0·0001). No severe ketoacidosis, nor severe hyoglycaemic events or fatal adverse events occurred. All 25 adverse events (18 with the closed-loop system, seven with the open-loop system) were related to the treatment. INTERPRETATION: The closed-loop Diabeloop system decreased hypoglycaemic episodes and provided good metabolic control in prepubescent children with type 1 diabetes, under real-life conditions. This finding supports the safe use of closed-loop technology in this paediatric population. FUNDING: Diabeloop. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Is there an optimal strategy for real-time continuous glucose monitoring in pediatrics? A 12-month French multi-center, prospective, controlled randomized trial (Start-In!).

AIM: To compare the efficacy of three strategies for real-time continuous glucose monitoring (RT-CGM) over 12 months in children and adolescents with type 1 diabetes. METHODS: A French multicenter trial (NCT00949221) with a randomized, controlled, prospective, open, and parallel-group design was conducted. After 3 months of RT-CGM, patients were allocated to one of three groups: return to self-monitoring of blood glucose, continuous CGM (80% of the time), or discontinuous CGM (40% of the time). The primary outcome was hemoglobin A1c (HbA1c) levels from 3 to 12 months. The secondary outcomes were acute metabolic events, hypoglycemia, satisfaction with CGM and cost. RESULTS: We included 151 subjects, aged 2 to 17 years, with a mean HbA1c level of 8.5% (SD0.7; 69 mmol/mol). The longitudinal change in HbA1c levels was similar in all three groups, at 3, 6, 9 and 12 months. The medical secondary endpoints did not differ between groups. The rate of severe hypoglycemia was significantly lower than that for the pretreatment year for the entire study population. Subjects reported consistent use and good tolerance of the device, regardless of age or insulin treatment. The use of full-time RT-CGM for 3 months costs the national medical insurance system €2629 per patient. CONCLUSION: None of the three long-term RT-CGM strategies evaluated in pediatric type 1 diabetes was superior to the others in terms of HbA1c levels. CGM-use for 3 months decreased rates of severe hypoglycemia. Our results confirm the feasibility of long-term RT-CGM-use and the need to improve educational support for patients and caregivers.

[Patient education in pediatric diabetology]. / L'éducation thérapeutique en diabétologie pédiatrique.

Therapeutic education in paediatric diabetology consists of initial education and follow-up education. It can be individual or collective. It forms part of a planned and organised systemic approach, with a skills framework adapted to the patient's age. Supporting the families as well as schools is essential.

[The return home of a child or adolescent after a diabetes diagnosis]. / Le retour à domicile de l'enfant ou de l'adolescent après un diagnostic de diabète.

The diagnosis of diabetes in a child or adolescent upsets the family dynamics. After the initial shock of the diagnosis, the child and their parents are given guidance to help them acquire a level of autonomy adapted to their needs. The aim of this early therapeutic education is to enable them to envisage resuming existing activities or organising new projects, as soon as they leave hospital.

Neuropsychological dysfunction and developmental defects associated with genetic changes in infants with neonatal diabetes mellitus: a prospective cohort study [corrected].

BACKGROUND: Neonatal diabetes mellitus is a rare genetic form of pancreatic ß-cell dysfunction. We compared phenotypic features and clinical outcomes according to genetic subtypes in a cohort of patients diagnosed with neonatal diabetes mellitus before age 1 year, without ß-cell autoimmunity and with normal pancreas morphology. METHODS: We prospectively investigated patients from 20 countries referred to the French Neonatal Diabetes Mellitus Study Group from 1995 to 2010. Patients with hyperglycaemia requiring treatment with insulin before age 1 year were eligible, provided that they had normal pancreatic morphology as assessed by ultrasonography and negative tests for ß-cell autoimmunity. We assessed changes in the 6q24 locus, KATP-channel subunit genes (ABCC8 and KCNJ11), and preproinsulin gene (INS) and investigated associations between genotype and phenotype, with special attention to extra-pancreatic abnormalities. FINDINGS: We tested 174 index patients, of whom 47 (27%) had no detectable genetic defect. Of the remaining 127 index patients, 40 (31%) had 6q24 abnormalities, 43 (34%) had mutations in KCNJ11, 31 (24%) had mutations in ABCC8, and 13 (10%) had mutations in INS. We reported developmental delay with or without epilepsy in 13 index patients (18% of participants with mutations in genes encoding KATP channel subunits). In-depth neuropsychomotor investigations were done at median age 7 years (IQR 1-15) in 27 index patients with mutations in KATP channel subunit genes who did not have developmental delay or epilepsy. Developmental coordination disorder (particularly visual-spatial dyspraxia) or attention deficits were recorded in all index patients who had this testing. Compared with index patients who had mutations in KATP channel subunit genes, those with 6q24 abnormalities had specific features: developmental defects involving the heart, kidneys, or urinary tract (8/36 [22%] vs 2/71 [3%]; p=0·002), intrauterine growth restriction (34/37 [92%] vs 34/70 [48%]; p<0·0001), and early diagnosis (median age 5·0 days, IQR 1·0-14·5 vs 45·5 days, IQR 27·2-95·0; p<0·0001). Remission of neonatal diabetes mellitus occurred in 89 (51%) index patients at a median age of 17 weeks (IQR 9·5-39·0; median follow-up 4·7 years, IQR 1·5-12·8). Recurrence was common, with no difference between the groups who had 6q24 abnormalities versus mutations in KATP channel subunit genes (82% vs 86%; p=0·36). INTERPRETATION: Neonatal diabetes mellitus is often associated with neuropsychological dysfunction and developmental defects that are specific to the underlying genetic abnormality. A multidisciplinary assessment is therefore essential when patients are diagnosed. Features of neuropsychological dysfunction and developmental defects should be tested for in adults with a history of neonatal diabetes mellitus. FUNDING: Agence Nationale de la Recherche-Maladies Rares Research Program Grant, the Transnational European Research Grant on Rare Diseases, the Société Francophone du Diabète-Association Française du Diabète, the Association Française du Diabète, Aide aux Jeunes Diabétiques, a CIFRE grant from the French Government, HRA-Pharma, the French Ministry of Education and Research, and the Société Française de Pédiatrie.

Pancreatic enzyme replacement therapy for young cystic fibrosis patients.

UNLABELLED: Maldigestion in cystic fibrosis (CF) affects approximately 90% of patients. As soon as pancreatic insufficiency is identified, enzyme supplementation is prescribed even with breast fed infants. A pancreatic enzyme preparation developed particularly for infants, Creon for children (CfC), contains smaller granules to be administered with a dosing spoon (5000 lipase units per scoop). PATIENTS AND METHODS: In a prospective, randomised, multi-centre study, 40 infants and toddlers received both CfC and Creon 10000 (C10) for two weeks each in a cross-over design. Dosing of pancreatic enzymes was continued as applied before the study. The primary endpoint was the parents' treatment preference. Secondary endpoints included coefficient of fat absorption (CFA), clinical symptoms and safety parameters. RESULTS: 20 parents (51%) from the N=39 intent to treat sample preferred CfC, 9 (23%) preferred C10, and 10 (26%) had no preference The applied doses led to a mean CFA with similar results for both treatments (77.8% vs. 78.7%). Gastrointestinal symptoms were reported on a number of study days, and some children had abnormal results for laboratory parameters of malabsorption. Safety and tolerability of the preparations were good and all these parameters were comparable for both treatments. CONCLUSION: Those parents who had a preference favoured CfC over C10. Both enzyme preparations improved malabsorption to a similar degree, although the applied dosages could have been too low in some children reflected in a suboptimal CFA. These data support the use of CfC for young patients with cystic fibrosis improving the daily care of this cohort detected mainly now through neonatal screening programmes.

Educating diabetic children: integrating representations by children aged 7 to 11 and their parents.

OBJECTIVE: A patient living with a chronic disease develops illness-related knowledge, representations, and specific behaviour leading to attitudes. Our objective was to assess the interaction between representations from diabetic children 7 to 11 years of age and their parents, on the disease and its treatment, in order to improve the therapeutic education process. METHOD: A qualitative approach was developed. Semi-structured interviews and free association technique were used on 10 children 7 to 11 years of age and 10 parents, in the Toulouse Hospital, France. Qualitative and quantitative (Alceste(R) software) discourse analysis relating to representations was performed (distribution, frequency, and meaning of word sequences were compared). RESULTS: Children seemed to cope naturally with their environment in order to manage their disease. Their attitudes were neutral and their behaviour pragmatic. The parents' representations were more conceptual and negative. They expressed their fear of the disease, their difficulty to endorse the responsibilities and overcome everyday constraints. CONCLUSION: The educator must adapt his language level to integrate the child's universe and facilitate assimilation of knowledge. The therapeutic education process for diabetic children should integrate a specific support and training for parents. These results have influenced our choice of a strategy involving continuous group education focusing parents.