[Early Detection Of Type 1 Diabetes By Islet Autoantibody Screening: A Position Paper Of The Fr1daplex Project Leaders And Training Centres, Bvkj Bavaria And Paednetz (Registered) Bavaria]. / Früherkennung von Typ-1-Diabetes durch Inselautoantikörper-Screening ­ ein Positionspapier der Fr1daPlex-Projektleiter und -Schulungszentren, des BVKJ Bayern und PaedNetz Bayern e.V.

This position paper is based on the authors' many years of clinical experience and basic science research on the diagnosis and treatment of children and adolescents with a presymptomatic early stage of type 1 diabetes. The benefits as well as potential disadvantages of early detection of type 1 diabetes by islet autoantibody screening are critically discussed. In addition, the perspectives of delaying the onset of the clinical metabolic disease through treatment with teplizumab are addressed. Today, we see the chance for a relevant improvement in therapeutic options and life perspectives of affected children and adolescents. Important next steps for the implementation of islet autoantibody screening in Germany are the training of pediatricians who should inform families about the screening, establishment of a few transregional laboratories that carry out the test, and expansion of regional capacities for the training and care of children with an early stage of type 1 diabetes.

Children diagnosed with presymptomatic type 1 diabetes through public health screening have milder diabetes at clinical manifestation.

AIMS/HYPOTHESIS: We aimed to determine whether disease severity was reduced at onset of clinical (stage 3) type 1 diabetes in children previously diagnosed with presymptomatic type 1 diabetes in a population-based screening programme for islet autoantibodies. METHODS: Clinical data obtained at diagnosis of stage 3 type 1 diabetes were evaluated in 128 children previously diagnosed with presymptomatic early-stage type 1 diabetes between 2015 and 2022 in the Fr1da study and compared with data from 736 children diagnosed with incident type 1 diabetes between 2009 and 2018 at a similar age in the DiMelli study without prior screening. RESULTS: At the diagnosis of stage 3 type 1 diabetes, children with a prior early-stage diagnosis had lower median HbA1c (51 mmol/mol vs 91 mmol/mol [6.8% vs 10.5%], p<0.001), lower median fasting glucose (5.3 mmol/l vs 7.2 mmol/l, p<0.05) and higher median fasting C-peptide (0.21 nmol/l vs 0.10 nmol/l, p<0.001) compared with children without previous early-stage diagnosis. Fewer participants with prior early-stage diagnosis had ketonuria (22.2% vs 78.4%, p<0.001) or required insulin treatment (72.3% vs 98.1%, p<0.05) and only 2.5% presented with diabetic ketoacidosis at diagnosis of stage 3 type 1 diabetes. Outcomes in children with a prior early-stage diagnosis were not associated with a family history of type 1 diabetes or diagnosis during the COVID-19 pandemic. A milder clinical presentation was observed in children who participated in education and monitoring after early-stage diagnosis. CONCLUSIONS/INTERPRETATION: Diagnosis of presymptomatic type 1 diabetes in children followed by education and monitoring improved clinical presentation at the onset of stage 3 type 1 diabetes.

Fasting hypoglycemia is associated with disease progression in presymptomatic early stage type 1 diabetes.

OBJECTIVE: In children with presymptomatic type 1 diabetes, intermittent hyperglycemia and rising hemoglobin A1c levels are a known signal of progression toward insulin-dependency. Episodes of hypoglycemia, however, have also been reported in one published case. We investigated the prevalence of hypoglycemia and its association with disease progression in children with presymptomatic type 1 diabetes. METHODS: We compared the frequency of hypoglycemic fasting blood glucose levels (<60 mg/dL) in 48 autoantibody negative and 167 multiple ß-cell autoantibody positive children aged 2 to 5 years. We classified the autoantibody positive children into three categories based on their glucose levels in fasting state (hypoglycemic [<60 mg/dL], normoglycemic [60-99 mg/dL] or hyperglycemic [≥100 mg/dL]). We then compared the glucose levels under challenge during oral glucose tolerance tests (OGTTs) between the three categories. RESULTS: In the autoantibody positive children, 5.1% of the fasting samples were hypoglycemic, while in the autoantibody negative children no hypoglycemia was observed. Hypoglycemia occurred more often in autoantibody positive children who had already entered stage 2 or stage 3 of type 1 diabetes than in stage 1 patients (P = 0.02). Children who had hypoglycemic compared to normoglycemic fasting blood glucose values had higher 120-minute blood glucose values under OGTT challenge, and a higher rate of pathological OGTTs (P = 0.04). CONCLUSIONS: Fasting hypoglycemia seems to be an indicator of disease progression in presymptomatic type 1 diabetes and may therefore represent a novel marker for the identification of children who should be monitored more closely for progression toward insulin-dependent type 1 diabetes.

[Anorexia nervosa: does the incidence increase during the coronavirus pandemic?] / Anorexia nervosa: Steigt die Inzidenz in der Coronapandemie?

Since the beginning of the coronavirus pandemic and the associated lockdown measures, the number of children treated in this children's hospital for eating disorders and in particular anorexia nervosa has significantly increased.An increased focus on the control of body weight with restrictive eating habits or otherwise induced weight loss (sport) can compensate for fears of loss of control. Thinking and behavioral patterns which are typical for anorexia can be assessed as dysfunctional coping strategies of the corona pandemic in order to regain control (in the sense of a substitute structure) but also as a means of coping better with feelings of depression and anxiety.

[Anorexia nervosa: does the incidence increase during the coronavirus pandemic?] / Anorexia nervosa: Steigt die Inzidenz in der Coronapandemie?

Since the beginning of the coronavirus pandemic and the associated lockdown measures, the number of children treated in this children's hospital for eating disorders and in particular anorexia nervosa has significantly increased.An increased focus on the control of body weight with restrictive eating habits or otherwise induced weight loss (sport) can compensate for fears of loss of control. Thinking and behavioral patterns which are typical for anorexia can be assessed as dysfunctional coping strategies of the corona pandemic in order to regain control (in the sense of a substitute structure) but also as a means of coping better with feelings of depression and anxiety.

Intermittently Scanned Glucose Values for Continuous Monitoring: Cross-Sectional Analysis of Glycemic Control and Hypoglycemia in 1809 Children and Adolescents with Type 1 Diabetes.

Background and Objective: Intermittent scanning continuous glucose monitoring (iscCGM) is increasingly used for glycemic monitoring in diabetes care. In this cross-sectional real-world analysis, iscCGM data were compared to traditional parameters of glycemic control in young people with type 1 diabetes. Methods: Using the DPV registry, most recent data from children and adolescents aged <18 years with uploaded iscCGM sensor profiles with at least 14 days of data and a > 50% completeness were evaluated using recommended parameters of sensor metrics. Analysis was performed stratified by age group, glycemic control, and type of therapy; data were taken from DPV data pool in February 2020. Results: Glucose sensor profiles and clinical data from 1809 individuals (mean age 13.4 years, 53% male, and mean diabetes duration 5.02 years) were evaluated in this study. More than 50% of this population (n = 965) reached the current German treatment target of hemoglobin A1c (HbA1c) <7.5%. In this target, the mean scanning frequency was higher than in groups with HbA1c >7.5 or >8.0% (12.0 vs. 10.2 vs 7.6 times per day). The group of preschool children had the highest frequency of scanning (16.6 vs. 13.3 times per day in school kids and 7.9 in adolescents), the lowest HbA1c level, and the lowest risk for hypoglycemia (low blood glucose index 0.8 vs. 1.0 vs 1.2). Conclusion: Real-world data will help to determine the value of iscCGM to improve clinical and patient-related outcomes in pediatric diabetology. Not only the use of a device but also the intensity of use seems to have a high and direct impact on glycemic control.

Recruiting young pre-symptomatic children for a clinical trial in type 1 diabetes: Insights from the Fr1da insulin intervention study.

BACKGROUND: Although detection of children at high risk of developing type 1 diabetes and diagnosis of early stages is possible, up to now there exists no approved therapy to delay or prevent type 1 diabetes. Thus it is vital to develop evidence-based interventions. For this a sufficient number of trial participants is crucial but difficult to obtain especially in asymptomatic children. AIM: Identifying family characteristics that lead to or impede trial participation and analyze reasons stated by families for non-participation. METHODS: Participants for the Fr1da Insulin Intervention study are recruited from the Fr1da study, a population based screening for early stage type 1 diabetes in Bavaria. Families with eligible children were invited to enroll. We analyzed sex and age of the child, distance of the family to the study center in Munich and the existence of a first degree family member with type 1 as possible influential factors for study participation. We also analyzed reasons stated by families who declined study participation in a phone interview. RESULTS: Of 146 eligible children 77 (53%) were enrolled into the trial. None of the tested family characteristics differed significantly between the enrolling and the families not participating, but in general enrolling families lived closer to the study site than families not participating. This is also reflected in the reasons given by non-participating families. The most frequent reason stated were time restrictions. The second most frequent reason was the venous blood draw. CONCLUSION: The factors for non-participation identified in this project need be taken into account for the design of future trials in young children to ensure proper recruitment and thus to generate valid results for medical treatment of children. More research on the reason of participation and non-participation in clinical trials is needed.