Zusammenfassung Die Deutsche Diabetes Gesellschaft (DDG) bewertet im vorliegenden Positionspapier Chancen und Risiken eines bevölkerungsbasierten Screenings auf Typ‑1‑Diabetes mittels Insel‑Autoantikörpern in verschiedenen Kontexten. Der Nachweis multipler Antikörper erlaubt die frühe Identifikation präsymptomatischer Stadien mit hohem Progressionsrisiko, bei weiterhin begrenzter individueller Vorhersagbarkeit von Manifestationszeitpunkt und ‑verlauf. Ein potenzieller Nutzen besteht in der Reduktion diabetischer Ketoazidosen und einer möglichen Progressionsverzögerung durch immunmodulatorische Therapien, ist jedoch abhängig von strukturierter Nachsorge und hoher Versorgungsqualität. Dem stehen Einschränkungen durch unzureichend standardisierte Testverfahren, variable Verläufe, fehlende Langzeitdaten sowie psychologische und ethische Aspekte gegenüber. Zudem zeigen gesundheitsökonomische Analysen eine hohe Ressourcenbindung bei unklarer Kosteneffektivität. Insgesamt sieht die DDG derzeit keine Grundlage für ein populationsweites Screening; erforderlich sind bessere Evidenz, validierte Testverfahren und gesicherte Versorgungsstrukturen.

INTRODUCTION:This study analyzed the effects of the COVID-19 pandemic and body weight on islet and endocrine autoimmunity in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS:Data from 11 973 children and adolescents aged 0.5 to <18 years with new-onset T1D (2015-2023) from the Diabetes Prospective Follow-up Registry were evaluated. Rates of autoantibodies against beta cells (islet antigen 2 (IA2), zinc transporter 8 (ZnT8), glutamic acid decarboxylase (GAD), insulin), thyroid, transglutaminase (TGA), and adrenals were assessed. Logistic regression models adjusted for age and sex examined associations with COVID-19 and body mass index (BMI). RESULTS:6136 (51%) children were diagnosed with T1D before, and 5837 (49%) after the beginning of the COVID-19 pandemic. Beta-cell autoantibodies were present in 94.3%, thyroid autoantibodies in 7.7%, TGA autoantibodies in 8.3%, and adrenal autoantibodies in 5.6%. During versus before COVID-19, IA2 and GAD autoantibody positivity significantly increased (63.3% vs 60.5%, p=0.002, and 65.9% vs 64.0%, p=0.04, respectively), ZnT8 autoantibodies declined (68.0% vs 71.9%, p=0.002), while insulin autoantibodies remained unchanged (p=0.06). Prevalence of IA2, ZnT8, and insulin, but not GAD autoantibodies, showed positive associations with BMI. Thyroid and TGA autoantibodies were not related, while adrenal autoantibodies were negatively related to the pandemic. CONCLUSIONS:The COVID-19 pandemic and body weight influenced autoimmunity in children with T1D. The rise in IA2 autoantibody positivity may suggest a faster progression from pre-existing autoimmunity to clinical disease. The pandemic did not appear to trigger associated endocrine autoimmunity.

Prädiktion und Prävention des Typ-1-Diabetes bilden den Rahmen für die Diskussion, ob ein Antikörperscreening Teil der Regelversorgung werden sollte. Der Inselautoantikörpertest charakterisiert nicht die Stoffwechselsituation, sondern ist eine Momentaufnahme von Autoimmunität und ermöglicht eine Prognose des künftigen Typ-1-Diabetes-Risikos. Für Personen mit positivem Test bietet er jedoch keine verlässliche, individuelle Vorhersage, wann die Erkrankung auftreten wird. Eine medikamentöse Therapie zur Prävention des Typ-1-Diabetes ist aktuell noch nicht verfügbar. Somit konfrontiert ein positiver Test Betroffene mit einer Krankheitsprognose, ohne dass ein sinnvolles Therapieangebot existiert. Die psychologische Belastung des Tests kann daher erheblich sein. Weitere klinische Studien sind erforderlich, um Nutzen und Risiken des Inselautoantikörpertests zu untersuchen.

Introduction: Children and adolescents with diabetes are increasingly using technological devices to maintain normoglycemia. However, skin problems associated with these devices are becoming a significant issue. This study aimed to investigate prevalence of skin issues in children and adoles-cents with diabetes globally and identify important factors associated with these skin problems. Methods: This multinational study involved 22 pediatric diabetes centers. Over a 4-week period, pseud anonymized data were collected on children and adolescents using diabetes devices, includ-ing demographic factors, visual skin problems, type of devices and products being used. Uni-variate logistic regression was applied to identify associations with skin problems. Results: A total of 1719 children and adolescents were included. Skin problems were present in 52% of pump users compared to 30% of sensor users. Eczema was found in 9% of participants at both insulin pump and glucose sensor sites, whereas scars, wounds and lipodystrophies were significant-ly more frequent at insulin pump sites than at glucose sensor sites. Skin characteristicsBoth xerosis cutis and keratosis pilaris were strongly associated with almost all types of skin problems, increasing the risk two to fivefold. Conclusion: Skin problems are a serious concern that limits the use of diabetes devices in children and adolescents, consequently increasing risk for long-term complications. This study highlights the extent of the problem in a real-world setting of unselected participants despite the use of preven-tive strategies. Consequently, the development of more skin-friendly devices is needed to ensure that all children and adolescents with diabetes can effectively use these devices in the long term.

Background The effect of closed-loop insulin delivery on the risk of acute diabetes complications in people with type 1 diabetes is unclear. We investigated whether the rates of severe hypoglycaemia and diabetic ketoacidosis are lower with hybrid closed-loop insulin therapy compared with sensor-augmented (open-loop) pump therapy in a large cohort of young people. Methods In this population-based cohort study, we evaluated young people with type 1 diabetes from 250 diabetes centres in Germany, Austria, Switzerland, and Luxembourg participating in the Diabetes Prospective Follow-up (DPV) initiative. Included participants were aged 2-20 years, with diabetes duration of more than 1 year, and were treated between Jan 1, 2021, and Dec 31, 2023. The primary outcomes were the rates of severe hypoglycaemia and ketoacidosis in people using closed-loop therapy versus open-loop therapy. Key secondary outcomes were differences in HbA1c levels, percentage of time in glucose range of 39-100 mmol/L, and glycaemic variability. To account for relevant confounders, we applied propensity score inverse probability of treatment weighting considering several baseline characteristics. Findings 13 922 young people (median age 132 years [IQR 100 to 160]; 51% male) in the DPV database met inclusion criteria and were included in the analysis. 7088 used closed-loop therapy and 6834 used open-loop therapy, with a median observation time of 16 years [IQR 11 to 24]. Individuals using closed-loop therapy had a higher rate of ketoacidosis (174 per 100 patient-years) than those using open-loop therapy (096 per 100 patient-years; incidence rate ratio 181 [137 to 240], p<00001) and there was no significant difference between groups in the rate of severe hypoglycaemia (559 per 100 patient-years vs 663 per 100 patient-years; incidence rate ratio 084 [95% CI 069 to 103], p=0089). Individuals using closed-loop therapy had a lower rate of hypoglycaemic coma (062 per 100 patient-years) compared with individuals using open-loop therapy (091 per 100 patient-years; incidence rate ratio 068 [95% CI 048 to 097], p=0034). Those in the closed-loop therapy group also had a lower HbA1c level (734% vs 750%; difference -016% [95% CI -020 to -013], p=00007), higher percentage of time in target glucose range of 39-100 mmol/L (64% vs 52%, difference 12% [10 to 14], p<00001), and less glycaemic variability (coefficient of variation 354% vs 383%; difference -29% [-33 to -25], p<00001) than those in the open-loop therapy group. The rate of ketoacidosis was particularly high in young people with HbA1c of 85% or higher in the closed-loop therapy group (525 per 100 patient- years) compared with the open-loop therapy group (153 per 100 patient-years; incidence rate ratio 343 [95% CI 169 to 697], p<00001). Interpretation Hybrid closed-loop insulin delivery has no significant effect on the rate of severe hypoglycaemia, and is associated with an increased risk of diabetic ketoacidosis, but is associated with a reduced risk of hypoglycaemic coma and improved glycaemia. These findings indicate the need for additional educational measures for the use of closed- loop insulin delivery.

OBJECTIVE:This study was conducted to evaluate the effects of early clinical diagnosis of type 1 diabetes by comparison of clinical parameters at diagnosis and during follow-up in patients with pediatric type 1 diabetes with early, intermediate, and late diagnosis. RESEARCH DESIGN AND METHODS:In a population-based analysis, data on 14,292 pediatric patients with type 1 diabetes diagnosed between 2015 and 2019 were retrieved from the Diabetes Prospective Documentation (DPV) registry in March 2023. Patients were divided into four groups: one with diabetic ketoacidosis (DKA) at diagnosis and three with early, intermediate, or late diagnosis based on age-dependent HbA1c terciles. Laboratory-measured HbA1c values and those estimated from continuous glucose monitoring were aggregated as a combined glucose indicator (CGI). Insulin dose-adjusted CGI values <9% were defined as partial remission. RESULTS:At diagnosis, patients had a median age of 9.8 years (IQR 6.8; 13.0). Three years later, patients with early diagnosis had lower CGI than patients with late diagnosis or DKA (mean [95% CI] 7.46% [7.40; 7.53] vs. 7.81% [7.75; 7.87] or 7.74% [7.68; 7.79], respectively; each P < 0.001). More patients experienced partial remission (12.6% [11.0; 14.4] vs. 9.1% [7.7; 10.7] or 8.6% [7.3; 10.0]; each P < 0.001), and 11.7% [10.2; 13.5] of patients with intermediate diagnosis were in partial remission. CONCLUSIONS:Early clinical diagnosis of type 1 diabetes may be beneficial for metabolic control and remission after 3 years of follow-up. Patients diagnosed early may represent a distinct group with better resources or with a different disease biology and slower β-cell destruction, which needs further evaluation.

Objective: To compare demographic, clinical, and therapeutic characteristics of children with type 1 diabetes aged <6 years across three international registries: Diabetes Prospective Follow-up Registry (DPV, Europe), T1D Exchange Quality Improvement Network (T1DX-QI, USA) and Australasian Diabetes Data Network (ADDN, Australasia). Research Design and Methods: Analysis of 2019-2021 prospective registry data from 8,004 children were compared. Results: Mean±SD age at diabetes diagnosis was 3.2±1.4 (DPV, ADDN), and 3.7±1.8 years (T1DX-QI). Diabetes duration was 1.4±1.3 (DPV), 1.4±1.6 (T1DX-QI), and 1.5±1.3 years (ADDN). and BMI z scores were in the overweight range in 36.2% (DPV), 41.8% (T1DX-QI), and 50.0% (ADDN). and Mean±SD HbA1c varied between registries: DPV 7.3±0.9% (56±10mmol/mol, T1DX-QI 8.0±1.4% (64±16mmol/mol), ADDN 7.7±1.2% (61±13mmol/mol). Overall, 37.5% of children achieved target HbA1c of <7.0% (53mmol/mol); 43.6% in DPV, 25.5% in T1DX-QI and 27.5% in ADDN. Use of diabetes technologies varied between registries for use of insulin pump: DPV 86.6%, T1DX 46.6%, and ADDN 39.2%; and continuous glucose monitoring (CGM): DPV 85.1%, T1DX-QI 57.6%, and ADDN 70.5%. Use of hybrid closed loop (HCL) systems was uncommon (0.5% (ADDN) to 6.9% (DPV)). Conclusions: Across three major registries, over half of children aged <6 years did not achieve target HbA1c of <7.0% (53 mmol/mol). CGM was used by most participants, while insulin pump use varied across registries and HCL use was rare. The differences seen in glycemia and use of diabetes technologies between registries requires further investigation to determine potential contributing factors and areas to target to improve the care of this vulnerable group.

Background The effect of continuous glucose monitoring on the risk of severe hypoglycaemia and ketoacidosis in patients with diabetes is unclear. We investigated whether rates of acute diabetes complications are lower with continuous glucose monitoring, compared with blood glucose monitoring, and which metrics predict its risk in young patients with type 1 diabetes. Methods In this population-based cohort study, patients were identified from 511 diabetes centres across Austria, Germany, Luxembourg, and Switzerland participating in the Diabetes Prospective Follow-up initiative. We included people with type 1 diabetes aged 1 center dot 5-25 center dot 0 years, with a diabetes duration of more than 1 year, who had been treated between Jan 1, 2014, and June 30, 2021, and had an observation time of longer than 120 days in the most recent treatment year. Severe hypoglycaemia and ketoacidosis rates during the most recent treatment year were examined in people using continuous glucose monitoring and in those using blood glucose monitoring. Adjustments of statistical models included age, sex, diabetes duration, migration background, insulin therapy (pump or injections), and treatment period. Rates of severe hypoglycaemia and diabetic ketoacidosis were evaluated by several continuous glucose monitoring metrics, including percentage of time below target glucose range (<3 center dot 9 mmol/L), glycaemic variability (measured as the coefficient of variation), and mean sensor glucose. Findings Of 32 117 people with type 1 diabetes (median age 16 center dot 8 years [IQR 13 center dot 3-18 center dot 1], 17 056 [53 center dot 1%] males), 10 883 used continuous glucose monitoring (median 289 days per year), and 21 234 used blood glucose monitoring. People using continuous glucose monitoring had lower rates of severe hypoglycaemia than those using blood glucose monitoring (6 center dot 74 [95% CI 5 center dot 90-7 center dot 69] per 100 patient-years vs 8 center dot 84 [8 center dot 09-9 center dot 66] per 100 patient-years; incidence rate ratio 0 center dot 76 [95% CI 0 center dot 64-0 center dot 91]; p=0 center dot 0017) and diabetic ketoacidosis (3 center dot 72 [3 center dot 32-4 center dot 18] per 100 patient-years vs 7 center dot 29 [6 center dot 83-7 center dot 78] per 100 patient-years; 0 center dot 51 [0 center dot 44-0 center dot 59]; p<0 center dot 0001). Severe hypoglycaemia rates increased with percentage of time below target glucose range (incidence rate ratio 1 center dot 69 [95% CI 1 center dot 18-2 center dot 43]; p=0 center dot 0024, for 4 center dot 0-7 center dot 9% vs <4 center dot 0% and 2 center dot 38 [1 center dot 51-3 center dot 76]; p<0 center dot 0001, for =8 center dot 0% vs <4 center dot 0%) and glycaemic variability (coefficient of variation =36% vs <36%; incidence rate ratio 1 center dot 52 [95% CI 1 center dot 06-2 center dot 17]; p=0 center dot 022). Diabetic ketoacidosis rates increased with mean sensor glucose (incidence rate ratio 1 center dot 77 [95% CI 0 center dot 89-3 center dot 51], p=0 center dot 13, for 8 center dot 3-9 center dot 9 mmol/L vs <8 center dot 3 mmol/L; 3 center dot 56 [1 center dot 83-6 center dot 93], p<0 center dot 0001, for 10 center dot 0-11 center dot 6 mmol/L vs <8 center dot 3 mmol/L; and 8 center dot 66 [4 center dot 48-16 center dot 75], p<0 center dot 0001, for =11 center dot 7 mmol/L vs <8 center dot 3 mmol/L). Interpretation These findings provide evidence that continuous glucose monitoring can reduce severe hypoglycaemia and ketoacidosis risk in young people with type 1 diabetes on insulin therapy. Continuous glucose monitoring metrics might help to identify those at risk for acute diabetes complications.

AimTo assess effects of the SARS-CoV2 pandemic on metabolic control in youth with type 1 diabetes (T1D) in Germany in a population-based analysis.MethodsData from 33,372 pediatric T1D patients from the Diabetes Prospective Follow-up (DPV) registry, with face-to-face visits or telemedicine contacts in the years 2019-2021, were available. Datasets from eight time periods between March 15, 2020, and December 31, 2021, according to SARS-CoV2 incidence waves, were compared to those from five control time periods. Parameters of metabolic control were assessed with adjustment for sex, age, diabetes duration, and repeated measurements. Laboratory-measured HbA1c values and those estimated from CGM were aggregated into a combined glucose indicator (CGI).ResultsThere was no clinically relevant difference in metabolic control between pandemic and control time periods with adjusted CGI values ranging from 7.61% [7.60-7.63] (mean [95% confidence interval (CI)]) in the third quarter of 2019 to 7.83% [7.82-7.85] in the time period from January 1 to March 15 2020, in the other control periods, and during the pandemic, CGI values lay between these values. BMI-SDS rose during the pandemic from 0.29 [0.28-0.30] (mean [95% CI]) in the third quarter of 2019 to 0.40 [0.39-0.41] during the fourth wave. Adjusted insulin dose rose during the pandemic. Event rates for hypoglycemic coma and diabetic ketoacidosis remained unchanged.ConclusionsWe found no clinically relevant change of glycemic control or incidence of acute diabetes complications during the pandemic. The observed BMI increase may represent an important health risk for youth with T1D.

We aimed to identify differences in care and outcomes of very young children with T1D onset from 3 multicenter registries from three continents: T1DX-QI (US), DPV (Germany/Austria/Switzerland/Luxembourg), and ADDN (Australia/New Zealand). These results are an update of 2,011 children of this age-group treated in 2011/2012 in European/US centers (Diabetologia 57:1578-585, 2014). For treatment years 2019-2021, there were 8,004 children with T1D <6 years of age in the 3 registries. The most recent treatment year per child was analyzed. To ensure data protection, analyses were pre-defined and conducted separately by each group. Age at onset, median diabetes duration and gender ratio, as well as anthropometry, and insulin requirement were very similar between the three registries (Table). In DPV, the vast majority of children in this age-group used insulin pumps and glucose sensors, followed by ADDN and T1DX-QI. HbA1c was lowest in DPV, followed by ADDN. Severe hypoglycemia and DKA were rare. Celiac disease was reported most often in Europe, while thyroid disease was more prevalent in the US. Both T1DX-QI and DPV improved metabolic control in this age-group compared to an analysis 10 years ago. However, the majority of children still do not reach currently recommended A1C levels. This young group of subjects needs extensive resources in terms of education, insulin dose adjustment, and family support. Disclosure S.R.Tittel: None. M.E.Craig: None. O.Ebekozien: Advisory Panel; Medtronic, Research Support; Eli Lilly and Company, Dexcom, Inc. E.Fröhlich-reiterer: None. J.L.Sandy: None. S.Rompicherla: None. B.Karges: None. S.James: None. N.Noor: None. A.Zimmermann: None. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. R.W.Holl: None.

ZUSAMMENFASSUNG Jeder 4.–5. Patient mit Typ-1-Diabetes hat eine zusätzliche Autoimmunerkrankung. Die häufigsten Funktionsstörungen sind Hypothyreose und Zöliakie, die ohne eindeutige klinische Symptome auftreten können. Daher wird ein Screening dieser Erkrankungen bei Diabetesmanifestation und im Verlauf empfohlen. Diagnostische Kriterien der Autoimmunthyreoiditis sind positive Schilddrüsen-Autoantikörper und sonografisch ein echoarmes, inhomogenes Parenchym. Eine Therapie mit Levothyroxin ist nur bei Hypothyreose oder Struma sinnvoll, nicht bei Euthyreose. Die Zöliakie wird durch positive Antikörper gegen Gewebstransglutaminase und Endomysium im Serum diagnostiziert, zusätzlich sichert die Dünndarmbiopsie mit Nachweis der Zottenatrophie die Diagnose. Die glutenfreie Diät mit Erreichen einer Seronegativität ist auch für asymptomatische Patienten mit Typ-1-Diabetes vorteilhaft. Morbus Basedow, Autoimmungastritis und Morbus Addison sind bei Patienten mit Typ-1-Diabetes häufiger als bei Individuen ohne Diabetes, insgesamt aber seltener, sodass die spezifische Diagnostik nur bei klinischem Verdacht oder bei autoimmunen polyendokrinen Syndromen (z. B. APS-2) sinnvoll ist.