Association of Diabetic Ketoacidosis in Childhood New-Onset Type 1 Diabetes With Day of Presentation in Germany.

OBJECTIVE: Whether the day of the week on which the child presents affects timely diagnosis and risk of diabetic ketoacidosis (DKA) in children with new-onset type 1 diabetes (T1D) is not known. RESEARCH DESIGN AND METHODS: We used data of 30,717 children with new-onset T1D during the last 10 years from the German Prospective Diabetes Registry. We determined the odds ratios of T1D diagnosis and DKA on a weekday, public holiday, and school vacation. RESULTS: Compared with workdays, the odds ratios of being diagnosed with T1D were lower on weekends (0.39 [95% CI, 0.38-0.41]), public holidays (0.57 [0.53-0.63]), and school vacations (0.83 [0.80-0.85]). The odds of DKA diagnosis were also reduced on weekends (0.55 [0.52-0.59]), public holidays (0.73 [0.63-0.84]), and school vacations (0.85 [0.80-0.90]). Results did not change during the coronavirus 2019 pandemic. CONCLUSIONS: New-onset T1D and DKA in children are more often diagnosed during weekdays than weekends and holidays.

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.

Use of Continuous Glucose Monitoring in Pump Therapy Sensor Augmented Pump or Automated Insulin Delivery in Different Age Groups (0.5 to <26 Years) With Type 1 Diabetes From 2018 to 2021: Analysis of the German/Austrian/Swiss/Luxemburg DPV Registry.

AIM: Insulin pump, continuous glucose monitoring (CGM), and sensor augmented pump (SAP) technology have evolved continuously leading to the development of automated insulin delivery (AID) systems. Evaluation of the use of diabetes technologies in people with T1D from January 2018 to December 2021. METHODS: A patient registry (Diabetes Prospective Follow-up Database [DPV]) was analyzed for use of SAP (insulin pump + CGM ≥90 days, no automated dose adjustment) and AID (HCL or LGS/PLGS). In total 46,043 people with T1D aged 0.5 to <26 years treated in 416 diabetes centers (Germany, Austria, Luxemburg, and Switzerland) were included and stratified into 4 groups A-D according to age. Additionally, TiR and HbA1c were analyzed. RESULTS: From 2018 to 2021, there was a significant increase from 28.7% to 32.9% (sensor augmented pump [SAP]) and 3.5% to 16.6% (AID) across all age groups, with the most frequent use in group A (<7 years, 38.8%-40.2% and 10.3%-28.5%). A similar increase in SAP and AID use was observed in groups B (7 to <11 years) and C (11 to <16 years): B: +15.8 PP, C: +15.9 PP. HbA1c improved significantly in groups C and D (16 to <26 years) (both P < .01). Time in range (TiR) increased in all groups (A: +3 PP; B: +5 PP; C: +5 PP; D: +5 PP; P < 0.01 for each group). Insulin pumps (61.0% versus 53.4% male) and SAP (33.5% versus 28.9% male) are used more frequently in females. CONCLUSION: In recent years, we found an increasing use of new diabetes technologies and an improvement in metabolic control (TiR) across all age groups.

Incidence of Type 1 Diabetes in Children and Adolescents During the COVID-19 Pandemic in Germany: Results From the DPV Registry.

OBJECTIVE: The aim of this study was to investigate the incidence of type 1 diabetes in children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic in Germany compared with previous years. RESEARCH DESIGN AND METHODS: Based on data from the multicenter German Diabetes Prospective Follow-up Registry, we analyzed the incidence of type 1 diabetes per 100,000 patient-years in children and adolescents from 1 January 2020 through 30 June 2021. Using Poisson regression models, expected incidences for 2020/21 were estimated based on the data from 2011 to 2019 and compared with observed incidences in 2020/21 by estimating incidence rate ratios (IRRs) with 95% CIs. RESULTS: From 1 January 2020 to 30 June 2021, 5,162 children and adolescents with new-onset type 1 diabetes in Germany were registered. The observed incidence in 2020/21 was significantly higher than the expected incidence (24.4 [95% CI 23.6-25.2] vs. 21.2 [20.5-21.9]; IRR 1.15 [1.10-1.20]; P < 0.001). IRRs were significantly elevated in June 2020 (IRR 1.43 [1.07-1.90]; P = 0.003), July 2020 (IRR 1.48 [1.12-1.96]; P < 0.001), March 2021 (IRR 1.29 [1.01-1.65]; P = 0.028), and June 2021 (IRR 1.39 [1.04-1.85]; P = 0.010). CONCLUSIONS: A significant increase in the incidence of type 1 diabetes in children was observed during the COVID-19 pandemic, with a delay in the peak incidence of type 1 diabetes by ∼3 months after the peak COVID-19 incidence and also after pandemic containment measures. The underlying causes are yet unknown. However, indirect rather than direct effects of the pandemic are more likely to be the cause.

Diabetic Ketoacidosis at Manifestation of Type 1 Diabetes in Childhood and Adolescence­Incidence and Risk Factors.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening metabolic disorder that can occur with manifestation of type 1 diabetes mellitus (T1D). The aim of this study was to analyze the incidence of DKA at the time of the diagnosis of T1D in childhood and adolescence, the risk factors, and regional approaches to reduce the incidence of ketoacidosis. METHODS: We investigated the proportion of patients under 18 years of age with DKA (defined as pH <7.3, severe DKA pH <7.1) at the manifestation of T1D in Germany in the period 2000-2019, based on data from the German-Austrian registry of diabetes (Diabetes-Patienten-Verlaufsdokumentation, DPV). The influence of the following factors was evaluated: year of manifestation, age, sex, family history of migration (MiH), and distance from the hospital. Moreover, data from the region with and the region without a pilot screening project from 2015 onwards were compared. RESULTS: Of the 41 189 patients with manifestation of T1D, 19.8% presented with DKA (n = 8154, slight increase [p <0.001] over the study period) and 6.1% (n = 2513) had severe DKA. Children under 6 years of age had DKA more often than adolescents (12-17 years) (21.7% versus 18.6%, OR 1.22 {95% CI: [1.14; 1.30]}). Girls had a higher rate of DKA than boys (20.5% versus 19.2%, OR 1.10 [1.03; 1.14]), and patients with MiH were more likely to have DKA than those without MiH (21.4% versus 18.2%, OR 1.40 [1.32; 1.48]). In the region with a pilot screening project, the DKA rate stayed the same, at 20.6%, while in the control region the rate was 22.7% with a decreasing tendency. CONCLUSION: The frequency of DKA at the time of diagnosis of T1D did not decrease between 2000 and 2019 and increased towards the end of the observation period. Children with MiH, children under 6, and girls were at a higher risk of DKA.

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.

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.

Simultaneous radiochemotherapy in pediatric patients with high-grade glioma: a phase I study.

BACKGROUND: Sandwich chemotherapy as first postoperative treatment might cause resistance to ensuing irradiation. Simultaneous radiochemotherapy might prevent this. PATIENTS AND METHODS: Twenty-nine children with high-grade glioma were treated from 1997-1999. The median age was 11.1 years. Tumor locations included: cerebral cortex 12, deep cerebral locations 11, cerebellum 3, spinal cord 3. Pons was excluded. Total (n = 9), subtotal (n = 3) and partial (n = 9) tumor resection or biopsy (n = 7) were followed by radiochemotherapy: fractionated radiation (1.8 Gyld up to 59.4 Gy) was given simultaneously with two cycles of chemotherapy (cisplatin 20 mg/m2/d x 5d, etoposide 100 mg/m2/d x 3d, and cisplatin, etoposide, ifosfamide: 1.5 g/m2/d). The data of a previous protocol (Cancer 89: 2131-7, 2000) in the same population were used as controls. RESULTS: Early progressive disease (PD 2 out of 25 patients) was significantly less frequent as compared to the control group (p = 0.031). The toxicity appeared tolerable.