The incidence of type 1 diabetes (T1D) in children increased significantly during the COVID-19 pandemic (1,2). However, it is not known whether this increase is a persistent phenomenon, which would have significant implications for future patient care. The aim of this study was to investigate the long-term incidence of childhood T1D in Germany during the nine years before and four years after the emergence of COVID-19.

OBJECTIVES:The incidence of type 1 diabetes (T1D) in children increased during the first two years of the COVID-19 pandemic and declined thereafter. It is not known whether the decline is associated with COVID-19 vaccination rates in children. This study investigates whether COVID-19 vaccination rates are associated with T1D incidence in children. METHODS:Population-based ecological study of children with new-onset T1D in the years 2022 and 2023 from the German Prospective Diabetes Registry. COVID-19 vaccination rates (VR) for 2022 were obtained from the Digital Vaccination Rate Monitoring-Project of the Robert-Koch-Institute. Spatial Spearman correlation analysis between period-averaged COVID-19 VR and T1D standardized incidence ratios (SIR) per county were used for the year 2022. Bayesian conditional autoregressive (CAR) Poisson models, including a time lag of 0-12 months between COVID-19 VR and T1D SIR, were used to assess their association. RESULTS:Data of 6,736 children and adolescents with new-onset T1D in the years 2022 and 2023 and of 4,208,377 vaccinated children aged 5-17 years across 336 German counties were analyzed. Neither the month-averaged spatial analysis (5-11 years: r=-0.029 [95%CI -0.136; 0.079]; 12-17 years: r=0.031 [95%CI -0.077; 0.138]) nor the spatiotemporal CAR models including time shifts of 0-12 months showed significant correlations between T1D SIR and COVID-19 VR. CONCLUSIONS:This study found no significant associations between childhood COVID-19 vaccination rates and the subsequent incidence of type 1 diabetes over the next 12 months. Further research is needed to investigate the relationship in younger children.

Hintergrund: Die Inzidenz des Diabetes mellitus Typ 2 bei Kindern und Jugendlichen steigt in Deutschland kontinuierlich an [1]. Daten US-amerikanischer Kohortenstudien zeigen, dass arterielle Hypertension, diabetische Nephropathie, Retinopathie und Neuropathie bei Jugendlichen mit Typ-2-Diabetes (T2D) früher und häufiger als bei Jugendlichen mit Typ-1-Diabetes auftreten (T1D) [2] [3]. Ob diese Beobachtungen auch für Kinder und Jugendliche mit T2D in Deutschland zutreffen, ist derzeit unbekannt.

BackgroundIndividuals with maturity-onset diabetes of the young (MODY) are often misdiagnosed as type 1 or type 2 diabetes and receive inappropriate care. We aimed to investigate the characteristics and treatment of all MODY types in a multicenter, real-world setting.MethodsIndividuals with MODY from the diabetes prospective follow-up (DPV) registry were studied. We compared clinical parameters during the first year of diabetes and the most recent treatment year after MODY diagnosis.ResultsA total of 1640 individuals were identified with GCK-MODY (n = 941) and HNF1A-MODY (n = 417) as the most frequent types. Among these, 912 individuals were available with information during the first and the most recent treatment year (median duration of follow-up: 4.2 years [2.6-6.6]). Positive beta cell autoantibodies were present in 20.6% (15.2% IAA). Median age at diagnosis ranged from 9.9 years in GCK-MODY (Q1-Q3: 6.2-13.1 years) and INS-MODY (2.7-13.7 years) to 14.3 years (5.0-17.1) in KCNJ11-MODY. Frequency of oral antidiabetic agents (OAD) use increased and insulin decreased in HNF4A-MODY (OAD: 18% to 39%, insulin: 34% to 23%) and in HNF1A-MODY (OAD: 18% to 31%, insulin: 35% to 25%). ABCC8-MODY was characterized by a decrement in nonpharmacological treatment (26% to 16%) and "insulin only" treatment (53% to 42%), while the proportion of individuals treated with OAD but no insulin increased from 0% to 21%.ConclusionsOur results indicate that some teams caring for individuals with MODY are hesitant with regard to current recommendations. Registries are an essential source of information and provide a basis for discussing treatment guidelines for MODY. imageConclusionsOur results indicate that some teams caring for individuals with MODY are hesitant with regard to current recommendations. Registries are an essential source of information and provide a basis for discussing treatment guidelines for MODY. image

Hintergrund und Fragestellung: Glucokinase-Gen (GCK) Varianten sind ursächlich für eine der häufigsten Formen des «Maturity Onset Diabetes of the Young», dem GCK-MODY. Gemäss Leitlinien soll bei Personen mit Diabetes mellitus und negativem Antikörperstatus, fehlender Insulinresistenz und positiver Familienanamnese aufgrund therapeutischer Konsequenzen eine molekulargenetische Diagnostik auf monogene Diabetesformen initiiert werden. So kommen Personen mit GCK-Varianten in aller Regel ohne pharmakologische Therapie aus. Ziel unserer Studie war die Kuratierung der im DPV-Register dokumentierten GCK-Varianten und die klinische Charakterisierung der Betroffenen.

Objective: We investigated the incidence of pediatric type 2 diabetes (T2D) in Germany during two years of the COVID-19 pandemic (2020-2021), compared with the control period 2011-2019. Study design and methods: Data on T2D in children (6 to <18 years) were obtained from the DPV registry. Poisson regression was used to estimate incidences for 2020 and 2021 based on data from 2011 to 2019, and these were compared with observed incidences in 2020/2021 by estimating incidence rate ratios (IRRs) with 95% CIs. Results: The incidence of youth-onset T2D increased from 0.75 per 100,000 patient-years [PY] in 2011 (95% CI 0.58; 0.93) to 1.25 per 100,000 PY in 2019 (95% CI 1.02; 1.48), an annual increase of 6.8% (95% CI 4.1; 9.6). In 2020, T2D incidence increased to 1.49 per 100,000 PY (95% CI 1.23; 1.81), which was not significantly higher than predicted (IRR 1.15, 95% CI 0.90; 1.48). In 2021, the observed incidence was significantly higher than expected (1.95 [95% CI 1.65; 2.31] vs. 1.38 [1.13; 1.69] per 100,000 PY; IRR 1.41 [1.12; 1.77]). While there was no significant increase in incidence in girls in 2021, the observed incidence in boys (2.16 [1.73; 2.70] per 100,000 PY) significantly exceeded the predicted rate (IRR 1.55 [1.14; 2.12]), leading to a reversal of the sex ratio of pediatric T2D incidence. Conclusions: In Germany, incidence of pediatric type 2 diabetes increased significantly in 2021. Adolescent males were more affected by this increase, resulting in a reversal of the sex ratio of youth-onset T2D.

Fragestellung Erste Untersuchungen zeigen einen Anstieg des Körpergewichts und eine Zunahme von Adipositas während der Covid-19-Pandemie. Adipositas und ein inaktiver Lebensstil gehören zu den Risikofaktoren eines Typ-2-Diabetes. Ziel war es zu untersuchen, wie sich die Anzahl der Typ-2-Diabetesneudiagnosen bei Kindern und Jugendlichen seit Beginn der Covid-19-Pandemie entwickelt hat.

The multi-center collaborative COACH consortium (Chronic Conditions in Adolescents - Implementation and Evaluation of Patient-centered Collaborative Healthcare) aims to examine mental health comorbidities in adolescents and young adults with chronic diseases. 1023 patients with type 1 diabetes at the age of 12 to 21 years were screened for symptoms of anxiety using the Generalized Anxiety Disorder Scale (GAD-7) and depression using the Patient Health Questionnaire (PHQ-9) during routine visits. Almost every third patient showed a positive screening test result. 17.8% of screenings for anxiety and 25.6 % of screenings for depression were pathological with screening results >= 7, respectively. In these patients with positive screenings, glycated hemoglobin (HbA(1c)), reflecting the adjustment and control of blood glucose, was higher than in those with negative screenings (p<0.0001). As early diagnosis and intervention have relevant impact for treatment of the somatic disease all adolescents with type 1 diabetes should be regularly screened for mental comorbidities. Based on the COACH study results evidence-based recommendations for treatments of adolescents and young adults with chronic diseases will be developed so that mental health problems will be better taken into account in the future.

Objective: The aim of this study was to investigate the incidence of type 1 diabetes in children and adolescents during the Covid-19 pandemic in Germany compared to previous years. Research Design and Methods: Based on data from the multicenter German Diabetes Prospective Follow-up Registry (DPV), we analyzed the incidence of type 1 diabetes per 100,000 patient years in children and adolescents from January 1, 2020, through June 30, 2021. Using Poisson regression models, expected incidences for 2020/21 were estimated based on the data from 2011 to 2019, and compared to observed incidences in 2020/21 by estimating incidence rate ratios (IRRs) with its 95% confidence interval (CI). Results: From January 1, 2020, to June 30, 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 [95% CI, 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 approximately three months after the peak Covid-19 incidence and also after pandemic containment measures. The underlying causes are yet unknown. However, indirect effects of the pandemic are more likely to be the cause than direct ones.

Background Diet modification has the potential to influence glycemic control and diabetes outcome in patients with type 1 diabetes (T1D). This cross-sectional study aimed to assess types of diets being reported by patients with T1D and documented in the Diabetes Patients Follow-Up Registry (DPV).Methods The DPV registry was screened for additional free text entries containing information about certain diets and/or physician-based diagnoses requiring special diets e. g. celiac disease. Descriptive analysis and unadjusted comparisons between patients with T1D following at least one special diet and controls (T1D without diet) were performed.Results Overall, 113,894 patients with T1D of all ages were included. In 2.3% (n = 2,595; median age 11.3 yrs [Q1; Q3: 7.0; 15.2]), at least one kind of diet was documented. These patients were significantly younger at diabetes onset than controls (median age 7.5 yrs [Q1; Q3: 3.9; 11.4] vs. 11.1 yrs [6.6; 16.7]; p < 0.001) and showed a significantly lower BMI-SDS (median [Q1; Q3]: 0.220 [−0.427;0.812] vs. 0.450 [−0.211;1.088]). Diet was more often reported in females (55.7% vs. 44.3%, p < 0.001). The three most common diets were gluten-free diet due to celiac disease, low-protein diet, and lactose-restricted diet due to lactose intolerance. A combination of two diagnoses in one patient (n = 44, 1.7% of the entire diet group) was predominantly intolerance to both fructose and lactose. Among all diet subgroups the highest BMI-SDS was found in the group diets for weight loss.Conclusions This study revealed a wide range of eating habits in patients with T1D. A special diet was more frequently documented in females. The main reason for adhering to a diet was a concomitant disease. As any diet modification could impact glycemic control, health care providers should be encouraged to regularly ask their patients about their eating habits and provide training and support by specialized dietitians.

INTRODUCTION:We evaluated sequelae of disease and therapy in adolescents with chronic endocrinopathies using a medical and psychological workup to record health-related quality of life (HRQoL), near final height (NFH) and body compositions during the transition period from paediatric to adult care.METHODS:Near final height, weight, body mass index (BMI), grip strength (GS), hip and waist circumference (HC; WC), skin folds (SF) and HRQoL T-scores by KIDSCREEN and DISABKIDS were assessed in 134 patients (70 females and 64 males) from May 2010 to March 2016 diagnosed with congenital adrenal hyperplasia (CAH; n = 22), multiple pituitary hormone deficiency (MPHD; n = 17), growth hormone deficiency (GHD; n = 37), Turner syndrome (TS; n = 27), SGA-short stature (SGA; n = 20) and Klinefelter syndrome (KS; n = 11).RESULTS:Median HRQoL T-scores for KIDSCREEN (50.6-56.5) and DISABKIDS (52.7-58.9) ranged within references with considerable variations but without significant deficit in any diagnosis. Median-corrected height SDS (CoH-SDS: NFH-SDS-TH [target height]-SDS) was >-1, except in KS (SDS + 1.3) and in TS (SDS - 1.9; P < .0001) without correlations with HRQoL. Median BMI was below 25 kg/m2 in all patients except MPHD (26.5 kg/m2 ; SDS 1.5; P = .006). BMI correlated negatively in CAH females with self-perception (rs  = -.64, P = .0338), physical well-being (rs  = -.8; P = .0086), social exclusion rs  = -.65; P = .031) and emotions (rs  = -.7; P = .0169).CONCLUSION:Health-related quality of life and body compositions were similar to those of healthy adolescents. Lower scores in HRQoL dimensions as self-perception, physical well-being, social exclusion and emotions were detected and correlated negatively with BMI. Treatment strategies and psychological support should consider HRQoL and adapted in specific treatment guidelines.

Abstract Background 11β-hydroxylase deficiency (11βOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5–8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11βOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11βOHD. Methods Clinical, biochemical and radiological data of patients with 11βOHD were analysed in this retrospective single-centre analysis. Results Six male patients of four unrelated families with 11βOHD were identified (0.1–13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA–CA: 5.5 years, range 1.5–9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11βOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years. Conclusion The diagnosis of CAH due to 11βOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11βOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.

Background: Paediatric prolactinomas are rare. The aim of this study was to investigate the clinical features and outcome of paediatric patients with prolactinomas. Methods: In this single-centre retrospective analysis, clinical, biochemical, and radiological features of all paediatric patients with pituitary adenomas diagnosed between 2000 and 2016 were evaluated. Results: Among 21 patients with pituitary adenomas, 12 patients with prolactinomas (median age 14.2 years, range 11–16.6 years, 8 females, 4 males) were identified (7 macro- and 5 microprolactinomas). The most common clinical symptoms were headaches (67%) and pubertal delay (67%). All patients with macroprolactinomas with prolactin concentrations >10,000 mU/L had at least 1 pituitary hormone deficiency. Cabergoline as first-line treatment (n = 11, median follow-up of 37 months, range 12–89 months) induced normoprolactinemia (n = 8), reduced the mean tumour volume by 80%, and ameliorated headaches (p = 0.016) and pubertal delay (p = 0.031), whereas intermittent moderate side effects occurred in 55%. Conclusion: Adolescents with headaches and pubertal delay should be investigated for prolactinomas. Treatment with cabergoline is well tolerated and effective in reducing clinical symptoms and prolactin concentrations was well as inducing tumour shrinkage. Further clinical prospective studies are needed to standardize paediatric treatment modalities.

Diabetes mellitus (DM) is not a single disease, but several pathophysiological conditions where synthesis, release, and/or action of insulin are disturbed. A progressive autoimmune/autoinflammatory destruction of islet cells is still considered the main pathophysiological event in the development of T1DM, but there is evidence that T1DM itself is a heterogeneous disease. More than 50 gene regions are closely associated with T1DM and a variety of epigenetic factors and metabolic patterns have been characterized, which may play a role in the development of T1DM. The pathogenesis and genetics of type 2 DM (T2DM) are distinct from T1DM. Genes associated with T2DM are distinct from those in T1DM. Characteristic metabolic patterns, different from those in T1DM were reported in T2DM, and some children with T2DM also express islet-antibodies. Huge progress has been made in the characterization of other specific types of DM, which had been considered very rare before. The molecular clarification of maturity-onset diabetes of the young (MODY) has greatly improved our understanding of the pathophysiology of DM. There are genetic overlaps between T2DM and monogenetic DM. Neonatal DM has been shown to be monogenetic in most cases, and genetic elucidation leads to more precise and individualized therapies. Cystic fibrosis related DM (CFRDM) should be considered a genuine part of cystic fibrosis, and not a complication, since pancreatic fibrosis does not sufficiently explain the pathophysiology of CFRDM. Disturbances of cystic fibrosis transmembrane conductance regulator (CFTR) as well as autoimmunity are involved in the pathogenesis of CFRDM.

Typ–1–Diabetes ist bei Kindern mit Abstand der häufigste Diabetestyp. Die Behandlung muss von Anfang an mit Insulin oder Insulin–Analoga erfolgen. Die intensivierte Insulintherapie, sei es in Form von multiplen Insulininjektionen oder mittels kontinuierlicher subkutaner Insulininfusion (Insulinpumpentherapie), ist heute Standard in der pädiatrischen Diabetologie. Die Insulintherapie muss individuell angepasst werden und das Alter, den Entwicklungsstand und das familiäre Umfeld berücksichtigen. Insulin–Analoga stellen eine wichtige Ergänzung in der Insulintherapie dar und ermöglichen eine differenziertere Therapie. Eine altersangepasste Schulung und Betreuung der Kinder und ihrer Eltern durch ein pädiatrisches Diabetesteam ist aber unabhängig von der Art und Weise der Insulintherapie die wichtigste Vorraussetzung für eine erfolgreiche Diabetesbehandlung.