Search

Background. The COVID-19 pandemic has an impact on the incidence of type 1 diabetes and frequency of diabetic ketoacidosis. However, the exact relationships are unclear. It is also not known whether this is a short-term phenomenon or whether the effects have long-term relevance. Furthermore, it is not known whether these changes during the pandemic are due to direct effects of SARS-CoV-2 or to changes in the patient’s environment during the pandemic. Methods. We conducted an extensive literature search on PubMed. For the estimation of relative risks of new-onset type 1 diabetes, we applied a Poisson regression model and for the comparison of incidences and we included the logarithm of person-years. Furthermore, we performed a meta-analysis using the logarithm of the relative risk for new-onset type 1 diabetes as effect size. Results. Pooling the relative risk estimates in a random-effects meta-analysis revealed that the type 1 diabetes incidence rate increased by 20% (relative risk 1.200 (95% CI 1.125, 1.281)), and that the risk of new-onset type 1 diabetes after a SARS-CoV-2 infection increased by 62% (relative risk 1.622 (95% CI 1.347, 1.953)) compared with the prepandemic period. Conclusion. There is considerable evidence that there is an increase in type 1 diabetes in children during the COVID-19 pandemic. Many studies suggesting a direct effect of SARS-CoV-2 have methodological weaknesses. As no evidence of an increase in presymptomatic cases with isolated islet autoimmunity was found, this could also suggest an accelerated transition from presymptomatic patients to clinically overt type 1 diabetes. Furthermore, there was a marked exacerbation of the preexisting increase in the prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes during the pandemic. Both the increased incidence of paediatric type 1 diabetes and the higher prevalence of diabetic ketoacidosis at diagnosis led to a massive rise in the number of children with diabetic ketoacidosis during the pandemic.

To provide estimates of the nationwide prevalence of type 1 diabetes (T1D) and type 2 diabetes (T2D) in individuals younger than 20 years of age in Germany from 2002 to 2020 and to identify trends.Data were obtained from the electronic health record "Diabetes Prospective Follow-up Registry (DPV)" specific to diabetes care. Prevalence was estimated based on prevalent cases at the end of each year for the years 2002, 2008, 2014, and 2020 per 100 000 persons assuming a Poisson distribution and directly age- and/or sex-standardized to the population in 2020. Individuals younger than 20 years of age with a clinical diagnosis of T1D or 10-19-year-olds with T2D were eligible for inclusion in the study.The standardized T1D prevalence per 100 000 persons was 138.9 (95% CI: 137.1; 140.6) in 2002 and 245.6 (243.1; 248.0) in 2020. The standardized T2D prevalence per 100 000 persons was 3.4 (3.1; 3.8) in 2002 and 10.8 (10.1; 11.5) in 2020. The annual percent change (APC) in prevalence declined over the three periods 2002-2008/2008-2014/2014-2020 (T1D: 6.3% [3.6%; 9.0%]/3.1% [0.7%; 5.5%]/0.5% [-1.7%; 2.85], T2D: 12.3% [5.3%; 20.8%]/4.7% [-0.6%; 10.3%]/3.0% [-1.8%; 8.0%]). From 2014 to 2020, the highest APCs were observed among 15-19-year-olds (T1D: 2.5% [1.3%; 3.6%], T2D: 3.4% [-0.5%; 7.5%]).The increase in diabetes prevalence has slowed, but medical care should be prepared for an increase in adolescents with diabetes.研究背景:评估2002~2020年德国20岁以下人群中1型糖尿病(T1D)和2型糖尿病(T2D)的患病率, 并确定其趋势。 方法:数据来源于糖尿病前瞻性随访登记系统(Diabetes Prospective Follow-up Registry, DPV)。根据2002年、2008年、2014年和2020年每10万人年末发病例数, 采用Poisson分布和直接对2020年人群进行年龄和(或)性别标化, 估算患病率。小于20岁临床诊断为T1D的患者或10~19岁的T2D患者符合纳入标准。 结果:在2020年, 标化T1D患病率为138.9 / 10万(95% CI: 137.1;140.6)和245.6 (243.1;248.0), 标化T2D患病率为3.4/10万 (3.1;3.8)和10.8 (10.1;11.5)。2002-2008年/ 2008-2014年/ 2014-2020年3个时期患病率的年度变化百分比(APC)均呈下降趋势(T1D: 6.3% (3.6%;9.0%) / 3.1% (0.7%;5.5%) / 0.5% (-1.7%;2.85)、T2d:12.3% (5.3%;20.8%) / 4.7% (-0.6%;10.3%) / 3.0% (-1.8%;8.0%))。2014-2020年, 15 ~ 19岁人群APC最高(T1D: 2.5% (1.3%;3.6%), T2D: 3.4% (-0.5%;7.5%))。 结论:青少年糖尿病患病率的增长速度有所减缓, 但应做好医疗保健准备。.

Background: An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic. Methods: For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006–19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker. Findings: 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27·3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1·6% (95% CI 1·3 to 1·9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39·4% (95% CI 34·0 to 45·6) in 2020 and 38·9% (33·6 to 45·0) in 2021, significantly higher than the predicted prevalence of 32·5% (27·8 to 37·9) for 2020 and 33·0% (28·3 to 38·5) for 2021 (p

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.

Objectives Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare autosomal recessive disorders characterized by near/total absence of body fat. Pathogenic variants in polymerase-I and transcript release factor gene (PTRF), or CAVIN1, is responsible for CGL4. In addition to generalized fat loss, patients with CGL4 were reported to suffer from myopathy, malignant cardiac arrhythmias, gastrointestinal disorders, and skeletal abnormalities. Here we describe the phenotype of a child with CGL4 due to a rare, novel pathogenic variant in the PTRF/CAVIN1 gene and the long-term effects of metreleptin substitution on comorbidities. Case presentation We describe a now 20-year-old female patient. At the age of 14-years, she was referred to the University Clinic because of uncontrolled diabetes with an HbA1c of 9.3%, requiring 2.4 IU insulin/kg total-body-weight to normalize blood glucose, hepatomegaly, and hypertriglyceridemia of 515 mg/dL. Additionally, she was suffering from malignant cardiac arrhythmia, myopathy, and hyperCKemia. In light of these clinical findings, she was diagnosed with CGL due to a rare, novel variant in the PTRF gene, and was started on metreleptin, a synthetic analog of human leptin. After the initiation of metreleptin treatment, insulin therapy could be stopped and improvement of sonographically assessed liver size was observed, even though serum liver function test stayed mildly elevated. Furthermore, a noticeable improvement of the serum triglyceride levels was also seen. Medical care and regular follow-up visits are being carried out by a multi-disciplinary team. Conclusions Although CGL4 is rare, due to its life-threatening comorbidities and the opportunity for an early intervention, it is important that the clinicians should recognise these patients.

This study investigated the diagnostic delay and the subsequent quality of care during the Covid-19 pandemic among children with new-onset type 1 diabetes.We compared the HbADuring the Covid-19 pandemic, HbAThis increase in HbA

ZusammenfassungKinder und Jugendliche mit chronischen Erkrankungen wie Adipositas stehen im Zuge der COVID-19 Pandemie vor besonderen Herausforderungen. Ziel der multizentrischen Längsschnittstudie ist es, den Einfluss der COVID-19 Pandemie auf das physische und psychische Wohlbefinden der Betroffenen und ihrer Familien zu untersuchen. Die Untersuchung erfolgt im Rahmen der Standard-Erhebung im APV-Register und wird durch einen Kurzfragebogen für die Kinder und Jugendlichen und ihre Eltern zur Versorgungssituation, Risikowahrnehmung und zum Wohlbefinden ergänzt. Im zweiten Schritt werden alle Beteiligten gebeten, an einer weiterführenden online-Befragung zur psychosozialen Situation und vorhandenen Ressourcen teilzunehmen. Nach einem Jahr findet eine erneute Befragung statt.Die gewonnenen Daten sollen Hinweise darauf geben, wie das Gesundheitssystem verbessert und die betroffenen Familien unterstützt werden können. Der Vergleich mit gleichzeitig stattfindenden Befragungen bei Kindern und Jugendlichen mit Rheuma und Diabetes trägt dazu bei, generische und krankheitsspezifische Belastungsprofile zu eruieren.

Aim Screening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed. Methods This was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis. Results Of 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, pp1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period. Conclusions Our study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed. Graphical abstract

Objective To investigate whether socioeconomic deprivation and urbanization are associated with the frequency of diabetic ketoacidosis (DKA) at diagnosis of pediatric type 1 diabetes. Research Design and Methods Children and adolescents aged ≤18 years, living in Germany, with newly diagnosed type 1 diabetes documented between 2016 and 2019 in the prospective diabetes follow-up registry (DPV) were assigned to a quintile of regional socioeconomic deprivation (German Index of Socioeconomic Deprivation) and to a degree of urbanization (Eurostat), using their residence postal code. With multiple logistic regression models, we investigated whether the frequency of DKA at diagnosis was associated with socioeconomic deprivation or urbanization, and if associations differed by age group, sex or migration status. Results In 10,598 children and adolescents with newly diagnosed type 1 diabetes, the frequency of DKA was lowest in the least deprived regions (Q1: 20.6% [95%-CI: 19.0-22.4%], and increased with growing socioeconomic deprivation to 26.9% [25.0-28.8%] in the most deprived regions (Q5) (P for trend Conclusions This study provides evidence that prevention of DKA at diagnosis by means of awareness campaigns and screening for pre-symptomatic type 1 diabetes should particularly target socioeconomically disadvantaged regions and rural areas.

Summary Background Although continuous subcutaneous insulin infusion therapy (ie, insulin pump therapy) is associated with improved metabolic control compared with multiple daily insulin injections in children with type 1 diabetes, it is unclear when it is best to start it after diagnosis. In this study, we aimed to compare the outcomes between early and delayed start of insulin pump therapy in young patients with type 1 diabetes. Methods We based the current study on data from the multicentre, prospective diabetes follow-up registry (ie, Diabetes-Patienten-Verlaufsdokumentation [DPV]). The DPV registry comprises 501 diabetes centres from Germany, Austria, Switzerland, and Luxembourg. We included patients diagnosed with type 1 diabetes between 2004 and 2014, who were aged between 6 months and 15 years at the time of diagnosis, who had started insulin pump therapy either within the first 6 months (ie, the early treatment group) or in the second to third year (ie, the delayed treatment group) after diabetes diagnosis, and who were treated with insulin pump therapy for at least 1 year. The outcome parameters included the glycated haemoglobin (HbA1c) values, the cardiovascular risk profile, and rates of acute complications and diabetes-associated hospital admissions (ie, hospitalisation) during the most recent documented treatment year with insulin pump therapy. Statistical models were adjusted for age at diabetes diagnosis, year of diagnosis, sex, immigrant background, use of continuous glucose monitoring, centre size, and the German Index of Socioeconomic Deprivation 2012 terciles. Findings Our study sample comprised 8332 patients from 311 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The early treatment group consisted of 4004 (48·1%) of 8332 patients, and the delayed treatment group consisted of 4328 (51·9%). The median diabetes duration during follow-up was 6·7 years (IQR 5·1–8·7 in the early group; 5·0–8·7 in the delayed group) in both groups. Patients with early initiation of insulin pump therapy compared with those with delayed initiation of insulin pump therapy had significantly lower estimated mean HbA1c values (7·9% [95% CI 7·8–7·9] and 62·6 mmol/mol [95% CI 62·1–63·2] vs 8·0% [8·0–8·1] and 64·1 mmol/mol [63·6–64·6]; p=0·0006), and lower rates of hypoglycaemic coma (incidence risk ratio 0·44 [95% CI 0·24–0·79]; p=0·0064) and hospitalisation (0·86 [95% CI 0·78–0·94]; p=0·0016). A better cardiovascular risk profile was observed in patients with early initiation of insulin pump therapy than in those with delayed initiation: an estimated mean systolic blood pressure of 117·6 mm Hg (95% CI 117·2–117·9) versus 118·5 mm Hg (118·2–118·9), p=0·0007; and HDL cholesterol of 62·8 mg/dL (95% CI 62·2–63·5) versus 60·6 mg/dL (60·0–61·2), p Interpretation Our findings provide evidence for improved clinical outcomes associated with the early initiation of insulin pump therapy in children with type 1 diabetes. Funding The German Center for Diabetes Research (Deutsches Zentrum fur Diabetesforschung), German Robert Koch Institute, German Diabetes Association, and Diabetes Agenda 2010.

Summary Case presentation We report a case of severe glycogenic hepatopathy in a 17-year-old boy with poorly controlled type 1 diabetes. On presentation, major findings included unexplained pronounced hepatomegaly and increased liver enzymes, ferritin, and triglycerides. Histology and electron microscopy evaluation showed severe glycogen storage, steatosis, and signs of fibrosis, resembling the histomorphological findings of Mauriac syndrome. After information about the nature of the disease and intensification of insulin therapy with insulin pump, liver enzymes, ferritin, and triglycerides normalized within 1 month. Conclusion Glycogenic hepatopathy is a rare but important potential complication in poorly controlled juvenile diabetic patients. With improved metabolic control, it is fully reversible.

OBJECTIVE To investigate whether socioeconomic deprivation and urbanization are associated with the frequency of diabetic ketoacidosis (DKA) at diagnosis of pediatric type 1 diabetes. RESEARCH DESIGN AND METHODS Children and adolescents aged ≤18 years, living in Germany, with newly diagnosed type 1 diabetes documented between 2016 and 2019 in the Diabetes Prospective Follow-up Registry (DPV; Diabetes-Patienten-Verlaufsdokumentation), were assigned to a quintile of regional socioeconomic deprivation (German Index of Socioeconomic Deprivation) and to a degree of urbanization (Eurostat) by using their residence postal code. With multiple logistic regression models, we investigated whether the frequency of DKA at diagnosis was associated with socioeconomic deprivation or urbanization and whether associations differed by age-group, sex, or migration status. RESULTS In 10,598 children and adolescents with newly diagnosed type 1 diabetes, the frequency of DKA was lowest in the least deprived regions (Q1: 20.6% [95% CI 19.0–22.4], and increased with growing socioeconomic deprivation to 26.9% [25.0–28.8] in the most deprived regions [Q5]; P for trend CONCLUSIONS This study provides evidence that prevention of DKA at diagnosis by means of awareness campaigns and screening for presymptomatic type 1 diabetes should particularly target socioeconomically disadvantaged regions and rural areas.

Background Treatment of children with classic congenital adrenal hyperplasia (CAH) is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined. Objective Cluster analysis of the urinary steroid metabolome obtained by targeted gas chromatography–mass spectrometry (GC–MS) for treatment monitoring of children with CAH. Methods We evaluated 24-h urinary steroid metabolome analyses of 109 prepubertal children aged 7.0 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. 24-h urinary steroid metabolite excretions were transformed into CAH-specific z-scores. Subjects were divided into groups (metabotypes) by k-means clustering algorithm. Urinary steroid metabolome and clinical data of patients of each metabotype were analyzed. Results Four unique metabotypes were generated. Metabotype 1 (N = 21 (19%)) revealed adequate metabolic control with low cortisol metabolites (mean: −0.57z) and suppressed androgen and 17α-hydroxyprogesterone (17OHP) metabolites (−0.79z). Metabotype 2 (N = 23 (21%)) showed overtreatment consisting of a constellation of elevated urinary cortisol metabolites (0.62z) and low metabolites of androgens and 17OHP (−0.75z). Metabotype 3 (N = 32 (29%)) demonstrated undertreated patients with low cortisol metabolites (−0.69z) and elevated metabolites of androgens and 17OHP (0.50z). Metabotype 4 (N = 33 (30%)) presented patients with treatment failure reflected by unsuppressed androgen- and 17OHP metabolites (0.71z) despite elevated urinary cortisol metabolites (0.39z). Conclusion Metabotyping, which means grouping metabolically similar individuals, helps to monitor treatment of children with CAH using GC–MS urinary steroid metabolome analysis. This method allows classification in adequately-, over-, or undertreated children as well as identification of patients with treatment failure.

Background Treatment of children with classic congenital adrenal hyperplasia (CAH) with glucocorticoids is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined. Achievement of a normal growth rate is the most important therapeutic goal. Methods We retrospectively evaluated 123 24-hour gas chromatography–mass spectrometry urinary steroid metabolome analyses together with their corresponding 1-year height velocity (HV) z scores in 63 prepubertal children aged 7.2 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. Results Multivariate linear mixed effects model analysis revealed a positive influence of CAH-specific z scores of summed urinary androgen metabolites (B = 0.97 ± 0.20, t = 4.87, P < 0.0001) and a negative influence of the cortisol metabolite tetrahydrocortisol (B = −1.75 ± 0.79, t = −2.20, P = 0.03) on HV z scores. Receiver operating characteristic analysis demonstrated that adrenal androgen excess, defined as HV >1.5 z, was best determined by a z score of all urinary androgen metabolites of >0.512 [accuracy, 66.2%; sensitivity, 57.1%; specificity, 74.4%; positive prediction value (PPV), 66.7%; negative prediction value (NPV), 65.9%]. Tetrahydrocortisol excretion >1480 µg/m2 BSA/d in conjunction with suppressed urinary androgen metabolites Conclusion We established target values for urinary steroid metabolite excretions in children with CAH based on their growth rate. Urinary steroid metabolome analysis represents a highly suitable method for monitoring metabolic control in children with CAH.

OBJECTIVES With this study, our aim was to quantify the relative risk (RR) of diabetic ketoacidosis at diagnosis of type 1 diabetes during the year 2020 and to assess whether it was associated with the regional incidence of coronavirus disease 2019 (COVID-19) cases and deaths. METHODS Multicenter cohort study based on data from the German Diabetes Prospective Follow-up Registry. The monthly RR for ketoacidosis in 2020 was estimated from observed and expected rates in 3238 children with new-onset type 1 diabetes. Expected rates were derived from data from 2000 to 2019 by using a multivariable logistic trend regression model. The association between the regional incidence of COVID-19 and the rate of ketoacidosis was investigated by applying a log-binomial mixed-effects model to weekly data with Germany divided into 5 regions. RESULTS The observed versus expected frequency of diabetic ketoacidosis was significantly higher from April to September and in December (mean adjusted RRs, 1.48–1.96). During the first half of 2020, each increase in the regional weekly incidence of COVID-19 by 50 cases or 1 death per 100 000 population was associated with an increase in the RR of diabetic ketoacidosis of 1.40 (95% confidence interval, 1.10–1.77; P = .006) and 1.23 (1.14–1.32; P < .001), respectively. This association was no longer evident during the second half of 2020. CONCLUSIONS These findings suggest that the local severity of the pandemic rather than health policy measures appear to be the main reason for the increase in diabetic ketoacidosis and thus the delayed use of health care during the pandemic.

OBJECTIVE The aim of this study was to investigate the frequency of newly diagnosed type 1 diabetes without evidence of autoimmunity and the respective frequencies of ketoacidosis in children, adolescents, and young adults during the coronavirus disease 2019 (COVID-19) pandemic in Germany compared with the previous decade. RESEARCH DESIGN AND METHODS Based on data from the German Diabetes Prospective Follow-up Registry (DPV), we compared data from 715 children, adolescents, and young adults, newly diagnosed with type 1 diabetes during the COVID-19 pandemic in Germany between 1 March and 30 June 2020, with data from 5,428 children, adolescents, and young adults of the same periods from 2011 to 2019. Adjusted differences and relative risks (RRs) of negative β-cell autoantibody test results and diabetic ketoacidosis were estimated using multivariable log-binomial regression analysis. An upper noninferiority test (margin 1%) was applied to evaluate whether the autoantibody-negativity rate in 2020 was not higher than that in 2011 to 2019. RESULTS The estimated frequencies of autoantibody negativity in 2020 and 2011–2019 were 6.6% (95% CI 5.1–8.4) and 7.2% (95% CI 6.5–8.0), respectively, with an absolute difference of −0.68% (90% CI −2.07 to 0.71; Pupper noninferiority = 0.023). The increase of the estimated frequency of diabetic ketoacidosis during the COVID-19 pandemic was similar between autoantibody-negative and -positive type 1 diabetes (adjusted RRs 1.28 [95% CI 0.80–2.05] and 1.57 [1.41–1.75], respectively). CONCLUSIONS This study found no evidence that the COVID-19 pandemic leads to a significantly increased number of new cases with autoantibody-negative type 1 diabetes in children, adolescents, and young adults. In addition, autoantibody-negative type 1 diabetes showed no particular susceptibility to ketoacidosis, neither before nor during the pandemic.

Idiopathic nephrotic syndrome is the most frequent glomerular disease in children in most parts of the world. Children with steroid-sensitive nephrotic syndrome (SSNS) generally have a good prognosis regarding the maintenance of normal kidney function even in the case of frequent relapses. The course of SSNS is often complicated by a high rate of relapses and the associated side effects of repeated glucocorticoid (steroid) therapy. The following recommendations for the treatment of SSNS are based on the comprehensive consideration of published evidence by a working group of the German Society for Pediatric Nephrology (GPN) based on the systematic Cochrane reviews on SSNS and the guidelines of the KDIGO working group (Kidney Disease - Improving Global Outcomes). Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05135-3.

Hintergrund Die diabetische Ketoacidose (DKA) ist ein lebensbedrohlicher Notfall bei Manifestation eines Diabetes mellitus Typ 1 (DM1) bei Kindern und Jugendlichen, häufig bei verspäteter Diagnosestellung oder vorheriger Fehldiagnose. Während der Zeit des „Coronavirus-disease-2019(COVID-19)-Lockdowns“ in Deutschland stellten sich weniger Patienten in Notfallambulanzen und Arztpraxen vor. Fragestellung Hat sich der Anteil der DKA bei Manifestation eines DM1 in der pädiatrischen Population in diesem Zeitraum verändert, und welche Gruppen sind besonders gefährdet, eine DKA zu erleiden? Material und Methoden Die DKA-Häufigkeit in der Zeit vom 13.03.2020 bis 13.05.2020 wurde bei Patienten

Background Treatment of children with classic congenital adrenal hyperplasia (CAH) is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined. Objective Cluster analysis of the urinary steroid metabolome obtained by targeted gas chromatography–mass spectrometry (GC–MS) for treatment monitoring of children with CAH. Methods We evaluated 24-h urinary steroid metabolome analyses of 109 prepubertal children aged 7.0 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. 24-h urinary steroid metabolite excretions were transformed into CAH-specific z-scores. Subjects were divided into groups (metabotypes) by k-means clustering algorithm. Urinary steroid metabolome and clinical data of patients of each metabotype were analyzed. Results Four unique metabotypes were generated. Metabotype 1 (N = 21 (19%)) revealed adequate metabolic control with low cortisol metabolites (mean: −0.57z) and suppressed androgen and 17α-hydroxyprogesterone (17OHP) metabolites (−0.79z). Metabotype 2 (N = 23 (21%)) showed overtreatment consisting of a constellation of elevated urinary cortisol metabolites (0.62z) and low metabolites of androgens and 17OHP (−0.75z). Metabotype 3 (N = 32 (29%)) demonstrated undertreated patients with low cortisol metabolites (−0.69z) and elevated metabolites of androgens and 17OHP (0.50z). Metabotype 4 (N = 33 (30%)) presented patients with treatment failure reflected by unsuppressed androgen- and 17OHP metabolites (0.71z) despite elevated urinary cortisol metabolites (0.39z). Conclusion Metabotyping, which means grouping metabolically similar individuals, helps to monitor treatment of children with CAH using GC–MS urinary steroid metabolome analysis. This method allows classification in adequately-, over-, or undertreated children as well as identification of patients with treatment failure.

Aims We aimed to analyze the relationship between epilepsy and glutamic acid decarboxylase autoantibodies (GADA) in patients with type 1 diabetes mellitus (T1DM) and the impact of GADA on demographic, clinical, and metabolic data in T1DM patients with epilepsy. Methods We searched for patients with T1DM ≤20 years and GADA measurements, and within this group for patients with epilepsy. We formed groups: T1DM + Epilepsy + GADA positive; T1DM + Epilepsy + GADA negative; T1DM + GADA positive; T1DM + GADA negative. We used logistic regression to analyze the relationship between epilepsy and GADA with odds ratio adjusted for sex, duration of diabetes (DOD), and age at diabetes onset (ADO). We used logistic regression with odds ratio adjusted for DOD and ADO onset using epilepsy as a dependent variable and GADA, HbA1c, ketoacidosis, severe hypoglycemia (SH), sex, celiac disease, and autoimmune thyroiditis as independent variables. We conducted regression analyses adjusted for sex, DOD, and ADO to analyze differences in clinical/metabolic parameters between the groups. Results Epilepsy was not more frequent in GADA-positive patients (GPP). Logistic regression including all patients with GADA measurements showed that hypoglycemia with coma (HC) correlated with epilepsy when compared to no SH. We found no differences in clinical and metabolic data between GPP and GADA-negative patients (GNP) with epilepsy. SH occurred more often in GPP with epilepsy in comparison to GPP without epilepsy. GNP with epilepsy had a higher rate of HC than GPP without epilepsy. Conclusion We found no relationship between epilepsy and GADA. A relationship between T1DM and epilepsy might be explainable by SH.

Primary adrenal insufficiency (PAI) in children is mostly due to genetic defects. The understanding of the molecular genetics of the causes of adrenal insufficiency in the pediatric population has made significant progress during the last years. It has been shown that inherited PAI can lead to certain clinical manifestations and health problems in children beyond the adrenals. Organ dysfunctions associated with different forms of PAI in children include a wide range of organs such as gonads, brain, heart, bone, growth, bone marrow, kidney, skin, parathyroid, and thyroid. Diagnosing the correct genetic cause of PAI in children is therefore crucial to adequately control long-term treatment and follow-up in such patients.

Psychological stress is a known general health risk potentially increasing the risk of type 1 diabetes. Consistent with this hypothesis, there were reports of a higher incidence of type 1 diabetes after other stressful catastrophic events, e.g., the Chernobyl incident in 1986 or the Los Angeles earthquake in 1994 (1,2). Over the past few months, coronavirus disease 2019 (COVID-19) and subsequent social distancing have affected biological, psychological, economic, and social aspects of life. Social distancing during the lockdown could be perceived as a stressful situation for children and adolescents, who could not attend kindergarten or school and were unable to pursue hobbies like sports or meeting friends. Perceived stress caused by feelings of isolation may have increased the risk of type 1 diabetes (3). Since type 1 diabetes is also associated with viral infections (4), explaining, for example, the higher type 1 diabetes incidence during winter months, COVID-19 infection may have caused an increase of type 1 diabetes manifestations by affecting immune regulation or by directly damaging pancreatic β-cells (5 …

Als Cushing-Syndrom (CS) bezeichnet man die klinischen Folgen eines chronischen Hyperkortisolismus. Im Kindesalter ist das iatrogene CS nach lang dauernder Therapie mit hoch dosierten Glukokortikoiden oder auch adrenokortikotropem Hormon (ACTH) am haufigsten. Das im Kindesalter seltene endogene CS wird in ACTH-abhangige und in ACTH-unabhangige Formen unterteilt. Bei Ersteren verursacht ein ACTH-produzierendes Hypophysenadenom (meist Mikroadenom) eine adrenale Kortisoluberproduktion, was man als Morbus Cushing bezeichnet. Der Morbus Cushing ist unter den endogenen CS-Formen die haufigste Ursache und ist bei Kindern uber 7 Jahren fur ca. 75 % der CS-Falle verantwortlich. Das ACTH-unabhangige CS wird durch eine autonome Kortisoluberproduktion der Nebennieren verursacht und ist vor dem Schulalter fur die meisten CS-Falle verantwortlich. Zu den klinischen Zeichen des Hyperkortisolismus gehoren eine Wachstumsstorung, Gewichtszunahme mit Entwicklung einer stammbetonten Adipositas, ein gerotetes „Vollmondgesicht“, eine dunne Haut, Striae distensae, Akne, ein „Buffelnacken“, Bluthochdruck, Muskelschwache und psychische Auffalligkeiten. Die Labordiagnostik dient der Bestatigung der Diagnose sowie der Unterscheidung in ACTH-abhangige und -unabhangige Formen.

Die Nebenniere besteht embryologisch und anatomisch aus zwei Anteilen: der Nebennierenrinde und dem Nebennierenmark. Die Nebennierenrinde ist mesodermalen Ursprungs. Hingegen ist das Nebennierenmark neuroektodermaler Herkunft. Die ersten Vorlaufer der Rindenzellen kann man als Verdickung des Zolomepithels neben der primitiven Nierenanlage ungefahr in der 4. Woche post conceptionem identifizieren. Diese Zellen sind der Ursprung der steroidbildenden Zellen der Nebenniere und der Gonaden. Nach der Teilung der Nebennieren- und Gonadenanlage wandern die primitiven adrenalen Zellen zum Oberpol des Mesonephros, bevor es in der 8. Woche zur Einwanderung neuroektodermaler Zellen in die unreife Nebenniere kommt, die spater das Mark bilden werden. Die fetale Nebennierenrinde besteht aus einer auseren definitiven Zone und einer inneren fetalen Zone. Die Letztere ist um ein Vielfaches groser und stellt die Synthese von Dehydroepiandrosteron (DHEA) und Dehydroepiandrosteron-Sulfat (DHEA-S) sicher, das fur die plazentare Synthese von Ostriol genutzt wird. Nach der Geburt kommt es bis zum 6.–12. Lebensmonat zur Involution der fetalen Rinde. Die Entwicklung der Nebenniere ist durch verschiedene Transkriptionsfaktoren gesteuert. Durch Untersuchungen von Patienten mit Nebennierenentwicklungsstorungen ist bekannt, dass der Wnt-Signalweg, das Tumorsuppressorgen WT-1, die Transkriptionsfaktoren SF-1 und DAX-1, Koregulatoren wie CITED2 oder Telomerasefaktoren wie ACD eine Rolle spielen. Weiter sind die trophischen Effekte von adrenokortikotropem Hormon (ACTH) und ACTH-Rezeptorsignaltransduktion wichtig fur die Nebennierenrindenentwicklung.

Die primare Nebenniereninsuffizienz ist durch eine erniedrigte Produktion von Glukokortikoiden (Kortisol) mit oder ohne erniedrigter Produktion von Mineralokortikoiden (Aldosteron) gekennzeichnet. Die Diagnose der Nebenniereninsuffizienz ist wegen seiner unspezifischen klinischen Symptome oft verzogert. Allerdings konnen eine verpasste Diagnose einer Nebenniereninsuffizienz oder deren unzureichende Behandlung todlich sein. Bei den Ursachen der primaren Nebenniereninsuffizienz im Kindesalter lassen sich genetische Storungen der Nebennierenentwicklung (adrenale Dysgenesien), der einzelnen enzymatischen Schritte der Steroidhormonsynthese, der ACTH-Wirkung, metabolische Storungen sowie erworbene, hauptsachlich autoimmune, Ursachen unterscheiden.

Individuals affected with autosomal recessive cutis laxa type 2B and 3 usually show translucent skin with visible veins and abnormal elastic fibers, intrauterine and/or postnatal growth restriction and a typical triangular facial gestalt. Here we describe three unrelated individuals in whom such a cutis laxa syndrome was suspected, especially after electron microscopy revealed immature and less dense dermal elastic fibers in one of them. However, one of these children also displayed optic atrophy and two hypogammaglobulinemia. All had elevated liver enzymes and acute liver failure during febrile episodes leading to early demise in two of them. The only surviving patient had been treated with immunoglobulins. Through exome sequencing we identified mutations in NBAS, coding for a protein involved in Golgi-to-ER transport. NBAS deficiency causes several rare conditions ranging from isolated recurrent acute liver failure to a multisystem disorder mainly characterized by short stature, optic nerve atrophy and Pelger-Huet anomaly (SOPH). Since we subsequently verified Pelger-Huet anomaly in two of the patients the diagnosis SOPH syndrome was unequivocally proven. Our data show that SOPH syndrome can be regarded as a differential diagnosis for the progeroid forms of cutis laxa in early infancy and that possibly treatment of the hypogammaglobulinemia can be of high relevance for the prognosis.

One major issue of newborn screening programs for 21-hydroxylase deficiency (21OHD) is the high rate of false-positive results, especially in preterm neonates. Urinary steroid metabolite analysis using gas chromatography-mass spectrometry (GC-MS) is suitable as a confirmatory diagnostic tool. The objective of this study was to analyze retrospectively diagnostic metabolite ratios in neonates and infants with and without 21OHD using GC-MS with emphasis on glucocorticoid metabolism, and to develop reference values for the steroid metabolite ratios for the diagnosis of 21OHD. We retrospectively analyzed urinary steroid hormone metabolites determined by GC-MS of 95 untreated neonates and infants with 21OHD (1-148 days), and 261 neonates and infants (100 preterms) without 21OHD (0-217 days). Metabolites of 17α-hydroxyprogesterone showed specificities below 98%, whereas the 21-deoxycortisol metabolite pregnanetriolone clearly separated 21OHD from non-21OHD subjects. The best diagnostic ratio for 21OHD was pregnanetriolone to 6α-hydroxy-tetrahydrocortisone. The lowest value of this ratio in the 21OHD group (0.47) was at least eight times higher than the highest values in the non-21OHD group (0.055). We have given appropriate reference values for steroid metabolite ratios in the largest 21OHD cohort so far described. Consideration of glucocorticoid metabolism, especially the use of typical neonatal 6α-hydroxylates metabolites, leads to improvement of diagnostic metabolite ratios.