Andreas Beyerlein

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit (Bavarian Health and Food Safety Authority)

Abstract Background Older age is a risk factor for a fatal course of SARS-CoV‑2 infection, possibly due to comorbidities whose exact role in this context, however, is not yet well understood. In this paper, the characteristics and comorbidities of persons who had died of COVID-19 in Bavaria by July 2022 are shown and compared with the characterist...

This study used a population-based individual patient data set that included diagnoses of COVID-19 to determine whether there was a temporal association between COVID-19 and type 1 diabetes in children.

Background: It is not yet entirely clear to what extent vaccine-induced or hybrid immunity protects individuals in Germany from death during the omicron wave of the COVID-19 pandemic. Methods: In this retrospective study, we evaluated 470 159 cases over age 59 in the German federal state of Bavaria who tested positive for SARS-CoV-2 between 1 Ja...

Background: There is a lack of population-based studies on the effectiveness and durability of the SARS-CoV-2-induced immune protection during the Omicron wave. Methods: This retrospective study included 470 159 cases aged 60 years or older, who tested positive for SARS-CoV-2 between January 1 and June 30, 2022 in Bavaria, Germany. We examined time...

Background: Inadequate quality of medical postmortem examinations has been discussed in the forensic medical literature for many years. It is known that older deceased persons are less likely to have a non-natural cause of death certified and autopsies are performed less frequently compared to younger deceased persons. Methods: Death certificate...

The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 1...

Gleich S, Beyerlein A, Schmidt S, Koncz V: Impfdurchbrüche nach Impfung mit dem mRNA-Impfstoff Comirnaty (Biontech) in Münchner Pflegeeinrichtungen. Epid Bull 2021;50:23-35 | DOI 25646/9327. https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2021/Ausgaben/50_21.pdf?__blob=publicationFile

Background The efficacy of the BioNTech-Pfizer BNT162b2 vaccination in the elderly (≥80 years) could not be fully assessed in the BioNTech-Pfizer trial due to low numbers in this age group. We aimed to evaluate the effectiveness of the BioNTech-Pfizer (BNT162b2) vaccine to prevent SARS-CoV-2 infection and severe outcomes in octo- and novo-generians...

Background The effect of the BioNTech-Pfizer BNT162b2 vaccination in the elderly (>=80 years) could not be fully assessed in the BioNTech-Pfizer trial due to low numbers in this age group. We aimed to evaluate the effectiveness of the BioNTech-Pfizer (BNT162b2) vaccine to prevent SARS-CoV-2 infection and severe outcomes in octo- and novo-generians...

Background: Breastfeeding has beneficial effects on numerous health outcomes. Objectives: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort. Methods: Infants with genetic susceptibility for type 1 diabetes (n = 867...

Aim To describe the incidence of term and preterm neonatal cerebral sinovenous thrombosis (CSVT) and identify perinatal risk factors. Method This was a national capture‐recapture calculation‐corrected surveillance and nested case–control study. Infants born preterm and at term with magnetic resonance imaging‐confirmed neonatal CSVT were identified...

Purpose The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail. Material and Methods We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (⁶⁰Co source; 0.063 Gy/min) at young adult age of 10 weeks w...

Background We investigated associations of area-level deprivation with obstetric and perinatal outcomes in a large population-based routine dataset. Methods We used the data of n = 827,105 deliveries who were born in hospitals between 2009 to 2016 in Bavaria, Germany. The Bavarian Index of Multiple Deprivation (BIMD) on district level was assigned...

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietar...

Precise knowledge of the health status of experimental fish is crucial to obtain high scientific and ethical standards in biomedical research. In addition to the use of sentinel fish, the examination of diseased fish is a fundamental part of all health monitoring concepts. PCR assays offer excellent sensitivity and the ability to test a broad varie...

Aim To identify maternal, obstetric, and neonatal risk factors related to perinatal arterial ischaemic stroke (PAIS) diagnosed within 28 days after birth and to understand the underlying pathophysiology. Method For case and control ascertainment, we used active surveillance in 345 paediatric hospitals and a population‐based perinatal database for...

The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes (n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the dive...

Aims/hypothesis: Exposure to an intrauterine hyperglycaemic environment has been suggested to increase the offspring's later risk for being overweight or having metabolic abnormalities, but conclusive evidence for pregnancies affected by maternal type 1 diabetes is still lacking. This study aims to analyse the relationship between maternal type 1...

Aim Recommendations for maximum blood draw in children range from 1‐5% despite limited evidence. The aim of the study was to assess the safety of blood draws in children aged six months to 12 years targeting volumes of 3% of total blood volume. Methods Children who experienced three‐monthly blood draws during participation in one of three investig...

Background Progression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown. Methods In 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determ...

Aims Children and adolescents with a family history of diabetes are at increased risk of overweight, but little is known about the potentially beneficial effects of physical activity on these children. The objective of this study was to investigate the association between moderate to vigorous physical activity (MVPA) and metabolic and inflammatory...

Aims In children with presymptomatic type 1 diabetes, intermittent hyperglycemia and rising HbA1c levels are a known signal of progression towards 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 childr...

Background In the Fr1da study (“Typ 1 Diabetes: Früh erkennen – Früh gut behandeln”), children between 2 and 5 years of age are screened for presymptomatic type 1 diabetes in Bavaria, Germany. Objectives Here, we show preliminary results on the success and acceptance of the Fr1da screening. Materials and methods Participation rates, analytic qual...

Aims To investigate whether there has been further improvement in the risk of adverse outcomes in pregnancies in women with diabetes during 2008–2016 in Bavaria, Germany. Methods Using cross‐sectional data on all 1716 170 deliveries in Bavarian hospitals between 2001 and 2016, we assessed the risks of stillbirth, early neonatal death, preterm deli...

Background Around 0.3% of newborns will develop autoimmunity to pancreatic beta cells in childhood and subsequently develop type 1 diabetes before adulthood. Primary prevention of type 1 diabetes will require early intervention in genetically at-risk infants. The objective of this study was to determine to what extent genetic scores (two previous g...

Genetic scores and estimated risk for type 1 diabetes in the cases and controls with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype. Genetic scores calculated using the Winkler model (left panels) and the Oram model (right panels) in the UK Biobank and Wellcome Trust Case Control Consortium (WTCCC) controls, and in WTCCC cases with the HLA DR3/DR4...

Cumulative risks of 1 or more islet autoantibody, multiple islet autoantibody, and type 1 diabetes development in TEDDY children with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype stratified by their Winkler and Oram score. Cumulative risks of developing 1 or more islet autoantibodies (A, B), multiple islet autoantibodies (C, D), and type 1 diabe...

Time-dependent discrimination accuracy of the genetic scores to identify TEDDY children who developed multiple islet autoantibodies. Three scores are compared (RO = Oram score, WI = Winkler score, ME = merged score). (A) We calculated the integral of a time-dependent receiver operating characteristic curve [33], indicated on the y-axis for each gen...

Risk of developing 1 or more islet autoantibodies by age 6 years and the proportion of cases positive for any islet autoantibodies (sensitivity) in TEDDY children with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype stratified by their merged genetic score, with corresponding 95% confidence intervals. (DOC)

Risk of developing type 1 diabetes by age 10 years and the proportion of cases positive for type 1 diabetes (sensitivity) in TEDDY children with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotypes stratified by their merged genetic score, with corresponding 95% confidence intervals. (DOC)

Winkler and Oram genetic scores in TEDDY children according to their islet autoantibody outcome, geographic location, and sex. Islet autoantibody outcome (A); geographic location (B); sex (C). Red horizontal lines indicate the median genetic score value in each group. (TIF)

Cumulative risks of 1 or more islet autoantibody, multiple islet autoantibody, and type 1 diabetes development in TEDDY children with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype stratified by their merged genetic score and their HLA genotype. Cumulative risks of developing 1 or more islet autoantibodies (A, B), multiple islet autoantibodies (C,...

Weights for single nucleotide polymorphisms used to calculate the genetic scores. (DOC)

Frequencies of risk alleles in TEDDY children with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype. (DOC)

Cumulative risks of 1 or more islet autoantibody, multiple islet autoantibody, and type 1 diabetes development in TEDDY children with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype stratified by geographic location and sex. Cumulative risks of the development of 1 or more islet autoantibodies (A, B), multiple islet autoantibodies (C, D), and type...

Risk of developing multiple islet autoantibodies by age 6 years and the proportion of cases positive for multiple islet autoantibodies (sensitivity) in TEDDY children with the HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype stratified by their merged genetic score, with corresponding 95% confidence intervals. (DOC)

TEDDY manuscript proposal submission form. (DOC)

Background/aim Exposure to the intrauterine hyperglycemic environment has been suggested to increase the offspring’s later overweight and metabolic risk, but conclusive evidence for pregnancies affected by maternal type 1 diabetes (T1D) is still lacking. Further, it is unknown whether changes in the offspring’s metabolome are in the potential pathw...

Objective Women with insulin-requiring gestational diabetes mellitus (GDM) are at high risk of developing diabetes within a few years postpartum. We implemented this phase II study to test the hypothesis that vildagliptin, a dipeptidyl peptidase-4 inhibitor, is superior to placebo in terms of reducing the risk of postpartum diabetes. Methods Women...

Physical activity (A) and dietary behavior (B) in women with a recent history of insulin-requiring GDM treated with 50 mg vildagliptin or placebo twice daily. Physical activity and dietary behavior were assessed at baseline/screening for up to 36 months after randomization. Black and grey bars represent the median in each group per visit.

Background and aims: Glut1 Deficiency (Glut1D) is caused by impaired glucose transport into brain. The resulting epileptic encephalopathy and movement disorders can be treated effectively by high-fat carbohydrate-restricted ketogenic diet therapies (KDT) mimicking fasting and providing ketones as an alternative cerebral fuel. Recently 6-24 months...

Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women wi...

Aims The onset of clinical type 1 diabetes (T1D) is preceded by the occurrence of disease-specific autoantibodies. The level of autoantibody titers is known to be associated with progression time from the first emergence of autoantibodies to the onset of clinical symptoms, but detailed analyses of this complex relationship are lacking. We aimed to...

Objective: Caesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. Methods: From 2004 to 2010 infants from the general population who tested positive for HLA DR3-...

Objective: The associations of energy, protein, carbohydrate, and fat intake with weight status up to the age of 5.5 years were prospectively assessed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Methods: Food record data (over 3 days) and BMI measurements between 0.25 and 5.5 years were available from 5,563 children...

Early infections have been suggested to be associated with increased risk for later celiac disease (CD). We analyzed prospective claims data of n = 295,420 infants from Bavaria, Germany, born between 2005 and 2007 containing information on medically attended infectious diseases according to ICD-10 code on a quarterly basis to calculate hazard ratio...

Scientific Reports 6 : Article number: 30828 10.1038/srep30828 ; published online: 26 August 2016 ; updated: 02 May 2017 In the original version of this Article, the author list for the “TEDDY Study Group” was incomplete. This has now been corrected in the PDF and HTML versions of this Article.

Aims/hypothesis: Vaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth...

Autoimmune diabetes is marked by sensitization to β cell self-antigens in childhood. We longitudinally followed at-risk children from infancy and performed single-cell gene expression in β cell antigen–responsive CD4⁺ T cells through pre- and established autoimmune phases. A striking divergence in the gene signature of β cell antigen–responsive naï...

Aims/hypothesis: We sought to identify minimal sets of serum peptide signatures as markers for islet autoimmunity and predictors of progression rates to clinical type 1 diabetes in a case-control study. Methods: A double cross-validation approach was applied to first prioritise peptides from a shotgun proteomic approach in 45 islet autoantibody-...

Objective: Studies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow's milk as the first formula is associated with reduced islet autoimmunity risk in a large prospective coh...

To the Editor We write to report errors that occurred in our article, “Respiratory Infections in Early Life and the Development of Islet Autoimmunity in Children at Increased Type 1 Diabetes Risk: Evidence From the BABYDIET Study,” that was published in JAMA Pediatrics (2013;167[9]:800-807).¹ We noticed the errors when we were asked by colleagues t...

The joint modeling of longitudinal and time-to-event data is an important tool of growing popularity to gain insights into the association between a biomarker and an event process. We develop a general framework of flexible additive joint models that allows the specification of a variety of effects, such as smooth nonlinear, time-varying and random...

Aims/hypothesis Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures...

Background: Gestational diabetes mellitus (GDM) occurs in 2-6 % of all pregnancies. We investigated whether area level deprivation is associated with a higher risk for GDM and whether GDM detection rates in deprived regions changed after the introduction of charge-free GDM screening in Germany in 2012. Methods: We analyzed population-based data...

Viral infections are associated with autoimmunity in type 1 diabetes. Here, we asked whether this association could be explained by variations in host immune response to a putative type 1 etiological factor, namely coxsackie B viruses (CVB). Heterogeneous antibody responses were observed against CVB capsid proteins. Heterogeneity was largely define...

In Reply Dr Rahmoune and colleagues and Mr Uzoigwe suggest that unmeasured confounding might have influenced the results of our study. The results are consistent with findings from a previous analysis that observed a strong association between respiratory infections during the first 6 months of life and development of beta cell autoimmunity in infa...

Background: Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD), insulinoma-associa...

Fragestellung: Diabetes wahrend der Schwangerschaft beeinflusst moglicherweise die Entwicklung des kindlichen Immunsystems. Ziel der ImmunDiabRisk-Studie ist die Untersuchung von Unterschieden in der Reifung des Immunsystems bei Kindern von Muttern mit und ohne Diabetes. Methodik: Der Thymus wurde bei Feten von Schwangeren mit Typ-1-Diabetes (n = 2...

A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 5...

Background and aims: Subclinical atherosclerosis assessed by sonographic intima-media-thickness measurement of the carotid artery (cIMT) is considered to be an early precursor of cardiovascular disease already in childhood. Structural analysis of the carotid intimal layer (carotid intima-media-roughness, cIMR) improves cardiovascular risk profilin...

This population epidemiology study uses regional claims data from Germany to investigate associations between infections in the first 2 years of life and development of type 1 diabetes.Viral infections, particularly enteroviruses,1 have been hypothesized to cause type 1 diabetes (T1D).2 Recent studies suggest that respiratory tract infections are a...

Introduction Type 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) r...

Aims: Lactation for > 3 months in women with gestational diabetes is associated with a considerably reduced long-term risk for type 2 diabetes that persists for up to 15 years postpartum. However, the underlying protective mechanisms are unknown. We examined whether lactation for > 3 months is associated with altered metabolomic signatures postpart...

Background: Several studies indicate associations between early growth and type 1 diabetes (T1D). However, it remains an open question whether these findings can be translated to typical growth patterns associated with increased risk for T1D-associated islet autoimmunity. Methods: We analyzed pooled data from 2236 children followed up in two lar...

The pregnancy outcomes in women with gestational diabetes mellitus (GDM) and 'overt diabetes in pregnancy' were compared and the need for further subclassification was investigated with respect to postpartum outcome risk. Data from 944 women who had been uniformly diagnosed as having GDM in Munich, Germany, between 1998 and 2010, were re-classified...

Aims: Women with gestational diabetes mellitus (GDM) have an increased risk of diabetes postpartum. We developed a score to predict the long-term risk of postpartum diabetes using clinical and anamnestic variables recorded during or shortly after delivery. Methods: Data from 257 GDM women who were prospectively followed for diabetes outcome over...