A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes.

Aims/introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically at-risk for type 1 diabetes followed from birth who had developed islet autoantibodies ("seroconverted"), by measuring mucosa-associated cytokines in their sera.

Neuropathy in paediatric type 1 diabetes mellitus - clinical characterization and analysis of risk factors in the diabetes prospective follow-up registry DPV (Diabetes-Patienten-Verlaufsdokumentation)-registry.

Objectives: Data on the prevalence, clinical features and risk factors associated with paediatric diabetic neuropathy (DN) are scarce.

Methods: We retrospectively analysed data from the DPV registry, including patients under 20 years of age, treated for type 1 diabetes mellitus (T1D) between 2005 and 2021. Patients with non-diabetic neuropathy were excluded.

Protocol for a nested case-control study design for omics investigations in the Environmental Determinants of Islet Autoimmunity cohort.

The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals.

Metabolic control during the first two years of the COVID-19 pandemic in pediatric patients with type 1 diabetes: results from the German DPV initiative.

Aim: To assess effects of the SARS-CoV2 pandemic on metabolic control in youth with type 1 diabetes (T1D) in Germany in a population-based analysis.

Methods: Data from 33,372 pediatric T1D patients from the Diabetes Prospective Follow-up (DPV) registry, with face-to-face visits or telemedicine contacts in the years 2019-2021, were available. Datasets from eight time periods between March 15, 2020, and December 31, 2021, according to SARS-CoV2 incidence waves, were compared to those from five control time periods.

Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm.

Aim: To identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm.

Materials And Methods: Data from adults and children with type 1 diabetes and more than two diabetes-related visits were analysed from the Diabetes Prospective Follow-up Registry. Q-Finder, a supervised non-parametric proprietary subgroup discovery algorithm, was used to identify subgroups with clinical characteristics associated with increased DKA risk.

Diabetes in all hospitalized cases in Germany 2015-2019 and impact of the first COVID-19 year 2020.

Objective: To analyze the proportion of diabetes among all hospitalized cases in Germany between 2015 and 2020.

Methods: Using the nationwide Diagnosis-Related-Groups statistics, we identified among all inpatient cases aged ≥ 20 years all types of diabetes in the main or secondary diagnoses based on ICD-10 codes, as well all COVID-19 diagnoses for 2020.

Results: From 2015 to 2019, the proportion of cases with diabetes among all hospitalizations increased from 18.

The WHO-5 well-being questionnaire in type 1 diabetes: screening for depression in pediatric and young adult subjects.

Objectives: To evaluate the WHO-5 tool in pediatric and young adult subjects with type 1 diabetes, and to analyse associations with demographic/psychological characteristics.

Methods: We included 944 patients with type 1 diabetes 9-25 years of age, documented in the Diabetes Patient Follow-up Registry between 2018 and 2021. We used ROC curve analysis to determine optimal cut-off values for the WHO-5 scores to predict psychiatric comorbidity (ICD-10-diagnoses) and analysed associations with obesity, HbA, therapy regimen, and lifestyle via logistic regression.

Common procedures and conditions leading to inpatient hospital admissions in adults with and without diabetes from 2015 to 2019 in Germany : A comparison of frequency, length of hospital stay and complications.

Objective: To evaluate common surgical procedures and admission causes in inpatient cases with diabetes in Germany between 2015 and 2019 and compare them to inpatient cases without diabetes.

Methods: Based on the German diagnosis-related groups (G-DRG) statistics, regression models stratified by age groups and gender were used to calculate hospital admissions/100,000 individuals, hospital days as well as the proportion of complications and mortality in inpatient cases ≥ 40 years with or without a documented diagnosis of diabetes (type 1 or type 2).

Results: A total of 14,222,326 (21%) of all inpatient cases aged ≥ 40 years had a diagnosis of diabetes.

Reduced heart rate variability in people with type 1 diabetes and elevated diabetes distress: Results from the longitudinal observational DIA-LINK1 study.

Aims: People with type 1 diabetes have a higher risk for cardiovascular disease (CVD). Reduced heart rate variability (HRV) is a clinical marker for CVD. In this observational study using continuous HRV measurement across 26 days, we investigated whether psychological stressors (diabetes distress, depressive symptoms) and glycaemic parameters (hypo- and hyperglycaemic exposure, glycaemic variability and HbA ) are associated with lower HRV in people with type 1 diabetes.

Changes in cardiovascular risk factors among children and young adults with type 1 diabetes during the COVID-19 pandemic compared to previous years-Results from the German DPV registry.

Background: The diverse stages of the COVID-19 pandemic led to several social circumstances that influenced daily life and health behavior.

Purpose: To evaluate changes in cardiovascular risk factors and physical activity among children and young adults with type 1 diabetes (T1D) during the COVID-19 pandemic in Germany compared to previous years.

Methods: A total of 32 785 individuals aged 6-21 years at baseline with T1D from the German diabetes patient follow-up (DPV) registry contributed data on 101 484 person-years between 2016 and 2021.

Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

Background: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies.

Methods: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors.

Clinical characteristics and cardiovascular risk profile in children and adolescents with latent autoimmune diabetes: Results from the German/Austrian prospective diabetes follow-up registry.

Aims: To characterize children and adolescents with latent autoimmune diabetes of the young (LADY), and to assess the utility of classifying individuals as LADYs regarding their cardiovascular (CV) risk factors.

Methods: Data from 25,520 individuals (age at diagnosis <18 years) of the Prospective Diabetes Follow-up Registry Diabetes-Patienten Verlaufsdokumentation (DPV) were analyzed. LADY was defined as positivity of ≥one islet autoantibody (iAb+) and an insulin-free interval of ≥6 months upon diabetes diagnosis.

Diabetes-related antibody-testing is a valuable screening tool for identifying monogenic diabetes - A survey from the worldwide SWEET registry.

Aims: To evaluate access to screening tools for monogenic diabetes in paediatric diabetes centres across the world and its impact on diagnosis and clinical outcomes of children and youth with genetic forms of diabetes.

Methods: 79 centres from the SWEET diabetes registry including 53,207 children with diabetes participated in a survey on accessibility and use of diabetes related antibodies, c-peptide and genetic testing.

Results: 73, 63 and 62 participating centres had access to c-peptide, antibody and genetic testing, respectively.

The COVID-19 Pandemic Affects Seasonality, With Increasing Cases of New-Onset Type 1 Diabetes in Children, From the Worldwide SWEET Registry.

Objective: To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally.

Research Design And Methods: We analyzed data on 17,280 cases of T1D diagnosed during 2018-2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models.

Results: The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.

High-Throughput Human Complement C3 N-Glycoprofiling Identifies Markers of Early Onset Type 1 Diabetes Mellitus in Children.

Recently, it was shown that children at the onset of type 1 diabetes (T1D) have a higher proportion of oligomannose glycans in their total plasma protein N-glycome compared to their healthy siblings. The most abundant complement component, glycoprotein C3, contains two N-glycosylation sites occupied exclusively by this type of glycans. Furthermore, complement system, as well as C3, was previously associated with T1D.

Endothelial reactive oxygen-forming NADPH oxidase 5 is a possible player in diabetic aortic aneurysm but not atherosclerosis.

Atherosclerosis and its complications are major causes of cardiovascular morbidity and death. Apart from risk factors such as hypercholesterolemia and inflammation, the causal molecular mechanisms are unknown. One proposed causal mechanism involves elevated levels of reactive oxygen species (ROS).

Disease heterogeneity of adult diabetes based on routine clinical variables at diagnosis: Results from the German/Austrian Diabetes Follow-up Registry.

Aim: To cluster adults with diabetes using variables from real-world clinical care at manifestation.

Materials And Methods: We applied hierarchical clustering using Ward's method to 56 869 adults documented in the prospective Diabetes Follow-up Registry (DPV). Clustering variables included age, sex, body mass index (BMI), HbA1c, diabetic ketoacidosis (DKA), components of the metabolic syndrome (hypertension/dyslipidaemia/hyperuricaemia) and beta-cell antibody status.

Loss of LAMP5 interneurons drives neuronal network dysfunction in Alzheimer's disease.

In Alzheimer's disease (AD), where amyloid-β (Aβ) and tau deposits in the brain, hyperexcitation of neuronal networks is an underlying disease mechanism, but its cause remains unclear. Here, we used the Collaborative Cross (CC) forward genetics mouse platform to identify modifier genes of neuronal hyperexcitation. We found LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations.

Viability and Functionality of Neonatal Porcine Islet-like Cell Clusters Bioprinted in Alginate-Based Bioinks.

The transplantation of pancreatic islets can prevent severe long-term complications in diabetes mellitus type 1 patients. With respect to a shortage of donor organs, the transplantation of xenogeneic islets is highly attractive. To avoid rejection, islets can be encapsulated in immuno-protective hydrogel-macrocapsules, whereby 3D bioprinted structures with macropores allow for a high surface-to-volume ratio and reduced diffusion distances.