Associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes: analysis at the municipality level in North Rhine-Westphalia, Germany.

Aim: To analyse the associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes in the German federal state of North Rhine-Westphalia.

Methods: Data of incident type 1 diabetes cases in children and adolescents aged <20 years between 2007 and 2014 were extracted from a population-based diabetes register. Population data, indicators of area deprivation and urban/rural traits at the municipality level (396 entities) were obtained from official statistics.

Physiological and Epigenetic Features of Yoyo Dieting and Weight Control.

Obesity and being overweight have become a worldwide epidemic affecting more than 1.9 billion adults and 340 million children. Efforts to curb this global health burden by developing effective long-term non-surgical weight loss interventions continue to fail due to weight regain after weight loss.

Incidence and relative risk of renal replacement therapy in people with and without diabetes between 2002 and 2016 in a German region.

Aims/hypothesis: Data on trends of end-stage renal disease among people with diabetes are lacking. We analysed the incidence of end-stage renal disease, defined as renal replacement therapy, among people with and without diabetes, and the corresponding relative risk. Moreover, we investigated time trends for the period 2002-2016.

Higher frequency of vertebrate-infecting viruses in the gut of infants born to mothers with type 1 diabetes.

Background: Microbial exposures in utero and early life shape the infant microbiome, which can profoundly impact on health. Compared to the bacterial microbiome, very little is known about the virome. We set out to characterize longitudinal changes in the gut virome of healthy infants born to mothers with or without type 1 diabetes using comprehensive virome capture sequencing.

Regeneration of Mitochondrial Function in Gastrocnemius Muscle in Peripheral Arterial Disease After Successful Revascularisation.

Objective: Myopathy, characterised by altered mitochondrial function, is a central part of the pathophysiology of peripheral arterial disease and the aim of this study was to investigate the effect of revascularisation on mitochondrial function.

Methods: High resolution respirometry was used to investigate mitochondrial respiration and the results were normalised to citrate synthase activity (CSA), a marker of mitochondrial content. Ten patients with symptomatic peripheral arterial disease (study group) and 10 subjects without ischaemia (control group) were included.

Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention: a cost-effectiveness analysis.

Aims: Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA.

Methods: We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk.

Management of patients with type 2 diabetes in cardiovascular rehabilitation.

The clinical benefits of rehabilitation in cardiovascular disease are well established. Among cardiovascular disease patients, however, patients with type 2 diabetes mellitus require a distinct approach. Specific challenges to clinicians and healthcare professionals in patients with type 2 diabetes include the prevalence of peripheral and autonomic neuropathy, retinopathy, nephropathy, but also the intake of glucose-lowering medication.

Evaluation of a near-infrared light ultrasound system as a non-invasive blood glucose monitoring device.

The aim of this study was to evaluate the newly developed non-invasive blood glucose system NIRLUS® (Near-Infra Red Light Ultra Sound; NIRLUS Engineering AG, Lübeck, Germany) under standardized conditions. Seventeen healthy men of normal weight (body mass index 22.4 ± 1.

Increased fatty acid oxidation and mitochondrial proliferation in liver are associated with increased plasma kynurenine metabolites and nicotinamide levels in normolipidemic and carnitine-depleted rats.

Dysregulation of the tryptophan (Trp)-NAD pathway has been related to several pathological conditions, and the metabolites in this pathway are known to influence mitochondrial respiration and redox status. The aim of this project was to investigate if stimulation of beta-oxidation and mitochondrial proliferation by the mitochondrial-targeted compound 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA) would influence metabolites of the Trp-Kyn-NAD pathway. We wished to investigate how carnitine depletion by meldonium-treatment influenced these metabolites.

Implementation of Urgent Start Peritoneal Dialysis Reduces Hemodialysis Catheter Use and Hospital Stay in Patients with Unplanned Dialysis Start.

Background: Unplanned start of renal replacement therapy is common in patients with end-stage renal disease and often accomplished by hemodialysis (HD) using a central venous catheter (CVC). Urgent start using peritoneal dialysis (PD) could be an alternative for some of the patients; however, this requires a hospital-based PD center that offers a structured urgent start PD (usPD) program.

Methods: In this prospective study, we describe the implementation of an usPD program at our university hospital by structuring the process from presentation to PD catheter implantation and start of PD within a few days.

Defining subpopulations of differential drug response to reveal novel target populations.

Personalised medicine has predominantly focused on genetically altered cancer genes that stratify drug responses, but there is a need to objectively evaluate differential pharmacology patterns at a subpopulation level. Here, we introduce an approach based on unsupervised machine learning to compare the pharmacological response relationships between 327 pairs of cancer therapies. This approach integrated multiple measures of response to identify subpopulations that react differently to inhibitors of the same or different targets to understand mechanisms of resistance and pathway cross-talk.

The Transatlantic HbA gap: differences in glycaemic control across the lifespan between people included in the US T1D Exchange Registry and those included in the German/Austrian DPV registry.

Aim: To compare HbA levels across the lifespan in people with type 1 diabetes in the USA with those in Germany/Austria, and to examine potential differences in HbA levels between sexes, insulin delivery methods and minority status.

Methods: Data were extracted from the US T1D Exchange Registry (n=18 381 participants from 73 sites) and from the German/Austrian Prospective Diabetes Follow-up Registry, the DPV (n=32 643 participants from 362 sites). Mean HbA was calculated for each year of age for individuals aged ≤25 years, and at 2-year age intervals for individuals aged >25 years.

Aldh1b1 expression defines progenitor cells in the adult pancreas and is required for Kras-induced pancreatic cancer.

The presence of progenitor or stem cells in the adult pancreas and their potential involvement in homeostasis and cancer development remain unresolved issues. Here, we show that mouse centroacinar cells can be identified and isolated by virtue of the mitochondrial enzyme Aldh1b1 that they uniquely express. These cells are necessary and sufficient for the formation of self-renewing adult pancreatic organoids in an Aldh1b1-dependent manner.

Regulation of the endosomal SNX27-retromer by OTULIN.

OTULIN (OTU Deubiquitinase With Linear Linkage Specificity) specifically hydrolyzes methionine1 (Met1)-linked ubiquitin chains conjugated by LUBAC (linear ubiquitin chain assembly complex). Here we report on the mass spectrometric identification of the OTULIN interactor SNX27 (sorting nexin 27), an adaptor of the endosomal retromer complex responsible for protein recycling to the cell surface. The C-terminal PDZ-binding motif (PDZbm) in OTULIN associates with the cargo-binding site in the PDZ domain of SNX27.

Applying synergy metrics to combination screening data: agreements, disagreements and pitfalls.

Synergistic drug combinations are commonly sought to overcome monotherapy resistance in cancer treatment. To identify such combinations, high-throughput cancer cell line combination screens are performed; and synergy is quantified using competing models based on fundamentally different assumptions. Here, we compare the behaviour of four synergy models, namely Loewe additivity, Bliss independence, highest single agent and zero interaction potency, using the Merck oncology combination screen.

Genetic characterization of early renal changes in a novel mouse model of diabetic kidney disease.

Genetic factors influence susceptibility to diabetic kidney disease. Here we mapped genes mediating renal hypertrophic changes in response to diabetes. A survey of 15 mouse strains identified variation in diabetic kidney hypertrophy.

Distinct trajectories of HbA in newly diagnosed Type 2 diabetes from the DPV registry using a longitudinal group-based modelling approach.

Aim: To identify groups of heterogeneous HbA trajectories over time in newly diagnosed Type 2 diabetes.

Methods: The study comprised 6355 adults with newly diagnosed Type 2 diabetes (55% men, median age 62 years, baseline BMI 31 kg/m ) from the Diabetes Patienten Verlaufsdokumentation (DPV) prospective multicentre diabetes registry (Germany, Austria). Individuals were assessed during the first 5 years after diabetes diagnosis if they had ≥ 3 aggregated HbA measurements during follow-up.

Age at diagnosis of Type 2 diabetes in Germany: a nationwide analysis based on claims data from 69 million people.

Aim: For many European countries, including Germany, no valid estimates are available on age at diagnosis of Type 2 diabetes. Thus, we aimed to estimate the age at diagnosis in Germany.

Methods: Age at diagnosis of Type 2 diabetes in Germany was estimated based on Type 2 diabetes prevalence and incidence and the age distribution of the German population.

Role of diet in type 2 diabetes incidence: umbrella review of meta-analyses of prospective observational studies.

Objective: To summarise the evidence of associations between dietary factors and incidence of type 2 diabetes and to evaluate the strength and validity of these associations.

Design: Umbrella review of systematic reviews with meta-analyses of prospective observational studies.

Data Sources: PubMed, Web of Science, and Embase, searched up to August 2018.

Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan.

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas.