No association between variation in the NR4A1 gene locus and metabolic traits in white subjects at increased risk for type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The nuclear receptor NR4A1 is implicated in metabolic regulation in insulin-sensitive tissues, such as liver, adipose tissue, and skeletal muscle. Functional loss of NR4A1 results in insulin resistance and enhanced intramuscular and hepatic lipid content. Therefore, we investigated in a cohort of white European subjects at increased risk for type 2 diabetes whether genetic variation within the <it>NR4A1 </it>gene locus contributes to prediabetic phenotypes, such as insulin resistance, ectopic fat distribution, or β-cell dysfunction.</p> <p>Methods</p> <p>We genotyped 1495 subjects (989 women, 506 men) for five single nucleotide polymorphisms (SNPs) tagging 100% of common variants (MAF = 0.05) within the <it>NR4A1 </it>gene locus with an r²= 0.8. All subjects underwent an oral glucose tolerance test (OGTT), a subset additionally had a hyperinsulinemic-euglycemic clamp (n = 506). Ectopic hepatic (n = 296) and intramyocellular (n = 264) lipids were determined by magnetic resonance spectroscopy. Peak aerobic capacity, a surrogate parameter for oxidative capacity of skeletal muscle, was measured by an incremental exercise test on a motorized treadmill (n = 270).</p> <p>Results</p> <p>After appropriate adjustment and Bonferroni correction for multiple comparisons, none of the five SNPs was reliably associated with insulin sensitivity, ectopic fat distribution, peak aerobic capacity, or indices of insulin secretion (all p ≥ 0.05).</p> <p>Conclusions</p> <p>Our data suggest that common genetic variation within the <it>NR4A1 </it>gene locus may not play a major role in the development of prediabetic phenotypes in our white European population.</p

Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

INTRODUCTION: Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. METHODS: In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. RESULTS: The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m(2) but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found. DISCUSSION: We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk

An 8-week diet high in cereal fiber and coffee but free of red meat does not improve beta-cell function in patients with type 2 diabetes mellitus: a randomized controlled trial

Background: Higher dietary intake of fibers and coffee, but lower red meat intake is associated with reduced risk for type 2 diabetes in epidemiological studies. We hypothesized that a calorie-restricted diet, which is high in fiber and coffee, but free of red meat, improves beta-cell function in patients with T2D. Methods: In a randomized parallel-group pilot trial, obese type 2 diabetes patients were randomly allocated to consume either a diet high in cereal fiber and coffee, but free of red meat (n = 17) (L-RISK) or a diet low in fiber, free of coffee but high in red meat (n = 20) (H-RISK) for 8 weeks. Insulin secretion was assessed from glucagon stimulation tests (GST) and mixed-meal tolerance tests (MMTT) before and after dietary intervention. Results: Both diets resulted in comparable reduction of fasting concentrations of insulin (H-RISK -28% vs. L-RISK -32%, both p &lt; 0.01), C-peptide (H-RISK -26% vs. L-RISK -30%, both p &lt; 0.01) and blood glucose (H-RISK -6.8%, p &lt; 0.05 vs. L-RISK -10%, p &lt; 0.01). Gastric inhibitory peptide (GIP) secretion increased by 24% after 8 weeks in the L-RISK only (p &lt; 0.01). However, GST and MMTT showed no differences in insulin secretion after intervention. Conclusions: Calorie restriction independent of the intake of fiber, coffee or meat failed to improve beta-cell function, but improved GIP secretion in obese patients with type 2 diabetes. Trial registration: Registration at Clinicaltrials.gov, Identifier number: NCT01409330 , Registered 4 August 2011 – Retrospectively registered

Making positive use of the fibrillation of lyocell fibres in composite materials

The present study investigates the influence of surface fibrillation of lyocell fibres on the adhesion and resulting properties of short fibre-reinforced polypropylene (PP) and polylactide (PLA) composites. Fibrillation was shown to reduce the tensile strength and elongation at break of the fibres, while not affecting Young's modulus. It was demonstrated that fibrillation improved adhesion significantly compared to non-fibrillated (untreated) fibres, and the critical fibre length determined by microbond tests was reduced. Despite the reduced tensile strength of the fibrillated lyocell fibres, the tensile strength of the composites was increased by a factor of 1.15 for PP and 1.62 for PLA compared to composites produced with untreated fibres. The Young's modulus of the composites was increased using fibrillated fibres by a factor of 1.41 for PP and 1.20 for PLA. The impact strength was also improved by using fibrillated fibres by a factor of 1.38 for PP-based and 1.23 for PLA-based composites. Surface fibrillation of lyocell offers interesting application possibilities, particularly for short fibre-reinforced materials, as the higher specific fibre surface reduces the critical fibre length of lyocell, leading to improved stress transfer from the matrix to the fibre. These fibres seem particularly promising to enhance the mechanical properties of short-fibre reinforced composites for 3D printing applications

3d print of heart rhythm model with cryoballoon catheter ablation of pulmonary vein

The visualization of heart rhythm disturbance and atrial fibrillation therapy allows the optimization of new cardiac catheter ablations. With the simulation software CST (Computer Simulation Technology, Darmstadt) electromagnetic and thermal simulations can be carried out to analyze and optimize different heart rhythm disturbance and cardiac catheters for pulmonary vein isolation. Another form of visualization is provided by haptic, three-dimensional print models. These models can be produced using an additive manufacturing method, such as a 3d printer. The aim of the study was to produce a 3d print of the Offenburg heart rhythm model with a representation of an atrial fibrillation ablation procedure to improve the visualization of simulation of cardiac catheter ablation. The basis of 3d printing was the Offenburg heart rhythm model and the associated simulation of cryoablation of the pulmonary vein. The thermal simulation shows the pulmonary vein isolation of the left inferior pulmonary vein with the cryoballoon catheter Arctic Front AdvanceTM from Medtronic. After running through the simulation, the thermal propagation during the procedure was shown in the form of different colors. The three-dimensional print models were constructed on the base of the described simulation in a CAD program. Four different 3d printers are available for this purpose in a rapid prototyping laboratory at the University of Applied Science Offenburg. Two different printing processes were used and a final print model with additional representation of the esophagus and internal esophagus catheter was also prepared for printing. With the help of the thermal simulation results and the subsequent evaluation, it was possible to draw a conclusion about the propagation of the cold emanating from the catheter in the myocardium and the surrounding tissue. It was measured that just 3 mm from the balloon surface into the myocardium the temperature dropped to 25 °C. The simulation model was printed using two 3d printing methods. Both methods, as well as the different printing materials offer different advantages and disadvantages. All relevant parts, especially the balloon catheter and the conduction, are realistically represented. Only the thermal propagation in the form of different colors is not shown on this model. Three-dimensional heart rhythm models as well as virtual simulations allow very clear visualization of complex cardiac rhythm therapy and atrial fibrillation treatment methods. The printed models can be used for optimization and demonstration of cryoballoon catheter ablation in patients with atrial fibrillation

3d print of heart rhythm model with cryoballoon catheter ablation of pulmonary vein

The visualization of heart rhythm disturbance and atrial fibrillation therapy allows the optimization of new cardiac catheter ablations. With the simulation software CST (Computer Simulation Technology, Darmstadt) electromagnetic and thermal simulations can be carried out to analyze and optimize different heart rhythm disturbance and cardiac catheters for pulmonary vein isolation. Another form of visualization is provided by haptic, three-dimensional print models. These models can be produced using an additive manufacturing method, such as a 3d printer. The aim of the study was to produce a 3d print of the Offenburg heart rhythm model with a representation of an atrial fibrillation ablation procedure to improve the visualization of simulation of cardiac catheter ablation. The basis of 3d printing was the Offenburg heart rhythm model and the associated simulation of cryoablation of the pulmonary vein. The thermal simulation shows the pulmonary vein isolation of the left inferior pulmonary vein with the cryoballoon catheter Arctic Front Advance™ from Medtronic. After running through the simulation, the thermal propagation during the procedure was shown in the form of different colors. The three-dimensional print models were constructed on the base of the described simulation in a CAD program. Four different 3d printers are available for this purpose in a rapid prototyping laboratory at the University of Applied Science Offenburg. Two different printing processes were used and a final print model with additional representation of the esophagus and internal esophagus catheter was also prepared for printing. With the help of the thermal simulation results and the subsequent evaluation, it was possible to draw a conclusion about the propagation of the cold emanating from the catheter in the myocardium and the surrounding tissue. It was measured that just 3 mm from the balloon surface into the myocardium the temperature dropped to 25 °C. The simulation model was printed using two 3d printing methods. Both methods, as well as the different printing materials offer different advantages and disadvantages. All relevant parts, especially the balloon catheter and the conduction, are realistically represented. Only the thermal propagation in the form of different colors is not shown on this model. Three-dimensional heart rhythm models as well as virtual simulations allow very clear visualization of complex cardiac rhythm therapy and atrial fibrillation treatment methods. The printed models can be used for optimization and demonstration of cryoballoon catheter ablation in patients with atrial fibrillation

Abstract: 3D print of heart rhythm model with cryoballoon catheter ablation of pulmonary vein

The visualization of heart rhythm disturbance and atrial fibrillation therapy allow the optimization of new cardiac catheter ablations. With the simulation software CST (Computer Simulation Technology, Darmstadt) electromagnetic and thermal simulations can be carried out to analyze and optimize different heart rhythm disturbance and cardiac catheters for pulmonary vein isolation. Another form of visualization is provided by haptic, three-dimensional print models. These models can be produced using an additive manufacturing method, such as a 3D printer. The aim of the study was to produce a 3D print of the Offenburg heart rhythm model with a representation of an atrial fibrillation ablation procedure to improve the visualization of simulation of cardiac catheter ablation. The basis of 3D printing was the Offenburg heart rhythm model and the associated simulation of cryoablation of the pulmonary vein. The thermal simulation shows the pulmonary vein isolation of the left inferior pulmonary vein with the cryoballoon catheter Arctic Front AdvanceTM from Medtronic. After running through the simulation, the thermal propagation during the procedure was shown in the form of different colors. The three-dimensional print models were constructed on the base of the described simulation in a CAD program. Four different 3D printers are available for this purpose in a rapid prototyping laboratory at the University of Applied Science Offenburg. Two different printing processes were used: 1. a binder jetting printer with polymer gypsum and 2. a multi-material printer with photopolymer. A final print model with additional representation of the esophagus and internal esophagus catheter was also prepared for printing. With the help of the thermal simulation results and the subsequent evaluation, it was possible to make a conclusion about the propagation of the cold emanating from the catheter in the myocardium and the surrounding tissue. It could be measured that already 3 mm from the balloon surface into the myocardium the temperature drops to 25 °C. The simulation model was printed using two 3D printing methods. Both methods as well as the different printing materials offer different advantages and disadvantages. While the first model made of polymer gypsum can be produced quickly and cheaply, the second model made of photopolymer takes five times longer and was twice as expensive. On the other hand, the second model offers significantly better properties and was more durable overall. All relevant parts, especially the balloon catheter and the conduction, are realistically represented. Only the thermal propagation in the form of different colors is not shown on this model. Three-dimensional heart rhythm models as well as virtual simulations allow a very good visualization of complex cardiac rhythm therapy and atrial fibrillation treatment methods. The printed models can be used for optimization and demonstration of cryoballoon catheter ablation in patients with atrial fibrillation

3D-Druck der Ablation von Vorhofflimmern

Um medizinische Behandlungsverfahren in der Praxis besser verstehen und anwenden zu können, gewinnt die Visualisierung der Prozesse an immer größerer Bedeutung. Durch Anwendung der Computer-Simulationssoftware CST können elektromagnetische und thermische Simulationen zur Analyse verschiedener Herzrhythmusstörungen durchgeführt werden. Eine weitere Form der Visualisierung erfolgt durch haptische, dreidimensionale Druckmodelle. Diese Modelle können mit einem generativen Herstellungsverfahren, wie z. B. einem 3D-Drucker, in kürzester Zeit hergestellt werden.In order to better understand and apply medical treatment procedures in practice, the visualization of processes is becoming increasingly important. By using the computer simulation software CST, electromagnetic and thermal simulations can be carried out to analyse various cardiac arrhythmias. Another form of visualization is the use of haptic, three-dimensional pressure models. These models can be produced with a generative manufacturing process, such as a 3D printer, in a very short time