Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance

BACKGROUND: Impaired glucose tolerance (IGT) is associated with increased cardiovascular risk. The pathophysiological mechanisms linking post-challenge hyperglycemia to accelerated atherosclerosis, however remain to be elucidated. METHODS: A prospective, open, randomised, cross-over study was performed to investigate the effect of 2 mg repaglinide on hyperglycemia and endothelial function during an oral glucose tolerance test (75 g glucose) in 12 subjects with diagnosed IGT. Blood samples for determination of plasma glucose were drawn fasting, 1 and 2 hours after glucose ingestion. Endothelial function was assessed by measuring flow-mediated dilatation (FMD) of the brachial artery with high-resolution ultrasound. RESULTS: Administration of repaglinide resulted in a significant reduction of plasma glucose at 2 hours (172.8+/-48.4 vs. 138.3+/-41.2 mg/dl; p < 0.001). The flow-mediated dilatation (FMD) 2 hours after the glucose-load was significantly reduced in comparison to fasting in the control group (6.21+/-2.69 vs. 7.98+/-2.24 %; p = 0.028), whereas after theadministration of repaglinide the FMD was not significantly different to fasting values (7.24+/-2.57 vs. 8.18+/-2.93 %; p = n.s.). Linear and logistic regression analysis revealed that only the change of glucose was significantly correlated to the change of FMD observed (p < 0.001). Regression analysis after grouping for treatment and time confirmed the strong negative association of the changes of plasma glucose and FMD and indicate that the effect of repaglinide observed is based on the reduction glycemia. CONCLUSION: In subjects with IGT, the endothelial dysfunction observed after a glucose challenge is related to the extent of hyperglycemia. Reduction of hyperglycemia by repaglinide reduces endothelial dysfunction in a glucose dependent manner

In situ study of dynamic recrystallization and hot deformation behavior of a multiphase titanium aluminide alloy

Hot-compression tests were conducted in a high-energy synchrotron x-ray beam to study in situ and in real time microstructural changes in the bulk of a β-solidifying titanium aluminide alloy. The occupancy and spottiness of the diffraction rings have been evaluated in order to access grain growth and refinement, orientation relationships, subgrain formation, dynamic recovery, and dynamic recrystallization, as well as phase transformations. This method has been applied to an alloy consisting of two coexisting phases at high temperature and it was found that the bcc β-phase recrystallizes dynamically, much faster than the hcp α-phase, which deforms predominantly through crystallographic slip underpinned by a dynamic recovery process with only a small component of dynamic recrystallization. The two phases deform to a very large extent independently from each other. The rapid recrystallization dynamics of the β-phase combined with the easy and isotropic slip characteristics of the bcc structure explain the excellent deformation behavior of the material, while the presence of two phases effectively suppresses grain growth

Hot deformation of cast and extruded TiAl: An in-situ diffraction study

Intermetallic TiAl alloys are a class of innovative high-temperature materials which are developed to replace the substantially denser Ni-base alloys in low-pressure turbine blades of jet engines. By streamlining the production process of these parts, a substantial decrease in production costs can be achieved. To this end, a profound knowledge of the microstructural processes occurring during hot deformation is a prerequisite. To investigate the microstructural development during forming operations, cast and extruded as well as only cast specimens were hot-deformed and the microstructural development investigated in-situ by means of a novel diffraction method. This powder diffraction method utilizes the behavior of individual reflection spots on the Debye-Scherrer rings for deriving the materials response to the deformation imposed. It was found that the behavior of the two specimens is rather similar, although the starting microstructures show pronounced differences

In situ characterization of a Nb and Mo containing g-TiAl based alloy using neutron diffraction and high temperature microscopy

In recent times, novel titanium aluminides containing the bcc β-phase at high temperatures are being developed for improved hot-working capabilities, however, predictions of the phase diagrams are merely uncertain. Here we present in-situ neutron studies, which are particularly sensitive to the atomic disorder in the ordered phases. Complementary laser scanning confocal microscopy is employed for in-situ microstructural investigations

Advanced β-Solidifying Titanium Aluminides – Development Status and Perspectives

After almost three decades of intensive fundamental research and development activities intermetallic titanium aluminides based on the -TiAl phase have found applications in automotive and aircraft engine industries. The advantages of this class of innovative high-temperature materials are their low density as well as their good strength and creep properties up to 750°C. A drawback, however, is their limited ductility at room temperature, which is reflected by a low plastic strain at fracture. This behavior can be attributed to a limited dislocation movement along with microstructural inhomogeneity. Advanced TiAl alloys, such as β-solidifying TNM™ alloys, are complex multi-phase materials which can be processed by ingot or powder metallurgy as well as precision casting methods. Each production process leads to specific microstructures which can be altered and optimized by thermo-mechanical processing and/or subsequent heat-treatments. The background of these heat-treatments is at least twofold, i.e. concurrent increase of ductility at room temperature and creep strength at elevated temperature. In order to achieve this goal the knowledge of the occurring solidification processes and phase transformation sequences is essential. Therefore, thermodynamic calculations were conducted to predict phase fraction diagrams of engineering TiAl alloys. After experimental verification, these phase diagrams provided the base for the development of heat treatments to adjust balanced mechanical properties. To determine the influence of deformation and kinetic aspects, sophisticated ex- and in-situ methods have been employed to investigate the evolution of the microstructure during thermo-mechanical processing and subsequent multi-step heat-treatments. For example, in-situ high-energy X-ray diffraction was conducted to study dynamic recovery and recrystallization processes during hot-deformation tests. Summarizing all results a consistent picture regarding microstructure formation and its impact on mechanical properties in TNM alloys can be given