Showing papers by "Andreas Pfeiffer published in 2005"
TL;DR: In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponECTin, which is related to circulating HDL cholesterol.
Abstract: Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 +/- 1.2 to 32.8 +/- 1.1 kg/m(2), P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 +/- 0.5 to 6.1 +/- 0.6 microg/ml (P = 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 +/- 0.07 to 0.4 +/- 0.08 microg/ml, P = 0.042; MMW: 2.3 +/- 0.2 to 2.9 +/- 0.3 microg/ml, P = 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r = -0.695, P = 0.002) and positively with LMW (r = 0.579, P = 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r = 0.665, P = 0.007). Indeed, HMW and free fatty acids before weight reduction predicted approximately 60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol.
270 citations
TL;DR: A high score for the identified dietary pattern is associated with a more favourable biomarker profile and a substantially reduced incidence of type 2 diabetes.
Abstract: Aims/hypothesis
The aim of this study was to identify a dietary pattern associated with diabetes-related biomarkers and to investigate whether this pattern is associated with the incidence of type 2 diabetes.
216 citations
TL;DR: The consumption of highly purified insoluble dietary fibres accelerated the acute GIP and insulin response and was further associated with enhanced postprandial carbohydrate handling the following day upon ingestion of a control meal.
Abstract: Aims/hypothesis
Insoluble dietary fibre intake is associated, by unknown mechanisms, with a reduced risk of type 2 diabetes. We investigated whether a short-term dietary intervention with purified insoluble fibres influences acute and delayed responses of glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1.
185 citations
TL;DR: Levels of adiponectin, which are associated with markers of chronic subclinical inflammation, could be significantly increased after weight loss in morbidly obese patients, and was more pronounced in patients with NGT compared to those with T2D and IGT.
Abstract: Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women
180 citations
TL;DR: Findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals by promoting both apoptosis and proliferation in murine hepatocytes.
Abstract: We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals.
133 citations
TL;DR: In this article, the combined results on electron-pair production in 158 GeV/n {Pb-Au} ($\sqrt{s}$= 17.2 GeV) collisions taken at the CERN SPS in 1995 and 1996 were presented.
Abstract: We present the combined results on electron-pair production in 158 GeV/n {Pb-Au} ($\sqrt{s}$= 17.2 GeV) collisions taken at the CERN SPS in 1995 and 1996, and give a detailed account of the data analysis. The enhancement over the reference of neutral meson decays amounts to a factor of 2.31$\pm0.19 (stat.)\pm0.55 (syst.)\pm0.69 (decays)$ for semi-central collisions (28% $\sigma/\sigma_{geo}$) when yields are integrated over $m>$ 200 MeV/$c^2$ in invariant mass. The measured yield, its stronger-than-linear scaling with $N_{ch}$, and the dominance of low pair $p_t$ strongly suggest an interpretation as {\it thermal radiation} from pion annihilation in the hadronic fireball. The shape of the excess centring at $m\approx$ 500 MeV/$c^2$, however, cannot be described without strong medium modifications of the $\rho$ meson. The results are put into perspective by comparison to predictions from Brown-Rho scaling governed by chiral symmetry restoration, and from the spectral-function many-body treatment in which the approach to the phase boundary is less explicit.
103 citations
TL;DR: In this article, the combined results on electron-pair production in 158GeV/n Pb-Au ( √ s=17.2 GeV) collisions taken at the CERN SPS in 1995 and 1996 were presented.
Abstract: We present the combined results on electron-pair production in 158GeV/n Pb-Au ( √ s=17.2 GeV) collisions taken at the CERN SPS in 1995 and 1996, and give a detailed account of the data analysis. The enhancement over the reference of neutral meson decays amounts to a factor of 2.31±0.19 (stat.) ± 0.55(syst.) ±0.69 (decays) for semi-central collisions (28% σ/σgeo) when yields are in- tegrated over m >200MeV/c 2 in invariant mass. The measured yield, its stronger-than-linear scaling with Nch, and the dominance of low pair pt strongly suggest an interpretation as thermal radiation from pion annihilation in the hadronic fireball. The shape of the excess centring at m ≈500MeV/c 2 , however, cannot be described without strong medium modifications of the ρ meson. The results are put into perspective by comparison to predictions from Brown-Rho scaling governed by chiral symmetry restoration, and from the spectral-function many-body treatment in which the approach to the phase boundary is less explicit.
101 citations
TL;DR: In subjects with normal glucose regulation, the AX-enriched breakfast increased ghrelin levels without any significant difference in glucose or insulin response, so this effect is unlikely to be mediated by insulin, but the underlying mechanism remains to be elucidated.
Abstract: Soluble fibre like arabinoxylan (AX) is thought to have beneficial effects on metabolism. In this study, we investigated the effect of a breakfast enriched in AX fibre on glucose, insulin and ghrelin values. AX-enriched and control breakfasts were served to fifteen young volunteers (nine female, six male). Glucose, insulin and ghrelin responses were measured after the meal. To avoid effects from differences in glucose metabolism, further analysis was restricted to those subjects with known normal glucose regulation (seven female, four male). The AX fibre-enriched breakfast did not significantly change glucose levels for two hours after breakfast, but decreased insulin levels in the entire cohort (p = 0.035). Glucose response was also not significantly different in subjects with normal glucose regulation (p = 0.367), and the insulin responses after an AX-enriched breakfast showed only a tendency towards lower values (p = 0.065). Nevertheless, plasma ghrelin two hours after AX-enriched breakfast was higher than after the control meal (396.1 +/- 36.4 pg/ml vs. 328.3 +/- 32.6 pg/ml, p < 0.001). In subjects with normal glucose regulation, the AX-enriched breakfast increased ghrelin levels without any significant difference in glucose or insulin response. This effect is therefore unlikely to be mediated by insulin, but the underlying mechanism remains to be elucidated.
58 citations
TL;DR: The already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations, and the mechanisms underlying the gh Relin suppression after i.
Abstract: Objective: It is well known that i.m. glucagon administration stimulates GH and cortisol release in humans, although the mechanisms are unclear. These effects are similar to those described for ghrelin on somatotroph and corticotroph function. The aim of the present study was to investigate the role of ghrelin in mediating the stimulatory effects of glucagon and to evaluate the effect of glucagon on ghrelin secretion. Design and methods: We studied the endocrine and metabolic response to i.m. glucagon administration in 24 subjects (14 men, 10 women; age 19 – 65 years; body mass index, 25.3^1 kg/m 2 ), who were shown to have an intact anterior pituitary function as evaluated before enclosure. Results: Serum ghrelin concentrations fell significantly at 30, 60, 120 and 180 min after glucagon administration (means^S.E.M.; baseline, 377.9^34.5 pg/ml; nadir, 294.6^28.3 pg/ml (60 min); P , 0.01). Conversely, i.m. glucagon elicited an increase in GH (baseline, 1.5^0.4mg/l; peak, 14.2^2.7mg/l (180 min); P , 0.01) and cortisol concentrations (baseline, 452.6^35.2 nmol/l; peak, 622.1^44 nmol/l (180 min); P , 0.01). The changes in ghrelin concentration at both 120 and 180 min were still significant after correction for glucose and insulin (P , 0.05). Conclusions: We show that i.m. glucagon decreases ghrelin significantly. Therefore, the already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations. The mechanisms underlying the ghrelin suppression after i.m. glucagon are unlikely to include glucose or insulin variations and need to be further elucidated.
50 citations
TL;DR: In this article, the authors identified determinants of circulating adiponectin and its potential for reversing insulin resistance in 62 consecutive women with polycystic ovary syndrome (PCOS) who were compared with 35 healthy control women.
Abstract: The obesity and insulin resistance that characterize polycystic ovary syndrome (PCOS) predispose to both type 2 diabetes and atherosclerosis. Correction of metabolic abnormalities, particularly insulin resistance, reportedly can lessen hyperandrogenism and enhance fertility. Adiponectin recently was identified as an adipocytokine having insulin-sensitizing and possibly antiatherosclerotic effects. This study sought to identify determinants of circulating adiponectin and its potential for reversing insulin resistance in 62 consecutive women with PCOS who were compared with 35 healthy control women. In addition to a higher body mass index (BMI) and greater insulin resistance, women with PCOS had significantly higher levels of testosterone, androstenedione, and 17-OH-progesterone than did control women. Plasma adiponectin levels averaged 7.6 μg/mL in the patients with PCOS, significantly lower than the control mean of 9.8 μg/mL. In both groups, adiponectin levels were lower in obese women having a BMI of 25 kg/m 2 or higher, and no group difference was found after adjusting for BMI (Fig. 1). In both women with PCOS and control women, adiponectin concentrations correlated significantly with BMI, fasting insulin, and testosterone levels but not with androstenedione, 17-OH-progesterone, or the luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio. BMI accounted for 16% of variance in plasma adiponectin levels. In women with PCOS, insulin sensitivity correlated significantly with adiponectin, BMI, waist-to-hip ratio, body fat mass, trunk fat, and testosterone. Circulating adiponectin accounted for approximately 18% of the degree of insulin resistance, but testosterone did not contribute significantly. Six months of metformin treatment of insulin-resistant women with PCOS did not alter plasma adiponectin levels despite significant losses of body weight and fat mass and lessening of hyperandrogenemia. PCOS itself is not associated with low circulating adiponectin levels, suggesting that adiponectin is not a direct pathogenetic factor. Low levels of adiponectin may, however, contribute to the development and/or persistence of insulin resistance. This could be a link to the increased risk of type 2 diabetes and cardiovascular disease in women with PCOS.
36 citations
TL;DR: Changes of the hormonal system as a result of marathon training and running a marathon were examined, regarding the activation or inactivation of cortisol to cortisone by the 11β‐hydroxysteroid‐dehydrogenase system (11β‐HSD).
Abstract: OBJECTIVE Physical activity leads to changes in the hypothalamic-pituitary hormonal system. However, acute and long-term adaptations have not yet been precisely characterized. In this study, the changes of the hormonal system as a result of marathon training and running a marathon were examined. In particular, we focused on adaptations of the hypothalamic-pituitary-adrenocortical (HPA) axis, regarding the activation or inactivation of cortisol to cortisone by the 11beta-hydroxysteroid-dehydrogenase system (11beta-HSD). DESIGN Patient measurements: 8 healthy women and 11 healthy men volunteered for this study. Blood samples, 24-h urine and a dexamethasone suppression test were analysed for metabolic and hormonal parameters at five different dates 12 weeks around a marathon. RESULTS Cortisol and ACTH values decreased significantly 2 days after the marathon, whereas the activity of the whole body 11beta-HSD-1 was up-regulated. An increased suppression of cortisol levels was observed in the dexamethasone suppression test after 6 weeks of reduced training levels. Ghrelin was elevated 2 days after the marathon. Only minor changes in the other hypothalamic-pituitary-hormonal axes could be observed. However, the free androgen index increased significantly after 6 weeks of reduced training. CONCLUSIONS The HPA system appeared to become chronically activated by continuous physical training and therefore less sensitive to the dexamethasone suppression test. The acute stress of the marathon led to a central exhaustion of the HPA system with a paracrine counteraction by the activation of the 11beta-HSD system. Changes in the other hypothalamic-pituitary hormonal axes were the result of long-term differences in training levels and were not altered by the marathon.
TL;DR: There is no dose-dependent suppression of ghrelin by insulin in the hyperglycemic condition and further increases of hyperinsulinemia to supraphysiological and high supraphYSiological concentrations under GIP- and arginine-infusion do not significantly decrease gh Relin concentrations in healthy subjects.
TL;DR: The aim of this study was to investigate whether the FFA‐induced hepatic insulin resistance is mediated by increased activity of hepatic 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), accompanied by elevated hepatic cortisol levels.
Abstract: INTRODUCTION Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels. METHODS Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. RESULTS Lipid infusion increased FFAs (5.41 +/- 1.00 vs. 0.48 +/- 0.20 mmol/l; P < 0.005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6.02 +/- 2.60 vs. 4.08 +/- 2.15 mg/kg/min; P < 0.005]. After lipid and saline infusions no changes in 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios. CONCLUSIONS We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.
TL;DR: Evidence is obtained in two German Caucasian study populations that the variant of the rare CLPS Arg109Cys polymorphism might contribute to increased susceptibility of type 2 diabetes.
Abstract: The protein encoded by the pancreatic colipase (CLPS) gene is an essential cofactor needed by pancreatic triglyceride lipase (PNLIP) for efficient dietary lipid hydrolysis. Since the inhibition of lipase activity was shown to reduce the incidence of type 2 diabetes mellitus, we tested the hypothesis that genetic variations in the CLPS and PNLIP genes are associated with type 2 diabetes; 47 unrelated subjects were screened for polymorphisms of the CLPS and PNLIP genes. A nested-case control study of 192 incident type 2 diabetes subjects and 384 sex- and age-matched controls taken from the European Prospective Investigation into Cancer and Nutrition Potsdam Cohort (EPIC) was employed for association studies. The Metabolic Intervention Cohort Kiel (MICK) consisting of 716 males was used for verification. A novel putative functional polymorphism (Arg109Cys) was identified in the CLPS gene. The frequencies of the Arg/Cys genotype were 2.6% in EPIC and 2.2% in MICK study subjects. No homozygotes for the Cys/Cys genotype were found in either study population. Logistic regression analysis showed a statistically significant association of the Arg/Cys genotype with an increased risk of type 2 diabetes. The odds ratios estimated by the model were 3.75 (95%CI = 1.13-12.49, p = 0.03) in EPIC and 4.86 (95%CI = 1.13-20.95, p = 0.03) in MICK. No comparable associations were found with other traits of the insulin-resistance syndrome (e. g.; body mass index, waist to hip ratio). In conclusion, we obtained evidence in two German Caucasian study populations that the variant of the rare CLPS Arg109Cys polymorphism might contribute to increased susceptibility of type 2 diabetes.
TL;DR: In this article, the mean transverse momentum and net charge in Pb-Au collisions were measured by the CERES Collaboration at CERN-SPS, and the centrality and beam energy dependence were discussed.
TL;DR: Most parameters of the metabolic syndrome improved after successful weight reduction, although changes of most parameters were modest and did not reach statistical significance.
Abstract: Introduction Obesity is a risk factor for type 2 diabetes, hypertension, dyslipidemia and cardiovascular disease. We aimed to analyse the changes of parameters of the metabolic syndrome and to investigate which markers are useful in the prediction of a successful weight loss. Preliminary data of an ongoing study are presented. Methods 18 obese individuals (15 female, 3 male, mean age 50.9 years, mean BMI 36.1) finished a 12 month weight loss program. This weight loss program was based on a hypocaloric diet (50 % carbohydrates, 30 % fat, 20 % protein) and at least 60 min physical activity per week. At baseline, 6 months and 12 months physical examination, indirect calorimetry, bioimpedance analysis were performed and blood was taken for routine laboratory. An oral glucose tolerance test and an euglycemic hyperinsulinemic clamp (n = 13) were carried out at baseline and after 6 months. Results There was a decrease of the BMI (+/- SEM) from 36.1 +/- 1.3 to 33.4 +/- 1.2 after 6 months and 32.8 +/- 1.3 after 12 months. Waist circumference (-8.8 cm), fasting blood glucose (98.0 to 91.2 and 92.5 mg/dl) and HDL cholesterol (47.2 to 64.6 mg/dl after 12 months) improved significantly. Other parameters of the metabolic syndrome (blood pressure, lipids, insulin resistance) and adiponectin improved slightly, but changes failed to be significant. In a linear regression analysis age, insulin resistance (M-value) and adiponectin at baseline were significant and independent predictors of a successful weight loss. Conclusion In conclusion, most parameters of the metabolic syndrome improved after successful weight reduction, although changes of most parameters were modest and did not reach statistical significance.
Journal Article•
TL;DR: An increase in the uptake of indigestible roughage can be recommended as a means of reducing the risk of developing type 2 diabetes and cardiovascular diseases.
Abstract: On the basis of the currently available data, an increase in the uptake of indigestible roughage can be recommended as a means of reducing the risk of developing type 2 diabetes and cardiovascular diseases. In concert with other factors of a healthy lifestyle--including physical exercise, abstention from nicotine, the consumption of only moderate amounts of alcohol, reducing the intake of saturated fats, and--the main factor--ensuring that overweight does not develop, this dietary modification would appear to be an effective measure for avoiding most cases of type 2 diabetes.
CERN1
TL;DR: The "Physicist Interface" project of the LCG Application Area encompasses the interfaces and tools by which physicists will directly use the software, providing implementations based on agreed standards like the AIDA interfaces for data analysis.
Abstract: In the context of the LHC computing grid (LCG) project, the applications area develops and maintains that part of the physics applications software and associated infrastructure that is shared among the LHC experiments. The "physicist interface" (PI) project of the LCG application area encompasses the interfaces and tools by which physicists will directly use the software, providing implementations based on agreed standards like the analysis systems subsystem (AIDA) interfaces for data analysis. In collaboration with users from the experiments, work has started with implementing the AIDA interfaces for (binned and unbinned) histogramming, fitting and minimization as well as manipulation of tuples. These implementations have been developed by re-using existing packages either directly or by using a (thin) layer of wrappers. In addition, bindings of these interfaces to the Python interpreted language have been done using the dictionary subsystem of the LCG applications area/SEAL project. The actual status and the future planning of the project will be presented
Journal Article•
01 Jan 2005
TL;DR: A novel software toolkit has been developed encompassing an ample variety of statistical algorithms for the comparison of data distributions, such as Monte Carlo simulations and experimental data, which can be used by other data analysis systems or integrated in experimental software frameworks.
Abstract: A typical problem associated to Monte Carlo developments and application consists in the validation of the simulation models and results against experimental data. A novel software toolkit has been developed encompassing an ample variety of statistical algorithms for the comparison of data distributions, such as Monte Carlo simulations and experimental data. The toolkit contains a variety of goodness-of-fit tests, from chi-squared to Kolmogorov-Smirnov, to less known, but generally much more powerful tests such as Anderson-Darling, Cramer-von Mises, Kuiper, Tiku, etc. Thanks to the component-based design and the usage of the standard AIDA interfaces, this tool can be used by other data analysis systems or integrated in experimental software frameworks. We present the architecture of the system, the statistics methods implemented and some results of its applications to the comparison of Geant4 simulations with respect to experimental data.