Chronic and Postprandial Metabolic Responses to a Ketogenic Diet Compared to High-Carbohydrate and Habitual Diets in Trained Competitive Cyclists and Triathletes: A Randomized Crossover Trial

Extreme carbohydrate deficits during a ketogenic diet (KD) may result in metabolic adaptations reflective of low energy availability; however, the manifestation of these adaptations outside of exercise have yet to be elucidated in cyclists and triathletes. The purpose of this study is to investigate the chronic and postprandial metabolic responses to a KD compared to a high-carbohydrate diet (HCD) and habitual diet (HD) in trained competitive cyclists and triathletes. For this randomized crossover trial, six trained competitive cyclist and triathletes (F: 4, M: 2) followed an ad libitum KD and HCD for 14 d each after their HD. Fasting energy expenditure (EE), respiratory exchange ratio (RER), and fat and carbohydrate oxidation (FatOx and CarbOx, respectively) were collected during their HD and after 14 d on each randomly assigned KD and HCD. Postprandial measurements were collected on day 14 of each diet following the ingestion of a corresponding test meal. There were no significant differences in fasting EE, RER, FatOx, or CarbOx among diet conditions (all p \u3e 0.050). Although postprandial RER and CarbOx were consistently lower following the KD meal, there were no differences in peak postprandial RER (p = 0.452), RER incremental area under the curve (iAUC; p = 0.416) postprandial FatOx (p = 0.122), peak FatOx (p = 0.381), or FatOx iAUC (p = 0.164) between the KD and HD meals. An ad libitum KD does not significantly alter chronic EE or substrate utilization compared to a HCD or HD; postprandial FatOx appears similar between a KD and HD; this is potentially due to the high metabolic flexibility of cyclists and triathletes and the metabolic adaptations made to habitual high-fat Western diets in practice. Cyclists and triathletes should consider these metabolic similarities prior to a KD given the potential health and performance impairments from severe carbohydrate restriction

Appetite Alterations in Endurance Athletes Following the Ketogenic Diet

Recently, endurance athletes have utilized a very low-carbohydrate diet, the ketogenic diet (KD), to improve performance in competition. The KD may be associated with diminished appetite, but this has not been explored in endurance athletes. PURPOSE: The purpose of this study was to evaluate the effects of a KD compared to a high-carbohydrate diet (HCD) and habitual diet (HD) on both subjective and objective measures of appetite in highly-trained cyclists and triathletes. METHODS: Following their HD, six highly-trained (≥80th percentile for V02max based on age and sex) cyclists and triathletes (male = 2, female = 4; age: 37.2 ± 12.2) consumed a KD and HCD, for two weeks each, in a random order. At the end of each diet, perceptions of fasting hunger, desire to eat (DTE), prospective consumption of food (PCF) and fullness, and serum total ghrelin (GHR) and glucagon-like-peptide-1 (GLP-1) were assessed. Immediately after collection of the fasting measures, a test meal containing an energy content that was 60% of measured resting metabolic rate was administered. The test meal composition corresponded with the participants diets (ketogenic meal after the KD, high-carbohydrate meal after the HCD, and a standard American meal after their HD). After ingestion of the test meal, postprandial appetite measures were collected for 3 h at 30, 60, 120, and 180 min. RESULTS: Repeated measures analysis showed that fasting GHR was significantly lower following the KD than the HD (p=0.001) and HCD (p=0.031) and fasting GLP-1 was significantly higher following the KD than the HD (p=0.041) and HCD (p=0.033). Fasting hunger was also significantly higher following the KD compared with the HD (p=0.042) and HCD (p=0.004) and PCF was higher for the KD versus HD (p=0.020). There were no differences between diets for fasting DTE and fullness. Postprandial GHR was significantly lower following consumption of the ketogenic test meal than the standard meal (p=0.007) and high-carbohydrate meal (p=0.031). Peak concentrations of postprandial GHR and incremental area under the curve (iAUC) for GHR were also significantly lower following the ketogenic meal than the standard meal (p=0.025; p=0.016, respectively) and the high-carbohydrate meal (p=0.044; p=0.045, respectively). Postprandial GLP-1 was significantly higher following consumption of the ketogenic test meal than the standard meal (p=0.006) and high-carbohydrate meal (p=0.003). Peak concentrations of postprandial GLP-1 and GLP-1 iAUC were also significantly higher following the ketogenic meal than the standard meal (p=0.009; p=0.004, respectively) and the high-carbohydrate meal (p=0.008; p=0.002, respectively). There were no differences in postprandial ratings of appetite between diets. CONCLUSIONS: Both fasting and postprandial concentrations of GHR were lower and GLP-1 were higher following the KD than the HC and HD in endurance athletes. Subjective ratings of appetite did not correspond with the objective measures of appetite, however. More research is needed to confirm our findings, and to understand the relationship between subjective and objective measures of appetite in endurance athletes

Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency

Abstract Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130. Responsiveness to IL6 trans-signals is found to be niche-dependent as bone marrow stromal and endosteal cells down-regulate gp130 in premalignant mammary epithelial cells as opposed to vascular niche cells. PIK3CA activation renders cells independent from IL6 trans-signaling. Consistent with a bottleneck function of microenvironmental DCC control, we find PIK3CA mutations highly associated with late-stage metastatic cells while being extremely rare in early DCCs. Our data suggest that the initial steps of metastasis formation are often not cancer cell-autonomous, but also depend on microenvironmental signals

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Fluid-kinetic approach for 3D plasma edge transport in helium plasmas

The fluid edge plasma Monte-Carlo code in three dimensions (EMC3) coupled to the kinetic (neutral particle) transport code EIRENE has demonstrated good performance in describing and even predicting the experimental trends of a wide range of stellarator and tokamak edge plasma configurations, under a certain range of relevant limiter and divertor scenarios. One major limitation so far, however, has been the restriction of EMC3 to hydrogen isotopes, although in the initial operation phase of the newly built, optimised stellarator Wendelstein 7-X, (and probably also in ITER during its initial low activation phase) helium plasmas are used. An approach is presented on how to extend EMC3 and expand the use of EIRENE features in plasma edge simulations for helium edge plasmas. The approach is based on modelling He++ as a fluid, calculated by the plasma fluid code EMC3, and treating helium atoms and He+ ions as particles, calculated by the kinetic transport code EIRENE. The applicability, current limitations and future directions of this hybrid approach will be discussed. The first simulation results for Wendelstein 7-X helium edge plasma conditions demonstrate the feasibility of the present computational model

Chronic and Postprandial Metabolic Responses to a Ketogenic Diet Compared to High-Carbohydrate and Habitual Diets in Trained Competitive Cyclists and Triathletes: A Randomized Crossover Trial

Extreme carbohydrate deficits during a ketogenic diet (KD) may result in metabolic adaptations reflective of low energy availability; however, the manifestation of these adaptations outside of exercise have yet to be elucidated in cyclists and triathletes. The purpose of this study is to investigate the chronic and postprandial metabolic responses to a KD compared to a high-carbohydrate diet (HCD) and habitual diet (HD) in trained competitive cyclists and triathletes. For this randomized crossover trial, six trained competitive cyclist and triathletes (F: 4, M: 2) followed an ad libitum KD and HCD for 14 d each after their HD. Fasting energy expenditure (EE), respiratory exchange ratio (RER), and fat and carbohydrate oxidation (FatOx and CarbOx, respectively) were collected during their HD and after 14 d on each randomly assigned KD and HCD. Postprandial measurements were collected on day 14 of each diet following the ingestion of a corresponding test meal. There were no significant differences in fasting EE, RER, FatOx, or CarbOx among diet conditions (all p > 0.050). Although postprandial RER and CarbOx were consistently lower following the KD meal, there were no differences in peak postprandial RER (p = 0.452), RER incremental area under the curve (iAUC; p = 0.416) postprandial FatOx (p = 0.122), peak FatOx (p = 0.381), or FatOx iAUC (p = 0.164) between the KD and HD meals. An ad libitum KD does not significantly alter chronic EE or substrate utilization compared to a HCD or HD; postprandial FatOx appears similar between a KD and HD; this is potentially due to the high metabolic flexibility of cyclists and triathletes and the metabolic adaptations made to habitual high-fat Western diets in practice. Cyclists and triathletes should consider these metabolic similarities prior to a KD given the potential health and performance impairments from severe carbohydrate restriction

Perceptions of Appetite Do Not Match Hormonal Measures of Appetite In Trained Competitive Cyclists and Triathletes Following a Ketogenic Diet Compared To a High-Carbohydrate or Habitual Diet: A Randomized Crossover Trial

Endurance athletes may implement rigid dietary strategies, such as the ketogenic diet (KD), to improve performance. The effect of the KD on appetite remains unclear in endurance athletes. This study analyzed the effects of a KD, a high-carbohydrate diet (HCD), and habitual diet (HD) on objective and subjective measures of appetite in trained cyclists and triathletes, and hypothesized that the KD would result in greater objective and subjective appetite suppression. Six participants consumed the KD and HCD for 2-weeks each, in a random order, following their HD. Fasting appetite measures were collected after 2-weeks on each diet. Postprandial appetite measures were collected following consumption of a ketogenic meal after the KD, high-carbohydrate meal after the HCD, and standard American/Western meal after the HD. Fasting total ghrelin (GHR) was lower and glucagon-like peptide-1 (GLP-1) and hunger were higher following the KD versus HD and HCD. Fasting insulin was not different. Mixed-effects model repeated measures analysis and effect sizes and 95% confidence intervals showed that postprandial GHR and insulin were lower and GLP-1 was higher following the ketogenic versus the standard and high-carbohydrate meals. Postprandial appetite ratings were not different across test meals. In conclusion, both fasting and postprandial concentrations of GHR were lower and GLP-1 were higher following the KD than the HC and HD, and postprandial insulin was lower on the KD. Subjective ratings of appetite did not correspond with the objective measures of appetite in trained competitive endurance athlete. More research is needed to confirm our findings