Doctor-patient communication during the Corona crisis - web-based interactions and structured feedback from standardized patients at the University of Basel and the LMU Munich.

Background: Due to the pandemic-related restrictions in classroom teaching at the medical faculties of the LMU Munich and the University of Basel, teaching methods with standardized patients (SPs), were shifted to a digital, web-based format at short notice as of April 2020. We report on our experiences with the WebEncounter program, which was used for the first time in German-speaking countries. The program enables one-to-one encounters between SPs and students. Students receive an invitational email with brief instructions and background information on the case. SPs use case-specific criteria that are compliant with the learning objectives for digital evaluation during the encounter. A feedback session takes place immediately following the encounter. The SPs address the didactically relevant sections and can illustrate them with the corresponding video sequences. Finally, the students receive the links to the video recordings of the encounter and the feedback unit by email. Project description: The aim of this pilot study was to analyze the practicability of the program and its acceptance by students and SPs. In addition, we examined whether the operationalization of the learning objectives in the form of assessment items has an impact on the content and thematic development of courses in the area of doctor-patient communication. Methods: To implement the program, patient cases previously tested in communication seminars in Munich and Basel were rewritten and case-specific evaluation criteria were developed. SPs were trained to use the program, to present their patient figure online and to give feedback. The experience of those involved (faculty, SPs and SP trainers, students) in implementing the program was documented at various levels. The frequency and causes of technical problems were described. Student results on the patient cases and on the feedback items were collected quantitatively and, where possible, supplemented by free-text statements. Results: Data from 218/220 students in Basel and 120/127 students in Munich were collected and evaluated. Students were very satisfied with the patient cases, the encounter with the SPs and their feedback: 3.81±0.42. SPs experienced the training as an increase in their competence and the structured feedback as particularly positive. The training effort per SP was between 2.5 and 4 hours. The results show predominantly normally-distributed, case-specific sum scores of the evaluation criteria. The analysis of the individual assessment items refers to learning objectives that students find difficult to achieve (e.g. explicitly structuring the conversation). Problems in the technical implementation (<10 percent of the encounters) were due mainly to the use of insufficient hardware or internet connection problems. The need to define case-specific evaluation criteria triggered a discussion in the group of study directors about learning objectives and their operationalization. Summary: Web-based encounters can be built into the ongoing communication curriculum with reasonable effort. Training the SPs and heeding the technical requirements are of central importance. Practicing the virtual consultation was evaluated very positively by the students - in particular, the immediate feedback in the protected dialogue was appreciated by all involved.

Fostering medical students' clinical reasoning by learning from errors in clinical case vignettes: effects and conditions of additional prompting procedures to foster self-explanations.

The present study aims at fostering undergraduate medical students' clinical reasoning by learning from errors. By fostering the acquisition of "negative knowledge" about typical cognitive errors in the medical reasoning process, we support learners in avoiding future erroneous decisions and actions in similar situations. Since learning from errors is based on self-explanation activities, we provided additional prompting procedures to foster the effectiveness of the error-based instructional approach. The extent of instructional support in a web-based learning environment with erroneous clinical case examples was varied in a one-factorial design with three groups by either presenting the cases as (a) unsupported worked examples or by providing the participants with (b) closed prompts in the form of multiple-choice tasks or (c) with open reflection prompts during the learning process. Despite significant learning progress in all conditions, neither prompting procedure improved the learning outcomes beyond the level of the unsupported worked example condition. In contrast to our hypotheses, the unsupported worked example condition was the most effective with respect to fostering clinical reasoning performance. The effects of the learning conditions on clinical reasoning performance was mediated by cognitive load, and moderated by the students' self-efficacy. Both prompting procedures increased extraneous cognitive load. For learners with low self-efficacy, the prompting procedures interfered with effective learning from errors. Although our error-based instructional approach substantially improved clinical reasoning, additional instructional measures intended to support error-based learning processes may overtax learners in an early phase of clinical expertise development and should therefore only be used in moderation.

Effects of intraduodenal infusion of the branched-chain amino acid leucine on ad libitum eating, gut motor and hormone functions, and glycemia in healthy men.

BACKGROUND: Branched-chain amino acids (BCAAs), particularly leucine, act as nutrient signals regulating protein synthesis and degradation as well as glucose metabolism. In addition, leucine has been demonstrated in animal experiments to modulate eating and energy homeostasis. OBJECTIVE: We aimed to characterize the effects of physiologic and supraphysiologic loads of intraduodenal leucine on eating, gut hormone and motor functions, and blood glucose in humans. DESIGN: Twelve lean men were studied on 3 occasions in a randomized, double-blind order. Antropyloroduodenal motility, plasma ghrelin, cholecystokinin, glucagon-like peptide 1, peptide YY, insulin, glucagon, blood glucose, appetite perceptions, and gastrointestinal symptoms were measured during 90-min intraduodenal infusions of leucine at 0.15 kcal/min (total 3.3 g, 13.5 kcal), 0.45 kcal/min (total 9.9 g, 40.5 kcal), or saline (control). Ad libitum eating from a buffet lunch was quantified immediately after the infusions. RESULTS: Leucine at 0.45 kcal/min inhibited eating (energy intake by ∼13%, P < 0.05), increased plasma cholecystokinin, slightly reduced blood glucose and increased plasma insulin, and decreased antral pressures (all P < 0.05). Leucine at 0.15 kcal/min had no effect on food intake, blood glucose, or antral pressures but also slightly increased plasma cholecystokinin (P < 0.05). Neither dose affected plasma ghrelin, glucagon, glucagon-like peptide 1 and peptide YY, or pyloric and duodenal pressures. Plasma leucine concentrations were related to the dose of intraduodenal leucine, with substantial increases during both 0.15 and 0.45 kcal/min. CONCLUSIONS: The effects of intraduodenal infusions of free leucine on eating are probably not primarily mediated by changes in gut motor and hormone functions, with perhaps the exception of cholecystokinin. Instead, increased plasma leucine concentrations may be a potential signal mediating the eating-inhibitory effect of leucine. The study was registered as a clinical trial with the Australia and New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12613000899741.

Comparative effects of intraduodenal protein and lipid on ghrelin, peptide YY, and leptin release in healthy men.

Intraduodenal infusion of lipid or protein potently reduces subsequent energy intake. There is evidence that the underlying mechanisms differ significantly between the two nutrients. While intraduodenal lipid stimulates glucagon-like peptide-1 and CCK much more than protein, the release of insulin and glucagon is substantially greater in response to protein. Ghrelin and PYY are both involved in short-term regulation, while leptin is a long-term regulator, of energy balance; the acute effects of nutrients on leptin release are unclear. We investigated the comparative effects of intraduodenal lipid and protein on plasma ghrelin, PYY, and leptin concentrations. Thirteen lean, young men received 90-min intraduodenal infusions of protein (whey hydrolysate) or lipid (long-chain triglyceride emulsion) at a rate of 3 kcal/min, or saline control, on three separate days. Blood samples were collected at baseline and regularly during infusions. Both lipid and protein potently suppressed plasma ghrelin compared with control (both P < 0.001), with no difference between them. While both lipid and protein stimulated plasma PYY (P < 0.001), the effect of lipid was substantially greater than that of protein (P < 0.001). Neither intraduodenal lipid nor protein affected plasma leptin. In conclusion, intraduodenal lipid and protein have discrepant effects on the release of PYY, but not ghrelin. When considered with our previous findings, it appears that, with the exception of ghrelin, the energy intake-suppressant effects of lipid and protein are mediated by different mechanisms.

The effects of 5-hydroxytryptophan in combination with different Fatty acids on gastrointestinal functions: a pilot experiment.

Background. Fat affects gastric emptying (GE). 5-Hydroxythryptophan (5-HTP) is involved in central and peripheral satiety mechanisms. Influence of 5-HTP in addition to saturated or monounsaturated fatty acids (FA) on GE and hormone release was investigated. Subjects/Methods. 24 healthy individuals (12f : 12m, 22-29 years, BMI 19-25.7 kg/m²) were tested on 4 days with either 5-HTP + short-chain saturated FA (butter), placebo + butter, 5-HTP + monounsaturated FA (olive oil), or placebo + olive oil in double-blinded randomized order. Two hours after FA/5-HTP or placebo intake, a (13)C octanoid acid test was conducted. Cortisol, serotonin, cholecystokinin (CCK), and ghrelin were measured, as were mood and GE. Results. GE was delayed with butter and was normal with olive (P < 0.05) but not affected by 5-HTP. 5-HTP supplementation did not affect serotonin levels. Food intake increased plasma CCK (F = 6.136; P < 0.05) irrespective of the FA. Ghrelin levels significantly decreased with oil/5-HTP (F = 9.166; P < 0.001). The diurnal cortisol profile was unaffected by FA or 5-HTP, as were ratings of mood, hunger, and stool urgency. Conclusion. Diverse FAs have different effects on GE and secretion of orexigenic and anorexigenic hormones. Supplementation of 5-HTP had no effect on plasma serotonin and central functions. Further studies are needed to explain the complex interplay.

Effects of intraduodenal infusion of L-tryptophan on ad libitum eating, antropyloroduodenal motility, glycemia, insulinemia, and gut peptide secretion in healthy men.

CONTEXT: Changes in gut motor and hormonal function contribute to the eating-inhibitory and glucose-lowering effects of protein. The effect of amino acids, the digestive products of protein, on gastrointestinal function, eating, and glycemia has not been investigated comprehensively. OBJECTIVE: We tested the hypothesis that L-tryptophan (L-Trp) stimulates gastrointestinal motor and hormonal functions, inhibits eating, and modulates glycemia. Design, Settings, Participants, and Intervention: Ten healthy, normal-weight men were studied in randomized, double-blind fashion, each receiving a 90-minute intraduodenal infusion of L-Trp at 0.075 (total 6.75 kcal) or 0.15 (total 13.5 kcal) kcal/min or saline (control). MAIN OUTCOME MEASURES: Antropyloroduodenal motility, plasma ghrelin, cholecystokinin, glucagon-like peptide-1, peptide tyrosine tyrosine, insulin, glucagon, blood glucose, and appetite perceptions were measured. Food intake was quantified from a buffet meal after the infusion. RESULTS: Intraduodenal L-Trp suppressed antral pressures (P < .05) and stimulated pyloric pressures (P < .01) and markedly increased cholecystokinin and glucagon (both P < .001). Glucagon-like peptide-1 and peptide tyrosine tyrosine increased modestly (both P < .001), but there was no effect on total ghrelin. Insulin increased slightly (P < .05) without affecting blood glucose. Plasma L-Trp increased substantially (P < .001). All effects were dose-related and associated with increased fullness and substantially decreased energy intake (P < .001). There was a strong inverse correlation between energy intake and plasma L-Trp (r = -0.70; P < .001). CONCLUSIONS: Low caloric intraduodenal loads of L-Trp affect gut motor and hormonal function and markedly reduce energy intake. A strong inverse correlation between energy intake and plasma L-Trp suggests that, beyond gut mechanisms, direct effects of circulating L-Trp mediate its eating-inhibitory effect.

Functional dyspepsia patients have lower mucosal cholecystokinin concentrations in response to duodenal lipid.

BACKGROUND: Dyspeptic symptoms are frequently induced, or exacerbated, by fatty food ingestion. Excessive release of, and/or hypersensitivity to, cholecystokinin (CCK) may explain the exaggerated response to lipid in patients with functional dyspepsia (FD). Thus far, plasma CCK response has been evaluated. However, stimulation of CCK1 receptors on duodenal vagal afferents occurs in a paracrine manner, suggesting that mucosal CCK concentrations are relevant to quantify. Apolipoprotein A-IV stimulates mucosal CCK release. AIM: To investigate the hypothesis that fat-induced release of CCK and apolipoprotein A-IV (apoA-IV) is enhanced in the duodenum of FD patients. PATIENTS AND METHODS: Sixteen symptomatic FD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with intralipid 20%, 2 kcal/min, for 60 min. Symptoms were scored and blood samples were collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosal concentrations of CCK and apoA-IV were quantified. RESULTS: Abdominal discomfort (P=0.001), nausea (P=0.05), and fullness (P=0.005) in response to duodenal lipid increased significantly only in FD patients. Following lipid infusion, the mean mucosal CCK concentration was lower in FD patients compared with HV (P<0.0001). Fasting concentrations and plasma response of CCK were comparable in FD patients and HV. Plasma apoA-IV response appeared to differ between patients and HV, whereas mucosal apoA-IV concentrations were similar. CONCLUSION: Our results suggest excessive local release of CCK in response to duodenal lipid in FD. This likely causes exaggerated stimulation of duodenal vagal afferents, explaining dyspeptic symptom generation. The mechanisms underlying elevated mucosal CCK release warrant further investigation.

Cholecystokinin revisited: CCK and the hunger trap in anorexia nervosa.

OBJECTIVE: Despite a number of studies in the past decades, the role of Cholecystokinin (CCK) in anorexia nervosa (AN) has remained uncertain. In this study a highly specific assay for the biologically active part of CCK was used in patients with bulimic as well as with the restricting type of AN who were followed over the course of weight gain. METHODS: Ten patients with restricting and 13 with bulimic AN were investigated upon admission (T0), after a weight gain of at least 2 kg on two consecutive weighting dates (T1), and during the last week before discharge (T2) from inpatient treatment in a specialized clinic. Blood samples were drawn under fasting conditions and 20 and 60 minutes following a standard meal (250 kcal). Data were compared to those of eight controls matched for sex and age. Gastrointestinal complaints of patients were measured by a questionnaire at each of the follow-up time points. RESULTS: At admission, AN patients exhibited CCK-levels similar to controls both prior to and after a test meal. Pre and post-meal CCK levels increased significantly after an initial weight gain but decreased again with further weight improvement. CCK release was somewhat lower in bulimic than in restricting type AN but both subgroups showed a similar profile. There was no significant association of CCK release to either initial weight or BMI, or their changes, but CCK levels at admission predicted gastrointestinal symptom improvement during therapy. CONCLUSIONS: Normal CCK profiles in AN at admission indicates hormonal responses adapted to low food intake while change of eating habits and weight gain results in initially increased CCK release (counteracting the attempts to alter eating behavior) that returns towards normal levels with continuous therapy.

Influence of acute exposure to high altitude on basal and postprandial plasma levels of gastroenteropancreatic peptides.

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.

Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men.

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

Subjective and biological weight-related parameters in adolescents and young adults with schizophrenia spectrum disorder under clozapine or olanzapine treatment.

OBJECTIVE: Administration of atypical antipsychotics often induces significant weight gain and metabolic changes. Little is known about subjective weight-related parameters in adolescent patients. Therefore, this cross-sectional, explorative study aimed to assess these parameters and their relationship with biological weight-related parameters. METHOD: 74 patients (mean age: 19.9 [SD ± 2.3] years; 66.2% male) with schizophrenia under clozapine or olanzapine treatment were examined. Subjective well-being, eating behavior, body perception and social functioning were assessed, using the Three-Factor-Eating-Questionnaire, FKB-20 Body Perception Questionnaire, Subjective Well-being under Neuroleptics, Short Form and Global Assessment of Functioning. Patients' biological weight-related parameters were measured as well. Gender differences as well as associations between subjective and biological weight-related parameters were evaluated. RESULTS: Female patients reported significantly worse negative body appraisal and physical functioning than males. An elevated BMI was associated with impaired physical functioning in females and with negative body appraisal and hunger in males. CONCLUSIONS: In our sample of young patients with schizophrenia unter treatment with atypical antipsychotics, an elevated BMI was associated with impaired physical functioning and negative body appraisal, respectively. Bearing in mind the high risk of obesity in this population, the mentioned impairments should be accounted for, especially in terms of compliance and quality of life.

Altered psychobiological responsiveness in women with irritable bowel syndrome.

OBJECTIVE: Although stress has been considered an important pathophysiological factor in irritable bowel syndrome (IBS), there is incomplete understanding of its physiological mechanisms. The current study was designed to compare diurnal hypothalamic-pituitary-adrenal (HPA) axis activity in IBS patients and controls and their psychobiological response to a psychosocial stressor. METHODS: Basal and stimulated HPA axis activity was assessed in 57 women with IBS and 20 matched controls. Psychiatric comorbidity was assessed using a standardized clinical interview. Salivary morning cortisol and diurnal profile were obtained, and the Trier Social Stress Test (TSST) was administered. Levels of cortisol and adrenocorticotropic hormone (ACTH) were measured before and within 1 hour after the stressor. Overall stress experience and stress related to the TSST were assessed using standardized questionnaires. RESULTS: All subjects showed intact circadian variation of cortisol. However, IBS patients with predominant diarrhea exhibited substantially heightened cortisol levels at awakening (p < .03) and a blunted cortisol awakening response. In response to the TSST, patients exhibited significantly blunted cortisol (p < .05) and slightly attenuated ACTH secretion compared with controls. During the recovery period, ACTH levels were significantly lower (p < .04) in patients than those in healthy subjects. Women with IBS perceived higher stress susceptibility than control subjects did (p < .01). CONCLUSIONS: The enhanced morning cortisol levels in one subgroup of IBS patients may indicate an association between basal HPA axis activity and predominant bowel habit. The downregulated HPA axis reactivity in IBS after the TSST suggests a downregulated sensitivity of the endocrine system. On the contrary, all subjective stress ratings were increased in the IBS group, which may indicate increased stress susceptibility.

Slowly and rapidly digested fat emulsions are equally satiating but their triglycerides are differentially absorbed and metabolized in humans.

Little is known about the effect of dietary fat emulsion microstructure on plasma TG concentrations, satiety hormones, and food intake. The aim of this study was to structure dietary fat to slow digestion and flatten postprandial plasma TG concentrations but not increase food intake. Emulsions were stabilized by egg lecithin (control), sodium sterol lactylate, or sodium caseinate/monoglyceride (CasMag) with either liquid oil or a liquid oil/solid fat mixture. In a randomized, double-blind, crossover design, 4 emulsions containing 30 g of fat in a 350-mL preload were consumed by 10 men and 10 women (BMI = 25.1 ± 2.8 kg/m(2); age = 58.8 ± 4.8 y). Pre- and postprandial plasma TG, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) concentrations and food intake were measured. In a second experiment in a subset of the participants (n = 8, 4 men and 4 women), (13)C-labeled mixed TG was incorporated into 2 different emulsions and breath (13)C was measured over 6 h. In the first experiment, the postprandial rise in plasma TG concentrations following the CasMag-stabilized emulsion containing 30% solid fat was lower than all other emulsions at 90 and 120 min (P < 0.05). Plasma CCK (P < 0.0001), GLP-1 (P < 0.01), and PYY (P < 0.001) concentrations were also reduced following this emulsion compared with control. Food intake at a test meal, eaten 3 h after the preload, did not differ among the emulsions. In the second experiment, when measured by the (13)C breath test, 25% of the TG in the CasMag emulsion was absorbed and metabolized compared with control. In conclusion, fat can be structured to decrease its effect on plasma TG concentrations without increasing food intake.

Marked differences in gustatory and gastrointestinal sensitivity to oleic acid between lean and obese men.

BACKGROUND: Both orosensory stimulation and feedback from the gastrointestinal tract contribute to energy intake regulation. OBJECTIVE: We evaluated the hypothesis that overweight or obese subjects would be less sensitive to both oral and intraduodenal oleic acid exposure than would lean subjects. DESIGN: Eleven overweight or obese and 8 lean men were studied on 2 occasions, during which antropyloroduodenal pressures, plasma cholecystokinin and peptide YY, and appetite were measured during 90-min intraduodenal infusions of saline or oleic acid (18:1 load: 0.78 kcal/min); energy intake (buffet lunch) was determined immediately afterward. Oral detection thresholds for 18:1 and recent dietary intake (2-d recall) were also quantified. RESULTS: In lean subjects, the number of isolated pyloric pressure waves (IPPWs) was greater during 18:1 infusion than during saline infusion (P < 0.05); no significant differences were observed between the 18:1 and saline infusions in the overweight or obese subjects. In both groups, 18:1 stimulated plasma cholecystokinin and peptide YY and suppressed energy intake compared with saline (P < 0.05), with trends for reduced cholecystokinin and energy intake responses in the overweight or obese subjects. Detection thresholds for 18:1 were greater in overweight or obese (7.9 ± 0.1 mmol/L) than in lean (4.1 ± 0.4 mmol/L) subjects (P < 0.05). Overweight or obese subjects had greater recent energy (P < 0.05) and fat (P = 0.07) intakes than did lean subjects. There was a direct relation (r = 0.669) of body mass index with 18:1 detection thresholds and inverse relations (r < -0.51) of IPPWs with body mass index and 18:1 detection thresholds (P < 0.05). CONCLUSIONS: The ability to detect oleic acid both orally and within the gastrointestinal tract is compromised in obese men, and oral and gastrointestinal responses to oleic acid are related. This trial was registered at www.actr.org.au (Australian New Zealand Clinical Trials Registry) as 12609000557235.

Hypobaric hypoxia causes body weight reduction in obese subjects.

The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 +/- 4.1 years, BMI 33.7 +/- 1.0 kg/m(2)). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1-week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure.

Effect of meglitinides on postprandial ghrelin secretion pattern in type 2 diabetes mellitus.

BACKGROUND: A progressive weight gain is associated with various pharmacological options improving glycemic control in type 2 diabetes mellitus (T2DM). Ghrelin has been implicated in the regulation of feeding behavior and energy balance in humans. Based on evidence that functional ATP-sensitive channels are present in ghrelin-producing cells, we hypothesized that meglitinides may affect circulating ghrelin levels in subjects with type 2 diabetes. METHODS: In a single-blinded randomized three-period crossover study (n = 20), repaglinide or nateglinide was given in combination with metformin for two treatment periods over a 1-week period, respectively, separated by a 1-week treatment with placebo. Liquid meal challenge tests (LMCTs) with single preprandial doses of repaglinide (2 mg), nateglinide (120 mg), or placebo were performed at the end of each treatment period. Ten control subjects without diabetes underwent a single LMCT without any medication. RESULTS: Fasting ghrelin concentrations were not different between all treatments and between patients with diabetes and control subjects. Subjects with T2DM treated with placebo showed no suppression of ghrelin in the LMCT. After administration of meglitinides a nadir of serum ghrelin was observed at 60 min (8.6% of baseline [P = 0.038] for repaglinide and 7.5% of baseline [P = 0.081] for nateglinide), which was similar to the secretion pattern seen in control subjects. No correlations between postprandial insulin or glucose levels and circulating ghrelin concentrations were observed. CONCLUSIONS: Treatment with meglitinides reconstructed postprandial ghrelin secretion patterns to those of controls without diabetes. This observation may help to improve the control of feeding behavior in patients with T2DM.

The droplet size of intraduodenal fat emulsions influences antropyloroduodenal motility, hormone release, and appetite in healthy males.

BACKGROUND: The presence of fat in the small intestine modulates gastrointestinal motility, stimulates plasma cholecystokinin and peptide YY release, and suppresses appetite and energy intake. These effects are dependent on the lipolysis of fat. OBJECTIVE: Our aim was to evaluate the hypothesis that increasing the droplet size of a fat emulsion would attenuate these effects. DESIGN: Ten healthy, lean males were studied on 4 separate occasions in single-blind randomized order. Antropyloroduodenal pressures, plasma triglycerides, cholecystokinin, peptide YY, and appetite were measured during 120-min intraduodenal infusions of fat emulsions comprising 3 different droplet sizes: 1) 0.26 microm (LE-0.26), 2) 30 microm (LE-30), and 3) 170 microm (LE-170) in addition to saline (control). Energy intake at a buffet lunch was quantified immediately after the infusions. RESULTS: Increasing the droplet size of the lipid emulsion was associated with diminished suppression of antral (r = 0.75, P < 0.01) and duodenal (r = 0.80, P < 0.01) pressure waves and with stimulation of isolated (r = -0.72, P < 0.01) and basal (r = -0.83, P < 0.01) pyloric pressures. Increasing the droplet size was also associated with attenuation of the stimulation of plasma triglycerides (r = -0.73, P < 0.001), cholecystokinin (r = -0.73, P < 0.001), and peptide YY (r = -0.83, P < 0.001) as well as with reductions in the suppression of hunger (r = 0.75, P < 0.01) and energy intake (r = 0.66, P < 0.001). CONCLUSIONS: The acute effects of intraduodenal fat emulsions on gastrointestinal function and appetite are dependent on fat droplet size. These observations have implications for the design of functional foods to maximize effects on those gut functions that are involved in the suppression of appetite.

Effects of two whole blood systems (DALI and Liposorber D) for LDL apheresis on lipids and cardiovascular risk markers in severe hypercholesterolemia.

LDL apheresis is an extracorporal modality to lower the concentration of atherogenic lipoproteins, e.g., LDL cholesterol. We compared two recently introduced whole-blood LDL apheresis systems inpatients with hypercholesterolemia in a randomized cross-over trial with respect to their effects on lipoproteins as well as on other cardiovascular risk markers. Six patients (4 women, 2 men, median age 62.5 years, median BMI 25.9 kg/m(2)) on regular LDL apheresis were randomly assigned to receive six weekly treatments with either DALI (Fresenius) or Liposorber D (Kaneka). After 6 weeks, the patients were switched to the other device (again six weekly treatments). Blood was drawn before and immediately after LDL apheresis at three time points (last regular apheresis before the study; after six treatments with DALI and after six treatments with Liposorber D). LDL cholesterol concentration before the sixth apheresis (DALI 129 mg/dL, Liposorber D 132 mg/dL) as well as LDL cholesterol reduction during the sixth apheresis (DALI 68.3% and Liposorber D 68.4%) were similar with the two systems. CRP and fibrinogen concentrations were lower but interleukin-6, myeloperoxidase, and resistin concentrations were higher after the last Liposorber treatment compared with DALI (P < 0.05, respectively). No differences were observed concerning adiponectin, ghrelin, and PYY levels. In conclusion, both devices were highly effective in eliminating atherogenic lipoproteins. CRP and fibrinogen were better eliminated with Liposorber D. However, following Liposorber D, interleukin-6 levels were higher than after DALI possibly indicating an increased inflammatory activation.

Intravenous CCK-8, but not GLP-1, suppresses ghrelin and stimulates PYY release in healthy men.

We have investigated the effects of exogenous CCK-8 and GLP-1, alone and in combination, on ghrelin and PYY secretion. Nine healthy males were studied on four occasions. Plasma ghrelin and PYY concentrations were measured during 150 min intravenous infusions of: (i) isotonic saline, (ii) CCK-8 at 1.8 pmol/kg/min, (iii) GLP-1 at 0.9 pmol/kg/min or (iv) CCK-8 and GLP-1 combined. CCK-8 markedly suppressed ghrelin and stimulated PYY when compared with control between t=0-120 min (P<0.001 for both). GLP-1 had no effect on ghrelin, but decreased PYY slightly at 120 min (P<0.05). During infusion of CCK-8+GLP-1, there was comparable suppression of ghrelin (P<0.001), but the stimulation of PYY was less (P<0.001), than that induced by CCK-8, between t=20-120 min. In conclusion, in healthy subjects, in the doses evaluated, exogenous CCK-8 suppresses ghrelin and stimulates PYY, and exogenous GLP-1 has no effect on ghrelin and attenuates the effect of CCK-8 on PYY.

Wheat-fibre-induced changes of postprandial peptide YY and ghrelin responses are not associated with acute alterations of satiety.

Weight gain and risk of type 2 diabetes are inversely associated with a high intake of insoluble cereal fibres. Because nutrient-induced changes of 'satiety hormones' from the gut may play a role in this process, we evaluated the effects of purified insoluble fibres on postprandial responses of plasma peptide YY (PYY), serum ghrelin and satiety as secondary outcome measures of a study investigating effects of cereal fibres on parameters of glucose metabolism. Fourteen healthy women were studied on six occasions in a randomized, single-blind, controlled crossover design. After 24 h run-in periods and 10 h overnight fasts, subjects ingested isoenergetic and macronutrient matched portions of control white bread or fibre-enriched bread (wheat-fibre or oat-fibre) at 08.15 hours. Gut hormones and hunger scores were measured for 300 min. Basal PYY and ghrelin concentrations were not different between the test meals (P>0.15). Postprandial responses of PYY and ghrelin were blunted after the intake of wheat-fibre (total area under the curve (AUC) PYY, 177.9 (SEM 8.1) (pmol/l) min; P=0.016; ghrelin 51.0 (SEM 2.5) (pmol/l) min; P=0.003), but not after oat-fibre (PYY 226.7 (SEM 25.7) (pmol/l) min; P>0.15; ghrelin 46.2 (SEM 1.6) (pmol/l) min; P=0.127), compared to control (PYY 247.5 (SEM 25.6) (pmol/l) min; ghrelin 42.5 (SEM 1.3) (pmol/l) min). Postprandial hunger scores were unaffected by the different test meals (P>0.15). Thus, oat- and wheat-fibre consumption result in different postprandial responses of PYY and ghrelin, but interestingly do not differ in satiety effects.