Increased glucose-stimulated FGF21 response to oral glucose in obese nondiabetic subjects after Roux-en-Y gastric bypass.

OBJECTIVE: The positive metabolic outcome of Roux-en-Y gastric bypass (RYGB) surgery may involve fibroblast growth factor 21 (FGF21), in both the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal. DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Eight obese, nondiabetic patients underwent RYGB. Plasma FGF21 was measured both before and after surgery on three different days during oral glucose loads (25 g or 50 g glucose) or a mixed meal. Blood samples were taken right before the meal and at 15-min intervals until 90 min and at 150 min and 210 min relative to the start of the meal. RESULTS: Overall, fasting plasma FGF21 did not change significantly before and after surgery (262 ± 71 vs 411 ± 119 pg/ml), but for three subjects, fasting plasma FGF21 increased significantly after surgery. Furthermore, FGF21 levels increased significantly at t = 90 and t = 150 min in response to 50 g glucose, but not after a mixed meal. CONCLUSIONS: In conclusion, the observed increase in postprandial plasma FGF21 in response to glucose and the lack of FGF21 response to a mixed meal may have important implications for the physiologic role of FGF21. The increase in postprandial FGF21 in response to glucose in the early postoperative period may contribute to the metabolic improvements observed after gastric bypass.

Central 5-HT neurotransmission modulates weight loss following gastric bypass surgery in obese individuals.

The cerebral serotonin (5-HT) system shows distinct differences in obesity compared with the lean state. Here, it was investigated whether serotonergic neurotransmission in obesity is a stable trait or changes in association with weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery. In vivo cerebral 5-HT2A receptor and 5-HT transporter binding was determined by positron emission tomography in 21 obese [four men; body mass index (BMI), 40.1 ± 4.1 kg/m(2)] and 10 lean (three men; BMI, 24.6 ± 1.5 kg/m(2)) individuals. Fourteen obese individuals were re-examined after RYGB surgery. First, it was confirmed that obese individuals have higher cerebral 5-HT2A receptor binding than lean individuals. Importantly, we found that higher presurgical 5-HT2A receptor binding predicted greater weight loss after RYGB and that the change in 5-HT2A receptor and 5-HT transporter binding correlated with weight loss after RYGB. The changes in the 5-HT neurotransmission before and after RYGB are in accordance with a model wherein the cerebral extracellular 5-HT level modulates the regulation of body weight. Our findings support that the cerebral 5-HT system contributes both to establish the obese condition and to regulate the body weight in response to RYGB.

Effects of RYGB on energy expenditure, appetite and glycaemic control: a randomized controlled clinical trial.

OBJECTIVES: Increased energy expenditure (EE) has been proposed as an important mechanism for weight loss following Roux-en-Y gastric bypass (RYGB). However, this has never been investigated in a controlled setting independent of changes in energy balance. Similarly, only few studies have investigated the effect of RYGB on glycaemic control per se. Here, we investigated the effect of RYGB on EE, appetite, glycaemic control and specific signalling molecules compared with a control group in comparable negative energy balance. SUBJECTS/METHODS: Obese normal glucose-tolerant participants were randomized to receive RYGB after 8 (n=14) or 12 weeks (n=14). The protocol included a visit at week 0 and three visits (weeks 7, 11 and 78) where 24-h EE, appetite and blood parameters were assessed. Participants followed a low-calorie diet from weeks 0-11, with those operated at week 12 serving as a control group for those operated at week 8. RESULTS: Compared with controls, RYGB-operated participants had lower body composition-adjusted 24-h EE and basal EE 3 weeks postoperatively (both P<0.05) but EE parameters at week 78 were not different from preoperative values (week 7). Surgery changed the postprandial response of glucagon-like peptide-1 (GLP-1), peptide YY3-36 (PYY), ghrelin, cholecystokinin, fibroblast growth factor-19 and bile acids (all P<0.05). Particularly, increases in GLP-1, PYY and decreases in ghrelin were associated with decreased appetite. None of HOMA-IR (homeostasis model assessment-estimated insulin resistance), Matsuda index, the insulinogenic index, the disposition index and fasting hepatic insulin clearance were different between the groups, but RYGB operated had lower fasting glucose (P<0.05) and the postprandial glucose profile was shifted to the left (P<0.01). CONCLUSIONS: Our data do not support that EE is increased after RYGB. More likely, RYGB promotes weight loss by reducing appetite, partly mediated by changes in gastrointestinal hormone secretion. Furthermore, we found that the early changes in glycaemic control after RYGB is to a large extent mediated by caloric restriction.

Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass.

OBJECTIVE: To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB). DESIGN: Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender. MATERIALS AND METHODS: Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3-36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite. RESULTS: Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition. CONCLUSION: Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) greatly improves glycaemic control in morbidly obese patients with type 2 diabetes, in many even before significant weight loss. Understanding the responsible mechanisms may contribute to our knowledge of the pathophysiology of type 2 diabetes and help identify new drug targets or improve surgical techniques. This review summarises the present knowledge based on pathophysiological studies published during the last decade. Taken together, two main mechanisms seem to be responsible for the early improvement in glycaemic control after RYGB: (1) an increase in hepatic insulin sensitivity induced, at least in part, by energy restriction and (2) improved beta cell function associated with an exaggerated postprandial glucagon-like peptide 1 secretion owing to the altered transit of nutrients. Later a weight loss induced improvement in peripheral insulin sensitivity follows.

Implementation of robot-assisted groin hernia repair diminishes the prospects of young surgeons' training: a nationwide register-based cohort study.

PURPOSE: Robot-assisted groin hernia repair is becoming more popular in recent years but may remove operations from surgical trainees. We aimed to investigate the educational level of the surgeons who performed robot-assisted groin hernia repair and the rate of supervision and compare this to open and laparoscopic groin hernia repair. METHODS: This register-based study was reported according to the RECORD statement and used linked data from the Danish Hernia Database and the Danish Patient Safety Authority's Online Register. We included surgeons that performed robot-assisted, laparoscopic, and/or open groin hernia repairs performed between January 1, 2015, and June 15, 2021 in Denmark. RESULTS: A total of 916 surgeons performing 43,856 groin hernia repairs were included in this study. Surgical specialists performed 98% of the robot-assisted groin hernia repairs, 89% of the laparoscopic repairs (p < 0.0001), and 54% of the Lichtenstein repairs (p < 0.0001). Only 5% of the robot-assisted groin hernia repairs were supervised compared with 11% of the laparoscopic repairs (p < 0.0001) and 28% of the open repairs (p < 0.0001). CONCLUSION: Almost all groin hernia repairs performed with the robot-assisted technique were performed by surgeons specialized in general surgery. The proportions of surgeons specialized in surgery were higher for robot-assisted operations compared with laparoscopic or open groin hernia surgery. Thus, our data suggest a lack of involvement of surgeons in training, and this diminishes the educational potential in the pool of groin hernia operations by the use of robot-assisted repairs.

Cerebral serotonin transporter binding is inversely related to body mass index.

Overweight and obesity is a health threat of increasing concern and understanding the neurobiology behind obesity is instrumental to the development of effective treatment regimes. Serotonergic neurotransmission is critically involved in eating behaviour; cerebral level of serotonin (5-HT) in animal models is inversely related to food intake and body weight and some effective anti-obesity agents involve blockade of the serotonin transporter (SERT). We investigated in 60 healthy volunteers body mass index (BMI) and regional cerebral SERT binding as measured with [(11)C]DASB PET. In a linear regression model with adjustment for relevant covariates, we found that cortical and subcortical SERT binding was negatively correlated to BMI (-0.003 to -0.012 BP(ND) unit per kg/m(2)). Tobacco smoking and alcohol consumption did not affect cerebral SERT binding. Several effective anti-obesity drugs encompass blockade of the SERT; yet, our study is the first to demonstrate an abnormally decreased cerebral SERT binding in obese individuals. Whether the SERT has a direct role in the regulation of appetite and eating behaviour or whether the finding is due to a compensatory downregulation of SERT secondary to other dysfunction(s) in the serotonergic transmitter system, such as low baseline serotonin levels, remains to be established.

Comparison of image quality in chest, hip and pelvis examinations between mobile equipment in nursing homes and static indirect radiography equipment in the hospital.

INTRODUCTION: A hospital environment can be a significant burden and a health risk especially for dementia patients. Mobile x-ray equipment (ME) is used to enable imaging of these patients at home. The aim was to compare image quality (IQ) of chest, hip and pelvis images from ME to the stationary equipment (SE) used in a hospital department. METHODS: We analysed examinations of the chest (n = 20), hip (n = 64) and pelvis (n = 32). Images were equally obtained from each setting of ME and SE. All images were graded using Visual Grading Analysis (VGA) by three radiographers (hip and pelvis) and three radiologists (chest). Technical IQ assessment was done by 80 additional images of a Contrast-Detail Radiography phantom (CDRAD). RESULTS: All chest images were approved for diagnostic use, as well as the hip AP and pelvis images from SE. 'Approved proportion of ME images was for HIP antero-posterior (AP) and pelvis, 78% [95% CI: 52-94%] and 81% [95% CI: 54-96%] respectively. Hip axial had an overall low, but not significant different approval rate. Ordered logistic regression indicated higher IQ of HIP AP and pelvic images from SE. This contrasts that the CDRAD substudy indicated better IQ, expressed as IQFinv, from ME. CONCLUSION: The VGA showed higher IQ for the SE system, while the CDRAD showed higher IQ for the ME system. IMPLICATIONS FOR PRACTICE: Dementia patients can be examined at their home if the acquisition is optimised according to image quality in conjunct to radiation dose. Performing imaging out of the hospital and coordinating the patients' further treatment are new work areas for radiographers and requires excellent communication skills.

Thermogenic effects of sibutramine in humans.

BACKGROUND: Sibutramine is an effective compound for the treatment of obesity, acting both on serotonergic and noradrenergic pathways. Animal studies have shown that sibutramine exerts its effect by enhancing satiety as well as by increasing thermogenesis. OBJECTIVE: We tried to compare the acute thermogenic effect of a single 30-mg dose of sibutramine with placebo on basal energy expenditure (EE) and diet-induced thermogenesis. DESIGN: The study was randomized, double-blind, and placebo controlled. Eleven healthy, normal-weight men underwent 4 distinct treatment regimens separated by washout periods of 6-10 d. EE was measured by indirect calorimetry before and for 5.5 h after sibutramine or placebo administration with or without a 2.1-MJ breakfast. Visual analogue scales for assessment of appetite were completed hourly. RESULTS: Sibutramine caused a significant increase in EE above that for placebo (over 5.5 h) during both the fed (34%, 0.15 kJ/min) and fasted (183%, 0.20 kJ/min) states (P < 0.02) as well as during the last 3.5 h of this 5.5-h period and in the fed (87%, 0.26 kJ/min) and fasted (152%, 0.22 kJ/min) states, respectively (P < 0.01). The sibutramine-induced increase in EE was accompanied by an increase in plasma epinephrine (P < 0.01), heart rate (P < 0.001), blood pressure (P < 0.05), and plasma glucose (P < 0.02). About 25% of the increased heart rate with sibutramine could be explained by increased thermogenesis. Sibutramine increased satiety more than did placebo (5-h area under the curve, P < 0.05). CONCLUSIONS: Sibutramine caused a significant increase in both EE and satiety, which may both contribute to its weight-reducing properties.

[The effect of sibutramine for the maintenance of weight loss. A randomized controlled clinical trial]. / Effekt af sibutramin til vaegttabsvedligeholdelse. En randomiseret klinisk kontrolleret undersøgelse.

INTRODUCTION: Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 18 months. METHODS: Eight European centres recruited 605 obese patients (BMI 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) in combination with an individualised dietary deficit programme of 600 kcal/day based on the measured resting rates of energy expenditure. Of these 605, 467 (77%) patients with more than a 5% weight loss were then randomly assigned to 10 mg/day sibutramine (n = 352) or placebo (n = 115) for a further 18 months. Sibutramine was increased up to 20 mg/day if a weight regain occurred. RESULTS: One hundred and forty-eight (42%) subjects in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 subjects receiving sibutramine who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 subjects in the placebo group (odds ratio 4.64, p < 0.001). Substantial decreases were seen over the first six months in triglycerides, VDL cholesterol, insulin, C peptide, and uric acid; changes, which were sustained in the sibutramine group, but not in the placebo group. Concentrations of HDL cholesterol rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p < 0.001). Twenty (3%) patients were withdrawn because of raised blood pressure; in the sibutramine group, from baseline to two years systolic blood pressure rose by 0.1 mmHg (SD 12.9), diastolic blood pressure by 2.3 mmHg (9.4), and pulse rate by 4.1 beats/min (11.9). CONCLUSION: This individualised management programme achieved a weight loss in 77% of obese patients and a sustained weight loss in most patients continuing therapy for two years. Changes in the concentrations of HDL cholesterol, VDL cholesterol, and triglyceride, but not in the LDL cholesterol, exceed those expected either from a weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease.

Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) causes extensive changes in gastrointestinal anatomy and leads to reduced appetite and large weight loss, which partly is due to an exaggerated release of anorexigenic gut hormones. METHODS: To examine whether the altered passage of foods through the gastrointestinal tract after RYGB could be responsible for the changes in gut hormone release, we studied gastrointestinal motility with a scintigraphic technique as well as the secretion of the gut hormones glucagon-like peptide (GLP)-1 and peptide YY3-36 (PYY3-36 ) in 17 patients>1 year after RYGB and in nine healthy control subjects. KEY RESULTS: At meal completion, a smaller fraction of liquid and solid radiolabeled marker was retained in the pouch of RYGB patients than in the stomach of control subjects (P = 0.002 and P < 0.001, respectively). Accordingly, pouch emptying in patients was faster than gastric emptying in control subjects (P < 0.001 and P = 0.004, respectively liquid and solid markers). For the solid marker, small intestinal transit was slower in patients than control subjects (P = 0.034). Colonic transit rate did not differ between the groups. GLP-1 and PYY3-36 secretion was increased in patients compared to control subjects and fast pouch emptying of the liquid marker was associated with high gut hormone secretion. CONCLUSIONS & INFERENCES: After RYGB, the bulk of foods pass without hindrance into the small intestine, while the small intestinal transit is prolonged. The rapid exposure of the gut epithelium contributes to the exaggerated release of GLP-1 and PYY3-36 after RYGB.

Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping). METHODS: We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance. RESULTS: Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests. CONCLUSIONS: Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

Sibutramine and energy balance.

Obesity develops from a combination of low energy expenditure and increased energy intake. The current treatment strategy aims at reducing energy intake by a low-fat, high-complex-carbohydrate diet and increasing energy expenditure by increased physical activity. In a major proportion of obese patients, however, this treatment is ineffective and does not produce a satisfactory long-term result. Among the risk factors for weight gain and for an unsuccessful diet-induced weight loss in obese patients is a low metabolic rate, which can be attributed in part to a low sympathetic nervous system (SNS) activity. The low SNS activity may also have an adverse effect on appetite control. Pharmacological enhancement of the SNS may have a role in the normalization of the autonomic control of the disturbed energy balance in obesity. In animal studies, sibutramine causes a negative fat balance and weight loss, by a dual mechanism of action. Sibutramine enhances satiety by a combined noradrenergic and serotonergic effect, thus decreasing food intake. In addition, sibutramine stimulates thermogenesis by activating the SNS. Recent studies have demonstrated that sibutramine also enhances satiety, stimulates thermogenesis and diminishes the weight-loss induced decline in energy expenditure in humans, so the dual effect on energy balance seems to be responsible for the efficient fat loss and weight maintenance found in clinical trials on obese patients. In conclusion, sibutramine can contribute to normalization of the disturbed energy balance in obesity, by enhancing satiety and by the stimulation of energy expenditure.

The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction.

OBJECTIVE: To assess the contribution of a thermogenic effect to weight loss induced by eight weeks treatment with sibutramine (15mg/d) vs placebo in obese subjects. DESIGN: Randomised, placebo controlled, double blind study. SUBJECTS: Thirty-two (7 male, 25 female) healthy obese body mass index (BMI) 33.9+/-0.5 kg/m2 subjects completed the trial. MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry during a 32 h stay in a respiration chamber before and after 8 weeks treatment. Visual analogue scales were completed for assessment of appetite sensation. No dietary restriction was given. RESULTS: Sibutramine caused a significant weight loss compared with placebo (-2.4 kg vs+0.3 kg, P<0.001). Despite the larger weight loss after 8 weeks, 24-h EE did not decrease more in the sibutramine than in the placebo group (-2. 6% vs -2.5%, P=ns). When the changes in 24-h EE were adjusted for changes in body weight, 24-h EE decreased significantly less in the sibutramine group than in the placebo group (0.8% vs 3.8%, P<0.02). Sibutramine significantly decreased both hunger and anticipated food consumption, and increased satiety scores. CONCLUSIONS: The weight reducing effect of sibutramine in humans is caused by a dual mechanism: reduction of energy intake by increasing satiety and decreasing hunger and prevention of the decline in EE that follows weight loss.

Anionic photofragmentation of CO: a selective probe of core-level resonances.

Anion-yield spectroscopy using x rays is shown to be a selective probe of molecular core-level processes, providing unique experimental verification of shape resonances. For CO, partial anion and cation yields are presented for photon energies near the C K edge. The O- yield exhibits features above threshold related only to doubly excited states, in contrast to cation yields which also exhibit pronounced structure due to the well-known sigma* shape resonance. Because the shape resonance is completely suppressed for O-, anion spectroscopy thus constitutes a highly selective probe, yielding information unobtainable with absorption or electron spectroscopy.