Patient-Reported Long-Term Outcome is Superior After Treatment with Self-Expanding Metallic Stents in Esophageal Perforations.

BACKGROUND AND AIMS: Esophageal perforations are life threatening. Since the 1990s, placing of covered esophageal stents has become an alternative to surgery. Theoretically, this minimally invasive approach has several benefits; however, little data are available on long-term outcome in these patients. We aimed to evaluate how patient-reported outcome differed between full surgery and placement of self-expanding metallic stents when treating primary benign esophageal perforations. MATERIAL AND METHODS: Of 48 patients treated at our hospital in 2000-2015, 23 were alive and asked to answer three questionnaires. We used a short clinical questionnaire, the QLQ-OG25 from the European Organization for Research and Treatment of Cancer and a simplified quality-of-life instrument, the Check Your Health. Non-parametric statistics were used to evaluate differences between the two groups. RESULTS: In all, 20 (87%) individuals (13 men, 64 years of age) responded. At survey, surgical patients had lost 13 kg of initial weight, compared to no weight loss in the self-expanding metallic stents group (p = 0.01). This involuntary weight loss worried patients according to the QLQ-OG25; otherwise patient-experience measures did not differ between groups. For quality of life, surgical patients scored significantly lower physical health, emotional well-being, social functioning, and overall quality of life after treatment, but after stenting no differences were seen. CONCLUSIONS: In contrast to stenting, surgical treatment was associated with involuntary, and worrisome, weight loss as well as reduced quality of life. We therefore believe that self-expanding metallic stents should be used when possible in treating benign esophageal perforations.

Safe Introduction of Minimally Invasive Esophagectomy at a Medium Volume Center.

BACKGROUND AND AIMS: Minimally invasive esophagectomy is a favored alternative in high-volume centers. We evaluated the introduction of, and transition to, minimally invasive esophagectomy at a medium volume tertiary referral center (10-20 esophagectomies annually) with focus on surgical results. MATERIAL AND METHODS: Patients who underwent minimally invasive esophagectomy or open transthoracic surgery for carcinoma of the esophagus or gastroesophageal junction (Siewert I and II) during 2007-2016 were retrospectively studied. Sorted on surgical approach, perioperative data, surgical outcomes, and postoperative complications were analyzed and multivariate regression models were used to adjust for possible confounders. RESULTS: One hundred and sixteen patients were included, 51 minimally invasive esophagectomy (21 hybrid and 30 totally minimally invasive) and 65 open resections. The groups were well matched. However, higher body mass index, neoadjuvant chemoradiotherapy, and cervical anastomosis were more frequent in the minimally invasive esophagectomy group. Minimally invasive esophagectomy was associated with less peroperative bleeding (384 vs 607 mL, p = 0.036) and reduced length of stay (14 vs 15 days, p = 0.042). Duration of surgery, radical resection rate, and postoperative complications did not differ between groups. Lymph node yield was higher in the minimally invasive esophagectomy group, 18 (13-23) vs 12 (8-16), p < 0.001, confirmed in a multivariate regression model (adjusted odds ratio 3.15, 95% class interval 1.11-8.98, p = 0.032). CONCLUSION: The introduction of minimally invasive esophagectomy at a medium volume tertiary referral center resulted in superior lymph node yield, less peroperative blood loss and shorter length of stay, without compromising the rate of radical resection, or increasing the complication rate.

Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women.

Cardiometabolic diseases are primarily linked to enlarged visceral adipose tissue (VAT). However, some data suggest heterogeneity within the subcutaneous adipose tissue (SAT) depot with potential metabolic differences between the superficial SAT (sSAT) and deep SAT (dSAT) compartments. We aimed to investigate the heterogeneity of these three depots with regard to fatty acid (FA) composition and gene expression. Adipose tissue biopsies were collected from 75 obese women undergoing laparoscopic gastric bypass surgery. FA composition and gene expression were determined with gas chromatography and quantitative real-time-PCR, respectively. Stearoyl CoA desaturase-1 (SCD-1) activity was estimated by product-to-precursor FA ratios. All polyunsaturated FAs (PUFA) with 20 carbons were consistently lower in VAT than either SAT depots, whereas essential PUFA (linoleic acid, 18:2n-6 and α-linolenic acid, 18:3n-3) were similar between all three depots. Lauric and palmitic acid were higher and lower in VAT, respectively. The SCD-1 product palmitoleic acid as well as estimated SCD-1 activity was higher in VAT than SAT. Overall, there was a distinct association pattern between lipid metabolizing genes and individual FAs in VAT. In conclusion, SAT and VAT are two distinct depots with regard to FA composition and expression of key lipogenic genes. However, the small differences between sSAT and dSAT suggest that FA metabolism of SAT is rather homogenous.

Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver. METHODS: Ten morbidly obese women (BMI 42 ± 2.6 kg m-2 ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day-1 ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m-2 ) served as controls. RESULTS: At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. CONCLUSIONS: The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.

Large Buffering Effect of the Duodenal Bulb in Duodenal Switch: a Wireless pH-Metric Study.

INTRODUCTION: Bariatric procedures result in massive weight loss, however, not without side effects. Gastric acid is known to cause marginal ulcers, situated in the small bowel just distal to the upper anastomosis. We have used the wireless BRAVO™ system to study the buffering effect of the duodenal bulb in duodenal switch (DS), a procedure in which the gastric sleeve produces a substantial amount of acid. METHODS: We placed a pre- and a postpyloric pH capsule in 15 DS-patients (seven men, 44 years, BMI 33) under endoscopic guidance and verified the correct location by fluoroscopy. Patients were asked to eat and drink at their leisure, and to register their meals for the next 24 h. RESULTS: All capsules but one could be successfully placed, without complications. Total registration time was 17.2 (1.3-24) hours prepyloric and 23.1 (1.2-24) hours postpyloric, with a corresponding pH of 2.66 (1.74-5.81) and 5.79 (4.75-7.58), p < 0.01. The difference in pH between the two locations was reduced from 3.55 before meals to 1.82 during meals, p < 0.01. Percentage of time with pH < 4 was 70.0 (19.9-92.0) and 13.0 (0.0-34.6) pre and postpylorically, demonstrating a large buffering effect. CONCLUSION: By this wireless pH-metric technique, we could demonstrate that the duodenal bulb had a large buffering effect, thus counteracting the large amount of gastric acid passing into the small bowel after duodenal switch. This physiologic effect could explain the low incidence of stomal ulcers.

Use of Laparoscopy in Gastrointestinal Surgery in Sweden 1998-2014: A Nationwide Study.

BACKGROUND AND AIMS: One by one, minimally invasive alternatives to established gastrointestinal procedures have become clinical routine. We have studied the use of laparoscopy in four common procedures-cholecystectomy, appendectomy, reflux surgery, and bariatric surgery-as well as in major resectional gastrointestinal surgery in Sweden. MATERIALS AND METHODS: The National Patient Registry was used to identify all in-hospital procedures performed in patients above the age of 15 during 1998-2014, meeting our inclusion criteria. For each group, the annual number of procedures and proportion of laparoscopic surgery were studied, as well as applicable subgroups. Differences in age, gender, as well as geographical differences were evaluated in the most recent 3-year period (2012-2014). RESULTS: In total, 537,817 procedures were studied, 43% by laparoscopic approach. In 2012-2014, the proportion of laparoscopic surgery ranged from high rates in the four common procedures (cholecystectomy 81%, appendectomy 47%, reflux surgery 72%, and bariatric surgery 97%) to rather low numbers in resectional surgery (4%-10%), however, increasing in the last years. In appendectomy and cholecystectomy, men were less likely to have laparoscopic surgery (42% versus 51% and 74% versus 85%, respectively, p < 0.001). Substantial geographical differences in the use of laparoscopy were also noted, for example, the proportion of laparoscopic appendectomy varied from 11% to 76% among the 21 different Swedish counties. CONCLUSION: The proportion of laparoscopy was high in the four common procedures and low, but rising, in major resectional surgery. A large variation in the proportion of laparoscopic surgery by age, gender, and place of residence was noted.

Laparoscopy in Duodenal Switch: Safe and Halves Length of Stay in a Nationwide Cohort from the Scandinavian Obesity Registry.

BACKGROUND AND AIMS: Unsatisfactory weight loss after gastric bypass or sleeve gastrectomy in super-obese patients (body mass index > 50) is a growing concern. Biliopancreatic diversion with duodenal switch results in greater weight loss, but is technically challenging to perform, especially as a laparoscopic procedure (Lap-DS). The aim of this study was to compare perioperative outcomes of Lap-DS and the corresponding open procedure (O-DS) in Sweden. MATERIAL AND METHODS: The data source was a nationwide cohort from the Scandinavian Obesity Surgery Registry and 317 biliopancreatic diversion with duodenal switch patients (mean body mass index = 56.7 ± 6.6 kg/m2, 38.4 ± 10.2 years, and 57% females) were analyzed. Follow-up at 30 days was complete in 98% of patients. RESULTS: The 53 Lap-DS patients were younger than the 264 patients undergoing O-DS (35.0 vs 39.1 years, p = 0.01). Operative time was 163 ± 38 min for lap-DS and 150 ± 31 min for O-DS, p = 0.01, with less bleeding in Lap-DS (94 vs 216 mL, p < 0.001). There was one conversion to open surgery. Patients undergoing Lap-DS had a shorter length of stay than O-DS, 3.3 versus 6.6 days, p = 0.02. No significant differences in overall complications within 30 days were seen (12% and 17%, respectively). Interestingly, the two leaks in Lap-DS were located at the entero-enteric anastomosis, while three out of four leaks in O-DS occurred at the top of the gastric tube. CONCLUSION: Lap-DS can be performed by dedicated bariatric surgeons as a single-stage procedure. The use of laparoscopic approach halved the length of stay, without increasing the risk for complications significantly. Any difference in long-term weight result is pending.

Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake.

BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). METHODS: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m-2) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m-2), both before and 30 min after consumption of a standardized meal (~260 kcal). RESULTS: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups. CONCLUSION: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.

Gastrointestinal symptoms, weight loss and patient satisfaction 5 years after gastric bypass: a study of three techniques for the gastrojejunal anastomosis.

BACKGROUND: The optimal operative technique in gastric bypass (RYGB) is still under debate. We have studied patient-reported gastrointestinal symptoms and weight loss 5 years after RYGB performed with three different stapling techniques for the gastrojejunal anastomosis (GJ). METHODS: Out of 593 patients operated with RYGB, 489 patients [80.2% women, body mass index (BMI) 44.9 (33-68) kg/m(2)] answered our 5-year follow-up questionnaire concerning gastrointestinal symptoms (vomiting, reflux, dumping, abdominal pain or diarrhea), weight loss, need for postoperative endoscopic interventions and overall satisfaction with the procedure. We compared the results for three different GJ techniques: linear stapler (LS, n = 103), 21-mm circular stapler (C21, n = 88) and 25-mm circular stapler (C25, n = 298). RESULTS: Dumping was the most commonly reported symptom (14.1% of all patients on a weekly to daily basis), however, less frequently reported in the C25 group (p < 0.05). Vomiting, prevalent in 2.9% of all patients, was more frequently reported in the C21 group (p < 0.01). No group consistently showed greater weight loss compared to the other two groups. A higher incidence of endoscopic dilatations due to strictures was reported in the C21 group (12.5% compared to 4.5% of all patients, p < 0.05). Overall patient satisfaction was high (88%). CONCLUSION: Our data suggest that the technique for the construction of the GJ in RYGB affects gastrointestinal symptoms 5 years postoperatively. The difference is moderate but indicates that a narrow GJ results in increased frequency of vomiting and need for endoscopic interventions without improving the weight result.

Nitric oxide regulation of migrating motor complex: randomized trial of N(G)-monomethyl-L-arginine effects in relation to muscarinic and serotonergic receptor blockade.

AIM: The migrating motor complex (MMC) propels contents through the gastrointestinal tract during fasting. Nitric oxide (NO) is an inhibitory neurotransmitter in the gastrointestinal tract. Little is known about how NO regulates the MMC. In this study, the aim was to examine nitrergic inhibition of the MMC in man using N(G)-monomethyl-L-arginine (L-NMMA) in combination with muscarinic receptor antagonist atropine and 5-HT3 receptor antagonist ondansetron. METHODS: Twenty-six healthy volunteers underwent antroduodenojejunal manometry for 8 h with saline or NO synthase (NOS) inhibitor L-NMMA randomly injected I.V. at 4 h with or without atropine or ondansetron. Plasma ghrelin, motilin and somatostatin were measured by ELISA. Intestinal muscle strip contractions were investigated for NO-dependent mechanisms using L-NMMA and tetrodotoxin. NOS expression was localized by immunohistochemistry. RESULTS: L-NMMA elicited premature duodenojejunal phase III in all subjects but one, irrespective of atropine or ondansetron. L-NMMA shortened MMC cycle length, suppressed phase I and shifted motility towards phase II. Pre-treatment with atropine extended phase II, while ondansetron had no effect. L-NMMA did not change circulating ghrelin, motilin or somatostatin. Intestinal contractions were stimulated by L-NMMA, insensitive to tetrodotoxin. NOS immunoreactivity was detected in the myenteric plexus but not in smooth muscle cells. CONCLUSION: Nitric oxide suppresses phase III of MMC independent of muscarinic and 5-HT3 receptors as shown by nitrergic blockade, and acts through a neurocrine disinhibition step resulting in stimulated phase III of MMC independent of cholinergic or 5-HT3 -ergic mechanisms. Furthermore, phase II of MMC is governed by inhibitory nitrergic and excitatory cholinergic, but not 5-HT3 -ergic mechanisms.

Formation of the Scandinavian Obesity Surgery Registry, SOReg.

BACKGROUND: Obesity surgery is expanding, the quality of care is ever more important, and learning curve assessment should be established. A large registry cohort can show long-term effects on obesity and its comorbidities, complications, and long-term side effects of surgery, as well as changes in health-related quality of life (QoL). Sweden is ideally suited to the task of data collection and audit, with universal use of personal identification numbers, nation-wide registries permitting cross-matching to analyze causes of death, in-hospital care, and health-related absenteeism. METHOD: In 2004, the Scandinavian Obesity Surgery Registry (SOReg) was initiated and government financing secured. A project group created a national database covering all public as well as private hospitals. Data entry was to be made online, operative definitions of comorbidity were formed, and complication severity scored. Several forms of audit were devised. RESULTS: After pilot studies, the system has been running in its present form since 2007. Since 15 January 2013, SOReg covers all bariatric surgery centers in Sweden. The number of operations in the database exceeded 40,000 (March 2014), with a median follow-up of 2.94 years. Audit shows that >98% of data are correct. All results are publicized annually on the Internet. COMMENTS: Using this systematic approach, it has been possible to cover >99% of all bariatric surgery, cross-matching our data with nation-wide registries for in-hospital care, cause of death, and permitting regular nation-wide audit. Several scientific studies have used, or are using, what seems to be the most comprehensive database in obesity surgery.

Predictions of Cu toxicity in three aquatic species using bioavailability tools in four Swedish soft freshwaters.

BACKGROUND: The EU member countries are currently implementing the Water Framework Directive to promote better water quality and overview of their waters. The directive recommends the usage of bioavailability tools, such as biotic ligand models (BLM), for setting environmental quality standards (EQS) for metals. These models are mainly calibrated towards a water chemistry found in the south central parts of Europe. However, freshwater chemistry in Scandinavia often has higher levels of DOC (dissolved organic carbon), Fe and Al combined with low pH compared to the central parts of Europe. In this study, copper (Cu) toxicities derived by two different BLM software were compared to bioassay-derived toxicity for Pseudokirchneriella subcapitata, Daphnia magna and D. pulex in four Swedish soft water lakes. RESULTS: A significant under- and over prediction between measured and BLM calculated toxicity was found; for P. subcapitata in three of the four lakes and for the daphnids in two of the four lakes. The bioassay toxicity showed the strongest relationship with Fe concentrations and DOC. Furthermore, DOC was the best predictor of BLM results, manifested as positive relationships with calculated LC50 and NOEC for P. subcapitata and D. magna, respectively. CONCLUSION: Results from this study indicate that the two investigated BLM softwares have difficulties calculating Cu toxicity, foremost concerning the algae. The analyses made suggest that there are different chemical properties affecting the calculated toxicity as compared to the measured toxicity. We recommend that tests including Al, Fe and DOC properties as BLM input parameters should be conducted. This to observe if a better consensus between calculated and measured toxicity can be established.

Open duodenal switch for treatment of super obesity--surgical technique.

BACKGROUND AND AIMS: Bariatric surgery is increasing worldwide; however, standard techniques, for example, gastric bypass, are often insufficient in super obese patients, body mass index > 50 kg/m(2). Duodenal switch, a more powerful procedure, is often considered technically demanding and is, therefore, underutilized according to some authors. This might result in nonoptimal surgical care for super obese patients, not having the possibility to obtain massive weight loss. MATERIAL AND METHODS: In this report, we present our open duodenal switch technique, which we have found durable in an academic center performing 30-40 cases annually, parallel to other upper abdominal surgery. The present technique, performed through a short upper midline incision, consists of a gastric tube, a 1.5-m alimentary limb, and a 1-m common limb of the distal ileum. CONCLUSION: With correct follow-up to reduce the risk of malnutrition, we encourage the use of duodenal switch and see no rational surgical obstacles.

Duodenal switch versus Roux-en-Y gastric bypass for morbid obesity: systematic review and meta-analysis of weight results, diabetes resolution and early complications in single-centre comparisons.

Long-term weight loss after Roux-en-Y gastric bypass (RYGB) in super-obese patients has not been ideal. Biliopancreatic diversion with duodenal switch (DS) is argued to be better; however, additional side effects are feared. The aim of the present study was to determine differences in results after DS and RYGB in publications from single-centre comparisons. A systematic review of studies containing DS and RYGB performed at the same centre was performed. Outcome data were weight results, resolution of comorbid conditions, perioperative results and complications. Main outcome was difference in weight loss after DS and RYGB. Secondary outcomes were difference in resolution of comorbidities, perioperative results and complications. The final analysis included 16 studies with in total 874 DS and 1,149 RYGB operations. When comparing weight results at the longest follow-up of each study, DS yielded 6.2 (95% confidence interval 5.0-7.5) body mass index units additional weight loss compared with RYGB, P < 0.001. Operative time and length of stay were significantly longer after DS, as well as the risk for post-operative leaks, P < 0.05. DS is more effective than RYGB as a weight-reducing procedure. However, this comes at the price of more early complications and might also yield slightly higher perioperative mortality.

Differences in early complications between circular and linear stapled gastrojejunostomy in laparoscopic gastric bypass.

BACKGROUND: Laparoscopic gastric bypass (LGBP) is the most common bariatric procedure worldwide. The gastrojejunostomy can be stapled with a circular or linear stapler, each with their own specific advantages. We have evaluated differences in postoperative complications between the two techniques. METHODS: We studied operative data and postoperative complications in 560 patients (79.8 % females, median age 42, BMI 42.5) operated with LGBP between 2008 and 2012 at our center. The gastrojejunostomy was initially performed using a circular stapler (CS) in 288 patients and later by linear stapler (LS) in 272. Complications, operative time, and length of stay were retrieved from our database. The risk of developing a port site infection was evaluated with multivariate logistic regression. RESULTS: Port site infections were more common with CS than LS, 5.2 and 0.4 %, respectively (p < 0.01). Multivariate analysis demonstrated CS to be an independent risk factor for port site infections (OR 16.3 (2.09-126), p < 0.01), as well as for stomal ulcers (OR 10.1, 1.15-89, p = 0.04). Major postoperative complications remained unchanged (anastomotic leak 1.0 vs. 1.1 %, abscess 0.7 vs. 0.4 %), while operative time and length of stay were found to be shorter using the LS (122 vs. 83 min, p < 0.001 and 4 vs. 3 days, p < 0.001). CONCLUSIONS: The linear stapled technique yielded lower incidence of port site infections, probably by avoiding the passage of a contaminated circular stapler through the abdominal wall. No difference in major complications was seen, but operative time was shorter using a linear stapler instead of a circular stapler.

Vasoreactivity is rapidly improved in obese subjects after gastric bypass surgery.

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. We investigated vasoreactivity in conduit and resistance arteries in morbidly obese subjects, and the effect of weight loss after gastric bypass surgery. METHODS: A total of 19 obese subjects (body mass index (BMI): 43.8+/-3.1 kg m(-2), 75% female, mean age 41 years) were investigated before surgery and after 1 and 12 months of surgery. Nineteen non-obese controls matched for age and gender were examined. Vasoreactivity was evaluated by ultrasound to measure flow-mediated dilation (FMD, evaluating a conduit vessel) and pulse-wave analysis with terbutaline provocation (change in reflectance index (RI), evaluating resistance vessels). RESULTS: Before surgery, the obese showed a low change in RI (18+/-12 vs 37+/-15% in controls, P=0.0001), but not significantly regarding FMD (7.9+/-6.4 vs 8.9+/-5.4% in controls). Surgery resulted in a weight loss of 9% at 1 month and 30% at 1 year. Change in RI markedly improved to 36+/-12% at 1 month (P=0.0001 vs baseline) and further to 44+/-11% at 1 year (P=0.014 vs 1 month). FMD did not change significantly. Heart rate and brachial artery diameter were reduced, with no significant change in blood pressure. The improvement in resistance vessel vasodilation, estimated as change in RI, was not correlated to changes in weight or measures of glucose and lipid metabolism. CONCLUSIONS: Obese patients showed impaired vasoreactivity in resistance arteries that was normalized already 1 month after gastric bypass surgery. The basis for this remarkable outcome, not significantly related to changes in body weight and metabolic variables, remains to be clarified.

Postprandial changes in gut regulatory peptides in gastric bypass patients.

OBJECTIVE: The marked weight loss induced by Roux-en-Y gastric bypass (RYGBP) for morbid obesity is still incompletely understood. It has been suggested that, besides the restriction imposed by the surgical procedure, alterations in gut regulatory peptides signaling the brain might contribute. The aim of this study was to measure the putative satiety peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP) and pro-neurotensin (pro-NT) in response to fasting and feeding. DESIGN: The study is a cross-sectional study. After a prolonged overnight 14 h fast, a standardized mixed meal (574 kcal) was provided. Blood samples for peptide measurements were obtained before and after the meal. SUBJECTS: Forty subjects (20 males and females) were included; 10 morbidly obese; (mean age 41+/-7 years; mean BMI 44+/-3 kg/m(2)), 10 operated with RYGBP (age 45+/-5 years; BMI 35+/-6 kg/m(2)), 10 aged-matched lean (age 44+/-5 years; BMI 24+/-3 kg/m(2)) and 10 young lean subjects (age 26+/-2 years; BMI 23+/-2 kg/m(2)). MEASUREMENTS: Plasma concentrations of PYY, GLP-1, PP and pro-NT were obtained. RESULTS: PYY levels increased more in the RYGBP group than in the other groups after the test meal. GLP-1 levels rose in the RYGBP patients, with a small increase seen in the age-matched lean group. PP concentrations increased similarly in all groups postprandially. Pro-NT levels were highest in surgical patients, with no meal effect. CONCLUSION: RYGBP subjects displayed exaggerated PYY and GLP-1 responses to a standardized meal and demonstrated higher pro-NT levels both pre- and postprandially. The findings indicate that possibly the alterations in gut peptide secretion may promote weight loss after gastric bypass surgery.

Lipid mobilization following Roux-en-Y gastric bypass examined by magnetic resonance imaging and spectroscopy.

BACKGROUND: Recent developments of magnetic resonance imaging (MRI) and spectroscopy have made it possible to quantify lipid deposited in different tissues. To what extent an improvement of glucose tolerance shortly after Roux-en-Y gastric bypass surgery (RYGBP) is reflected in lipid levels in liver and skeletal muscle, markers of insulin resistance, has not been clarified. METHODS: Whole-body MRI and MR spectroscopy (MRS) of liver and muscle and measurements of biochemical markers of glucose and lipid metabolism were performed at baseline and 1, 6, and 12 months following surgery in seven morbidly obese women. Volumes of adipose tissue depots and liver and muscle lipids were assessed from the MRI/MRS data. RESULTS: At 1 month postoperatively, body mass index and visceral and subcutaneous adipose tissues were reduced by 9%, 26%, and 10%, respectively, whereas no reductions in intrahepatocellular or skeletal intramyocellular lipid concentrations were found. Free fatty acid and beta-hydroxybutyrate levels were elevated two- and sixfold, respectively; glucose and insulin levels were lowered, indicating increased insulin sensitivity. Further weight loss up to 1 year was associated with reductions in all investigated lipid depots investigated, with the exception of the intramyocellular compartment. CONCLUSION: RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.

Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion.

AIMS: Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). METHODS: Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI) +/- sd, 34.8 +/- 6.2 kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44 +/- 3.1 kg/m2) and 12 NW control subjects (BMI 23.2 +/- 2.4 kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. RESULTS: Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90-180 min in the MO subjects (P < 0.001). CONCLUSIONS: MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.