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We aimed to explore the relationship between GLP-1 receptor ( GLP-1R ) expression in adipose tissue (AT) and incretin secretion, glucose homeostasis and weight loss, in patients with morbid obesity and type 2 diabetes undergoing bariatric surgery. RNA was extracted from subcutaneous (SAT) and visceral (VAT) AT biopsies from 40 patients randomized to metabolic gastric bypass, sleeve gastrectomy or greater curvature plication. Biochemical parameters, fasting plasma insulin, glucagon and area under the curve (AUC) of GLP-1 following a standard meal test were determined before and 1 year after bariatric surgery. GLP-1R expression was higher in VAT than in SAT. GLP-1R expression in VAT correlated with weight (r = −0.453, p = 0.008), waist circumference (r = −0.494, p = 0.004), plasma insulin (r = −0.466, p = 0.007), and systolic blood pressure (BP) (r = −0.410, p = 0.018). At 1 year, GLP-1R expression in VAT was negatively associated with diastolic BP (r = −0.361, p = 0.039) and, following metabolic gastric bypass, with the increase of GLP-1 AUC, (R 2  = 0.46, p = 0.038). Finally, GLP-1R in AT was similar independently of diabetes outcomes and was not associated with weight loss after surgery. Thus, GLP-1R expression in AT is of limited value to predict incretin response and does not play a role in metabolic outcomes after bariatric surgery.

Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans. This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity.

Introduction Laparoscopic sleeve gastrectomy is one of the most common techniques in bariatric surgery, but there is no consensus on the optimal distance from the pylorus to start the gastric transection. The aim of this study is to determine the differences in gastric emptying, gastric distension and metabolic response between two starting distances. Material and Methods This is a prospective randomised study of 60 patients (30 patients with the section at 3 cm and 30 patients at 8 cm from the pylorus). We calculate at 6 and 12 months from surgery gastric emptying by scintigraphy (T1/2 min), gastric volume by CT scan (cc) and metabolic response by blood sample analysis (glucose, HbA1c, insulin, HOMA-IR, GLP-1, GIP and C-peptide). Results Gastric emptying increases the speed significantly in both groups but is greater in the 3-cm group ( p  < 0.05). Dividing groups into type 2 diabetic patients and non-diabetic patients, the speed in non-diabetic patients is significantly higher for the 3-cm group. Residual volume increases significantly in both groups, and there are no differences between them. One year after surgery, there are significant improvements in the hyperinsulinaemia in the patients of the 3-cm group with respect to the 8-cm group, but only in diabetic patients. No differences between groups are found regarding changes in GLP-1 or GIP. Conclusions Gastric emptying is faster in patients with antrum resection. The distance does not influence the gastric emptying of diabetic patients. Other mechanisms may explain metabolic response besides GLP-1 and its association with improvements in diabetes via gastric emptying.

BackgroundBariatric surgery has proven a successful approach in the treatment of morbid obesity and its concomitant diseases such as diabetes mellitus and arterial hypertension. Aiming for optimal management of this challenging patient cohort, tailored concepts directly guided by individual patient physiology may outperform standardized care. Implying esophageal pressure measurement and electrical impedance tomography—increasingly applied monitoring approaches to individually adjust mechanical ventilation in challenging circumstances like acute respiratory distress syndrome (ARDS) and intraabdominal hypertension—we compared our institutions standard ventilator regimen with an individually adjusted positive end expiratory pressure (PEEP) level aiming for a positive transpulmonary pressure (PL) throughout the respiratory cycle.MethodsAfter obtaining written informed consent, 37 patients scheduled for elective bariatric surgery were studied during mechanical ventilation in reverse Trendelenburg position. Before and after installation of capnoperitoneum, PEEP levels were gradually raised from a standard value of 10 cm H2O until a PL of 0 +/− 1 cm H2O was reached. Changes in ventilation were monitored by electrical impedance tomography (EIT) and arterial blood gases (ABGs) were obtained at the end of surgery and 5 and 60 min after extubation, respectively.ResultsTo achieve the goal of a transpulmonary pressure (PL) of 0 cm H2O at end expiration, PEEP levels of 16.7 cm H2O (95% KI 15.6–18.1) before and 23.8 cm H2O (95% KI 19.6–40.4) during capnoperitoneum were necessary. EIT measurements confirmed an optimal PEEP level between 10 and 15 cm H2O before and 20 and 25 cm H2O during capnoperitoneum, respectively. Intra- and postoperative oxygenation did not change significantly.ConclusionPatients during laparoscopic bariatric surgery require high levels of PEEP to maintain a positive transpulmonary pressure throughout the respiratory cycle. EIT monitoring allows for non-invasive monitoring of increasing PEEP demand during capnoperitoneum. Individually adjusted PEEP levels did not result in improved postoperative oxygenation.

Background Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia. Methods Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated ( n  = 192) or control ( n  = 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM. Results Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m 2 , and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively. Conclusions VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

Background/Objectives: Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (S I ) and β-cell function in obese non-diabetic subjects. Exercise also improves S I and may be an effective adjunct therapy to RYGB surgery. However, the mechanisms by which exercise or weight loss improve peripheral S I after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs) mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in S I and cardiometabolic risk factors. Subjects/Methods: Ninety-four miRNAs implicated in metabolism were profiled in plasma samples from 22 severely obese subjects who were recruited 1–3 months after RYGB surgery and followed for 6 months of RYGB surgery-induced weight loss, with (exercise program (EX), N =11) or without (CON, N =11) an exercise training intervention. The subjects were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis. Results: Mirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, S I , and other cardiometabolic risk factors. Conclusions: These findings present novel insights into the RYGB surgery-induced molecular changes and the effects of mild exercise to facilitate and/or maintain the benefits of a ‘comprehensive’ weight-loss intervention with concomitant improvements in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.

Background Several studies indicate that increasing the alimentary limb length in gastric bypass surgery produces only a minor improvement of excess BMI loss. Few studies have addressed the efficacy of increasing the length of the pancreatico-biliary limb. Methods Here, we present a prospective randomized study of 187 consecutive laparoscopic Roux-Y gastric bypass operations operated over 2 years (2004–2005) in Iceland. The patients were operated with a gastric bypass with either a 2-m biliopancreatic (BP)-limb and a 60-cm alimentary (A)-limb ( n  = 93) or with a 150-cm A-limb and a 60-cm BP-limb ( n  = 94). Results Preoperative median BMI was 44.1 (38–70), median age 35.5 (17–74) years, and 85 % of the patients were female. Follow-up rate after 5 years was 85 %. Eighteen months following surgery, the weight loss was significantly higher in the BP-limb group ( p  < 0.001), and this difference remained 7 years after surgery. Weight regain occurred in both groups, and 7 years after surgery, excess BMI loss (EBMIL) was 78.4 % in the BP-limb group compared to 67.1 % in the A-limb group ( p  < 0.001). Most patients (78 %) needed supplementation adjustment (iron, vitamin D and calcium) during the study period, significantly more often in the BP-limb group compared to the A-limb group ( p  < 0.001). Patients in the BP-limb group had more frequent stools than patients in the A-limb group; otherwise, gastro-intestinal symptoms rating scoring were comparable. Complication rate was similar. Conclusions Gastric bypass with a 2-m BP-limb gives better weight loss than gastric bypass with a 60-cm BP-limb and a 150-cm A-limb. Metabolic follow-up is of utmost importance, as most patients needed repeated adjustments of their supplementation.

Objective This trial’s objective was to investigate the effect of an exercise program with and without cognitive-behavioral therapy (CBT), compared by a control group, on weight, functional capacity, and cardiometabolic profile of morbidly obese individuals while waiting for bariatric surgery. Materials and Methods This randomized controlled trial investigated the effect of a 4-month low-intensity exercise program (two weekly sessions of 25 min each) on 66 morbidly obese individuals awaiting bariatric surgery. Participants were randomly divided into three groups: EXER, exercise program; EXER + CBT, exercise program plus support group sessions for lifestyle modification, with a CBT; and CONTROL, routine treatment. They were compared on weight, functional capacity, and cardiometabolic profile. Results The weight change (Kg) was −7.4 (−9.6 to 5,1); −4,2 (−6,8 to −1.6) and 2.9 (0.4 to 5.3) and the BMI change (kg/m 2 ) was −2.7 (−3.6 to −1.8); −1.4 (−2.4 to −0.4) and 1.1 (0.1 to 2.1) for groups EXER, EXER + CBT, and CONTROL, respectively. Changes were significant when compared to the control group ( p  < 0.001), but there were no differences between the two intervention arms ( p  = 0.2). Functional capacity and cardiometabolic parameters significantly improved in the intervention arms and worsened in the control group. The adherence to the exercise program in both groups was above 78 %. Conclusion A 4-month, twice-weekly supervised program of low-intensity physical activity that encourages individuals to adopt a more active lifestyle can positively interfere with weight loss and improvement in functional capacity and cardiometabolic parameters of morbidly obese individuals with and without the aid of support group sessions.

Purpose The aim of this study is to conduct a pilot randomized trial testing an exercise program specifically adapted for post-bariatric patients. Methods A total of 51 post-bariatric patients, 6–24 months post-surgery, were randomly assigned to usual care control ( n  = 25) or the exercise intervention ( n  = 26). The intervention included twice weekly 60-min group exercise classes with functional strength, flexibility, and aerobic activities; at least 3 days per week of self-directed exercise; daily pedometer; recording of steps and activities; and weekly telephone counseling. There was also a 6-month maintenance period. Results Patients were 49 ± 12 years old, 84 % female, 59 % non-Hispanic white, with a BMI of 32.9 ± 5.7 kg/m 2 and percent excess BMI loss since surgery of 56 ± 35 %. Patients were 14 ± 5 months post-surgery. A total of 44 patients (86 %) completed both phases of the program and all assessments. The following measures improved significantly for intervention participants with no significant change in control participants: yards walked in 6 min, seconds for 8-foot up-and-go, number of arm curls, and distance in inches for chair sit-and-reach. Intervention changes remained after 6 months of maintenance. Conclusions When compared to patients in usual care, a specially adapted exercise program for post-bariatric patients resulted in significant improvements in objectively monitored health outcomes. This program was delivered in a clinical setting and could be implemented in a variety of settings to improve health outcomes for post-bariatric patients.

Background: Obesity poses an enormous public health and economic burden worldwide. Visceral fat accumulation is associated with various metabolic and cardiovascular consequences, resulting in an increased prevalence of atherosclerotic conditions. We aimed to examine the impact of low-and moderate-intensity aerobic training on several anthropometric and cardiorespiratory parameters and markers of atherosclerosis, including inflammation, serum levels of lipoproteins and adipokines of extremely obese patients in poor condition. Methods: Forty severely obese patients were recruited and randomized into two groups, Group 1 and Group 2, for a six-week inpatient study. Group 1 received moderate-intensity (40–60% heart rate reserve) and Group 2 received low-intensity (30–39% of heart rate reserve) aerobic training combined with resistance training. The patients’ cardiorespiratory functions were assessed by ergospirometry. Anthropometric data were recorded, body composition was analyzed and functional tests were performed. We also investigated serum lipids and high-sensitive C-reactive protein levels and calculated the homeostatic model assessment-insulin resistance indices and adipokine levels as predictive biomarkers. Results: Functional abilities and some biochemical parameters, such as homeostatic model assessment-insulin resistance, serum lipids, apolipoprotein A and apolipoprotein-B improved in both groups in a positive direction. However, cardiorespiratory capacity and the serum levels of high-sensitive C-reactive protein and Lipocalin-2 decreased, while irisin and paraoxonase 1 increased significantly, but only in Group 1. Conclusions: Six weeks of aerobic training, regardless of its intensity, could induce favorable changes in functional tests, body composition and serum lipids, even in severely obese, extremely unconditioned patients in both groups. However, moderate-intensity aerobic training should at least increase cardiorespiratory capacity and yield a better lipid profile oxidative status and inflammation profile.