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Background: The EndoBarrier® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up. Objectives: The primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0; p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48; p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated. Conclusions: The results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss. Trial registration: Current Controlled Trials ISRCTN30845205. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.

A recent symposium and workshop in Khartoum, the capital of the Republic of Sudan, brought together broad expertise from three universities to address the current burden of communicable and non-communicable diseases facing the Sudanese healthcare system. These meetings identified common challenges that impact the burden of diseases in the country, most notably gaps in data and infrastructure which are essential to inform and deliver effective interventions. Non-communicable diseases, including obesity, type 2 diabetes, renal disease and cancer are increasing dramatically, contributing to multimorbidity. At the same time, progress against communicable diseases has been slow, and the burden of chronic and endemic infections remains considerable, with parasitic diseases (such as malaria, leishmaniasis and schistosomiasis) causing substantial morbidity and mortality. Antimicrobial resistance has become a major threat throughout the healthcare system, with an emerging impact on maternal, neonatal and paediatric populations. Meanwhile, malnutrition, micronutrient deficiency and poor perinatal outcomes remain common and contribute to a lifelong burden of disease. These challenges echo the United Nations (UN) sustainable development goals and concentrating on them in a unified strategy will be necessary to address the national burden of disease. At a time when the country is going through societal and political transition, we draw focus on the country and the need for resolution of its healthcare needs.

Abstract Background The guidelines of the American Diabetes Association and European Association for the Study of Diabetes suggest that patients with obesity type 2 diabetics and chronic kidney disease need either glucagon-like peptide 1 receptor analogues or sodium-glucose cotransporter-2 inhibitors. If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors is not well researched, and hence, the impact of the guidelines is limited. The aim of this randomized controlled trial is to test the impact of the combination of glucagon-like peptide 1 receptor analogues/sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage, in patients with type 1 diabetes and chronic kidney disease. In addition, we will explore the associated changes in the metabolic pathways with each of the treatments used in this randomized controlled trial. Methods In this 6-month randomized control trial, 60 participants aged between 21 and 65 years, with a body mass index above 25 kg/m2, and type 1 diabetics with chronic kidney disease will be randomized to receive 1 of 5 possible treatments: (1) standard care (control), (2) glucagon-like peptide 1 receptor analogues alone, (3) sodium-glucose cotransporter-2 inhibitors alone, (4) combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors and (5) combination of glucagonlike peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors with intensive lifestyle advice. The primary objective will be the percentage change in total body weight from baseline at 6 months. The secondary objectives are to compare the change in glycaemia; blood pressure; dyslipidaemia; albuminuria; proportion of participants reaching weight loss of ≥ 5%, ≥ 10% and ≥ 15%; and change in BMI (kg/m2) from baseline and change in waist circumference (cm). All the experiments will be conducted at the Dasman Diabetes Institute after approval from the local research and ethics committee. Discussion The present randomized controlled trial aims to investigate the impact of the combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage in patients with type 1 diabetes mellitus and chronic kidney disease, as well as exploring the associated changes in the metabolic pathways with each of the treatments used. This study addresses the current gap in the evidence base regarding the combination of these two drugs, which is particularly relevant given the American Diabetes Association and European Association for the Study of Diabetes guidelines recommending their combined use for patients with obesity, type 2 diabetes, and chronic kidney disease who do not achieve metabolic control with either drug alone. Trial registration ClinicalTrials.gov Identifier: NCT05390307 Trial registration date - 25th May 2022

Changes in eating behaviour including reductions in appetite and food intake, and healthier food cue reactivity, reward, hedonics and potentially also preference, contribute to weight loss and its health benefits after obesity surgery. Functional magnetic resonance imaging (fMRI) has been increasingly used to interrogate the neural correlates of eating behaviour in obesity, including brain reward-cognitive systems, changes after obesity surgery, and links with alterations in the gut-hormone-brain axis. Neural responses to food cues can be measured by changes in blood oxygen level dependent (BOLD) signal in brain regions involved in reward processing, including caudate, putamen, nucleus accumbens, insula, amygdala, orbitofrontal cortex, and top-down inhibitory control, including dorsolateral prefrontal cortex (dlPFC). This systematic review aimed to examine: (i) results of human fMRI studies involving obesity surgery, (ii) important methodological differences in study design across studies, and (iii) correlations and associations of fMRI findings with clinical outcomes, other eating behaviour measures and mechanistic measures.Of 741 articles identified, 23 were eligible for inclusion: 16 (69.6%) longitudinal, two (8.7%) predictive, and five (21.7%) cross-sectional studies. Seventeen studies (77.3%) included patients having Roux-en-Y gastric bypass (RYGB) surgery, six (26.1%) vertical sleeve gastrectomy (VSG), and five (21.7%) laparoscopic adjustable gastric banding (LAGB). The majority of studies (86.0%) were identified as having a very low risk of bias, though only six (27.3%) were controlled interventional studies, with none including randomisation to surgical and control interventions. The remaining studies (14.0%) had a low risk of bias driven by their control groups not having an active treatment.After RYGB surgery, food cue reactivity often decreased or was unchanged in brain reward systems, and there were inconsistent findings as to whether reductions in food cue reactivity was greater for high-energy than low-energy foods. There was minimal evidence from studies of VSG and LAGB surgeries for changes in food cue reactivity in brain reward systems, though effects of VSG surgery on food cue reactivity in the dlPFC were more consistently found. There was consistent evidence for post-operative increases in satiety gut hormones glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) mediating reduced food cue reactivity after RYGB surgery, including two interventional studies. Methodological heterogeneity across studies, including nutritional state, nature of food cues, post-operative timing, lack of control groups for order effects and weight loss or dietary/psychological advice, and often small sample sizes, limited the conclusions that could be drawn, especially for correlational analyses with clinical outcomes, other eating behaviour measures and potential mediators.This systematic review provides a detailed data resource for those performing or analysing fMRI studies of obesity surgery and makes suggestions to help improve reporting and design of such studies, as well as future directions.

ObjectivesGlucocorticoids produced by the adrenal cortex are essential for the maintenance of metabolic homeostasis. Glucocorticoid activation is catalysed by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). Excess glucocorticoids are associated with insulin resistance and hyperglycaemia. A small number of studies have demonstrated effects on glucocorticoid metabolism of bariatric surgery, a group of gastrointestinal procedures known to improve insulin sensitivity and secretion, which were assumed to result from weight loss. In this study, we hypothesize that a reduction in glucocorticoid action following bariatric surgery contributes to the widely observed euglycemic effects of the treatment.MethodsGlucose and insulin tolerance tests were performed at ten weeks post operatively and circulating corticosterone was measured. Liver and adipose tissues were harvested from fed mice and 11β-HSD1 levels were measured by quantitative RT-PCR or Western (immuno-) blotting, respectively. 11β-HSD1 null mice (Hsd11b1-/-) were generated using CRISPR/Cas9 genome editing. Wild type and littermate Hsd11b1-/- mice underwent Vertical Sleeve Gastrectomy (VSG) or sham surgery. ResultsUnder the conditions used, no differences in weight loss were observed between VSG treated and sham operated mice. However, both lean and obese WT VSG mice displayed significantly improved glucose clearance and insulin sensitivity. Remarkably, VSG restored physiological corticosterone production in HFD mice and reduced 11β-HSD1 expression in liver and adipose tissue post-surgery. Elimination of the 11β-HSD1/Hsd11b1 gene by CRISPR/Cas9 mimicked the effects of VSG on body weight and tolerance to 1g/kg glucose challenge. However, at higher glucose loads, the euglycemic effect of VSG was superior to Hsd11b1 elimination.ConclusionsBariatric surgery improves insulin sensitivity and reduces glucocorticoid activation at the tissular level, under physiological and pathophysiological (obesity) conditions, irrespective of weight loss. These findings point towards a physiologically relevant gut-glucocorticoid axis, and suggest that lowered glucocorticoid exposure may represent an additional contribution to the health benefits of bariatric surgery.

Background: Metabolic syndrome (MetS) is defined by at least three of the following five criteria: blood pressure ⩾130/85 mmHg, fasting blood glucose ⩾5.6 mmol/l, triglycerides concentration ⩾1.7 mmol/l, waist circumference ⩾102 cm (for men), and high-density lipoprotein cholesterol concentration

Abstract Background Most studies on obesity surgery have measured renal function using the estimated GFR. However, due to the reduction of muscle mass, and therefore creatinine that accompanies weight loss, such measures can falsely suggest an improvement in renal function. To balance the risks of surgery versus any potential benefits on renal function, we need to be able to determine renal function using valid and reliable methodologies. In this pilot study we aimed to measure renal function in patients with CKD undergoing obesity surgery using the gold standard 51Cr-EDTA GFR clearance methodology which is independent of measures of muscle mass. Methods Nine consecutive obese patients with CKD underwent obesity surgery. Their renal function was assessed using 51Cr-EDTA GFR, cystatin C and serum creatinine as well as using eGFR equations including MDRD CKD Epi, Cockcroft Gault and CKD Epi cystatin before and 12 months after surgery. Results Renal function using the 51Cr-EDTA measured GFR did not change significantly after surgery. Similar results were obtained when Cystatin C, CKD Epi cystatin, CKD Epi cystatin creatinine and adjusted Cockcroft Gault Creatinine clearance methods were used. In contrast there were either trends or significant improvements in renal function measured using the MDRD and CKD Epi equations. Conclusions In this pilot study using the gold standard 51Cr-EDTA method we found stabilisation in renal function after obesity surgery. Until further definitive data emerge it is critical to balance the risk and benefits of surgery, especially if renal function may not improve as often as previously suggested. Trial registration ClinicalTrials.gov NCT01507350. Registered June 2011.

Type 2 diabetes prevalence is increasing dramatically worldwide. Metabolic surgery is the most effective treatment for selected patients with diabetes and/or obesity. When compared to intensive medical therapy and lifestyle intervention, metabolic surgery has shown superiority in achieving glycemic improvement, reducing number of medications and cardiovascular risk factors, which translates in long-term benefits on cardiovascular morbidity and mortality. The mechanisms underlying diabetes improvement after metabolic surgery have not yet been clearly understood but englobe a complex interaction among improvements in beta cell function and insulin secretion, insulin sensitivity, intestinal gluconeogenesis, changes in glucose utilization, and absorption by the gut and changes in the secretory pattern and morphology of adipose tissue. These are achieved through different mediators which include an enhancement in gut hormones release, especially, glucagon-like peptide 1, changes in bile acids circulation, gut microbiome, and glucose transporters expression. Therefore, this review aims to provide a comprehensive appraisal of what is known so far to better understand the mechanisms through which metabolic surgery improves glycemic control facilitating future research in the field.