Publications
20 results found
Goldstone A, Bhargava R, Luur S, et al., 2023, Post-prandial increases in liver-gut hormone LEAP2 correlate with attenuated eating behaviour in adults without obesity, Journal of the Endocrine Society, Vol: 7, Pages: 1-19, ISSN: 2472-1972
Background: The novel liver-gut hormone LEAP2 is a centrally acting inverse agonist, and competitive antagonist of orexigenic acyl ghrelin (AG), at the growth hormone secretagogue receptor, reducing food intake in rodents. In humans, the effects of LEAP2 on eating behaviour and mechanisms behind the post-prandial increase in LEAP2 are unclear, though this is reciprocal to the post-prandial decrease in plasma AG.Methods: Plasma LEAP2 was measured in a secondary analysis of a previous study. Twenty-two adults without obesity attended after an overnight fast (Fasted-saline), consuming a 730kcal meal without (Fed-saline) or with (Fed-ghrelin) subcutaneous AG administration. Post-prandial changes in plasma LEAP2 were correlated with post-prandial changes in appetite, high-energy (HE) or low-energy (LE) food cue reactivity using functional MRI, ad libitum food intake, and plasma/serum AG, glucose, insulin and triglycerides.Results: Post-prandial plasma LEAP2 increased by 24.5-52.2% at 70-150 min, but was unchanged by exogenous AG administration. Post-prandial increases in LEAP2 correlated positively with post-prandial decreases in appetite, and cue reactivity to HE/LE and HE food in anterior/posterior cingulate cortex, paracingulate cortex, frontal pole, middle frontal gyrus, with similar trend for food intake. Post-prandial increases in LEAP2 correlated negatively with body mass index, but did not correlate positively with increases in glucose, insulin or triglycerides, nor decreases in AG.Conclusions: These correlational findings are consistent with a role for post-prandial increases in plasma LEAP2 in suppressing human eating behaviour in adults without obesity. Post-prandial increases in plasma LEAP2 are unrelated to changes in plasma AG and the mediator(s) remain uncertain.
Pugh J, Anjum A, Petropoulou K, et al., 2022, Increase in colonic PRopionate as a method of prEVENTing weight gain in adults aged 20-40 years (iPREVENT): A multi-centre, double-blind, randomised, parallel-group study to investigate the efficacy of inulin-propionate ester versus inulin (control) in the prevention of weight gain over 12 months, F1000Research, Vol: 11, Pages: 1-14, ISSN: 2046-1402
Introduction: Overweight and obesity affects over 70% of the UK population and is a major risk factor for the development of co-morbidities, including type 2 diabetes and cardiovascular disease. There now exists a considerable evidence base for the management of obesity. However, this is not the case for the prevention of obesity. Preventing weight gain in periods of life where there is an elevated risk of fat mass expansion could be beneficial to preventing associated diseases in later life. This protocol investigates the impact of novel food ingredient inulin propionate ester (IPE) in the prevention of weight gain. This trial aims to investigate the primary hypothesis that IPE has a superior effect on preventing body weight gain, compared with inulin, in young (<40 years old) adults over 12 months, whilst also investigating several complementary mechanisms that may explain the prevention of weight gain and improved long-term energy balance from consuming IPE. Methods: In this multi-centre, double-blind, randomised, parallel-group study, eligible participants will be randomly assigned to consume 10g IPE or 10g inulin (control) daily for 12 months. Study visits will be conducted at baseline, two-month, six-month and 12-month time points. The primary outcome is weight gain from baseline to 12 months. Secondary outcomes will examine changes in metabolic and cardiovascular health biomarkers, body composition and appetite. A mechanistic sub-group will explore causal mechanisms around energy balance, body composition, appetite regulation and the gut microbiota. Based on the power calculation, the sample size required is 270 participants or 135 per study group.Ethics and dissemination: The trial protocol and participant-facing documents have been reviewed and approved, by the London Hampstead Ethics Committee (REC Reference 19/LO/0095, 29th January 2019). Upon completion, the trial results will be published in peer-reviewed journals and presented at scientific confer
Aldhwayan MM, Al-Najim W, Ruban A, et al., 2022, Does bypass of the proximal small intestine impact food intake, preference, and taste function in humans? An experimental medicine study using the duodenal-jejunal bypass liner, Nutrients, Vol: 14, ISSN: 2072-6643
The duodenal-jejunal bypass liner (Endobarrier) is an endoscopic treatment for obesity and type 2 diabetes mellitus (T2DM). It creates exclusion of the proximal small intestine similar to that after Roux-en-Y Gastric Bypass (RYGB) surgery. The objective of this study was to employ a reductionist approach to determine whether bypass of the proximal intestine is the component conferring the effects of RYGB on food intake and sweet taste preference using the Endobarrier as a research tool. A nested mechanistic study within a large randomised controlled trial compared the impact of lifestyle modification with vs. without Endobarrier insertion in patients with obesity and T2DM. Forty-seven participants were randomised and assessed at several timepoints using direct and indirect assessments of food intake, food preference and taste function. Patients within the Endobarrier group lost numerically more weight compared to the control group. Using food diaries, our results demonstrated similar reductions of food intake in both groups. There were no significant differences in food preference and sensory, appetitive reward, or consummatory reward domain of sweet taste function between groups or changes within groups. In conclusion, the superior weight loss seen in patients with obesity and T2DM who underwent the Endobarrier insertion was not due to a reduction in energy intake or change in food preferences.
Ruban A, Miras A, glaysher M, et al., 2022, Duodenal-jejunal bypass liner for the management of Type 2 diabetes and obesity: a multicenter randomized controlled trial, Annals of Surgery, Vol: 275, Pages: 440-447, ISSN: 0003-4932
Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary Background Data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44–2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8–39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial Registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research
Glaysher M, Ward J, Aldhwayan M, et al., 2021, The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, Clinical Nutrition, Vol: 40, Pages: 2343-2354, ISSN: 0261-5614
Background & aimsDuodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs).MethodsSub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group.ResultsWeight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group.ConclusionOne year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation.
Ruban A, Glaysher MA, Miras AD, et al., 2020, A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT, Efficacy and Mechanism Evaluation, Vol: 7, Pages: 1-130, ISSN: 2050-4365
BackgroundThe 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.ObjectivesThe 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 < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up
Glaysher M, Ward J, Aldhwayan M, et al., 2020, The effect of a duodenal-jejunal bypass liner device (Endobarrier (R)) on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S16-S17, ISSN: 0960-8923
Ruban A, Prechtl C, Glaysher M, et al., 2019, Effectiveness of different recruitment strategies in an RCT of a surgical device:;Experience from the Endobarrier trial, BMJ Open, Vol: 9, ISSN: 2044-6055
Recruiting participants into clinical trials is notoriously difficult and poses the greatest challenge when planning any investigative study. Poor recruitment may not only have financial ramifications owing to increased time and resources being spent but could adversely influence the clinical impact of a study if it becomes underpowered. Herein we present our own experience of recruiting into a nationally funded, multi-centre, randomised controlled trial (RCT) of the Endobarrier vs. standard medical therapy in obese patients with type 2 diabetes. Despite these both being highly prevalent conditions, there were considerable barriers to the effectiveness of different recruitment strategies across each study site. Although recruitment from primary care proved extremely successful at one study site, this largely failed at another site prompting the implementation of multimodal recruitment strategies including a successful media campaign to ensure sufficient participants were enrolled and the study was adequately powered. From this experience we propose where appropriate the early engagement and investment in media campaigns to enhance recruitment into clinical trials.
Glaysher M, Mohanaruban A, Prechtl CG, et al., 2017, A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus, BMJ Open, Vol: 7, ISSN: 2044-6055
Introduction The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight.Methods and analysis In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18–65 years with a body mass index 30–50 kg/m2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58–97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression.
Miras AD, Al-Najim W, Jackson SN, et al., 2014, Psychological characteristics, eating behavior, and quality of life assessment of obese patients undergoing weight loss interventions., Scand J Surg, ISSN: 1457-4969
Bariatric surgery is the most effective treatment for obesity. However, not all patients have similar weight loss following surgery and many researchers have attributed this to different pre-operative psychological, eating behavior, or quality-of-life factors. The aim of this study was to determine whether there are any differences in these factors between patients electing to have bariatric surgery compared to less invasive non-surgical weight loss treatments, between patients choosing a particular bariatric surgery procedure, and to identify whether these factors predict weight loss after bariatric surgery.
Scholtz S, Miras AD, Chhina N, et al., 2014, Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding, Gut, Vol: 63, Pages: 891-902, ISSN: 0017-5749
Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations.Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity.Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients.Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour.
Goldstone AP, Prechtl CG, Scholtz S, et al., 2014, Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 99, Pages: 1319-1330, ISSN: 0002-9165
Seyfried F, Miras AD, Bueter M, et al., 2013, Effects of preoperative exposure to a high-fat versus a low-fat diet on ingestive behavior after gastric bypass surgery in rats, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 27, Pages: 4192-4201, ISSN: 0930-2794
Prechtl C, Beaver JD, Croese C, et al., 2009, Dietary Restraint Influence Brain Activation to Food Pictures of Different Caloric Value, The Rank Prize Fund, Mini-symposium on Regulation of Appetite
Prechtl C, Beaver JD, Croese C, et al., 2009, Fasting Biases Brain Reward Systems Towards High-Calorie Foods, British Endocrine Society
Prechtl C, Beaver JD, Croese C, et al., 2009, Reward Sensitivity and Positive Affect Influence Brain Activation to Food Pictures of Different Caloric Value, ISMRM 17th Scientific Meeting
Goldstone AP, de Hernandez CG, Beaver JD, et al., 2009, Fasting biases brain reward systems towards high-calorie foods, Vol: 30, Pages: 1625-1635, ISSN: 1460-9568
Prechtl C, Goldstone AP, Beaver JD, et al., 2008, Skipping breakfast biases brain reward systems towards high-calorie foods, NuGOWeek 2008, 5th annual conference meeting
Prechtl C, Goldstone AP, Beaver JD, et al., 2008, Increased desire for food when fasted is associated with increased fMRI activation in the ventral striatum, insula and amygdala, ISMRM
IntroductionFunctional magnetic resonance imaging (fMRI) studies have demonstrated that activity within brain reward regions is modulated byrewarding properties of food (e.g. viewing high-calorie vs. low-calorie foods), internal cues such as nutritional state, individual rewardsensitivity, mood, and obesity [1-9]. For example, we previously reported that fasting selectively increases activation to pictures ofhigh-calorie over low-calorie food in the ventral striatum, amygdala, anterior insula, and medial and lateral orbitofrontal cortex (OFC)[9]. We now examine whether the individual differences in activation within these brain reward systems to viewing food pictures whenfasted is influenced by reward sensitivity and mood.Material and MethodsTwenty healthy, non-obese subjects (10 male, age 26 ± 1 years (mean ± SEM), range 19-35, body mass index (BMI) 22.1 ± 0.5 kg/m2,range 18.2-27.1) were scanned twice on separate days in randomized order, once after fasting overnight (15.9 ± 0.3h since supper) orwhen fed (1.6 ± 0.1h since breakfast). fMRI was performed while viewing pictures of (i) high-calorie or (ii) low-calorie foods in ablock design (6 pictures per block, 2.5sec per picture, 0.5sec ISI) using a 3T Philips Intera MR scanner (EPI, TR 3sec, TE 30ms,SENSE 2, 44 x 3.25mm slices, 2mm voxels). SPM5 (Wellcome Trust Centre for Neuroimaging, UCL, UK) was used for preprocessingwith motion and slice timing correction, registration to standard EPI MNI template, smoothing (8mm FWHM), and GLMwith random effects region of interest (ROI) analysis using statistical threshold of P<0.005 uncorrected. The co-ordinates of peakvoxel activation in each ROI for high-calorie vs. low-calorie food contrast at the group level when fasted were used to extract themagnitude of activation separately for each hemisphere for individual subjects when fasted and when fed (MarsBar).To assess reward sensitivity we used the Behavioral Inhibition and Activation Sc
Prechtl C, Goldstone AP, Beaver JD, et al., 2008, Increased desire for food when fasted is associated with increased activation of the ventral striatum, insula and amygdala in humans, British Endocrine Society
Using functional MRI, we examined how regional brain activity varies with nutritional state when viewing food pictures of different caloric density and appeal.Eighteen non-obese healthy volunteers (BMI 22.2±0.5 kg/m2, age range 19–36 years, 8 male) were studied on 2 separate mornings after an overnight fast (mean±S.E.M. 15.5±0.3 h) or when fed (1.2±0.1 h after breakfast, food intake 45±4% of estimated REE). Appetite was scored using visual analogue scales.fMRI was performed while viewing pictures of: i) high-calorie and ii) low-calorie foods, and iii) non-food related household objects using a 3T MR scanner (TR 3 s, 44×3.25 mm slices, 2.5 mm voxels). Subjects rated how ‘appealing’ they found each picture while being scanned. SPM5 was used for image pre-processing and GLM analysis using a priori regions of interest (ventral striatum, insula and amygdala) with a statistical threshold of P<0.005. Average activation in each ROI per subject was determined using the MarsBar tool.‘Hunger’ and ‘pleasantness-to-eat’ ratings were greater in the fasted versus fed state (P<0.001). Both high- and low-calorie food pictures were more appealing when fasted than when fed (P<0.001). High-calorie pictures were more appealing than object and low-calorie pictures when fasted (P<0.001 and 0.01), but not when fed (P=0.7 and 0.2).There was activation of the ventral striatum, insula and amygdala when viewing high-calorie versus object, or high- versus low-calorie, pictures when fasted, but minimal if any when fed. The greater average activation of these brain regions when fasted versus fed (P<0.05) reflected the difference in rating for the pictures (P<0.001).Thus increased hunger and desire for food, particularly high-calorie foods, when fasted (versus fed) is associated with increased activation in brain regions involved in reward, craving and emotion (ventral striatum, insula and amygdala
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