Imperial College London

Dr Alex Miras

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)7958 377 674a.miras

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

141 results found

Currie A, Bolckmans R, Askari A, Byrne J, Ahmed AR, Batterham RL, Mahawar K, Miras AD, Pring CM, Small PK, Welbourn Ret al., 2023, Bariatric-metabolic surgery for NHS patients with type 2 diabetes in the United Kingdom National Bariatric Surgery Registry., Diabet Med

AIM: Bariatric-metabolic surgery is approved by the National Institute of Health and Care Excellence (NICE) for people with severe obesity and type 2 diabetes (T2DM) (including class 1 obesity after 2014). This study analysed baseline characteristics, disease severity and operations undertaken in people with obesity and T2DM undergoing bariatric-metabolic surgery in the UK National Health Service (NHS) compared to those without T2DM. METHODS: Baseline characteristics, trends over time and operations undertaken were analysed for people undergoing primary bariatric-metabolic surgery in the NHS using the National Bariatric Surgical Registry (NBSR) for 11 years from 2009 to 2019. Clinical practice before and after the publication of the NICE guidance (2014) was examined. Multivariate logistic regression was used to determine associations with T2DM status and the procedure undertaken. RESULTS: 14,948/51,715 (28.9%) participants had T2DM, with 10,626 (71.1%) on oral hypoglycaemics, 4322 (28.9%) on insulin/other injectables, and with T2DM diagnosed 10+ years before surgery in 3876 (25.9%). Participants with T2DM, compared to those without T2DM, were associated with older age (p < 0.001), male sex (p < 0.001), poorer functional status (p < 0.001), dyslipidaemia (OR: 3.58 (CI: 3.39-3.79); p < 0.001), hypertension (OR: 2.32 (2.19-2.45); p < 0.001) and liver disease (OR: 1.73 (1.58-1.90); p < 0.001), but no difference in body mass index was noted. Fewer people receiving bariatric-metabolic surgery after 2015 had T2DM (p < 0.001), although a very small percentage increase of those with class I obesity and T2DM was noted. Gastric bypass was the commonest operation overall. T2DM status was associated with selection for gastric bypass compared to sleeve gastrectomy (p < 0.001). CONCLUSION: NHS bariatric-metabolic surgery is used for pe

Journal article

Llewellyn DCC, Ellis HL, Aylwin SJB, Ostarijas E, Green S, Sheridan W, Chew NWS, le Roux CWW, Miras ADD, Patel AGG, Vincent RPP, Dimitriadis GKKet al., 2022, The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review, OBESITY, ISSN: 1930-7381

Journal article

Akalestou E, Lopez-Noriega L, Christakis I, Hu M, Miras A, Leclerc I, Rutter Get al., 2022, Vertical Sleeve Gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice, Frontiers in Endocrinology, Vol: 13, Pages: 1-16, ISSN: 1664-2392

Objectives: Glucocorticoids 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 associatedwith insulin resistance and hyperglycaemia. A small number of studies have demonstrated effects on glucocorticoid metabolism ofbariatric surgery, a group of gastrointestinal procedures known to improve insulin sensitivity and secretion, which were assumedto result from weight loss. In this study, we hypothesize that a reduction in glucocorticoid action following bariatric surgerycontributes to the widely observed euglycemic effects of the treatment. Methods: Glucose and insulin tolerance tests wereperformed at ten weeks post operatively and circulating corticosterone was measured. Liver and adipose tissues were harvestedfrom fed mice and 11β‐HSD1 levels were measured by quantitative RT‐PCR or Western (immuno‐) blotting, respectively. 11β‐HSD1null mice (Hsd11b1-/-) were generated using CRISPR/ Cas9 genome editing. Wild type (WT) and littermate Hsd11b1-/- miceunderwent Vertical Sleeve Gastrectomy (VSG) or sham surgery. Results: WT VSG-treated mice displayed significantly improvedglucose tolerance versus sham controls, and this effect was observed in both regular chow- and HFD-fed animals. VSG lowered bodyweight in HFD but not regular chow-fed mice. Remarkably, VSG restored physiological corticosterone production in HFD mice andreduced 11β‐HSD1 expression in liver and adipose tissue post‐surgery. Elimination of the 11β‐HSD1/Hsd11b1 gene mimicked theeffects of VSG on body weight and tolerance to 1g/kg glucose challenge. However, at 3 g/kg glucose, the impact of VSG on glucoseexcursion was indistinguishable between WT and Hsd11b1-/- mice, suggesting that the euglycemic effect of VSG was superior toHsd11b1 elimination. Conclusions: Bariatric surgery improves insulin sensitivity and reduces glucocorticoi

Journal article

Docherty NG, Swan P, Johnson B, Samarasinghe S, Cowley M, le Roux CW, Miras ADet al., 2022, Alpha-melanocyte stimulatory hormone (alpha MSH): a novel and potent regulator of glucose tolerance in humans, Publisher: SPRINGER, Pages: S106-S106, ISSN: 0012-186X

Conference paper

Kamocka A, Chidambaram S, Erridge S, Vithlani G, Miras AD, Purkayastha Set al., 2022, Length of biliopancreatic limb in Roux-en-Y gastric bypass and its impact on post-operative outcomes in metabolic and obesity surgery-systematic review and meta-analysis, International Journal of Obesity, Vol: 46, Pages: 1983-1991, ISSN: 0307-0565

BackgroundRoux-en-Y gastric bypass (RYGB) is a gold-standard procedure for treatment of obesity and associated comorbidities. No consensus on the optimal design of this operation has been achieved, with various lengths of bypassed small bowel limb lengths being used by bariatric surgeons. This aim of this systematic review and meta-analysis was to determine whether biliopancreatic limb (BPL) length in RYGB affects postoperative outcomes including superior reduction in weight, body mass index (BMI), and resolution of metabolic comorbidities associated with obesity.MethodsA systematic search of the literature was conducted up until 1st June 2021. Meta-analysis of primary outcomes was performed utilising a random-effects model. Statistical significance was determined by p value < 0.05.ResultsTen randomised controlled trials were included in the final quantitative analysis. No difference in outcomes following short versus long BLP in RYGB was identified at 12–72 months post-operatively, namely in BMI reduction, remission or improvement of type 2 diabetes mellitus, hypertension, dyslipidaemia, and complications (p > 0.05). Even though results of four studies showed superior total body weight loss in the long BPL cohorts at 24 months post-operatively (pooled mean difference −6.92, 95% CI –12.37, −1.48, p = 0.01), this outcome was not observed at any other timepoint.ConclusionBased on the outcomes of the present study, there is no definitive evidence to suggest that alteration of the BPL affects the quantity of weight loss or resolution of co-existent metabolic comorbidities associated with obesity.

Journal article

Ruban A, Miras A, Glaysher M, Goldstone T, Prechtl C, Byrne Jet al., 2022, DUODENAL-JEJUNAL BYPASS LINER FOR THE MANAGEMENT OF TYPE 2 DIABETES: RESULTS FROM A MULTICENTRE RANDOMISED CONTROLLED TRIAL. Endoscopic and percutaneous interventional procedures, Publisher: SPRINGER, Pages: 153-153, ISSN: 0960-8923

Conference paper

Kamocka A, Ilesanmi I, Miras A, Purkayastha S, Moorthy K, Patel Aet al., 2022, THREE-YEAR OUTCOMES OF THE LONG LIMB TRIAL. LONG VS STANDARD BILIOPANCREATIC LIMB IN THE ROUXEN-Y GASTRIC BYPASS, Publisher: SPRINGER, Pages: 567-567, ISSN: 0960-8923

Conference paper

Livingstone MBE, Redpath T, Naseer F, Boyd A, Martin M, Finlayson G, Miras AD, Bodnar Z, Kerrigan D, Pournaras DJ, le Roux CW, Spector AC, Price RKet al., 2022, Food intake following gastric bypass surgery: patients eat less but do not eat differently., The Journal of Nutrition, Vol: 152, Pages: 2319-2332, ISSN: 0022-3166

BACKGROUND: Lack of robust research methodology for assessing ingestive behaviour has impeded clarification of the mediators of food intake following gastric bypass (GBP) surgery. OBJECTIVE: To evaluate changes in directly measured 24hr energy intake (EI), energy density (ED) (primary outcomes), eating patterns and food preferences (secondary outcomes) in patients and time matched weight-stable comparator participants. DESIGN: Patients (n = 31,77% female, BMI 45.5±1.3) and comparators (n = 32, 47% female, BMI 27.2±0.8) were assessed for 36hr under fully residential conditions at baseline (1-mo pre-surgery) and at 3- and 12-mo post-surgery. Participants had ad libitum access to a personalised menu (n = 54 foods) based on a 6 macronutrient mix paradigm. Food preferences were assessed by the Leeds Food Preference Questionnaire. Body composition was measured by whole-body dual-energy x-ray absorptiometry. RESULTS: In the comparator group there was an increase in relative fat intake at 3-mo post-surgery, otherwise no changes were observed in food intake or body composition. At 12-mo post-surgery, patients lost 27.7±1.6% of initial body weight (p<0.001). The decline in EI at 3-mo post-surgery (-44% from baseline, P<0001)) was followed by a partial rebound at 12-mo (-18% from baseline) but at both times dietary ED and relative macronutrient intake remained constant. The decline in EI was due to eating the same foods as consumed pre-surgery and by decreasing the size (g, MJ), but not the number, of eating occasions. In patients, reduction in explicit liking at 3-mo (-11.56±4.67, P = 0.007) and implicit wanting at 3- (-15.75±7.76, P = 0.01) and 12-mo (-15.18±6.52, P = 0.022) for sweet foods was not matched by reduced intake of these foods. Patients with the greatest reduction in ED post-surgery reduced both EI and preference for sweet foods. CONCLUSION: After GBP patients continue to eat the same foods but in smaller amounts. T

Journal article

Sudlow A, Miras AD, Cohen RV, Kahal H, Townley J, Heneghan H, Le Roux C, Pournaras DJet al., 2022, Medication following bariatric surgery for type 2 diabetes mellitus (BY-PLUS ) study: rationale and design of a randomised controlled study, BMJ OPEN, Vol: 12, ISSN: 2044-6055

Journal article

Shibib L, Al-Qaisi M, Ahmed A, Miras AD, Nott D, Pelling M, Greenwald SE, Guess Net al., 2022, Reversal and remission of T2DM - an update for practitioners, Vascular Health and Risk Management, Vol: 18, Pages: 417-443, ISSN: 1176-6344

Over the past 50 years, many countries around the world have faced an unchecked pandemic of obesity and type 2 diabetes (T2DM). As best practice treatment of T2DM has done very little to check its growth, the pandemic of diabesity now threatens to make health-care systems economically more difficult for governments and individuals to manage within their budgets. The conventional view has been that T2DM is irreversible and progressive. However, in 2016, the World Health Organization (WHO) global report on diabetes added for the first time a section on diabetes reversal and acknowledged that it could be achieved through a number of therapeutic approaches. Many studies indicate that diabetes reversal, and possibly even long-term remission, is achievable, belying the conventional view. However, T2DM reversal is not yet a standardized area of practice and some questions remain about long-term outcomes. Diabetes reversal through diet is not articulated or discussed as a first-line target (or even goal) of treatment by any internationally recognized guidelines, which are mostly silent on the topic beyond encouraging lifestyle interventions in general. This review paper examines all the sustainable, practical, and scalable approaches to T2DM reversal, highlighting the evidence base, and serves as an interim update for practitioners looking to fill the practical knowledge gap on this topic in conventional diabetes guidelines.

Journal article

Aldhwayan MM, Al-Najim W, Ruban A, Glaysher MA, Johnson B, Chhina N, Dimitriadis GK, Prechtl CG, Johnson NA, Byrne JP, Goldstone AP, Teare JP, Le Roux CW, Miras ADet 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.

Journal article

Swan P, Johnson B, Samarasinghe S, De Vito G, Cowley M, Le Roux C, Miras A, Docherty Net al., 2022, Alpha-melanocyte stimulatory hormone: a novel player in post-prandial glucose disposal in skeletal muscle in humans, The Official Journal of ATTD Advanced Technologies & Treatments for Diabetes, Publisher: Mary Ann Liebert, Pages: A44-A44, ISSN: 1520-9156

Background and Aims: Studies in rodents demonstrate that increases in circulating pituitary‐derived alpha‐melanocyte stimulatory hormone (α‐MSH) contribute to post‐prandial glycaemic control. Moreover, intravenous administration of exogenous α‐MSH lowers glucose excursions during oral glucose tolerance testing (OGTT) in mice. We set out to interrogate whether this action translated to human physiology both in vivo and in vitroMethods: Using a randomized double‐blinded cross‐over design, fifteen healthy volunteers received infusions of physiological saline, 15, 150 and 1500 ng/kg/hr α‐MSH initiated 30 minutes prior to the administration of a standard OGTT. Plasma glucose and insulin was measured during the OGTT. To assess the effect of α‐MSH on glucose disposal into skeletal muscle disposal, 15 subjects underwent sequential hyperinsulinaemic‐euglycaemic clamp, concomitant to either saline or 150ng/kg/hr α‐MSH infusion. In a separate cohort of healthy volunteers (n = 6), vastus lateralis muscle biopsies were obtained and used to establish cultures of primary human myotubes. Tritiated 2‐deoxy‐D‐glucose was used to monitor glucose uptake in response to α‐MSH.Results: Infusion of α‐MSH (1500ng/kg/hr) reduced the incremental area under the curve (iAUC) for plasma glucose (p = 0.02), and plasma insulin (p = 0.006) by approximately 20%. At high steady state insulin concentrations in clamp studies, α‐MSH increased glucose requirements for the maintenance of euglycaemia. Primary human myotube cultures expressed melanocortin receptor subtypes (MC1R>MC3R≈MC4R) and both 10nM and 100nM α‐MSH increased glucose uptake by two‐fold versus vehicle (p = 0.001).Conclusions: These findings substantiate a role for peripheral α‐MSH as a hitherto undescribed component of the endocrine control of glycaemia in human physiology.

Conference paper

Al-Alsheikh AS, Alabdulkader S, Johnson B, Goldstone AP, Miras ADet al., 2022, Effect of obesity surgery on taste, Nutrients, Vol: 14, Pages: 1-24, ISSN: 2072-6643

Obesity surgery is a highly efficacious treatment for obesity and its comorbidities. The underlying mechanisms of weight loss after obesity surgery are not yet fully understood. Changes to taste function could be a contributing factor. However, the pattern of change in different taste domains and among obesity surgery operations is not consistent in the literature. A systematic search was performed to identify all articles investigating gustation in human studies following bariatric procedures. A total of 3323 articles were identified after database searches, searching references and deduplication, and 17 articles were included. These articles provided evidence of changes in the sensory and reward domains of taste following obesity procedures. No study investigated the effect of obesity surgery on the physiological domain of taste. Taste detection sensitivity for sweetness increases shortly after Roux-en-Y gastric bypass. Additionally, patients have a reduced appetitive reward value to sweet stimuli. For the subgroup of patients who experience changes in their food preferences after Roux-en-Y gastric bypass or vertical sleeve gastrectomy, changes in taste function may be underlying mechanisms for changing food preferences which may lead to weight loss and its maintenance. However, data are heterogeneous; the potential effect dilutes over time and varies significantly between different procedures.

Journal article

Akalestou E, Miras A, Rutter G, Le Roux Cet al., 2022, Mechanisms of weight loss after obesity surgery, Endrocrine Reviews, Vol: 43, Pages: 19-34, ISSN: 0163-769X

Obesity surgery remains the most effective treatment for obesity and its complications.Weight loss was initially attributed to decreased energy absorption from the gut buthave since been linked to reduced appetitive behaviour and potentially increasedenergy expenditure. Implicated mechanisms associating rearrangement of thegastrointestinal tract with these metabolic outcomes include central appetite control,release of gut peptides, change in microbiota and bile acids. However, the exactcombination and timing of signals remain largely unknown. In this review, we surveyrecent research investigating these mechanisms, and seek to provide insights onunanswered questions over how weight loss is achieved following bariatric surgerywhich may eventually lead to safer, nonsurgical weight-loss interventions orcombinations of medications with surgery

Journal article

Miras AD, le Roux CW, 2022, Metabolicsurgery versus conventional therapy intype 2 diabetes (vol 397, pg 256, 2021), LANCET, Vol: 399, Pages: 520-520, ISSN: 0140-6736

Journal article

Borodavkin P, Sheridan W, Coelho C, Ostarijas E, Zair ZM, Miras AD, McGowan B, le Roux CW, Vincent RP, Dimitriadis GKet al., 2022, Effects of glucagon-like peptide-1 receptor agonists on histopathological and secondary biomarkers of non-alcoholic steatohepatitis: A systematic review and meta-analysis, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 24, Pages: 337-342, ISSN: 1462-8902

Journal article

Omran A, Leca BM, Ostarijas E, Graham N, Da Silva AS, Zair ZM, Miras AD, le Roux CW, Vincent RP, Cardozo L, Dimitriadis GKet al., 2021, Metabolic syndrome is associated with prostate enlargement: a systematic review, meta-analysis, and meta-regression on patients with lower urinary tract symptom factors, Therapeutic Advances in Endocrinology and Metabolism, Vol: 12, Pages: 1-39, ISSN: 2042-0188

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 <1.03 mmol/l (for men). MetS has been associated with worse lower urinary tract symptoms (LUTS) and higher International Prostate Symptom questionnaire scores.Materials and Methods:MEDLINE, Cochrane, ClinicalTrials.gov, and SCOPUS were critically appraised for all peer-reviewed manuscripts that suitably fulfilled our protocol’s inclusion criteria established a priori. Meta-analytical and meta-regression calculations were performed in R using the Sidik–Jonkman and Hartung–Knapp random effects model and predefined covariates.Results:A total of 70 studies (n = 90,206) were included in qualitative synthesis. From these, 60 studies focused on MetS and LUTS: 44 reported positive correlations, 5 reported negative correlations, 11 reported no association, and 10 studies focused on MetS and total prostate volume (TPV). MetS positively correlated with moderate LUTS [odds ratio (OR)  = 1.56, 95% confidence interval (CI) = 1.35–1.80], severe LUTS (OR = 2.35, 95% CI = 1.82–3.03), overactive bladder (OAB; OR = 3.2, 95% CI = 1.6–5.8), and nocturia severity (OR = 2.509, 95% CI = 1.571–4.007) at multivariate analysis. A total of 30 studies (n = 22,206) were included in meta-analysis; MetS was significantly associated with higher TPV (mean differences = 4.4450 ml, 95% CI = 2.0177–6.8723), but no significant predictive factors for effect sizes were discovered.Conclusion:Our meta-analysis demonstrates a significant association between the

Journal article

Kaur V, Dimitriadis G, Perez-Pevida B, Bansi D, Jayasena C, Bate D, Houghton R, Fielding B, Balfoussia D, Webber L, Miao Y, Mears F, Jackson N, Coppin L, Pereze J, williams M, Johnson B, Umpleby M, Randeva H, Miras Aet al., 2021, Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome, Metabolism: clinical and experimental, Vol: 125, Pages: 1-8, ISSN: 0026-0495

BackgroundDuodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans.MethodsThirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention.ResultsA small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion.ConclusionsThese findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.

Journal article

Moussa O, Ortega P, Mansour S, Flod S, Cousins J, Hameed S, Tan T, Miras A, Chahal H, Hakky S, Moorthy K, Tsironis C, Ahmed A, Purkayastha Set al., 2021, Bariatric surgical services within a pandemic can continue safely: the initial experience of a UK centre of excellence., Obesity Surgery, ISSN: 0960-8923

Journal article

Salem V, Demetriou L, Behary P, Alexiadou K, Scholtz S, Tharakan G, Miras A, Purkayastha S, Ahmed A, Bloom S, Wall M, Dhillo W, Tan Tet al., 2021, Weight loss by low calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns: an functional MRI study, Diabetes Care, Vol: 44, Pages: 1842-1851, ISSN: 0149-5992

OBJECTIVE: Weight loss achieved with very-low-calorie diets (VLCDs) can produce remission of type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference.RESEARCH DESIGN AND METHODS: Sixteen participants underwent gastric bypass surgery, and 19 matched participants undertook a VLCD (meal replacement) for 4 weeks. Brain responses to food cues and resting-state functional connectivity were assessed with functional MRI pre- and postintervention and compared across groups.RESULTS: We show that Roux-en-Y gastric bypass surgery (RYGB) results in three divergent brain responses compared with VLCD-induced weight loss: 1) VLCD resulted in increased brain reward center food cue responsiveness, whereas in RYGB, this was reduced; 2) VLCD resulted in higher neural activation of cognitive control regions in response to food cues associated with exercising increased cognitive restraint over eating, whereas RYGB did not; and 3) a homeostatic appetitive system (centered on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD.CONCLUSIONS: Taken together, these findings point to divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast to enduring weight loss after RYGB.

Journal article

Sheridan W, Da Silva AS, Leca BM, Ostarijas E, Patel AG, Aylwin SJB, Vincent RP, Panagiotopoulos S, El-Hasani S, le Roux CW, Miras AD, Cardozo L, Dimitriadis GKet al., 2021, Weight loss with bariatric surgery or behaviour modification and the impact on female obesity-related urine incontinence: A comprehensive systematic review and meta-analysis, Clinical Obesity, Vol: 11, Pages: 1-19, ISSN: 1758-8103

Women with obesity are at risk of pelvic floor dysfunction with a 3-fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). The National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) recommend that women with a body mass index ≥30 kg/m2 should consider weight loss prior to consideration for incontinence surgery. This systematic review and meta-analysis will assess this recommendation to aid in the counselling of women with obesity-related urinary incontinence (UI). Medical Literature Analysis and Retrieval System online (MEDLINE), EMBASE, Cochrane, ClinicalTrials.gov, and SCOPUS were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori and presented original, empirical data relevant to weight loss intervention in the management of urinary incontinence. Thirty-three studies and their outcomes were meta-analysed. Weight loss interventions were associated in a decreased prevalence in UI (OR 0.222, 95% CI [0.147, 0.336]), SUI (OR 0.354, 95% CI [0.256, 0.489]), UUI (OR 0.437, 95% CI [0.295, 0.649]) and improved quality of life (PFDI-20, SMD -0.774 (95% CI [−1.236, −0.312]). This systematic review and meta-analysis provide evidence that weight loss interventions are effective in reducing the prevalence of obesity-related UI symptoms in women. Bariatric surgery in particular shows greater sustained weight loss and improvements in UI prevalence. Further large scale, randomized control trials assessing the effect of bariatric surgery on women with obesity-related UI are needed to confirm this study's findings.

Journal article

Salem V, Demetriou L, Behary P, Alexiadou K, Miras A, Scoltz S, Purkayastha S, Ahmed S, Dhillo W, Tan Tet al., 2021, Weight loss by low-calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns which may explain differences in long-term outcomes: an FMRI study, The Diabetes UK Professional Conference 2021, Publisher: Wiley, Pages: 1-1, ISSN: 0742-3071

Objective: Clinically significant weight loss can produce remission of type 2 diabetes. Bariatric surgery (specifically, Roux-en-Y gastric bypass, RYGB) produces durable weight loss that translates into reductions in mortality. In contrast, weight regain is very common after very low-calorie diets (VLCD). No study has investigated longitudinal changes in brain activity using functional MRI in patients living with obesity and prediabetes/type 2 diabetes to explain this difference.Methods: Visual food cue responses and resting state connectivity was assessed with functional MRI pre- and post-intervention and compared between 16 participants who underwent gastric bypass surgery and 19 age, gender, and disease stage matched participants who undertook a VLCD for 4 weeks.Results: Brain responses to RYGB-induced weight loss diverge from those induced by VLCD in three domains: (i) dieting resulted in increased responsiveness to visual food cues in reward areas whereas after RYGB this was reduced; (ii) dieting therefore engaged greater activation of brain regions involved in cognitive control, associated with the need to exercise increased restraint over eating; and (iii) a homeostatic appetitive system (centred on the hypothalamus) was better engaged following RYGB-induced weight loss than dieting.Conclusion: This study provides a holistic view of multiple divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast with the enduring weight loss after RYGB.

Conference paper

Samarasinghe S, Sudlow A, Dimitriadis GK, Ahmed AR, Purkayastha S, Tsironis C, Hakky S, Moorthy K, Aylwin SJB, Panagiotopoulos S, El-Hassani S, Patel AG, Chahal H, Hameed S, le Roux CW, Pournaras DJ, Miras ADet al., 2021, Simple tool to prioritize access to bariatric surgery for people living with obesity during the COVID-19 pandemic, British Journal of Surgery, Vol: 108, Pages: e179-e180, ISSN: 0007-1323

Journal article

Glaysher M, Ward J, Aldhwayan M, Ruban A, Prechtl CG, Fisk HL, Chhina N, Al-Najim W, Smith C, Klimowska-Nassar N, Johnson N, Falaschetti E, Goldstone AP, Miras AD, Byrne JP, Calder PC, Teare Jet 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.

Journal article

Miras AD, Kamocka A, Tan T, Pérez-Pevida B, Chahal H, Moorthy K, Purkayastha S, Patel A, Umpleby AM, Frost G, Bloom SR, Ahmed AR, Rubino Fet al., 2021, Long limb compared with standard limb Roux-en-Y gastric bypass for type 2 diabetes and obesity: the LONG LIMB RCT, Efficacy and Mechanism Evaluation, Vol: 8, ISSN: 2050-4365

BackgroundRoux-en-Y gastric bypass is recognised as a standard of care in the treatment of diabetes mellitus and obesity. However, the optimal length of the Roux-en-Y gastric bypass limbs remains controversial, with substantial variation in practice. Specifically, a longer biliopancreatic limb length of 150 cm (‘long limb’) has been hypothesised to be better for the treatment of diabetes mellitus because it increases the postprandial secretion of gut hormones, such as glucagon-like peptide 1, and increases insulin sensitivity, compared with the Roux-en-Y gastric bypass utilising a standard biliopancreatic limb length of 50 cm (‘standard limb’).ObjectiveTo evaluate the mechanisms, clinical efficacy and safety of long limb versus the standard limb Roux-en-Y gastric bypass in patients undergoing metabolic surgery for obesity and diabetes mellitus.DesignA double-blind, mechanistic randomised controlled trial was conducted to evaluate the mechanisms, clinical efficacy and safety of the two interventions.SettingImperial College London, King’s College London and their associated NHS trusts.ParticipantsPatients with obesity and type 2 diabetes mellitus who were eligible for metabolic surgery.InterventionsParticipants were randomly assigned (1 : 1) to 150-cm (long limb) or 50-cm (standard limb) biliopancreatic limb Roux-en-Y gastric bypass with a fixed alimentary limb of 100 cm. The participants underwent meal tolerance tests to measure glucose excursions, glucagon-like peptide 1 and insulin secretion, and hyperinsulinaemic–euglycaemic clamps with stable isotopes to measure insulin sensitivity preoperatively, at 2 weeks after the surgery and at matched 20% total body weight loss. Clinical follow-up continued up to 1 year.Main outcome measuresPrimary – postprandial peak of active glucagon-like peptide 1 concentration at 2 weeks after intervention. Secondary – fasting and postprandial glucose an

Journal article

Ilesanmi I, Tharakan G, Alexiadou K, Behary P, Alessimii H, Bovill-Taylor C, Kenkre J, Choudhury S, Doyle C, Purkayastha S, Miras A, Tsironis C, Chahal H, Bloom SR, Oliver NS, Ahmed AR, Khoo B, Tan TM-Met al., 2021, Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study, DIABETES CARE, Vol: 44, Pages: 614-617, ISSN: 0149-5992

Journal article

Miras A, Kamocka A, Pérez-Pevida B, Purkayastha S, Moorthy K, Patel A, Chahal H, Frost G, Bassett P, Castagnetto-Gissey L, Coppin L, Jackson N, Umpleby M, Bloom S, Tan T, Ahmed A, Rubino Fet al., 2021, The effect of standard versus longer intestinal bypass on GLP-1 regulation and glucose metabolism in patients with type 2 diabetes undergoing roux-en-Y gastric bypass. The long-limb study, Diabetes Care, Vol: 44, Pages: 1-9, ISSN: 0149-5992

ObjectiveRoux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial levels of Glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial peak in GLP-1, translating into higher insulin secretion and thus additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.Research Design and MethodsFifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery.ResultsBoth groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. ConclusionThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Journal article

Miras AD, le Roux CW, 2021, Metabolic surgery versus conventional therapy in type 2 diabetes, The Lancet, Vol: 397, Pages: 256-257, ISSN: 0140-6736

Journal article

Ruban A, Glaysher M, Ashrafian H, Miras A, Prechtl C, Goldstone A, Aldhwayan M, Chhina N, Al-Najim W, Li J, Byrne J, Teare Jet al., 2021, DUODENAL-JEJUNAL BYPASS LINER THERAPY (ENDOBARRIER (R)) CAUSES REDUCTIONS IN PLASMA TRIMETHYLAMINE-N-OXIDE IN OBESE PATIENTS WITH DIABETES, Publisher: BMJ PUBLISHING GROUP, Pages: A19-A19, ISSN: 0017-5749

Conference paper

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