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
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172 results found

Alabdulkader S, Al-Alsheikh AS, Miras AD, Goldstone APet al., 2024, Obesity surgery and neural correlates of human eating behaviour: a systematic review of functional MRI studies, NeuroImage: Clinical, Vol: 41, Pages: 103563-103563, ISSN: 2213-1582

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 foo

Journal article

Samarasinghe SNS, Woods C, Miras AD, 2024, Bariatric Surgery in Women with Polycystic Ovary Syndrome., Metabolism, Vol: 151

Polycystic ovary syndrome (PCOS) is the most common endocrine condition in premenopausal women and is a common cause of anovulatory subfertility. Although obesity does not form part of the diagnostic criteria, it affects a significant proportion of women with PCOS and is strongly implicated in the pathophysiology of the disease. Both PCOS and obesity are known to impact fertility in women; obesity also reduces the success of assisted reproductive technology (ART). With or without pharmacotherapy, lifestyle intervention remains the first-line treatment in women with PCOS and obesity. Bariatric surgery is still an experimental treatment in women with PCOS and subfertility. This review will present an overview of the pathophysiology of PCOS and obesity and the role of bariatric surgery. Although data are sparse regarding the impact of bariatric surgery on subfertility in women with PCOS and obesity, existing studies point to a beneficial role in treating metabolic and reproductive dysfunction.

Journal article

Salminen P, Kow L, Aminian A, Kaplan LM, Nimeri A, Prager G, Behrens E, White KP, Shikora S, IFSO Experts Panelet al., 2024, IFSO Consensus on Definitions and Clinical Practice Guidelines for Obesity Management-an International Delphi Study., Obes Surg, Vol: 34, Pages: 30-42

INTRODUCTION: This survey of international experts in obesity management was conducted to achieve consensus on standardized definitions and to identify areas of consensus and non-consensus in metabolic bariatric surgery (MBS) to assist in an algorithm of clinical practice guidelines for the management of obesity. METHODS: A three-round Delphi survey with 136 statements was conducted by 43 experts in obesity management comprising 26 bariatric surgeons, 4 endoscopists, 8 endocrinologists, 2 nutritionists, 2 counsellors, an internist, and a pediatrician spanning six continents over a 2-day meeting in Hamburg, Germany. To reduce bias, voting was unanimous, and the statements were neither favorable nor unfavorable to the issue voted or evenly balanced between favorable and unfavorable. Consensus was defined as ≥ 70% inter-voter agreement. RESULTS: Consensus was reached on all 15 essential definitional and reporting statements, including initial suboptimal clinical response, baseline weight, recurrent weight gain, conversion, and revision surgery. Consensus was reached on 95/121 statements on the type of surgical procedures favoring Roux-en-Y gastric bypass, sleeve gastrectomy, and endoscopic sleeve gastroplasty. Moderate consensus was reached for sleeve gastrectomy single-anastomosis duodenoileostomy and none on the role of intra-gastric balloons. Consensus was reached for MBS in patients > 65 and < 18 years old, with a BMI > 50 kg/m2, and with various obesity-related complications such as type 2 diabetes, liver, and kidney disease. CONCLUSIONS: In this survey of 43 multi-disciplinary experts, consensus was reached on standardized definitions and reporting standards applicable to the whole medical community. An algorithm for treating patients with obesity was explored utilizing a thoughtful multimodal approach.

Journal article

Hirani D, Alabdulkader S, Miras AD, Salem Vet al., 2023, What can functional brain imaging teach us about remission of type 2 diabetes?, Diabet Med, Vol: 40

AIMS: With a paradigm shift in attitudes towards type 2 diabetes (T2D), 'weight loss responsive' diabetes is now thought of as a curable disease state. As a result, national programmes are being orchestrated to induce T2D remission soon after diagnosis with aggressive dietary interventions-such as very low-calorie diets (VLCD). However, dietary interventions to achieve weight loss and diabetes remission lack the same long-term sustainability and cardiovascular risk reduction evidence as bariatric surgery. This review aims to explore how brain imaging has contributed to our understanding of human eating behaviours and how neural correlates are affected by T2D. METHODS: We summarise functional MRI (fMRI) studies looking at human eating behaviour and obesity. We explore how these neural correlates are affected by insulin resistance and T2D itself as well as its different treatment approaches. Finally, we comment on the need for more personalised approaches to maintaining metabolic health and how fMRI studies may inform this. CONCLUSION: fMRI studies have helped to fashion our understanding of the neurobiology of human appetite and obesity. Improving our understanding of the neural implications of T2D that promote disadvantageous eating behaviours will enable prevention of disease as well as mitigation against a vicious cycle of metabolic dysfunction and associated cognitive complications.

Journal article

Alabduljabbar K, Bonanos E, Miras AD, le Roux CWet al., 2023, Mechanisms of Action of Bariatric Surgery on Body Weight Regulation., Gastroenterol Clin North Am, Vol: 52, Pages: 691-705

Bariatric surgery is an effective treatment modality for obesity and obesity-associated complications. Weight loss after bariatric surgery was initially attributed to anatomic restriction or reduced energy absorption, but now it is understood that surgery treats obesity by influencing the subcortical areas of the brain to lower adipose tissue mass. There are three major phases of this process: initially the weight loss phase, followed by a phase where weight loss is maintained, and in a subset of patients a phase where weight is regained. These phases are characterized by altered appetitive behavior together with changes in energy expenditure. The mechanisms associated with the rearrangement of the gastrointestinal tract include central appetite control, release of gut peptides, change in microbiota and bile acids. However, the exact combination and timing of signals remain largely unknown.

Journal article

Al-Alsheikh AS, Alabdulkader S, Miras AD, Goldstone APet al., 2023, Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies, Obesity Reviews, Vol: 24, ISSN: 1467-7881

This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for 11C-raclopride, 18F-fallypride, 123I-IBZM; one for dopamine transporter, 123I-FP-CIT; one used tracer for serotonin 5-HT2A receptor, 18F-altanserin; two used tracers for serotonin transporter, 11C-DASB or 123I-FP-CIT; two used tracer for μ-opioid receptor, 11C-carfentanil; one used tracer for noradrenaline transporter, 11C-MRB); seven studies assessed glucose uptake using 18F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using 15O-H2O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using 18F-FTHA and one using 11C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies.

Journal article

Eng PC, Phylactou M, Qayum A, Woods C, Lee H, Aziz S, Moore B, Miras AD, Comninos AN, Tan T, Franks S, Dhillo WS, Abbara Aet al., 2023, Obesity-related hypogonadism in women, Endocrine Reviews, ISSN: 0079-9963

Obesity-related hypogonadotropic hypogonadism is a well-characterized condition in men (termed male obesity-related secondary hypogonadism; MOSH); however, an equivalent condition has not been as clearly described in women. The prevalence of polycystic ovary syndrome (PCOS) is known to increase with obesity, but PCOS is more typically characterized by increased gonadotropin-releasing hormone (GnRH) (and by proxy luteinizing hormone; LH) pulsatility, rather than by the reduced gonadotropin levels observed in MOSH. Notably, LH levels and LH pulse amplitude are reduced with obesity, both in women with and without PCOS, suggesting that an obesity-related secondary hypogonadism may also exist in women akin to MOSH in men. Herein, we examine the evidence for the existence of a putative non-PCOS “female obesity-related secondary hypogonadism” (FOSH). We précis possible underlying mechanisms for the occurrence of hypogonadism in this context and consider how such mechanisms differ from MOSH in men, and from PCOS in women without obesity. In this review, we consider relevant etiological factors that are altered in obesity and that could impact on GnRH pulsatility to ascertain whether they could contribute to obesity-related secondary hypogonadism including: anti-Müllerian hormone, androgen, insulin, fatty acid, adiponectin, and leptin. More precise phenotyping of hypogonadism in women with obesity could provide further validation for non-PCOS FOSH and preface the ability to define/investigate such a condition.

Journal article

Melson E, Miras AD, Papamargaritis D, 2023, Future therapies for obesity., Clin Med (Lond), Vol: 23, Pages: 337-346

Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in multiple obesity-related complications, but it is not scalable at the population level. Over the past few years, gut hormone-based pharmacotherapies for obesity and type 2 diabetes mellitus (T2DM) have rapidly evolved, and combinations of glucagon-like peptide 1 (GLP1) with other gut hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) as dual or triple agonists are under investigation to enhance and complement the effects of GLP1 on WL and obesity-related complications. Tirzepatide, a dual agonist of GLP1 and GIP receptors, marks a new era in obesity pharmacotherapy in which a combination of gut hormones could approach the WL achieved with bariatric surgery. In this review, we discuss emerging obesity treatments with a focus on gut hormone combinations and the concept of a multimodal approach for obesity management.

Journal article

Bolckmans R, Askari A, Currie A, Ahmed AR, Batterham RL, Byrne J, Hopkins J, Khan OA, Mahawar K, Miras AD, Pring CM, Small PK, Welbourn Ret al., 2023, Clinical characteristics of patients undergoing primary bariatric surgery in the United Kingdom based on the National Bariatric Surgery Registry, Clinical Obesity, Vol: 13, ISSN: 1758-8103

Baseline demographic characteristics and operations undertaken for patients having bariatric surgery in the United Kingdom are largely unknown. This study aimed to describe the profile of patients having primary bariatric surgery in the National Health Service (NHS) or by self-pay, and associated operations performed for both pathways. The National Bariatric Surgery Registry dataset for 5 years between January 2015 and December 2019 was used. 34 580 patients underwent primary bariatric surgery, of which 75.9% were NHS patients. Mean patient age and initial body mass index were significantly higher for NHS compared to self-pay patients (mean age 45.8 ± 11.3 [SD] vs. 43.0 ± 12.0 years and initial body mass index 48.0 ± 7.9 vs. 42.9 ± 7.3 kg/m2, p < .001). NHS patients were more likely to have obesity-related complications compared to self-pay patients: prevalence of Type 2 diabetes mellitus 27.7% versus 8.3%, hypertension 37.1% versus 20.1%, obstructive sleep apnoea 27.4% versus 8.9%, severely impaired functional status 19.3% versus 13.9%, musculoskeletal pain 32.5% versus 20.1% and being on medication for depression 31.0% versus 25.9%, respectively (all p < .001). Gastric bypass was the most commonly performed primary NHS bariatric operation 57.2%, but sleeve gastrectomy predominated in self-pay patients 48.7% (both p < .001). In contrast to self-pay patients, NHS patients are receiving bariatric surgery only once they are older and at a much more advanced stage of obesity-related disease complications.

Journal article

Behary P, Alessimii H, Miras AD, Tharakan G, Alexiadou K, Aldhwayan MM, Purkayastha S, Moorthy K, Ahmed AR, Bloom SR, Tan TMet al., 2023, Tripeptide gut hormone infusion does not alter food preferences or sweet taste function in volunteers with obesity and prediabetes/diabetes but promotes restraint eating: a secondary analysis of a randomized single-blind placebo-controlled study, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 25, Pages: 1731-1739, ISSN: 1462-8902

AimsTo investigate whether the elevation in postprandial concentrations of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux-en-Y gastric bypass (RYGB).Materials and methodsThis was a secondary analysis of a randomized single-blind study in which we infused GLP-1, OXM, PYY (GOP) or 0.9% saline subcutaneously for 4 weeks in 24 subjects with obesity and prediabetes/diabetes, to replicate their peak postprandial concentrations, as measured at 1 month in a matched RYGB cohort (ClinicalTrials.gov NCT01945840). A 4-day food diary and validated eating behaviour questionnaires were completed. Sweet taste detection was measured using the method of constant stimuli. Correct sucrose identification (corrected hit rates) was recorded, and sweet taste detection thresholds (EC50s: half maximum effective concencration values) were derived from concentration curves. The intensity and consummatory reward value of sweet taste were assessed using the generalized Labelled Magnitude Scale.ResultsMean daily energy intake was reduced by 27% with GOP but no significant changes in food preferences were observed, whereas a reduction in fat and increase in protein intake were seen post-RYGB. There was no change in corrected hit rates or detection thresholds for sucrose detection following GOP infusion. Additionally, GOP did not alter the intensity or consummatory reward value of sweet taste. A significant reduction in restraint eating, comparable to the RYGB group was observed with GOP.ConclusionThe elevation in plasma GOP concentrations after RYGB is unlikely to mediate changes in food preferences and sweet taste function after surgery but may promote restraint eating.

Journal article

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, Diabetic Medicine, Vol: 40, ISSN: 0742-3071

AimBariatric-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.MethodsBaseline 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.Results14,948/51,715 (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).ConclusionNHS bariatric-metabolic surgery is used for

Journal article

Abdel-Malek M, Yang L, Miras AD, 2023, Pharmacotherapy for chronic obesity management: a look into the future., Intern Emerg Med, Vol: 18, Pages: 1019-1030

Substantial leaps have been made in the drug discovery front in tackling the growing pandemic of obesity and its metabolic co-morbidities. Greater mechanistic insight and understanding of the gut-brain molecular pathways at play have enabled the pursuit of novel therapeutic agents that possess increasingly efficacious weight-lowering potential whilst remaining safe and tolerable for clinical use. In the wake of glucagon-like peptide 1 (GLP-1) based therapy, we look at recent advances in gut hormone biology that have fermented the development of next generation pharmacotherapy in diabesity that harness synergistic potential. In this paper, we review the latest data from the SURPASS and SURMOUNT clinical trials for the novel 'twincretin', known as Tirzepatide, which has demonstrated sizeable body weight reduction as well as glycaemic efficacy. We also provide an overview of amylin-based combination strategies and other emerging therapies in the pipeline that are similarly providing great promise for the future of chronic management of obesity.

Journal article

Ruban A, Aldubaikhi G, Johnson NA, Glaysher MA, Chhina N, Byrne J, Marchesi J, Teare JP, Goldstone AP, Miras A, Li JVet al., 2023, ENDOBARRIER®, A DUODENAL-JEJUNAL BYPASS LINER DEVICE, ALTERS THE GLOBAL METABOLIC AND THE GUT BACTERIAL PROFILES OF PATIENTS WITH OBESITY AND DIABETES, Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1457-S1457, ISSN: 0016-5085

Conference paper

Luli M, Yeo G, Farrell E, Ogden J, Parretti H, Frew E, Bevan S, Brown A, Logue J, Menon V, Isack N, Lean M, McEwan C, Gately P, Williams S, Astbury N, Bryant M, Clare K, Dimitriadis GK, Finlayson G, Heslehurst N, Johnson B, Le Brocq S, Roberts A, McGinley P, Mueller J, O'Kane M, Batterham RL, Miras ADet al., 2023, The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference, EClinicalMedicine, Vol: 58, ISSN: 2589-5370

Unlike various countries and organisations, including the World Health Organisation and the European Parliament, the United Kingdom does not formally recognise obesity as a disease. This report presents the discussion on the potential impact of defining obesity as a disease on the patient, the healthcare system, the economy, and the wider society. A group of speakers from a wide range of disciplines came together to debate the topic bringing their knowledge and expertise from backgrounds in medicine, psychology, economics, and politics as well as the experience of people living with obesity. The aim of their debate was not to decide whether obesity should be classified as a disease but rather to explore what the implications of doing so would be, what the gaps in the available data are, as well as to provide up-to-date information on the topic from experts in the field. There were four topics where speakers presented their viewpoints, each one including a question-and-answer section for debate. The first one focused on the impact that the recognition of obesity could have on people living with obesity regarding the change in their behaviour, either positive and empowering or more stigmatising. During the second one, the impact of defining obesity as a disease on the National Health Service and the wider economy was discussed. The primary outcome was the need for more robust data as the one available does not represent the actual cost of obesity. The third topic was related to the policy implications regarding treatment provision, focusing on the public's power to influence policy. Finally, the last issue discussed, included the implications of public health actions, highlighting the importance of the government's actions and private stakeholders. The speakers agreed that no matter where they stand on this debate, the goal is common: to provide a healthcare system that supports and protects the patients, strategies that protect the economy and broader society, and po

Journal article

Roser P, Leca BM, Coelho C, Schulte K-M, Gilbert J, Drakou EE, Kosmas C, Ling Chuah L, Wassati H, Miras AD, Crane J, Aylwin SJB, Grossman AB, Dimitriadis GKet al., 2023, Diagnosis and management of parathyroid carcinoma: a state-of-the-art review, Endocrine-Related Cancer, Vol: 30, ISSN: 1351-0088

Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management.

Journal article

Mazaheri T, Ansari S, Nallagonda M, Kollmann L, Nickel F, Seyfried F, Miras ADet al., 2023, Medikamentöse Therapie der Adipositas – Konkurrenz zur bariatrischen Chirurgie oder sinnvolle Ergänzung? [Pharmacotherapy of obesity-Competition to bariatric surgery or a meaningful supplement?], Die Chirurgie, Vol: 94, Pages: 497-505, ISSN: 2731-6971

Obesity is a complex chronic disease and requires a long-term multimodal approach. The current treatment algorithm for treatment of obesity mainly consists of a stepwise approach, which starts with a lifestyle intervention followed by or combined with medication treatment, whereas bariatric surgery is often reserved for the last option. This article provides an overview of the currently available conservative medicinal treatment regimens and the currently approved medications as well as medications currently undergoing approval studies with respect to the efficacy and possible side effects. Special attention is paid to the importance of combination treatment of pharmacotherapy and surgery in the sense of a multimodal treatment. The data so far show that using a multimodal approach an improvement in the long-term weight loss and metabolic benefits can be achieved for the patients.

Journal article

Samarasinghe SNS, Miras AD, 2023, Type 2 diabetes prevention goes digital, Lancet Reg Health Eur, Vol: 24

Journal article

Ansari S, Miras AD, 2023, Multimodal Care for Diabetes Combining Pharmacotherapy and Metabolic Surgery, Obesity, Bariatric and Metabolic Surgery: A Comprehensive Guide: Second Edition, Pages: 1013-1027, ISBN: 9783030605957

The tools available for the life-long management of type 2 diabetes mellitus (T2DM) include lifestyle modification, pharmacotherapy, and surgery which all share a common goal of optimizing glycemia, blood pressure, and lipids levels to prevent microvascular and cardiovascular disease. Metabolic surgery is the most effective treatment for achieving metabolic disease control; however, the improvements in glycemia attenuate after two or more years. Instead of waiting for T2DM to relapse after metabolic surgery, adjunctive pharmacotherapy can be used to sustain glycemic control and improve cardiovascular risk, and this is particularly true for the newer classes of medications used for the management of T2DM. The traditional stepwise management approach where surgery is the final treatment for T2DM should be reconsidered. Instead, metabolic surgery and pharmacotherapy, and, in particular, the newer classes of medications should complement each other as part of multimodal diabetes care. The recent advances in pharmacotherapy offer a new incentive to investigate clinically important outcomes that can be achieved with a multimodal approach to diabetes care that addresses glycemia, blood pressure, and lipids.

Book chapter

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., 2023, The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review, Obesity, Vol: 31, Pages: 20-30, ISSN: 1071-7323

ObjectivePostprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery.MethodsMEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429).Results and ConclusionsPostprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.

Journal article

Dischinger U, Kotzner L, Kovatcheva-Datchary P, Kleinschmidt H, Haas C, Perez J, Presek C, Koschker A-C, Miras AD, Hankir MK, Germer C-T, Fassnacht M, Herrmann MJ, Seyfried F, Vogel Jet al., 2023, Hypothalamic integrity is necessary for sustained weight loss after bariatric surgery: A prospective, cross-sectional study, METABOLISM-CLINICAL AND EXPERIMENTAL, Vol: 138, ISSN: 0026-0495

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 (αMSH): 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

Sharma M, Nayar R, Graham Y, Parretti HM, Abbott S, Tahrani A, Miras AD, Madhok B, Singhal R, Mahawar Ket al., 2022, Risk of Harm from Use of Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors in Patients Pre or Post Bariatric Surgery, OBESITY SURGERY, Vol: 32, Pages: 2469-2470, ISSN: 0960-8923

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

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