Publications
176 results found
Samarasinghe SNS, Ostarijas E, Long MJ, et al., 2024, Impact of insulin sensitization on metabolic and fertility outcomes in women with polycystic ovary syndrome and overweight or obesity-A systematic review, meta-analysis, and meta-regression., Obes Rev
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. This systematic review, meta-analysis, and meta-regression aims to compare the effect of insulin sensitizer pharmacotherapy on metabolic and reproductive outcomes in women with PCOS and overweight or obesity. We searched online databases MEDLINE via OVID, EMBASE, Clinicaltrials.gov, and EudraCT for trials published from inception to November 13, 2023. Inclusion criteria were double-blind, randomized controlled trials in women diagnosed with PCOS, body mass index (BMI) ≥ 25 kg/m2, which reported metabolic or reproductive outcomes. The intervention was insulin sensitization pharmacotherapy versus placebo or other agents. The primary outcomes were changes from baseline BMI, fasting blood glucose, and menstrual frequency. Nineteen studies were included in this review. Metformin had the most significant effect on the fasting plasma glucose and body mass index. Insulin sensitizer pharmacotherapy significantly reduced fasting plasma glucose, body mass index, fasting serum insulin, HOMA-IR, sex hormone binding globulin, and total testosterone, but the effect size was small. There was a lack of menstrual frequency and live birth data. The results indicate a role for insulin sensitizers in improving the metabolic and, to a lesser degree, reproductive profile in these women. Further research should examine insulin sensitizers' effects on objective measures of fecundity.
Eng PC, Phylactou M, Qayum A, et al., 2024, Obesity-related hypogonadism in women, Endocrine Reviews, Vol: 45, Pages: 171-189, 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.
Althukair NK, Abdeen GN, le Roux CW, et al., 2024, The Effects of Sleeve Gastrectomy on the Appetitive Domain of Taste Using the Progressive Ratio Task., Obes Surg
INTRODUCTION: Sleeve gastrectomy (SG) is an effective treatment for obesity in adolescents. The underlying weight loss mechanism may impact the peripheral and central gustatory system along with reward circuits in the brain. This study aims to assess changes in appetitive behavior in short-, medium-, and long-term follow-up. METHODS: In this prospective observational study, a total of 8 adolescents with obesity who underwent SG and 9 comparator unoperated participants were studied. Appetitive behaviour towards fat and sweet taste stimuli was assessed using the Progressive Ratio Task (PRT) over a 6 year period. RESULTS: Mean body mass index (BMI) of the surgical patients dropped from 51.5 ± 2.8 kg/m2 to 31.4 ± 1.9 and 30.9 ± 2.3 kg/m2 at 1 and 6 years follow-up, respectively. (p < 0.001). The median (interquartile range) total rewards earned during the PRT was 6 (5-7) pre-surgery, 5 (3-6) after one year and 4 (2-4) after six years from surgery (p = 0.007). CONCLUSION: SG reduced appetitive behaviour at 1 year with maintained the benefit over 6 years as measured by the progressive ratio task.
Al-Ozairi E, Narula K, Miras AD, et al., 2024, Obesity Treatments to Improve Type 1 Diabetes (OTID): a randomized controlled trial of the combination of glucagon-like peptide 1 analogues and sodium-glucose cotransporter 2 inhibitors-protocol for Obesity Treatments to Improve Type 1 Diabetes (the OTID trial), Trials, Vol: 25, ISSN: 1745-6215
BACKGROUND: The guidelines of the American Diabetes Association and European Association for the Study of Diabetes suggest that patients with obesity type 2 diabetics and chronic kidney disease need either glucagon-like peptide 1 receptor analogues or sodium-glucose cotransporter-2 inhibitors. If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors is not well researched, and hence, the impact of the guidelines is limited. The aim of this randomized controlled trial is to test the impact of the combination of glucagon-like peptide 1 receptor analogues/sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage, in patients with type 1 diabetes and chronic kidney disease. In addition, we will explore the associated changes in the metabolic pathways with each of the treatments used in this randomized controlled trial. METHODS: In this 6-month randomized control trial, 60 participants aged between 21 and 65 years, with a body mass index above 25 kg/m2, and type 1 diabetics with chronic kidney disease will be randomized to receive 1 of 5 possible treatments: (1) standard care (control), (2) glucagon-like peptide 1 receptor analogues alone, (3) sodium-glucose cotransporter-2 inhibitors alone, (4) combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors and (5) combination of glucagonlike peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors with intensive lifestyle advice. The primary objective will be the percentage change in total body weight from baseline at 6 months. The secondary objectives are to compare the change in glycaemia; blood pressure; dyslipidaemia; albuminuria; proportion of participants reaching weight loss of ≥ 5%, ≥ 10% and ≥ 15%; and change in BMI (kg/m2) from baseline and change in waist circumference (cm). A
Alabdulkader S, Al-Alsheikh AS, Miras AD, et 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
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.
Abdel-Malek M, Thayabaran D, Miras AD, 2024, Nonpharmacological, pharmacological, and surgical options for obesity-related cardiometabolic disorders, Insulin: Deficiency, Excess and Resistance in Human Disease, Pages: 339-369, ISBN: 9780323985697
Over the past decade, the treatment approach for type 2 diabetes mellitus has shifted from being “glucocentric” to preventative and “weight-centric” in combating the diabesity health burden. This is based on observations that sustained weight loss of greater than 15% has a disease-modifying effect. In this chapter, we review nonpharmacological, pharmacological, and surgical treatment options for weight reduction and the resultant effects on obesity-related cardiometabolic disorders. Firstly, we focus on the results of clinical studies in lifestyle interventions for weight loss in the prevention and remission of type 2 diabetes mellitus. We additionally discuss the wider impact of accompanying changes in anthropometric, glycaemic, blood pressure, and lipid parameters on cardiovascular risk as well as comorbid metabolic status. Secondly, we review the pharmacological approach for weight loss, including the evidence-base of landmark trials behind the use of GLP-1 analogues in type 2 diabetes mellitus, and other emerging therapies. Finally, we discuss the clinical impact of weight reduction, and the mechanisms underlying improved glucose control, following obesity surgery.
Salminen P, Kow L, Aminian A, et 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.
Alabduljabbar K, Bonanos E, Miras AD, et 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.
Hirani D, Alabdulkader S, Miras AD, et 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.
Al-Alsheikh AS, Alabdulkader S, Miras AD, et 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.
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.
Bolckmans R, Askari A, Currie A, et 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.
Behary P, Alessimii H, Miras AD, et 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.
Currie A, Bolckmans R, Askari A, et 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
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.
Ruban A, Aldubaikhi G, Johnson NA, et 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
Luli M, Yeo G, Farrell E, et 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
Roser P, Leca BM, Coelho C, et 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.
Mazaheri T, Ansari S, Nallagonda M, et 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.
Samarasinghe SNS, Miras AD, 2023, Type 2 diabetes prevention goes digital, Lancet Reg Health Eur, Vol: 24
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.
Dischinger U, Kotzner L, Kovatcheva-Datchary P, et 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
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Llewellyn DCC, Ellis HL, Aylwin SJB, et 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.
Akalestou E, Lopez-Noriega L, Christakis I, et 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
Docherty NG, Swan P, Johnson B, et 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
Kamocka A, Chidambaram S, Erridge S, et 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.
Ruban A, Miras A, Glaysher M, et 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
Kamocka A, Ilesanmi I, Miras A, et 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
Livingstone MBE, Redpath T, Naseer F, et 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
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