Publications
176 results found
Hankir MK, Seyfried F, Miras AD, et al., 2018, Brain feeding circuits after roux-en-Y gastric bypass, Trends in Endocrinology and Metabolism, Vol: 29, Pages: 218-237, ISSN: 1043-2760
Metabolic surgical procedures, such as Roux-en-Y gastric bypass (RYGB), uniquely reprogram feeding behavior and body weight in obese subjects. Clinical neuroimaging and animal studies are only now beginning to shed light on some of the underlying central mechanisms. We present here the roles of key brain neurotransmitter/neuromodulator systems in food choice, value, and intake at various stages after RYGB. In doing so, we elaborate on how known signals emanating from the reorganized gut, including peptide hormones and microbiota products, impinge on newly mapped homeostatic and hedonic brain feeding circuits. Continued progress in the rapidly evolving field of metabolic surgery will inform the design of more effective weight-loss compounds.
Dimitriadis GK, Kaur J, Adya R, et al., 2018, Chemerin induces endothelial cell inflammation: activation of nuclear factor-kappa beta and monocyte-endothelial adhesion, Oncotarget, Vol: 9, Pages: 16678-16690, ISSN: 1949-2553
Chemerin, a chemoattractant protein, acts via a G-protein coupled chemokine receptor, i.e. Chemokine like Receptor 1/ChemR23; levels of which are elevated in pro-inflammatory states such as obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM patients are at high risk of developing cardiovascular disorders such as atherosclerosis. We have reported that chemerin induces human endothelial cell angiogenesis and since dysregulated angiogenesis and endothelial dysfunction are hallmarks of vascular disease; we sought to determine the effects of chemerin on monocyte-endothelial adhesion, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a critical pro-inflammatory transcription factor. Human endothelial cells were transfected with pNF-kappaB-Luc plasmid. Chemerin induced NF-κB activation via the MAPK and PI3K/Akt pathways. Western blot analyses and monocyte-endothelial adhesion assay showed that chemerin increased endothelial cell adhesion molecule expression and secretion, namely E-selectin (Endothelial Selectin), VCAM-1 (Vascular Cell Adhesion Molecule-1) and ICAM-1 (Intracellular Adhesion Molecule-1), leading to enhancement of monocyte-endothelial adhesion. Additionally, we showed a synergistic response of the pro-inflammatory mediator, Interleukin-1β with chemerin induced effects. Chemerin plays an important role in endothelial inflammation, as it induces monocyte-endothelial adhesion, a critical step in the development of atherosclerosis.
Kamocka A, McGlone ER, Perez-Pevida B, et al., 2018, Surgical revision of candy cane after Roux-en-Y gastric bypass, Obesity Update 2018, Pages: CD2.3-CD2.3, ISSN: 1470-3947
Miras A, Pérez-Pevida B, Varela N, 2018, Peri-operative Management of the Obese Diabetic Patient, Core Topics in Anaesthesia and Peri-operative Care of the Morbidly Obese Surgical Patient, Pages: 186-188, ISBN: 9781107163287
Dimitriadis GK, Miras AD, 2018, Glucagon like peptide 2 (GLP-2), Encyclopedia of Endocrine Diseases, Pages: 561-564, ISBN: 9780128121993
The role of the gastrointestinal (GI) tract in energy homeostasis through the digestion and absorption of carbohydrates, and the production of incretin hormones remains well recognized in recent years. Studying the functional changes of the GI system following bariatric surgery, particularly involving the secretion of incretin hormones has led into understanding their interaction with areas of the brain to regulate metabolism and energy balance. In Type 2 Diabetes Mellitus (T2DM) and obesity, this homeostatic balance is disrupted, either through alterations in the levels of these hormones or through resistance to their actions. Although bariatric surgery is an effective treatment for T2DM and obesity, it cannot be applied to most patients. Hence, recapitulation of the changes of incretin hormone secretion after bariatric surgery in the post Glucagon-like peptide 1 (GLP-1) analogue era remains an attractive area for further research and the development of new treatments for T2DM and obesity. Glucagon-like peptide 2 (GLP-2) is a proglucagon-derived peptide produced by intestinal L-cells and by cells within the brainstem and other areas of the central nervous system. GLP-2 is implicated in regulation of energy absorption and maintenance of GI mucosal structure but as recent evidence suggests may also have a beneficial effect in glucose homeostasis, particularly in states associated with increased energy uptake such as obesity.
Kelm M, Seyfried F, Reimer S, et al., 2017, Proximal jejunal stoma as ultima ratio in case of traumatic distal duodenal perforation facilitating successful EndoVAC treatment: a case report, International Journal of Surgery Case Reports, Vol: 41, Pages: 401-403, ISSN: 2210-2612
IntroductionDuring damage control surgery for blunt abdominal traumata simultaneous duodenal perforations can be missed making secondary sufficient surgical treatment challenging. Endoluminal vacuum (EndoVAC™) therapy has been shown to be a revolutionary option but has anatomical and technical limits.Presentation of the caseA 59-year old man with hemorrhagic shock due to rupture of the mesenteric root after blunt abdominal trauma received damage control treatment. Within a scheduled second-look, perforation of the posterior duodenal wall was identified. Due to local and systemic conditions, further surgical treatment was limited. Decision for endoscopic treatment was made but proved to be difficult due to the distal location. Finally, double-barreled jejunal stoma was created for transstomal EndoVAC™ treatment. Complete leakage healing was achieved and jejunostomy reversal followed subsequently.DiscussionDuring damage control surgery simultaneous bowel injuries can be missed leading to life-threatening complications with limited surgical options. EndoVAC™ treatment is an option for gastrointestinal perforations but has anatomical limitations that can be sufficiently shifted by a transstomal approach for intestinal leakage.ConclusionIn trauma related laparotomy complete mobilization of the duodenum is crucial. As ultima ratio, transstomal EndoVAC™ is a safe and feasible option and can be considered for similar cases.
Glaysher M, Mohanaruban A, Prechtl CG, et al., 2017, A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus, BMJ Open, Vol: 7, ISSN: 2044-6055
Introduction The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight.Methods and analysis In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18–65 years with a body mass index 30–50 kg/m2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58–97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression.
Dimitriadis GK, Randeva MS, Miras AD, 2017, Potential hormone mechanisms of bariatric surgery, Current Obesity Reports, Vol: 6, Pages: 253-265, ISSN: 2162-4968
Purpose of ReviewIn recent years, the role of the gastrointestinal (GI) tract in energy homeostasis through modulation of the digestion and absorption of carbohydrates and the production of incretin hormones is well recognized.Recent FindingsBariatric surgery for obesity has been a very effective method in substantially improving weight, and numerous studies have focused on intestinal adaptation after bariatric procedures. A number of structural and functional changes in the GI tract have been reported postsurgery, which could be responsible for the altered hormonal responses. Furthermore, the change in food absorption rate and the intestinal regions exposed to carbohydrates may affect blood glucose response.SummaryThis review hopes to give new insights into the direct role of gut hormones, by summarising the metabolic effects of bariatric surgery.
Tharakan G, Behary P, Wewer Albrechtsen NJ, et al., 2017, Roles of increased glycemic variability, GLP-1 and glucagon in hypoglycaemia after Roux-en-Y gastric bypass., European Journal of Endocrinology, Vol: 177, Pages: 455-464, ISSN: 0804-4643
Objective Roux-en-Y Gastric Bypass (RYGB) surgery is currently the most effective treatment for diabetes and obesity. An increasingly recognized complication of RYGB surgery is postprandial hypoglycemia (PPH). The pathophysiology of PPH remains unclear with multiple mechanisms suggested including nesidioblastosis, altered insulin clearance and increased glucagon-like-1 peptide (GLP-1) secretion. Whilst many PPH patients respond to dietary modification, some have severely disabling symptoms. Multiple treatments have been trialled ranging from acarbose, to both GLP-1 agonists and antagonists, even to reversal of RYGB. A greater understanding of the pathophysiology of PPH could guide the development of new therapeutic strategies. Methods We studied a cohort of PPH patients at the Imperial Weight Center. We performed continuous glucose monitoring to characterize their altered glycemic variability. We also performed a mixed meal test (MMT) and measured gut hormone concentrations. Results We found increased glycemic variability in our cohort of PPH patients, specifically a higher Mean Amplitude Glucose Excursion (MAGE) score of 4.9. We also demonstrated significantly greater and earlier increases in insulin and GLP-1 concentration in patients who had hypoglycemia in response to an MMT (MMT Hypo) relative to those that did not (MMT Non-Hypo). There was a significantly increased glucagon secretion in the MMT Hypo group versus the Non-hypo group. No significant differences in oxyntomodulin, GIP or peptide YY secretion were seen between these two groups. Conclusion An early peak in GLP-1 and glucagon, due to post-operative L-cell hypertrophy and aberrant processing of proglucagon, may trigger an exaggerated insulinotropic response to eating in patients with PPH.
Perez-Pevida B, Kamocka A, Alasfour S, et al., 2017, LONG-TERM MICRONUTRIENT DEFICIENCIES IN POOR RESPONDERS AFTER BARIATRIC SURGERY Post-operative complications, Publisher: SPRINGER, Pages: 745-745, ISSN: 0960-8923
Mcglone ER, Kamocka A, Pevida BP, et al., 2017, IS REVISION OF THE 'CANDY CANE' AFTER ROUX-EN-Y GASTRIC BYPASS (RYGB) WORTHWHILE? Revisional surgery, Publisher: SPRINGER, Pages: 944-944, ISSN: 0960-8923
Khan OA, Mcglone ER, Miras A, et al., 2017, TYPE 2 DIABETES RESOLUTION IN THE INSULIN-DEPENDENT PATIENT - WHICH METABOLIC OPERATION? Type 2 diabetes and metabolic surgery, Publisher: SPRINGER, Pages: 254-254, ISSN: 0960-8923
Kamocka A, Miras A, Patel D, et al., 2017, OBESITY SURGERY MAKES PATIENTS HEALTHIER AND MORE FUNCTIONAL - ALYSIS OF THE UNITED KINGDOM NATIONAL BARIATRIC SURGERY REGISTRY Bariatric registries, Publisher: SPRINGER, Pages: 402-402, ISSN: 0960-8923
Miras AD, le Roux CW, 2017, Metabolic Surgery in a Pill, CELL METABOLISM, Vol: 25, Pages: 985-987, ISSN: 1550-4131
Dimitriadis GK, Randeva HS, Miras AD, 2017, Microvascular complications after metabolic surgery (vol 5, pg 240, 2017), The Lancet Diabetes and Endocrinology, Vol: 5, Pages: E3-E3, ISSN: 2213-8595
Dimitriadis GK, Randeva HS, Miras AD, 2017, Microvascular complications after metabolic surgery, The Lancet Diabetes and Endocrinology, Vol: 5, Pages: 240-241, ISSN: 2213-8595
Pérez-Pevida B, Miras AD, 2017, Latest developments and future perspectives in the field of obesity, European Endocrinology, Vol: 13, Pages: 17-18, ISSN: 1758-3772
The prevalence of obesity is increasing exponentially worldwide, becoming an international public health issue that affects quality of life, increases the risk of illness and raises healthcare costs in countries in all parts of the world. In this editorial, we analyse the latest progress in the management of obesity and associated cardiovascular risk factors, and summarise the latest randomised controlled trials that have had the biggest influence on the current changes we are experiencing in obesity management.
Vimalesvaran S, Narayanaswamy S, Yang L, et al., 2017, Using kisspeptin to assess GnRH function in an unusual case of primary amenorrhoea, Endocrinology, Diabetes & Metabolism, Vol: 16, ISSN: 2052-0573
SUMMARY: Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders. LEARNING POINTS: Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis.PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism.GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release.Confirmation of intact GnRH function helps consolidate a
Kamocka A, Miras A, Patel D, et al., 2017, Bariatric surgery makes obese patients healthier; analysis of the national bariatric surgery registry, 8th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: WILEY-BLACKWELL, Pages: 15-15, ISSN: 0007-1323
Panteliou E, Miras AD, 2017, What is the role of bariatric surgery in the management of obesity ?, CLIMACTERIC, Vol: 20, Pages: 97-102, ISSN: 1369-7137
Diet, exercise, cognitive behavioral therapy and pharmacotherapy are some of the means of assisting patients to lose weight, with bariatric surgery being the most effective. Over the last two decades, the increased awareness of the systemic benefits of bariatric surgery, as well as the improved safety and the wider use of the laparoscopic approach, has made bariatric surgery flourish. In the United Kingdom, the adjustable gastric band (10%), vertical sleeve gastrectomy (37%) and Roux-en-Y gastric bypass (45%) are the three most common procedures. Obesity-associated mortality and co-morbidities such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, renal dysfunction and depression improve significantly with bariatric surgery. The mechanisms of weight loss extend beyond restriction and malabsorption and include changes in hunger and satiety, food preferences, and possibly energy expenditure. Despite its safety and efficacy, bariatric surgery is underutilized as less than 1% of adults with obesity receive it. In view of the evolution of obesity into a global threat, access to bariatric surgery should be increased, whilst developing safer and less invasive weight loss treatments.
Pérez-Pevida B, Kamocka A, Alasfour S, et al., 2017, Long-term micronutrient deficiencies in poor responders after bariatric surgery, International Federation for Surgery for Obesity, Pages: 1-1253
Miras AD, Herring R, Vuisrikala A, et al., 2016, Measurement of hepatic insulin sensitivity early after the bypass of the proximal small bowel in humans, Obesity Science & Practice, Vol: 3, Pages: 95-98, ISSN: 2055-2238
Objective: Unlike gastric banding or sleeve gastrectomy procedures, intestinal bypass procedures, and the Roux-en-Y gastric bypass (RYGB) in particular, lead to rapid improvements in glycaemia early after surgery. The bypass of the proximal small bowel may have weight loss and even caloric restriction independent glucose-lowering properties on hepatic insulin sensitivity. In this first in humans mechanistic study, we examined this hypothesis by investigating the early effects of the duodeno-jejunal bypass liner (DJBL; GI Dynamics, USA) on the hepatic insulin sensitivity using the gold standard euglycaemic hyperinsulinaemic clamp methodology. Method: Seven patients with obesity underwent measurement of hepatic insulin sensitivity at baseline, one week after a low-calorie liquid diet and after a further one week following insertion of the DJBL whilst on the same diet.Results: DJBL did not improve the insulin sensitivity of hepatic glucose production (HGP) beyond the improvements achieved with caloric restriction. Conclusions: Caloric restriction may be the predominant driver of early increases in hepatic insulin sensitivity after the endoscopic bypass of the proximal small bowel. The same mechanism may be at play after RYGB and explain, at least in part, the rapid improvements in glycaemia.
Tharakan G, Scott R, Szepietowski O, et al., 2016, Limitations of the DiaRem Score in Predicting Remission of Diabetes Following Roux-En-Y Gastric Bypass (RYGB) in an ethnically Diverse Population from a Single Institution in the UK, Obesity Surgery, Vol: 27, Pages: 782-786, ISSN: 1708-0428
PurposeThis study aimed to determine the predictive power of the DiaRem score following Roux-en-Y gastric bypass to identify patients who would have diabetes remission at 1 year in an ethnically diverse population.MethodsWe performed a retrospective review of 262 patients with type 2 diabetes mellitus who underwent RYGB at the Imperial Weight Centre, UK, from 2007 to 2014. Data was collected on the parameters required to calculate the DiaRem score as well as pre- and post-surgical weight and the ethnicity of the subjects.ResultsThe studied cohort was ethnically diverse (61.3 % Caucasian, 10.3 % Asian, 5.3 % black, 2.6 % mixed and 20.6 % other). At 1-year post-surgery, there were significant reductions in mean weight (133.4 to 94.3 kg) and BMI (46.7 to 33.3 kg/m2). The mean HbA1c decreased from 8.2 to 6.1 %, and 32.5 % of the cohort underwent either partial or complete remission. 67.8 % of the patients that were classified in group 1 of the DiaRem score (most likely to have remission) had complete remission. However, 22.9 % of the patients predicted to have the least chance of remission had either partial or complete remission.ConclusionsIn this ethnically diverse cohort, the DiaRem score remains a useful tool to predict diabetes remission in those that have a low DiaRem score (high chance for remission) but was more limited in its predictive power in those with a high DiaRem score (least likely to have remission). Caution must be used in the application of this model in populations other than the US white Caucasian population used to derive the score.
Kumar P, Hamza N, Madhok B, et al., 2016, Copper Deficiency after Gastric Bypass for Morbid Obesity: a Systematic Review, OBESITY SURGERY, Vol: 26, Pages: 1335-1342, ISSN: 0960-8923
- Author Web Link
- Cite
- Citations: 43
Goldstone AP, Miras AD, Scholtz S, et al., 2015, Link between increased satiety gut hormones and reduced food reward following gastric bypass surgery for obesity, Journal of Clinical Endocrinology & Metabolism, Vol: 101, Pages: 599-609, ISSN: 1945-7197
Context: Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weightloss maintenance, reducing appetite, and also food reward, via unclear mechanisms.Objective: To investigate the role of elevated satiety gut hormones after RYGB, we examined foodhedonic-reward responses following their acute post-prandial suppression.Design: Randomised placebo-controlled double-blind cross-over experimental medicine studies.Patients: Two groups, over 5 months after RYGB for obesity (n7–11), compared with non-obesecontrols (n10), or patients after gastric banding (BAND) surgery (n9).Intervention: Studies were performed after acute administration of the somatostatin analogueOctreotide or saline. In one study, patients after RYGB, and non-obese controls, performed abehavioral progressive ratio task (PRT) for chocolate sweets. In another study, patients after RYGB,and controls after BAND surgery, performed a functional magnetic resonance imaging (fMRI) foodpicture evaluation task.Main outcome measures: Octreotide increased both appetitive food reward (breakpoint) in thePRT (n9), and food appeal (n9) and reward system blood oxygen level dependent (BOLD) signal(n7) in the fMRI task, in the RYGB group, but not in control groups.ISSN
Behary P, Miras AD, 2015, Food preferences and underlying mechanisms after bariatric surgery, PROCEEDINGS OF THE NUTRITION SOCIETY, Vol: 74, Pages: 419-425, ISSN: 0029-6651
- Author Web Link
- Cite
- Citations: 57
Seyfried F, Miras AD, Rotzinger L, et al., 2015, Gastric Bypass-Related Effects on Glucose Control, β Cell Function and Morphology in the Obese Zucker Rat, Obesity Surgery, Vol: 26, Pages: 1228-1236, ISSN: 0960-8923
Miras AD, Chuah LL, Khalil N, et al., 2015, Type 2 diabetes mellitus and microvascular complications 1 year after Roux-en-Y gastric bypass: a case-control study, DIABETOLOGIA, Vol: 58, Pages: 1443-1447, ISSN: 0012-186X
- Author Web Link
- Open Access Link
- Cite
- Citations: 56
Seyfried F, von Rahden BH, Miras AD, et al., 2015, Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin - a longitudinal experience from a prospectively collected database of 1108 patients, BMC Cancer, Vol: 15, Pages: 1-10, ISSN: 1471-2407
BackgroundComprehensive evidence on the incidence, time course and independent risk factors of metachronous peritoneal carcinomatosis (metaPC) in gastric cancer patients treated with curative intent in the context of available systemic combination chemotherapies is lacking.MethodsData from a prospectively collected single-institutional Center Cancer Registry with 1108 consecutive patients with gastric adenocarcinoma (GC), clinical, histological and survival data were analyzed for independent risk factors and prognosis with focus on the development of metaPC. Findings were then stratified to the time periods of treatment with surgery alone, 5-Fluorouracil-only and contemporary combined systemic perioperative chemotherapy strategies, respectively.ResultsDespite R0 D2 gastrectomy (n = 560), 49.6% (±5.4%) of the patients were diagnosed with tumour recurrence and 15.5% (±1.8%) developed metaPC after a median time of 17.7 (15.1-20.3) months after surgery resulting in a tumour related mortality of 100% with a median survival of 3.0 months (2.1 – 4.0). Independent risk factors for the development of metaPC were serosa positive T-category, nodal positive-status, signet cell and undifferentiated gradings (G3/G4). Contemporary systemic combination chemotherapy did not improve the incidence and prognosis of metaPC (p = 0.54).ConclusionsDespite significant improvements in the overall survival for the complete cohort with gastric cancer over time, those patients with metaPC did not experience the same benefits. The lack of change in the incidence, and persistent poor prognosis of metaPC after curative surgery expose the need for further prevention and/or improved treatment options for this devastating condition.
Miras AD, Mogford JT, Wright J, et al., 2015, Ovarian hyperstimulation from ectopic hypersecretion of follicle stimulating hormone, LANCET, Vol: 385, Pages: 392-392, ISSN: 0140-6736
- Author Web Link
- Cite
- Citations: 8
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.