Imperial College London

DrTriciaTan

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Practice (Metabolic Medicine & Endocrinology)
 
 
 
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+44 (0)20 3313 8038t.tan

 
 
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6N6ECommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
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109 results found

Kamocka A, McGlone ER, Pérez-Pevida B, Moorthy K, Hakky S, Tsironis C, Chahal H, Miras AD, Tan T, Purkayastha S, Ahmed ARet al., 2019, Candy cane revision after Roux-en-Y gastric bypass, Surgical Endoscopy, ISSN: 0930-2794

BACKGROUND: An excessively long-blind end of the alimentary limb following a Roux-en-Y gastric bypass (RYGB), known as a 'candy cane' (CC), may cause symptoms including abdominal pain, regurgitation and vomiting. Very few studies have examined the efficacy of surgical resection of the CC. OBJECTIVES: The aim of this study was to assess sensitivity of preoperative diagnostic tools for CC, as well as perioperative outcomes and symptom resolution after CC revision surgery. SETTING: High volume bariatric centre of excellence, United Kingdom. METHODS: Observational study of CC revisions from 2010 to 2017. RESULTS: Twenty-eight CC revision cases were identified (mean age 45 ± 9 years, female preponderance 9:1). Presenting symptoms were abdominal pain (86%), regurgitation/vomiting (43%), suboptimal weight loss (36%) and acid reflux (21%). Preoperative tests provided correct diagnosis in 63% of barium contrast swallows, 50% of upper gastrointestinal endoscopies and 29% computed tomographies. Patients presenting with pain had significantly higher CC size as compared with pain-free group (4.2 vs. 2 cm, p = 0.001). Perioperative complications occurred in 25% of cases. Complete or partial symptom resolution was documented in 73% of patients undergoing CC revision. Highest success rates were recorded in the regurgitation/vomiting group (67%). CONCLUSION: Surgical revision of CC is associated with good symptom resolution in the majority of patients, especially those presenting with regurgitation/vomiting. However, it carries certain risk of complications. CC diagnosis may frequently be missed; hence more than one diagnostic tool should be considered when investigating symptomatic patients after RYGB.

Journal article

Miras AD, Ravindra S, Humphreys A, Lascaratos G, Quartey KNK, Ahmed AR, Cousins J, Moorthy K, Purkayastha S, Hakky S, Tan T, Chahal HSet al., 2019, Metabolic changes and diabetes microvascular complications 5 years after obesity surgery., Obesity Surgery, ISSN: 0960-8923

BACKGROUND: Obesity surgery has pronounced effects on metabolic profile of patients with type 2 diabetes mellitus (T2DM); however, reports on long-term remission rates based on the standardised and holistic criteria by the International Diabetes Federation (IDF) and effects on T2DM microvascular complications are scarce in the literature. In this retrospective clinical trial, our objectives were to assess these variables 5 years after surgery. METHODS: Clinical data and direct measurements of renal and retinal damage were collected prospectively and analysed retrospectively for 82 patients with T2DM who underwent obesity surgery and were followed up for 5 years. RESULTS: The cohort of 82 patients with T2DM that were followed up 5 years after obesity surgery was predominantly female (71%) with a median age of 51 years, weight of 133.5 kg, BMI of 46.8 kg/m2 and pre-operative duration of T2DM of 8 years; 6% of patients had diet-controlled T2DM, 57% were on non-insulin treatment and 37% were on insulin treatment pre-operatively. Of the total 82 patients, 59 patients underwent Roux-en-Y gastric bypass, 15 sleeve gastrectomy and 8 patients underwent gastric band operations. At 5 years, 5% and 15% patients achieved optimisation and improvement of the metabolic state based on the IDF criteria respectively. Surgery was associated with almost halving of the albumin-creatinine ratio in 22 patients with pre-existing albuminuria (follow-up data available for 64 patients) and an overall stabilisation of retinopathy in 24 patients with retinal images available at 5 years. CONCLUSION: Whilst the findings on microvascular complications are encouraging, the rates of metabolic remission were lower than expected and raise the need for validated protocols to assist clinicians in managing these patients more aggressively post-operatively to achieve optimum cardio-metabolic risk factor control and hopefully further reduction in microvascular an

Journal article

Kamocka A, Miras AD, Perez-Pevida B, Umpleby AM, Chahal H, Moorthy K, Purkayastha S, Patel A, Tan T, Bloom S, Ahmed AR, Rubino Fet al., 2019, LONG VS STANDARD BILIOPANCREATIC LIMB ROUX-EN-Y GASTRIC BYPASS FOR TYPE 2 DIABETES. THE LONG LIMB TRIAL Type 2 diabetes and metabolic surgery, 24th World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO) / 21st SECO Congress, Publisher: SPRINGER, Pages: 234-234, ISSN: 0960-8923

Conference paper

Rose F, Bloom S, Tan T, Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years, EXPERT OPINION ON DRUG DISCOVERY, ISSN: 1746-0441

Journal article

McGlone ER, Tan T, Bloom SR, Walters JRFet al., 2019, What Can We Learn From Mouse Models About Bile Acid–Mediated Changes After Bariatric Surgery?, Gastroenterology, Vol: 157, Pages: 4-8, ISSN: 0016-5085

Journal article

Behary P, Tharakan G, Alexiadou K, Johnson N, Wewer Albrechtsen NJ, Kenkre J, Cuenco J, Hope D, Anyiam O, Choudhury S, Alessimii H, Poddar A, Minnion J, Doyle C, Frost G, Le Roux C, Purkayastha S, Moorthy K, Dhillo W, Holst JJ, Ahmed AR, Prevost AT, Bloom SR, Tan TMet al., 2019, Combined GLP-1, oxyntomodulin, and peptide YY improves body weight and glycemia in obesity and prediabetes/type 2 diabetes: a randomized single-blinded placebo controlled study, Diabetes Care, Vol: 42, Pages: 1446-1453, ISSN: 0149-5992

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity. RESEARCH DESIGN AND METHODS: In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring. RESULTS: GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD. CONCLUSIONS: GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.

Journal article

Suliman M, Buckley A, Al Tikriti A, Tan T, le Roux CW, Lessan N, Barakat Met al., 2019, Routine clinical use of liraglutide 3 mg for the treatment of obesity: Outcomes in non-surgical and bariatric surgery patients, DIABETES OBESITY & METABOLISM, Vol: 21, Pages: 1498-1501, ISSN: 1462-8902

Journal article

Miras AD, Pérez-Pevida B, Aldhwayan M, Kamocka A, McGlone ER, Al-Najim W, Chahal H, Batterham RL, McGowan B, Khan O, Greener V, Ahmed AR, Petrie A, Scholtz S, Bloom SR, Tan TMet al., 2019, Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial, The Lancet Diabetes & Endocrinology, ISSN: 2213-8587

Journal article

Alexiadou K, Anyiam O, Tan T, 2019, Cracking the combination: gut hormones for the treatment of obesity and diabetes, Journal of Neuroendocrinology, Vol: 31, Pages: e12664-e12664, ISSN: 0953-8194

Obesity and type 2 diabetes are a veritable global pandemic. There is an imperative to develop new therapies for these conditions that can be delivered at scale to patients, which deliver effective and titratable weight loss, amelioration of diabetes, prevention of diabetic complications and improvements in cardiovascular health. Although agents based on glucagon-like peptide-1 (GLP-1) are now in routine use for diabetes and obesity, the limited efficacy of such drugs means that newer agents are required. By combining the effects of GLP-1 with other gut and metabolic hormones such as glucagon (GCG), oxyntomodulin, glucose-dependent insulinotropic peptide (GIP) and peptide YY, we may obtain improved weight loss, increased energy expenditure and improved metabolic profiles. Drugs based on dual agonism of GLP1R/GCGR and GLP1R/GIPR are being actively developed in clinical trials. Triple agonism, for example with GLPR1/GCGR/GIPR unimolecular agonists or using GLP-1/oxyntomodulin/peptide YY, is also being explored. Multi-agonist drugs seem set to deliver the next generation of therapies for diabetes and obesity soon. This article is protected by copyright. All rights reserved.

Journal article

Choudhury S, Machenahalli P, Tan T, Meeran Ket al., 2019, Inadvertent treatment of hypoadrenalism with prednisolone in pemphigus: a case report, Clinical Case Reports, Vol: 7, Pages: 987-989, ISSN: 2050-0904

Pituitary and adrenal insufficiency must not be overlooked when weaning patients down from high‐dose steroids. Prednisolone can be used as glucocorticoid replacement therapy, with most patients needing 3‐4 mg once daily.

Journal article

Kamocka A, Perez-Pevida B, Miras AD, Markakis H, Castagneto-Gissey L, Casella J, Villa F, Panagiotopoulos S, Reyhani A, Petronio B, Patel A, Tan T, Moorthy K, Purkayastha S, Ahmed AR, Bloom S, Rubino Fet al., 2019, Total small bowel length varies considerably among patients with obesity and diabetes: Is there a role for individualisation of limb lengths in Roux-en-Y gastric bypass?, 10th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S11-S11, ISSN: 0960-8923

Conference paper

Szepietowski O, Alsters S, Mahir G, Murphy J, Ozdemir E, Murphy K, Dovey T, Le Roux C, Tan T, Ahmed A, Chahal H, Purkayastha S, Blakemore Aet al., 2019, Recent-Onset Type 2 Diabetes Is Defined As < 10 Years Duration, 10th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S11-S11, ISSN: 0960-8923

Conference paper

Armeni E, Almazrouei R, Hayes AR, Palazzo F, Todd J, Toumpanakis C, Wernig F, Grossman AB, Meeran K, Caplin M, Tan T, Khoo Bet al., 2019, Insight into the Management of Chromaffin Cell Derived Tumours - Experience from Two ENETS Centres of Excellence, 16th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Publisher: KARGER, Pages: 271-271, ISSN: 0028-3835

Conference paper

Izzi-Engbeaya CN, Comninos AN, Clarke S, Abbara A, Lewis M, Holmes E, Nicholson J, Tan T, Rutter G, Dhillo Wet al., 2018, The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans, Diabetes, Obesity and Metabolism, Vol: 20, Pages: 2800-2810, ISSN: 1462-8902

AimsTo investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.Materials and methodsIn 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).ResultsKisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.ConclusionsCollectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.

Journal article

McGlone ER, Tan M, Purkayastha S, Tan T, Ahmed Aet al., 2018, FEASIBILITY OF SINGLE STAGE REVISION OF GASTRIC BAND TO MINI-GASTRIC BYPASS Gastric Bypass Procedures Including RYGB And OAGB/MGB, 23rd World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 93-93, ISSN: 0960-8923

Conference paper

Szepietowski O, Alsters SI, Mahir G, Murphy J, Ozdemir E, Murphy KG, Dovey T, Le-Roux C, Tan TM, Chahal H, Purkayastha S, Blakemore Aet al., 2018, PREDICTING REMISSION OF NON-INSULIN TREATED TYPE 2 DIABETES AFTER RYGB, 23rd World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 191-191, ISSN: 0960-8923

Conference paper

Tharakan G, Miras A, Chahal H, Moorthy K, Purkayastha S, Tan T, Ahmed Aet al., 2018, BARIATRIC SURGERY OUTCOMES IN THE OVER-60S: A SINGLE CENTRE, OBSERVATIONAL STUDY FROM 2007-2012., 23rd World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 376-376, ISSN: 0960-8923

Conference paper

Kamocka A, McGlone ER, Pevida BP, Purkayastha S, Moorthy K, Hakky S, Chahal H, Tsironis C, Miras AD, Tan T, Ahmed Aet al., 2018, SURGICAL REVISION OF CANDY CANE AFTER ROUX-EN-Y GASTRIC BYPASS, 23rd World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 232-232, ISSN: 0960-8923

Conference paper

Tharakan G, Miras A, Chahal H, Tan T, Ahmed Aet al., 2018, MANAGEMENT OF POST PRANDIAL HYPOGLYCAEMIA USING LIRAGLUTIDE -COMPREHENSIVE PROFILING PRE AND POST INTERVENTION, 23rd World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 378-378, ISSN: 0960-8923

Conference paper

Hope DCD, Tan TMM, Bloom SR, 2018, No guts, no loss: Toward the ideal treatment for obesity in the twenty-first century, Frontiers in Endocrinology, Vol: 9, ISSN: 1664-2392

Over the last century, our knowledge of the processes which control appetite and weight regulation has developed significantly. The understanding of where gut hormones fit into the control of energy homeostasis in addition to the rapid advancement of pharmacotherapeutics has paved the way for the development of novel gut hormone analogs to target weight loss. Currently, bariatric surgery remains the most efficacious treatment for obesity. The emergence of gut hormone analogs may provide a useful non-surgical addition to the armamentarium in treating obesity. Simply targeting single gut hormone pathways may be insufficiently efficacious, and combination/multiple-agonist approaches may be necessary to obtain the results required for clear clinical impact.

Journal article

McGlone ER, Tan TM, 2018, Of Mice Not Men? Actions of Interleukin-6 on Glucose Tolerance, CELL METABOLISM, Vol: 27, Pages: 1157-1158, ISSN: 1550-4131

Journal article

Scott R, Minnion J, Tan T, Bloom SRet al., 2018, Oxyntomodulin analogue increases energy expenditure via the glucagon receptor, Peptides, Vol: 104, Pages: 70-77, ISSN: 0196-9781

The gut hormone oxyntomodulin (OXM) causes weight loss by reducing appetite and increasing energy expenditure. Several analogues are being developed to treat obesity. Exactly how oxyntomodulin works, however, remains controversial. OXM can activate both glucagon and GLP-1 receptors but no specific receptor has been identified. It is thought that the anorectic effect occurs predominantly through GLP-1 receptor activation but, to date, it has not been formally confirmed which receptor is responsible for the increased energy expenditure. We developed OX-SR, a sustained-release OXM analogue. It produces a significant and sustained increase in energy expenditure in rats as measured by indirect calorimetry. We now show that this increase in energy expenditure occurs via activation of the glucagon receptor. Blockade of the GLP-1 receptor with Exendin 9-39 does not block the increase in oxygen consumption caused by OX-SR. However, when activity at the glucagon receptor is lost, there is no increase in energy expenditure. Glucagon receptor activity therefore appears to be essential for OX-SR's effects on energy expenditure. The development of future 'dual agonist' analogues will require careful balancing of GLP-1 and glucagon receptor activities to obtain optimal effects.

Journal article

Jones B, Buenaventura T, Kanda N, Chabosseau P, Owen B, Scott R, Goldin R, Angkathunyakul N, Correa Jr IR, Bosco D, Johnson PR, Piemonti L, Marchetti P, Shapiro AMJ, Cochran B, Hanyaloglu A, Inoue A, Tan T, Rutter G, Tomas Catala A, Bloom Set al., 2018, Targeting GLP-1 receptor trafficking to improve agonist efficacy, Nature Communications, Vol: 9, ISSN: 2041-1723

Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but the functional and therapeutic consequences of modulating GLP-1R endocytic trafficking have not been clearly defined. Here, we investigate a novel series of biased GLP-1R agonists with variable propensities for GLP-1R internalization and recycling. Compared to a panel of FDA-approved GLP-1 mimetics, compounds that retain GLP-1R at the plasma membrane produce greater long-term insulin release, which is dependent on a reduction in β-arrestin recruitment and faster agonist dissociation rates. Such molecules elicit glycemic benefits in mice without concomitant increases in signs of nausea, a common side effect of GLP-1 therapies. Our study identifies a set of agents with specific GLP-1R trafficking profiles and the potential for greater efficacy and tolerability as T2D treatments.

Journal article

Choudhury S, Tan T, Meeran K, 2018, Once-daily, modified-release hydrocortisone in patients with adrenal insufficiency, LANCET DIABETES & ENDOCRINOLOGY, Vol: 6, Pages: 269-270, ISSN: 2213-8587

Journal article

Kamocka A, McGlone ER, Perez-Pevida B, Purkayastha S, Moorthy K, Hakky S, Chahal H, Tsironis C, Miras AD, Tan T, Ahmed Aet al., 2018, Surgical revision of candy cane after Roux-en-Y gastric bypass, Obesity Update 2018, Pages: CD2.3-CD2.3, ISSN: 1470-3947

Conference paper

Law J, Morris DE, Izzi-Engbeaya CN, Salem V, Coello C, Robinson L, Jayasinghe M, Scott R, Gunn R, Rabiner E, Tan T, Dhillo WS, Bloom SR, Budge H, Symonds MEet al., 2018, Thermal imaging is a non-invasive alternative to PET-CT for measurement of brown adipose tissue activity in humans, Journal of Nuclear Medicine, Vol: 59, Pages: 516-522, ISSN: 1535-5667

Obesity and its metabolic consequences are a major cause of morbidity and mortality. Brown adipose tissue (BAT) utilizes glucose and free fatty acids to produce heat, thereby increasing energy expenditure. Effective evaluation of human BAT stimulators is constrained by the current standard method of assessing BAT—PET/CT—as it requires exposure to high doses of ionizing radiation. Infrared thermography (IRT) is a potential noninvasive, safe alternative, although direct corroboration with PET/CT has not been established. Methods: IRT and 18F-FDG PET/CT data from 8 healthy men subjected to water-jacket cooling were directly compared. Thermal images were geometrically transformed to overlay PET/CT-derived maximum intensity projection (MIP) images from each subject, and the areas with the most intense temperature and glucose uptake within the supraclavicular regions were compared. Relationships between supraclavicular temperatures (TSCR) from IRT and the metabolic rate of glucose uptake (MR(gluc)) from PET/CT were determined. Results: Glucose uptake on MR(gluc)MIP was found to correlate positively with a change in TSCR relative to a reference region (r2 = 0.721; P = 0.008). Spatial overlap between areas of maximal MR(gluc)MIP and maximal TSCR was 29.5% ± 5.1%. Prolonged cooling, for 60 min, was associated with a further TSCR rise, compared with cooling for 10 min. Conclusion: The supraclavicular hotspot identified on IRT closely corresponded to the area of maximal uptake on PET/CT-derived MR(gluc)MIP images. Greater increases in relative TSCR were associated with raised glucose uptake. IRT should now be considered a suitable method for measuring BAT activation, especially in populations for whom PET/CT is not feasible, practical, or repeatable.

Journal article

Hameed S, Salem V, Tan T, Collins A, Shah K, Scholtz S, Ahmed A, Chahal Het al., 2018, Beyond weight loss; establishing a post-bariatric surgery patient support group. What do patients want?, Journal of Obesity, Vol: 2018, ISSN: 2090-0708

Purpose. There are limited resources for long-term specialist follow-up after bariatric surgery. In selected centres, patients can access a postoperative support group, but there is no clear evidence to guide their delivery. Materials and Methods. A retrospective study of bariatric surgery patients (n = 152) who had been discharged from specialist follow-up (mean time since surgery 5.5 years), covering weight history, physical and psychosocial comorbidities, and the need for a postoperative bariatric support group. Results. Fifty-eight percent wanted a postbariatric surgery patient support group. This was not associated with operation type or the amount of weight lost or regained. However, those who wanted a support group were significantly more likely to be struggling to keep the weight off, to be unhappy with the way they look, or to be experiencing difficulties returning to work. Conclusions. These data point to an unmet patient requirement for a postoperative support group that is independent of weight loss success. More research is required to ascertain how such a group should be delivered, but our data would suggest that supporting patients with weight loss maintenance, body image, and return to work is an important part of postoperative care, and these needs extend well beyond the immediate period of specialist follow-up.

Journal article

Loh WJ, Tharakan G, Todd J, Chahal H, Dhillo W, Martin N, Toumpanakis C, Caplin M, Spalding D, Meeran K, Tan T, Khoo Bet al., 2018, Sensitivity and Specificity of Insulin, C-Peptide and Nadir Glucose during 72 hr Supervised Fast in Diagnosis of Insulinoma, 15th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Publisher: KARGER, Pages: 297-297, ISSN: 0028-3835

Conference paper

Tharakan G, Behary P, Wewer Albrechtsen NJ, Chahal H, Kenkre J, Miras AD, Ahmed AR, Holst JJ, Bloom SR, Tan TMMet 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.

Journal article

Khoo B, Boshier PR, Freethy A, Tharakan G, Saeed S, Hill N, Williams EL, Moorthy K, Tolley N, Jiao LR, Spalding D, Palazzo F, Meeran K, Tan Tet al., 2017, Redefining the stress cortisol response to surgery., Clinical Endocrinology, Vol: 87, Pages: 451-458, ISSN: 1365-2265

BACKGROUND: Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less-specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay. METHODS: Euadrenal patients undergoing elective surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical day, induction and 1 hour, 2 hour, 4 hour and 8 hour after. Subsequent samples were taken daily at 8 am until postoperative day 5 or hospital discharge. Total cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding globulin (CBG) using a radioimmunoassay. Surgical severity was classified by POSSUM operative severity score. RESULTS: Ninety-three patients underwent surgery: Major/Major+ (n = 37), Moderate (n = 33) and Minor (n = 23). Peak cortisol positively correlated to severity: Major/Major+ median 680 [range 375-1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis test, P = .0031). CBG fell by 23%; the magnitude of the drop positively correlated to severity. CONCLUSIONS: The range in baseline and peak cortisol response to surgery is wide, and peak cortisol levels are lower than previously appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays might explain our observed lower peak cortisols. The criteria for the dynamic testing of cortisol response may need to be reduced to take account of these factors. Our data also support a lower-dose, stratified approach to dosing of steroid replacement in hypoadrenal patients, to minimize the deleterious effects of over-replacement.

Journal article

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