128 results found
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.
Williams EL, Choudhury S, Tan T, et al., 2016, Prednisolone replacement therapy mimics the circadian rhythm more closely than other glucocorticoids, The Journal of Applied Laboratory Medicine, Vol: 1, Pages: 152-161, ISSN: 2576-9456
BackgroundThis study examined the pharmacokinetic profile of prednisolone.MethodsUsing a newly developed ultra-performance liquid chromatography MS/MS method, prednisolone profiles in healthy volunteers and patients with adrenal insufficiency already treated with prednisolone were prospectively analyzed in a tertiary center.ResultsTwelve prednisolone day curves were analyzed. Six patients with secondary adrenal insufficiency provided 7 curves and 3 healthy volunteers provided 5 curves, 1 of which was with the prednisolone administered in divided doses. The mean prednisolone dose required for adequate replacement in hypoadrenal patients was 3.86 mg. The overall mean maximal serum concentration (Cmax) was 114.0 μg/L and was achieved at an average time to maximal concentration (Tmax) of 1.43 h. Total glucocorticoid exposure was represented by the mean area under the curve to 24 h (AUC0–24h), which was 518.2 μg|·|h/L. Splitting the dose substantially increased the total glucocorticoid exposure.ConclusionsThe pharmacokinetic profile of prednisolone is similar to the published profile of dual-release hydrocortisone. Once-daily prednisolone can thus be used as a replacement for hydrocortisone. Further studies need to be carried out to accurately calculate an equivalent replacement dose. Prednisolone levels are a useful adjunct to dose adjustment when low doses are being used for replacement.
Moussa OM, Macaskill A, Fakir N, et al., 2016, OUTCOMES IN 60 YEARS AND OLDER AT A HIGH VOLUME BARIATRIC SURGERY CENTER; IS IT SAFE?, 21st World Congress of International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: S444-S445, ISSN: 0960-8923
Pinato DJ, Black JRM, Ramaswami R, et al., 2016, Peptide receptor radionuclide therapy for metastatic paragangliomas, Medical Oncology, Vol: 33, ISSN: 1559-131X
There is little evidence to direct the management of malignant paragangliomas (mPGL) beyond initial surgical treatment. Peptide receptor radionuclide therapy (PRRT), using somatostatin analogues, is effective in other neuroendocrine tumours, but data on its efficacy in treating mPGL are scarce. We report safety and efficacy outcomes from a case series of five patients with advanced mPGLs treated with 177Lu-DOTATATE PRRT. The mean age of our cohort was 34 years (range 16–47); 4 patients were male with bone disease being the most prevalent metastatic site. PRRT scheme varied between 1 and 4 cycles, with premature cessation due to suspected pneumonitis in one case and disease progression in another. Three patients with previously documented progressive disease achieved stabilization following treatment; one had partial response and one was treatment refractory. Median progression-free survival was 17 months (range 0–78 months). 177-Lu-DOTATATE is an effective therapy in mPGLs in this molecularly defined patient cohort, warranting further investigation in larger studies including hereditary and sporadic mPGL.
Choudhury SM, Tan TM, Bloom SR, 2016, Gastrointestinal hormones and their role in obesity, Current Opinion in Endocrinology Diabetes and Obesity, Vol: 23, Pages: 18-22, ISSN: 1752-2978
Purpose of review: Pandemic obesity is the most pressing health issue of this century. The most successful treatment so far is bariatric surgery, but for various reasons, surgery cannot be applied to all patients who require treatment. Gastrointestinal hormones are likely to play a key role in the success of bariatric surgery. This article examines in detail three of these gut hormones: peptide YY, oxyntomodulin and pancreatic polypeptide, and reviews how recent developments may offer new targets for therapy.Recent findings: Both the free fatty acid 2 and the melanocortin 4 receptors have been discovered to regulate peptide YY and glucagon-like peptide-1 secretion, and drugs targeting these may represent new antiobesity therapies. Dual agonism of glucagon-like peptide-1 and glucagon receptors, for example with oxyntomodulin, has synergistic effects in reducing appetite and increasing energy expenditure. Plasma pancreatic polypeptide concentration correlates with visceral adiposity, and may serve as a biomarker for metabolic syndrome.Summary: Gut hormones continue to show promise on an individual basis as anti-obesity treatments, but combination therapies are needed to achieve beneficial effects comparable to bariatric surgery. Innovative pathways for stimulating native gut hormone secretion may well provide an alternative method for weight loss without necessitating the administration of gut hormone analogues via injection.
Salem V, Izzi-Engbeaya C, Coello C, et al., 2015, Glucagon increases energy expenditure independently of brown adipose tissue activation in humans, Diabetes Obesity & Metabolism, Vol: 18, Pages: 72-81, ISSN: 1463-1326
AimsTo investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans.MethodsIndirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent ¹⁸F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold-induced BAT activation on ¹⁸F-FDG PET/CT (n = 8) underwent a randomly allocated second ¹⁸F-FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4).ResultsWe observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold-induced increase in the metabolic activity of supraclavicular BAT on ¹⁸F-FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not.ConclusionsGlucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE.
Clarke REJ, Bloom SR, Tan T, 2015, Gut Hormones, Encyclopedia of Food and Health, Pages: 290-294, ISBN: 9780123849472
© 2016 Elsevier Ltd. All rights reserved. The gastrointestinal tract is a major endocrine organ secreting over 20 different hormones that contribute to digestion, absorption, energy homeostasis, and appetite. The different patterns of gut hormone release seen during fasting, and consumption of high-sugar or high-fat meals, allow us to understand how hunger and satiety are generated. This article considers ghrelin, gastrin, cholecystokinin, secretin, motilin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, glucagon-like peptide-2, oxyntomodulin, pancreatic polypeptide, and peptide YY. The therapeutic manipulation of gut hormones already allows us to treat type 2 diabetes mellitus and may be the answer to the obesity epidemic.
Cegla J, Cuenco J, Minnion J, et al., 2015, Pharmacokinetics and pharmacodynamics of subcutaneously administered PYY3-36 and its analogues in vivo, LANCET, Vol: 385, Pages: 28-28, ISSN: 0140-6736
Ramachandran R, Bech P, Murphy KG, et al., 2015, Comparison of the Utility of Cocaine- and Amphetamine-Regulated Transcript (CART), Chromogranin A, and Chromogranin B in Neuroendocrine Tumor Diagnosis and Assessment of Disease Progression, Journal of Clinical Endocrinology & Metabolism, Vol: 100, Pages: 1520-1528, ISSN: 1945-7197
Christakis I, Georgiou P, Minnion J, et al., 2015, Learning curve of vessel cannulation in rats using cumulative sum analysis, JOURNAL OF SURGICAL RESEARCH, Vol: 193, Pages: 69-76, ISSN: 0022-4804
Behary P, Cegla J, Tan TM, et al., 2015, Obesity: Lifestyle management, bariatric surgery, drugs, and the therapeutic exploitation of gut hormones, POSTGRADUATE MEDICINE, Vol: 127, Pages: 494-502, ISSN: 0032-5481
Howard JW, Kay RG, Tan T, et al., 2014, Identification of plasma protease derived metabolites of glucagon and their formation under typical laboratory sample handling conditions, Rapid Communications in Mass Spectrometry, Vol: 29, Pages: 171-181, ISSN: 1097-0231
RATIONALEGlucagon modulates glucose production, and it is also a biomarker for several pathologies. It is known to be unstable in human plasma, and consequently stabilisers are often added to samples, although these are not particularly effective. Despite this, there have not been any studies to identify in vitro plasma protease derived metabolites; such a study is described here. Knowledge of metabolism should allow the development of more effective sample stabilisation strategies.METHODSSeveral novel metabolites resulting from the incubation of glucagon in human plasma were identified using high-resolution mass spectrometry with positive electrospray ionisation. Tandem mass spectrometric (MS/MS) scans were acquired for additional confirmation using a QTRAP. Separation was performed using reversed-phase ultra-high-performance liquid chromatography. The formation of these metabolites was investigated during a time-course experiment and under specific stress conditions representative of typical laboratory handling conditions. Clinical samples were also screened for metabolites.RESULTSGlucagon3-29 and [pGlu]3glucagon3-29 were the major metabolites detected, both of which were also present in clinical samples. We also identified two oxidised forms of [pGlu]3glucagon3-29 as well as glucagon19-29, or 'miniglucagon', along with the novel metabolites glucagon20-29 and glucagon21-29. The relative levels of these metabolites varied throughout the time-course experiment, and under the application of the different sample handling conditions. Aprotinin stabilisation of samples had negligible effect on metabolite formation.CONCLUSIONSNovel plasma protease metabolites of glucagon have been confirmed, and their formation characterised over a time-course experiment and under typical laboratory handling conditions. These metabolites could be monitored to assess the effectiveness of new sample stabilisation strategies, and further investigations into their formation could suggest spe
Howard JW, Kay RG, Tan T, et al., 2014, Development of a high-throughput UHPLC-MS/MS (SRM) method for the quantitation of endogenous glucagon from human plasma, Bioanalysis, Vol: 6, Pages: 3295-3309, ISSN: 1757-6199
Scott RV, Tan TM, Bloom SR, 2014, Can Bayliss and Starling gut hormones cure a worldwide pandemic?, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 592, Pages: 5153-5167, ISSN: 0022-3751
Tzoulis P, Evans R, Falinska A, et al., 2014, Multicentre study of investigation and management of inpatient hyponatraemia in the UK, Postgraduate Medical Journal, Vol: 90, Pages: 694-698, ISSN: 1469-0756
Cegla J, Troke RC, Jones B, et al., 2014, Coinfusion of Low-Dose GLP-1 and Glucagon in Man Results in a Reduction in Food Intake, DIABETES, Vol: 63, Pages: 3711-3720, ISSN: 0012-1797
Tan TM, Salem V, Troke RC, et al., 2014, Combination of Peptide YY3-36 with GLP-1(7-36) amide Causes an Increase in First-Phase Insulin Secretion after IV Glucose, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 99, Pages: E2317-E2324, ISSN: 0021-972X
Allum M, Barnes S, Jackson J, et al., 2014, Repeat Adrenal Vein Sampling Demonstrating Bilateral Aldosterone Secretion after Initial Discordant Results in the Investigation of Conn's Syndrome, a Case Report, ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Christakis IC, Minnion JM, Tan TT, et al., 2014, A surgical rat model for investigating pharmacokinetic parameters of drug compounds, Annual Meeting of the Society-of-Academic-and-Research-Surgery, Publisher: WILEY-BLACKWELL, Pages: 27-27, ISSN: 0007-1323
Pinato DJ, Tan TM, Toussi STK, et al., 2014, An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes, BRITISH JOURNAL OF CANCER, Vol: 110, Pages: 115-122, ISSN: 0007-0920
Troke RC, Tan TM, Bloom SR, 2014, The future role of gut hormones in the treatment of obesity., Ther Adv Chronic Dis, Vol: 5, Pages: 4-14, ISSN: 2040-6223
The obesity pandemic presents a significant burden, both in terms of healthcare and economic outcomes, and current medical therapies are inadequate to deal with this challenge. Bariatric surgery is currently the only therapy available for obesity which results in long-term, sustained weight loss. The favourable effects of this surgery are thought, at least in part, to be mediated via the changes of gut hormones such as GLP-1, PYY, PP and oxyntomodulin seen following the procedure. These hormones have subsequently become attractive novel targets for the development of obesity therapies. Here, we review the development of these gut peptides as current and emerging therapies in the treatment of obesity.
Tan T, Bloom S, 2013, Gut hormones as therapeutic agents in treatment of diabetes and obesity, CURRENT OPINION IN PHARMACOLOGY, Vol: 13, Pages: 996-1001, ISSN: 1471-4892
Troke R, Tan TM, Bloom SR, 2013, PYY, Handbook of Biologically Active Peptides, Pages: 1160-1165, ISBN: 9780123850959
Tan TM, Bloom SR, 2013, Pancreatic Polypeptide, Handbook of Biologically Active Peptides, Pages: 1294-1299, ISBN: 9780123850959
Tharakan G, Chahal H, Tan T, et al., 2013, A Case Series Illustrating Successful Treatment of Obesity in Renal Transplant Patients with Sleeve Gastrectomies, 18th World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 1144-1144, ISSN: 0960-8923
Pinato DJ, Tan TM, Toloue-Kalami-Toussi S, et al., 2013, AN EXPRESSION SIGNATURE OF THE ANGIOGENIC RESPONSE IN GASTROINTESTINAL NEUROENDOCRINE TUMOURS: CORRELATION WITH TUMOUR PHENOTYPE AND SURVIVAL OUTCOMES, Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: BMJ PUBLISHING GROUP, Pages: A29-A29, ISSN: 0017-5749
Cegla J, Jones B, Seyani L, et al., 2013, Comparison of the overnight metyrapone and glucagon stimulation tests in the assessment of secondary hypoadrenalism, CLINICAL ENDOCRINOLOGY, Vol: 78, Pages: 738-742, ISSN: 0300-0664
Tan TM, Field BCT, McCullough KA, et al., 2013, Coadministration of Glucagon-Like Peptide-1 During Glucagon Infusion in Humans Results in Increased Energy Expenditure and Amelioration of Hyperglycemia, DIABETES, Vol: 62, Pages: 1131-1138, ISSN: 0012-1797
Kenkre J, Tan T, Bloom S, 2013, Treating the obese diabetic, EXPERT REVIEW OF CLINICAL PHARMACOLOGY, Vol: 6, Pages: 171-183, ISSN: 1751-2433
Pinato DJ, Ramachandran R, Toussi STK, et al., 2013, Immunohistochemical markers of the hypoxic response can identify malignancy in phaeochromocytomas and paragangliomas and optimize the detection of tumours with VHL germline mutations, BRITISH JOURNAL OF CANCER, Vol: 108, Pages: 429-437, ISSN: 0007-0920
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