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Cushing’s syndrome (CS) secondary to ectopic adrenocorticotrophic hormone (ACTH)-producing prostate cancer is rare with less than 50 cases reported. The diagnosis can be challenging due to atypical and variable clinical presentations of this uncommon source of ectopic ACTH secretion. We report a case of Cushing’s syndrome secondary to prostate adenocarcinoma who presented with symptoms of severe hypercortisolism with recurrent hypokalaemia, limb oedema, limb weakness, and sepsis. He presented with severe hypokalaemia and metabolic alkalosis (potassium 2.5 mmol/L and bicarbonate 36 mmol/L), with elevated 8 am cortisol 1229 nmol/L. ACTH-dependent Cushing’s syndrome was diagnosed with inappropriately normal ACTH 57.4 ng/L, significantly elevated 24-hour urine free cortisol and unsuppressed cortisol after 1 mg low-dose, 2-day low-dose, and 8 mg high-dose dexamethasone suppression tests. 68Ga-DOTANOC PET/CT showed an increase in DOTANOC avidity in the prostate gland, and his prostate biopsy specimen was stained positive for ACTH and markers for neuroendocrine differentiation. He was started on ketoconazole, which was switched to IV octreotide in view of liver dysfunction from hepatic metastases. He eventually succumbed to the disease after 3 months of his diagnosis. It is imperative to recognize prostate carcinoma as a source of ectopic ACTH secretion as it is associated with poor clinical outcomes, and the diagnosis can be missed due to atypical clinical presentations.

Background Adrenalectomy cures unilateral primary aldosteronism, and it improves or cures hypertension. However, a significant proportion of patients are classified with absent clinical success postsurgery, suggesting that surgery was ineffective. Methods We assessed all patients 6 to 12 months post-surgery for clinical outcomes using Primary Aldosteronism Surgical Outcomes (PASO), AVIS-2, and CONNsortium criteria. We estimated blood pressure changes after adjustment for changes in defined daily dosages of antihypertensive medications. We also reassessed all patients using PASO at their recent clinical visit. Results A total of 104 patients with unilateral primary aldosteronism underwent adrenalectomy at 2 tertiary centers from 2000 to 2019; 24 (23%), 31 (30%), and 54 (52%) patients were classified with absent clinical success using PASO, AVIS-2, and CONNsortium criteria, respectively. Among 24 patients with absent clinical success using PASO criteria, 10 had complete biochemical cure, 3 partial, 2 absent, and 9 had resolution of hypokalemia. On multivariable analysis, absent clinical success was associated with presence of hyperlipidemia, diabetes mellitus, and lower defined daily dosages at baseline. After adjustment for changes in defined daily dosages, 7 of 24 patients showed blood pressure improvement ≥20/10 mm Hg post-surgery. After a follow-up of mean 5.6 years, 12 of 24 patients showed partial or complete clinical success when reassessed using PASO criteria. Only 6 of 104 (5.8%) patients failed to show clinical improvement post-surgery using any of the 3 mentioned criteria or using PASO criteria at their recent clinical visit. Conclusion Although some patients may be classified with absent clinical success post-surgery, the assessment of clinical outcomes remains subject to many variables. In patients with unilateral primary aldosteronism, evidenced by lateralization on AVS, unilateral adrenalectomy should remain the recommended treatment.

Summary Activating mutation of glucokinase gene (GCK) causes resetting of insulin inhibition at a lower glucose threshold causing hyperinsulinaemic hypoglycaemia (GCK-HH). This is the first reported case who tolerated years of regular fasting during Ramadhan, presenting only with seizure and syncope now. We describe a case with GCK gene variant p.T65I diagnosed in a 51-year-old woman with hypoglycaemia unawareness even at glucose level of 1.6 mmol/L. Insulin and C-peptide levels during hypoglycaemia were suggestive of hyperinsulinism, but at a day after intravenous glucagon, hypoglycaemia occurred with low insulin and C-peptide levels, pointing against insulinoma as the underlying aetiology. Imaging studies of the pancreas and calcium arterial stimulation venous sampling were unremarkable. A review of old medical records revealed asymptomatic hypoglycaemia years ago. Genetic testing confirmed activating mutation of GCK. Hypoglycaemia was successfully controlled with a somatostatin analogue. This case highlights the importance of consideration of genetic causes of hypoglycaemia in adulthood, especially when imaging is uninformative. Learning points Consider genetic causes of endogenous hyperinsulinism hypoglycaemia in adulthood, especially when imaging is uninformative. Late presentation of activating mutation of GCK can occur because of hypoglycaemia unawareness. Long-acting somatostatin analogue may be useful for the treatment of activating mutation of GCK causing hypoglycaemia. Depending on the glucose level when the blood was taken, and the threshold of glucose-stimulated insulin release (GSIR), the serum insulin and C-peptide levels may be raised (hyperinsulinaemic) or low (hypoinsulinaemic) in patients with activating mutation of GCK. Glucagon may be useful to hasten the process of unmasking the low insulin level during hypoglycaemia below the GSIR level of which insulin released is suppressed.

CONTEXT Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery. OBJECTIVE To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA. DESIGN Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019. PATIENTS 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy. MEASUREMENTS Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control. RESULTS Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32-2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0-2.0) versus 2.6 (IQR 0.8-4.3), p

Although low vitamin D levels are associated with statin-associated muscle symptoms (SAMS), it remains unclear if vitamin D supplementation leads to symptom improvement.We performed a systematic review to evaluate the association of vitamin D supplementation with resolution of SAMS.We searched Medline (PubMed), Embase and Cochrane Library till 12 December 2021. Full length articles that reported on the association between vitamin D supplementation in adult patients with SAMS were included.We identified 8 interventional studies comprising 669 participants. Majority of the participants were of Caucasian ethnicity and the mean age of participants ranged from 59.5 to 64.8 years old. The studies recruited patients with initial mean pre-treatment vitamin D levels ranging from 17.8 to 22.0ng/mL. Follow up duration ranged from 2 to 24 months and mean post-treatment vitamin D levels ranged from 34.3 to 56.0ng/mL. We found that vitamin D supplementation was associated with improved statin tolerance in 509 out of 606 (83.9%) patients across the 7 studies which reported patient numbers after supplementation (95% CI = 0.81-0.87, I2 = 72% n = 7). None of the studies were randomized controlled trials (RCTs) and hence placebo effect of vitamin D could not be ruled out. Nocebo effect of statin was also not assessed by any of the studies.Vitamin D supplementation in patients with mild-moderate vitamin D insufficiency was associated with improvement of SAMS. However, quantitative efficacy analysis was not possible and this observed association is likely confounded by nocebo and placebo effects. RCTs are required to conclusively assess the utility of vitamin D supplementation in improving SAMS.

Background: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p

A 54-year-old woman with insulin-requiring type 2 diabetes mellitus presented with acute shortness of breath and drowsiness on a background of polydipsia, weakness and significant weight loss. One year ago, she had decided to stop her insulin and other medications and adopt lifestyle modifications instead. Initial emergency department (ED) blood samples were highly lipaemic and appeared strawberry pink. She was eventually diagnosed with diabetic ketoacidosis (DKA) with severe hypertriglyceridaemia, intubated for airway protection, and managed with fluid resuscitation and intravenous insulin to good effect. We share an uncommon DKA presentation at the ED. History was limited as the patient was drowsy and minimally communicative. Physical examination was unremarkable. Blood investigations were also delayed in view of the need for additional centrifugation. These contributed to a paucity of information in the acute setting and resulted in a diagnostic challenge.

Introduction Patients with primary aldosteronism (PA) have increased cardiovascular risk, and there are concerns about the efficacy of medical therapy. Objective We aimed to assess long-term tolerability and efficacy of medical therapy in PA patients. Methods We conducted a retrospective study on 201 PA patients treated with medical therapy (spironolactone, eplerenone, or amiloride) from 2000 to 2020 at 2 tertiary centers. Clinical and biochemical control and side effects were assessed. Results Among 155 patients on long-term medications, 57.4% achieved blood pressure (BP) 1 ng/mL/h. Concordance of biochemical control using potassium and renin levels was 49.1%. Side effects were experienced by 52.3% of patients, with 10.3% switching, 22.6% decreasing dose, and 11.0% stopping medications. Risk factors for side effects were spironolactone use, dose ≥ 50 mg, treatment duration ≥1 year, male gender, and unilateral PA. Patients with unilateral PA used higher spironolactone doses vs bilateral (57 vs 50 mg, P < 0.001) and had more side effects (63.2% vs 41.8%, P = 0.008). Forty-six unilateral PA patients who underwent surgery after initial medical therapy experienced improved BP (systolic from 141 to 135 mmHg, P = 0.045; diastolic from 85 to 79 mmHg, P = 0.002). Conclusion Dose-dependent side effects limit efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. For unilateral PA, surgery remains preferable, yielding better control with less long-term side effects.

Objective: Migrant workers, a marginalized and under-resourced population, are vulnerable to coronavirus disease 2019 (COVID-19) due to limited healthcare access. Moreover, metabolic diseases-such as diabetes mellitus (DM), hypertension, and hyperlipidemia-predispose to severe complications and mortality from COVID-19. We investigate the prevalence and consequences of undiagnosed metabolic illnesses, particularly DM and pre-diabetes, in international migrant workers with COVID-19. Methods: In this retrospective analysis, we analyzed the medical records of international migrant workers with laboratory-confirmed COVID-19 hospitalized at a tertiary hospital in Singapore from April 21 to June 1, 2020. We determined the prevalence of DM and pre-diabetes, and analyzed the risk of developing complications, such as pneumonia and electrolyte abnormalities, based on age and diagnosis of DM, and pre-diabetes. Results: Two hundred and fouty male migrant workers, with mean age of 44.2 years [standard deviation (SD), 8.5years], were included. Twenty one patients (8.8%) were diagnosed with pre-diabetes, and 19 (7.9%) with DM. DM was poorly controlled with a mean HbA1c of 9.9% (SD, 2.4%). 73.7% of the patients with DM and all the patients with pre-diabetes were previously undiagnosed. Pre-diabetes was associated with higher risk of pneumonia [odds ratio (OR), 10.8, 95% confidence interval (CI), 3.65-32.1; P < 0.0001], hyponatremia (OR, 8.83; 95% CI, 1.17-66.6; P = 0.0342), and hypokalemia (OR, 4.58; 95% CI, 1.52-13.82; P = 0.0069). Moreover, patients with DM or pre-diabetes developed COVID-19 infection with lower viral RNA levels. Conclusions: The high prevalence of undiagnosed pre-diabetes among international migrant workers increases their risk of pneumonia and electrolyte abnormalities from COVID-19.

Introduction Adrenal venous sampling (AVS) is the reference test for identifying unilateral primary aldosteronism (PA). However, in patients with corticol co-secreting adrenal nodules, elevated cortisol levels may affect the interpretation of aldosterone-cortisol (AC) ratios. ACTH-stimulation may further confound results. In such patients, the use of plasma metanephrines instead of cortisol as a correcting factor may be helpful. Case Summary A 54 year old lady presented with 8 years of hypertension and hypokalaemia (nadir 2.2mmol/L) while on amlodipine 10mg and valsartan 80mg daily. PA was confirmed by a post-saline infusion aldosterone 1075pmol/L. CT identified a 2.4cm right lipid rich adrenal adenoma. Serum cortisol post 1mg overnight dexa-suppression test was unsuppressed at 63mmol/L. First AVS was done sequentially under ACTH stimulation and suggested lateralization to the right, with lateralization ratio (LR) 3.4. However, this was She underwent right adrenalectomy and was cured of hypertension and hypokalaemia at 6 months post surgery. Aldosterone renin ratio has normalized: aldosterone Clinical Lessons While ACTH stimulation helps to improve success rates of cannulation by increasing cortisol gradients, most studies show that it lowers LR. Furthermore, this would be concerning in patients with cortisol co-secreting adenomas. In this case, repeat AVS without ACTH demonstrated improved lateralization to the right. The use of metanephrine as a correcting factor appears to be a better indicator of right sided disease. However, while plasma metanephrines have been shown to be useful to indicate correct catheter placement, it has not been adopted as a correction factor for dilution yet. Finally, in addition to affecting AVS results, cortisol-cosecreting tumors may also affect 11C-Metomidate PET-CT imaging. Conclusion In patients with suspected cortisol co-secreting adenomas, unstimulated AVS and use of plasma metanephrines may help to identify unilateral PA even when conventional AVS and metomidate scans fail to. Further studies on using metanephrines as a correcting factor for lateralisation would be helpful.

Contains fulltext : 220540.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Prediction models have been developed to predict either unilateral or bilateral primary aldosteronism, and these have not been validated externally. We aimed to develop a simplified score to predict both subtypes and validate this externally. METHODS: Our development cohort was taken from 165 patients who underwent adrenal vein sampling (AVS) in two Asian tertiary centres. Unilateral disease was determined using both AVS and postoperative outcome. Multivariable analysis was used to construct prediction models. We validated our tool in a European cohort of 97 patients enrolled in the SPARTACUS trial who underwent AVS. Previously published prediction models were also tested in our cohorts. RESULTS: Backward stepwise logistic regression analysis yielded a final tool using baseline aldosterone-to-lowest-potassium ratio (APR, ng/dl/mmol/l), with an area under receiver-operating characteristic curve of 0.80 (95% CI 0.70-0.89). In the Asian development cohort, probability of bilateral disease was 90.0% (with APR 15). Similar results were seen in the European validation cohort. Combining both cohorts, probability of bilateral disease was 76.7% (with APR 15). Other models had similar predictive ability but required more variables, and were less sensitive for identifying bilateral PA. CONCLUSION: The novel aldosterone-to-lowest-potassium ratio is a convenient score to guide clinicians and patients of various ethnicities on the probability of primary aldosteronism subtype. Using APR to identify patients more likely to benefit from AVS may be a cost-effective strategy to manage this common condition.

Background Randomized trials demonstrated a lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high...

Background Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans. Methods We compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco’s Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water. Results ELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo. Conclusions ELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.

BACKGROUND & AIMS We compared the effects of weight loss induced with the glucagon-like peptide-1 agonist liraglutide, with that of lifestyle modification, followed by weight maintenance after discontinuing intervention, in obese adults with non-alcoholic fatty liver disease (NAFLD). METHODS Thirty obese (mean age 40.7 ± 9.1 years, BMI 33.2 ± 3.6 kg/m2 , 90% male) adults with NAFLD defined as liver fat fraction (LFF) > 5% on magnetic resonance imaging without other causes of hepatic steatosis were randomized to a supervised programme of energy restriction plus moderate-intensity exercise to induce ≥ 5% weight loss (DE group, n = 15), or liraglutide 3 mg daily (LI group, n = 15) for 26 weeks, followed by 26 weeks with only advice to prevent weight regain. RESULTS Diet and exercise and LI groups had significant (P

Obesity is less prevalent in Asian subjects with type 2 diabetes mellitus (T2DM) in contrast to Caucasians. Whether higher axial bone mineral density (BMD) often reported in T2DM is independent of body mass index (BMI) has not been clearly shown. BMD characterization in T2DM patients with hip fractures has also not been performed. We compared the BMD of Asian diabetic and nondiabetic patients with new hip fractures and explored how BMD was influenced by BMI.We included 255 diabetic and 148 nondiabetic patients. BMD adjusted for age; BMI; race; sex; renal function; and use of statins, proton pump inhibitors, steroids, anticonvulsants, and calcium and/or vitamin D supplements were compared between the groups. We were particularly interested in the BMD comparison between underweight diabetics and nondiabetics with hip fractures.The presence of T2DM was associated with higher BMD (g/cm(2)) at the femoral neck (0.527 ± 0.103 vs. 0.491 ± 0.102, P.01) and lumbar spine [LS] (0.798 ± 0.147 vs. 0.723 ± 0.156, P.01). This association persisted after adjustment for multiple confounding variables including BMI. The age-, BMI-, and sex-adjusted LS BMD was higher in underweight (BMI18.5 kg/m(2)) diabetics compared to similar weight nondiabetics (0.733 ± 0.126 vs. 0.649 ± 0.131 g/cm(2), P = .014).T2DM is independently associated with higher axial BMD in patients with new hip fractures. The finding of higher BMD even in underweight diabetics with hip fractures compared to their nondiabetic counterparts suggests that higher BMD in subjects with T2DM is not due to higher BMI.BMD = bone mineral density BMI = body mass index CV = coefficient of variation DXA = dual-energy X-ray absorptiometry HbA1c = glycated hemoglobin IGF-1 = insulin growth factor-1 LS = lumbar spine 25(OH)D = 25-hydroxyvitamin D T2DM = type 2 diabetes mellitus.

Introduction: Whether parathyroidectomy is more beneficial to renal function when compared to medical therapy or observation in primary hyperparathyroidism (PHPT) is unclear. Neither has this premise been explored in non-Caucasian populations. The estimated glomerular filtration rate (eGFR) threshold below which parathyroid hormone (PTH) levels rise if at all in PHPT has also not been established. We determined if surgery was superior to medical therapy and observation in a multi-ethnic Asian patient population with PHPT and whether there was an eGFR threshold below which PTH levels further increased in them. Methods: Retrospective evaluation of patients with PHPT. Results: There were 68.6% Chinese, 17.4% Malays, 10.7% Indians, and 3.3% Eurasians. The median (interquartile range) follow-up was 18.0 months (4.5–46.8). At last follow-up, eGFR in the surgical (80 ± 30 ml/min) was higher than the medical (52 ± 32 ml/min) or observation groups (48 ± 33 ml/min); P < 0.01. This difference persisted after adjusting for age, gender, ethnicity, pre-intervention eGFR levels, nephrolithiasis, serum calcium, phosphate, urinary calcium, and duration of follow-up; P = 0.035. There was no definite eGFR level below which PTH values rose. Conclusion: Our study provides compelling evidence that in PHPT, surgery may be associated with a better renal outcome compared to medical management or observation. This has to be confirmed through prospective randomized controlled trials and the reasons for this finding have to be elucidated through functional and histological measures. The finding in our study of a lack of a specific eGFR threshold below which PTH levels further rose challenges the concept of a fixed renal threshold for secondary elevations of PTH in PHPT.

The short-acting glucagon-like peptide 1 receptor agonist exenatide reduces postprandial glycemia, partly by slowing gastric emptying, although its impact on small intestinal function is unknown. In this study, 10 healthy subjects and 10 patients with type 2 diabetes received intravenous exenatide (7.5 μg) or saline (230 to 240 min) in a double-blind randomized crossover design. Glucose (45 g), together with 5 g 3-O-methylglucose (3-OMG) and 20 MBq 99mTc-sulfur colloid (total volume 200 mL), was given intraduodenally (t = 0-60 min; 3 kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter and small intestinal transit using scintigraphy. In both groups, duodenal pressure waves and antegrade flow events were fewer, and transit was slower with exenatide, as were the areas under the curves for serum 3-OMG and blood glucose concentrations. Insulin concentrations were initially lower with exenatide than with saline and subsequently higher. Nausea was greater in both groups with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea. The inhibition of small intestinal motor function represents a novel mechanism by which exenatide can attenuate postprandial glycemia usc Refereed/Peer-reviewed

Many commentators have noted the impact that obesity is having both on society and health services across the world. The impact is wide ranging, from personal day‐to‐day issues through to the economic impact on health services and the wider economy. There is now general acceptance that we live in an obesogenic environment, and that the factors behind this are multifactorial and complex. However, a key question concerns the impact of weight management intervention and the cost or cost‐effective impact therein. By understanding this in more detail, informed decisions can be made around appropriate funding and commissioning for supporting people who wish to seek weight management interventions. This chapter aims to outline some key areas of impact being observed with the increasing rate of obesity and the resource burden of severe and complicated obesity. The impact of realistic and achievable weight change is also considered, as well as the cost‐effectiveness of currently available interventions for the management of obesity.

This study aims at assessing the gap in secondary fracture prevention at a regional general hospital setting in Singapore. Male patients have significantly lower rate of being investigated and treated for osteoporosis than their female counterparts. Vitamin D deficiency is prevalent in our population. Secondary fracture prevention services are not routine in Singapore; we seek to assess the treatment gap that exists in the lack of diagnosis and treatment of osteoporosis in fragility fracture patients. We performed a retrospective analysis of all admissions for fragility fractures between December 2013 and December 2014. Demographic data, rates of BMD performance, serum vitamin D investigation and calcium and vitamin D supplementation as well as antiresorptive initiation 1 year post admission were analysed. There were 125 fragility fractures in patients below 65 and 615 fractures in older patients. There was a slightly higher proportion of males in the younger population, whereas females predominated in the older population. Median vitamin D levels were low in both younger (19.1 μg/L) and older (22.0 μg/L) groups, but supplementation was lower in younger patients (4.8 versus 16.6%, p = 0.003). Rate of BMD performance was lower in younger patients (34.4 versus 64.6%, p

Background Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors of the adrenal glands and paraganglia, occurring sporadically or as a range of hereditary tumor syndromes. About 30% of PPGLs are attributed to germline mutations. Clinical presentation, including localization, malignant potential, and age of onset, varies depending on the genetic background. Genetic testing for PPGLs is not well studied in Southeast Asia. We reviewed clinical management of PPGLs in Singapore, highlighting current gaps in clinical practice. Methods Medical records of patients with PPGLs between 2005 and 2016 were reviewed. Diagnosis was confirmed histologically and stratified into sporadic or familial/syndromic (FS). Results Twenty-seven (21.8%) patients were referred to the Cancer Genetics Service (CGS). FS PPGLs (18.5%) and extra-adrenal PPGLs (58.1%) incidences were higher than previous studies. Referrals were lower for sporadic PPGLs compared to FS PPGLs (3.7% vs. 100%). Referrals were highest at diagnosis age

We compared the effects of weight loss induced by the glucagon-like peptide 1-agonist liraglutide with a structured lifestyle intervention in obese adults with non-alcoholic fatty liver disease (NAFLD). Obese (body mass index ≥30 kg/m2 , mean weight 96.0 ± 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on magnetic resonance imaging without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/d) plus moderate-intensity aerobic exercise (~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks. Both DE and LI groups had significant (P < .01) and similar reductions in weight (-3.5 ± 3.3 vs -3.5 ± 2.1 kg, respectively, P = .72), LFF (-8.9 ± 13.4 vs -7.2% ± 7.1%, P = .70), serum alanine aminotransferase (-42 ± 46 vs -34 ± 27 U/L, P = .52) and aspartate aminotransferase (-23 ± 24 vs -18 ± 15 U/L, P = .53). In this first randomized study comparing the 2 weight-loss modalities for improving NAFLD, liraglutide was as effective as structured lifestyle modification.

Aim:To evaluate the effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate during an intraduodenal glucose infusion in type 2 diabetes.Methods:Nine subjects with type 2 diabetes were randomised to receive intravenous exenatide or saline control in a crossover design. Glucose (3 kcal min−1) was infused via an intraduodenal manometry catheter for 60 min. Blood pressure, heart rate, and the frequency and amplitude of duodenal pressure waves were measured at regular intervals. Gastrointestinal symptoms were monitored using 100 mm visual analogue scales.Results:During intraduodenal glucose infusion (0–60 min), diastolic ( p(0–60) = 0.03) and mean arterial ( p(0–60) = 0.03) blood pressures and heart rate ( p(0–60) = 0.06; p(0–120) = 0.03)) were higher with exenatide compared to placebo. The increase in the area under the curve for diastolic blood pressure and mean arterial blood pressure was related directly to the suppression of the duodenal motility index with exenatide compared to control ( p = 0.007 and 0.04, respectively).Conclusion:In type 2 diabetes, intravenous exenatide increases mean arterial blood pressure and heart rate during an intraduodenal glucose infusion, supporting the need for further research with exenatide for its potential use in postprandial hypotension.

According to World Health Organization, in 2010 there were over 1 billion overweight adults worldwide with 400 million adults who were obese. Obesity is a major risk factor for diabetes, cardiovascular disease, musculoskeletal disorders, obstructive sleep apnea, and cancers (prostate, colorectal, endometrial, and breast). Obese people may present to the gastroenterologists with gastroesophageal reflux, non-alcoholic fatty liver, and gallstones. It is important, therefore, to recognize and treat obesity. The main cause of obesity is an imbalance between calories consumed and calories expended, although in a small number of cases, genetics and diseases such as hypothyroidism, Cushing's disease, depression, and use of medications such as antidepressants and anticonvulsants are responsible for fat accumulation in the body. The main treatment for obesity is dieting, augmented by physical exercise and supported by cognitive behavioral therapy. Calorie-restriction strategies are one of the most common dietary plans. Low-calorie diet refers to a diet with a total dietary calorie intake of 800-1500, while very low-calorie diet has less than 800 calories daily. These dietary regimes need to be balanced in macronutrients, vitamins, and minerals. Fifty-five percent of the dietary calories should come from carbohydrates, 10% from proteins, and 30% from fats, of which 10% of total fat consist of saturated fats. After reaching the desired body weight, the amount of dietary calories consumed can be increased gradually to maintain a balance between calories consumed and calories expended. Regular physical exercise enhances the efficiency of diet through increase in the satiating efficiency of a fixed meal, and is useful for maintaining diet-induced weight loss. A meta-analysis by Franz found that by calorie restriction and exercise, weight loss of 5-8.5 kg was observed 6 months after intervention. After 48 months, a mean of 3-6 kg was maintained. In conclusion, there is evidence that obesity is preventable and treatable. Dieting and physical exercise can produce weight loss that can be maintained.