Publications by authors named "Barbara McGowan"

25 Publications

  • Page 1 of 1

The Bariatric-Metabolic Physician's Role in Managing Clinically Severe Obesity.

Curr Obes Rep 2021 May 8. Epub 2021 May 8.

Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Purpose Of Review: The aim of this review is to outline the obesity physician's role in managing patients with severe obesity with a particular emphasis on bariatric surgery candidates.

Recent Findings: Obesity is a chronic, relapsing and progressive disease. Scoring systems that evaluate the severity of obesity based on the clinical assessment, rather than the Body Mass Index, are a valuable tool. The clinical assessment should explore the underlying contributors for weight gain and screen for obesity-related complications. Bariatric surgery remains the most effective management approach for severe and complex obesity. Nevertheless, pharmacotherapy and other non-surgical approaches play an important role. The bariatric-metabolic physician's role is paramount in delivering effective care to patients with obesity. The multiple complications of patients with clinically severe obesity highlight the complexity of their management and reinforce the need for adequate assessment and long-term follow-up to ensure optimal clinical outcomes.
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http://dx.doi.org/10.1007/s13679-021-00435-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106360PMC
May 2021

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

N Engl J Med 2021 03 10;384(11):989. Epub 2021 Feb 10.

From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.).

Background: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

Methods: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.

Results: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).

Conclusions: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
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http://dx.doi.org/10.1056/NEJMoa2032183DOI Listing
March 2021

A systematic review of randomized controlled trials of dietary interventions for weight loss in adults in the Middle East and north Africa region.

Clin Obes 2021 Apr 26;11(2):e12434. Epub 2020 Dec 26.

Department of Medicine, Weill Cornell Medicine, Doha, Qatar.

The prevalence and incidence of obesity, and associated complications, such as type 2 diabetes, in the Middle East and north Africa (MENA) region rank among the highest in the world. Little is known about the effectiveness of dietary weight loss interventions conducted in the MENA region. We conducted a systematic review of randomized clinical trials aiming to assess the effectiveness of dietary interventions for weight loss in the adult population originating from and residing in the MENA region. In accordance with PRISMA guidelines, PubMed, CINAHL, Cochrane, and EMBASE were systematically searched for randomized controlled trials (RCT) using dietary interventions for weight loss conducted in the MENA region. RCTs examining weight loss as an outcome in adults (≥ 18 years old) were included. The Cochrane Collaboration tool for assessing risk of bias was used to ascertain the quality of the eligible RCTs and the Template for Intervention Description and Replication for population health and policy interventions (TIDieR-PHP) checklist was used to evaluate the reporting of the interventions. Twenty-nine RCTs including 2792 adults from five countries in the MENA region met the search criteria. Study participants were predominantly middle-aged females. Duration of follow up was mostly 3 months or less. Weight loss ranged from -0.7 to 16 kg across all intervention groups and the average weight loss was 4.8 kg. There was paucity of description of the weight loss interventions and variations amongst studies did not allow a meta-analysis of findings. It was not possible to draw firm conclusions on the effectiveness of dietary weight loss interventions in the region. High quality studies using more structured interventions of longer duration with standardized outcome measures are needed in the MENA region to support clinical practice with evidence-based interventions for obesity.
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http://dx.doi.org/10.1111/cob.12434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988652PMC
April 2021

Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery.

Lancet Diabetes Endocrinol 2020 07 7;8(7):640-648. Epub 2020 May 7.

University of Washington Medicine Diabetes Institute, University of Washington, Seattle, WA, USA; Weight Management Program, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, WA, USA.

The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.
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http://dx.doi.org/10.1016/S2213-8587(20)30157-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252156PMC
July 2020

Effectiveness and cost of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in obesity services (STRIVE study): study protocol of an open-label, real-world, randomised, controlled trial.

BMJ Open 2020 02 13;10(2):e034137. Epub 2020 Feb 13.

Diabetes Research Centre, Leicester General Hospital, University of Leicester College of Medicine Biological Sciences and Psychology, Leicester, UK

Introduction: In the UK and Ireland, severe and complex obesity is managed in specialist weight management services (SWMS), which provide multicomponent lifestyle interventions to support weight loss, and use of medication if available. Liraglutide 3 mg (LIRA 3 mg) is an effective weight-loss medication, but weight loss in individual patients is variable, and its efficacy has not been assessed in SWMS. This study aims to investigate whether a targeted prescribing pathway for LIRA 3 mg with multiple prespecified stopping rules could help people with severe obesity and established complications achieve ≥15% weight loss in order to determine whether this could be considered a clinically effective and cost-effective strategy for managing severe and complex obesity in SWMS.

Methods And Analysis: In this 2-year, multicentre, open-label, real-world randomised controlled trial, 384 adults with severe and complex obesity (defined as body mass index ≥35 kg/m plus either prediabetes, type 2 diabetes, hypertension or sleep apnoea) will be randomised via a 2:1 ratio to receive either standard SWMS care (n=128) or standard SWMS care plus a targeted prescribing pathway for LIRA 3 mg with prespecified stopping rules at 16, 32 and 52 weeks (n=256).The primary outcome is to compare the proportion of participants achieving a weight loss of ≥15% at 52 weeks with a targeted prescribing pathway versus standard care. Secondary outcomes include a comparison of (1) the weight loss maintenance at 104 weeks and (2) the budget impact and cost effectiveness between the two groups in a real-world setting.

Ethics And Dissemination: The Health Research Authority and the Medicines and Healthcare products Regulatory Authority in UK, the Health Products Regulatory Authority in Ireland, the North West Deanery Research Ethics Committee (UK) and the St Vincent's University Hospital European Research Ethics Committee (Ireland) have approved the study. The findings of the study will be published in peer-reviewed journals.

Trial Registration Number: ClinicalTrials.gov-Identifier: NCT03036800.European Clinical Trials Database-Identifier: EudraCT Number 2017-002998-20.
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http://dx.doi.org/10.1136/bmjopen-2019-034137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044994PMC
February 2020

Low-energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin: a randomized trial.

BMJ Open Diabetes Res Care 2020 01;8(1)

Nutrition and Dietetic Research Group, Imperial College London, London, UK

Objectives: The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT.

Research Design And Methods: In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL).

Results: Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference -4.3 kg, 95% CI -6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (-18.6 units, 95% CI -29.2 to -7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01).

Conclusions: Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success.

Trial Registration Number: ISRCTN21335883.
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http://dx.doi.org/10.1136/bmjdrc-2019-001012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039597PMC
January 2020

Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial.

Lancet Diabetes Endocrinol 2019 07 4;7(7):549-559. Epub 2019 Jun 4.

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London and Imperial College Healthcare NHS Trust, London, UK. Electronic address:

Background: Many patients with type 2 diabetes do not achieve sustained diabetes remission after metabolic (bariatric) surgery for the treatment of obesity. Liraglutide, a glucagon-like peptide-1 analogue, improves glycaemic control and reduces bodyweight in patients with type 2 diabetes. Our aim was to assess the safety and efficacy of liraglutide 1·8 mg in patients with persistent or recurrent type 2 diabetes after metabolic surgery.

Methods: In the GRAVITAS randomised double-blind, placebo-controlled trial, we enrolled adults who had undergone Roux-en-Y gastric bypass or vertical sleeve gastrectomy and had persistent or recurrent type 2 diabetes with HbA levels higher than 48 mmol/mol (6·5%) at least 1 year after surgery from five hospitals in London, UK. Participants were randomly assigned (2:1) via a computer-generated sequence to either subcutaneous liraglutide 1·8 mg once daily or placebo, both given together with a reduced-calorie diet, aiming for a 500 kcal per day deficit from baseline energy intake, and increased physical activity. The primary outcome was the change in HbA from baseline to the end of the study period at 26 weeks, assessed in patients who completed the trial. Safety was assessed in the safety analysis population, consisting of all participants who received either liraglutide or placebo. This trial is registered with EudraCT, number 2014-003923-23, and the ISRCTN registry, number ISRCTN13643081.

Findings: Between Jan 29, 2016, and May 2, 2018, we assigned 80 patients to receive either liraglutide (n=53) or placebo (n=27). 71 (89%) participants completed the study and were included in the principal complete-cases analysis. In a multivariable linear regression analysis, with baseline HbA levels and surgery type as covariates, liraglutide treatment was associated with a difference of -13·3 mmol/mol (-1·22%, 95% CI -19·7 to -7·0; p=0·0001) in HbA change from baseline to 26 weeks, compared with placebo. Type of surgery had no significant effect on the outcome. 24 (45%) of 53 patients assigned to liraglutide and 11 (41%) of 27 assigned to placebo reported adverse effects: these were mainly gastrointestinal and in line with previous experience with liraglutide. There was one death during the study in a patient assigned to the placebo group, which was considered unrelated to study treatment.

Interpretation: These findings support the use of adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery.

Funding: JP Moulton Foundation.
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http://dx.doi.org/10.1016/S2213-8587(19)30157-3DOI Listing
July 2019

Clinical Practice Recommendations for the Management of Obesity in the United Arab Emirates.

Obes Facts 2018 30;11(5):413-428. Epub 2018 Oct 30.

With rapid urbanisation and improved living conditions as a result of rising incomes in Gulf Cooperation Council (GCC) countries, obesity has become a major and growing health problem for the region. The United Arab Emirates (UAE) has a resident population of 9.3 million (in 2016), many of whom (85.5%) lived in urban areas and led sedentary lifestyles. Based on the World Health Organisation (WHO) estimates for 2010, 25% of Emirati men and 40% of the women were obese. Obesity rates in this country has doubled from 16 to 34% compared to the year 2000, and severe obesity (BMI > 40 kg/m2) has risen dramatically from 2 to 11%. While a number of international guidelines for the management of obesity are already available in public domain, local guidelines for the UAE and the region, which are structured and individualized for the management of obesity, are sorely needed to help the family physician to provide affordable treatment for the patient at the point-of-care and to reduce the burden on the local healthcare system. A multi-disciplinary panel of international and regional experts who treat patients with overweight and obesity was convened with the aim of developing consensus recommendations for the UAE. The objective is to have a simple and easy-to-refer set of recommendations for busy clinicians as there were already many comprehensive international guidelines available. The panel reviewed and streamlined these recommendations in its entirety for relevance, coherence and usability in the local context. These recommendations for overweight and obesity management were circulated and endorsed by the local practising family medicine community, namely, the Emirates Medical Association and Family Medicine Society. We believe these recommendations would also be of interest to clinicians in other GCC countries. A summary and algorithm of these recommendations are provided.
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http://dx.doi.org/10.1159/000491796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257093PMC
September 2019

Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.

Lancet 2018 08 16;392(10148):637-649. Epub 2018 Aug 16.

Obesity and Endocrinology Research, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. Electronic address:

Background: Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss.

Methods: We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m or more. We randomly assigned participants (6:1) to each active treatment group (ie, semaglutide [0·05 mg, 0·1 mg, 0·2 mg, 0·3 mg, or 0·4 mg; initiated at 0·05 mg per day and incrementally escalated every 4 weeks] or liraglutide [3·0 mg; initiated at 0·6 mg per day and escalated by 0·6 mg per week]) or matching placebo group (equal injection volume and escalation schedule to active treatment group) using a block size of 56. All treatment doses were delivered once-daily via subcutaneous injections. Participants and investigators were masked to the assigned study treatment but not the target dose. The primary endpoint was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. This study is registered with ClinicalTrials.gov, number NCT02453711.

Findings: Between Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned (102-103 participants per active treatment group and 136 in the pooled placebo group). Mean baseline characteristics included age 47 years, bodyweight 111·5 kg, and BMI 39·3 kg/m. Bodyweight data were available for 891 (93%) of 957 participants at week 52. Estimated mean weight loss was -2·3% for the placebo group versus -6·0% (0·05 mg), -8·6% (0·1 mg), -11·6% (0·2 mg), -11·2% (0·3 mg), and -13·8% (0·4 mg) for the semaglutide groups. All semaglutide groups versus placebo were significant (unadjusted p≤0·0010), and remained significant after adjustment for multiple testing (p≤0·0055). Mean bodyweight reductions for 0·2 mg or more of semaglutide versus liraglutide were all significant (-13·8% to -11·2% vs -7·8%). Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37-65% receiving 0·1 mg or more of semaglutide (p<0·0001 vs placebo). All semaglutide doses were generally well tolerated, with no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea, as seen previously with GLP-1 receptor agonists.

Interpretation: In combination with dietary and physical activity counselling, semaglutide was well tolerated over 52 weeks and showed clinically relevant weight loss compared with placebo at all doses.

Funding: Novo Nordisk A/S.
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http://dx.doi.org/10.1016/S0140-6736(18)31773-2DOI Listing
August 2018

The Endocrine and Metabolic Characteristics of a Large Bardet-Biedl Syndrome Clinic Population.

J Clin Endocrinol Metab 2018 05;103(5):1834-1841

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Context: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder in which previous reports have described obesity and a metabolic syndrome.

Objective: We describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects.

Design: We performed a case-control study.

Setting: This study was performed at a hospital clinic.

Patients: Study patients had a clinical or genetic diagnosis of BBS.

Main Outcome Measurements: Our study determined the prevalence of a metabolic syndrome in our cohort.

Results: A total of 152 subjects were studied. Eighty-four (55.3%) were male. Mean (± standard deviation) age was 33.2 ± 1.0 years. Compared with age-, sex-, and body mass index-matched control subjects, fasting glucose and insulin levels were significantly higher in subjects with BBS (glucose: BBS, 5.2 ± 1.2 mmol/L vs control, 4.9 ± 0.9 mmol/L, P = 0.04; insulin: BBS, 24.2 ± 17.0 pmol/L vs control, 14.2 ± 14.8 pmol/L, P < 0.001). Serum triglycerides were significantly higher in subjects with BBS (2.0 ± 1.2 mmol/L) compared with control subjects (1.3 ± 0.8 mmol/L; P < 0.001), but total cholesterol, high-density lipoprotein, and low-density lipoprotein were similar in both groups. Systolic blood pressure was higher in the BBS group (BBS, 135 ± 18 mm Hg vs control subjects, 129 ± 16 mm Hg; P = 0.02). Alanine transaminase was raised in 34 (26.8%) subjects with BBS, compared with five (8.9%) control subjects (P = 0.01). The rate of metabolic syndrome, determined using International Diabetes Federation criteria, was significantly higher in the BBS group (54.3%) compared with control subjects (26% P < 0.001). Twenty-six (19.5%) of male subjects with BBS were hypogonadal (serum testosterone, 9.9 ± 5.3 mmol/L), but significant pituitary abnormalities were uncommon. Subclinical hypothyroidism was present in 24 of 125 (19.4%) patients with BBS, compared with 3 of 65 (4.6%) control subjects (P = 0.01).

Conclusions: Insulin resistance and the metabolic syndrome are increased in adult patients with BBS compared with matched control subjects. Increased subclinical hypothyroidism in the BBS cohort needs further investigation.
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http://dx.doi.org/10.1210/jc.2017-01459DOI Listing
May 2018

Making (mis) sense of asymptomatic marked hypercalcemia in pregnancy.

Clin Case Rep 2017 10 17;5(10):1587-1590. Epub 2017 Aug 17.

Department of Diabetes and Endocrinology Guy's and St Thomas' Hospital NHS Foundation Trust London SE1 7EH UK.

We describe a rare case of homozygous inactivating calcium-sensing receptor mutation detected during pregnancy and mimicking primary hyperparathyroidism. In pregnancy, the differential diagnosis of hypercalcaemia requires a cautious approach as physiological changes in calcium homeostasis may mask rare genetic conditions.
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http://dx.doi.org/10.1002/ccr3.1074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628236PMC
October 2017

Suboptimal rise in awakening-induced cortisol is an accurate marker of cortisol insufficiency in patients with normal renal function (eGFR >60 mL/min).

Ann Clin Biochem 2018 Jul 5;55(4):496-499. Epub 2017 Oct 5.

1 King's College London, London, UK.

Background The insulin tolerance test is the gold standard for diagnosis of cortisol insufficiency. However, it is cumbersome, invasive, requires supervised hospital facilities and has unpleasant side-effects. A non-invasive outpatient-based test will be useful. We hypothesized that free cortisol concentrations in multiple spot urine samples can be used to diagnose cortisol insufficiency in patients with normal renal function (eGFR > 60 mL/min). Method Patients and controls provided urine samples at bedtime (S1), and first (S2) and second (S3) void the next day. Cortisol and creatinine were measured in all three samples, and cortisol:creatinine ratio (S1, S2 and S3) was used for further analysis. The sum of S1 + S2 + S3 was used to calculate total cortisol secretion (T). Variation (V) in cortisol secretion in response to circadian rhythm was calculated as the modulus of the difference between S1 and S2 and S2 and S3. Results Samples were collected from 96 controls and 11 patients. S1 was significantly lower vs . S2 and S3 in controls ( P < 0.0001) but not in patients. S2, S3, T and V were significantly lower in patients vs . controls ( P < 0.0001). ROC curve analysis using insulin tolerance test as gold standard showed that S2, S3, T and V were all equally accurate diagnostic markers for cortisol insufficiency (AUC: 0.87, NPV: 100%). The best balance of sensitivity and specificity was achieved using T (sensitivity: 100%, specificity: 58%). Conclusion Multiple spot urine samples test is an accurate, relatively inexpensive, non-invasive, convenient outpatient-based screening test for exclusion of cortisol insufficiency.
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http://dx.doi.org/10.1177/0004563217732361DOI Listing
July 2018

A Practical Guide to Engaging Individuals with Obesity.

Obes Facts 2016 4;9(3):182-92. Epub 2016 Jun 4.

Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Obesity is officially recognised as a chronic disease and a top public health priority by several global societies and healthcare bodies. In some European countries, the majority of the adult population is either overweight or obese, with major implications for patient health and healthcare systems. General practitioners (GPs) are well-placed to tackle this epidemic, yet their engagement with patients is fraught with challenges and barriers. These include time limitations, a lack of evidence base, sensitivities around raising the topic of obesity with patients, inadequate availability of supporting local weight loss services, a lack of training for healthcare professionals (HCPs) on the management of obesity and a limited number of effective therapies. A number of steps need to be implemented to promote engagement between GPs and individuals with obesity. This article provides a European perspective on the obstacles that patients face in accessing healthcare services and discusses a variety of approaches for engaging individuals with obesity and facilitating the management of obesity as a chronic disease.
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http://dx.doi.org/10.1159/000445193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644811PMC
September 2017

The GLP-1 agonist, liraglutide, as a pharmacotherapy for obesity.

Ther Adv Chronic Dis 2016 Mar 16;7(2):92-107. Epub 2015 Dec 16.

Guy's and St Thomas' NHS Foundation Trust - Diabetes and Endocrinology, and King's College London - Diabetes and Nutritional Sciences, London, UK.

There is a global obesity epidemic that will continue to be a financial burden on healthcare systems around the world. Tackling obesity through diet and exercise should always be the first intervention, but this has not proved to be effective for a large number of patients. Pharmacotherapeutic options have been limited and many previously available drugs have been withdrawn due to safety concerns. Currently, only bariatric surgery has the capability to induce both substantial and durable weight loss. This article briefly reviews the history of pharmacotherapy for obesity before focusing on the clinical trial evidence for the use of the GLP-1 agonist liraglutide as a weight loss agent and comparing its efficacy with other emerging drug therapies for obesity.
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http://dx.doi.org/10.1177/2040622315620180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772342PMC
March 2016

The bariatric physician.

Clin Med (Lond) 2014 Feb;14(1):30-3

St Thomas' Hospital, London, UK.

Obesity is a rapidly increasing problem that has wide implications for the National Health Service. At present, obesity is not being addressed in a joined-up and standardised manner. This has downstream effects for the health service, the economy and society as a whole. As highlighted by a recent RCP report, there is a need for a new class of dedicated specialists who can evaluate individuals with health problems that are related to obesity, direct their care in a coordinated fashion, act as an advocate for their needs and be able to liaise with multiple different services to improve the provision of patient care. In this article, we discuss the role of this specialist - the bariatric physician.
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http://dx.doi.org/10.7861/clinmedicine.14-1-30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873615PMC
February 2014

Plasma insulin-like factor 3 (INSL3) in male patients with osteoporosis and Klinefelter's syndrome.

Ital J Anat Embryol 2013 ;118(1 Suppl):34-6

Insulin-like factor 3 (INSL3) is a peptide hormone produced in leydig cells of the testes. Its role in the adult male is unknown but INSL3 and its receptor RXFP2 have been linked to bone cell differentiation. It is speculated that low levels of INSL3 could be responsible for low bone mineral density in patients with primary osteoporosis and Klinefelter's Syndrome. The aim of this study was to assess plasma INSL3 in patients with osteoporosis and Klinefelter's Syndrome compared to healthy males. Fourteen healthy males, 21 males with osteoporosis (4 primary and 17 secondary) and 4 patients with Klinefelter's Syndrome were studied. Plasma INSL3, testosterone, LH, FSH and Sex hormone-binding globulin were evaluated. Plasma INSL3 concentrations were similar in osteoporosis patients compared to healthy controls (0.72 vs. 0.69 ng/mL, p = 0.26). INSL3 was significantly higher in patients with primary osteoporosis (n = 4) compared to age-matched healthy controls (n = 8) (0.845 vs. 0.665 ng/mL, p = 0.021). INSL3 levels in Klinefelter's Syndrome patients were significantly lower compared to healthy controls (0.39 vs. 0.69 ng/mL, p = 0.01). Plasma INSL3 levels were lower in Klinefelter's Syndrome reflecting testicular failure. INSL3 levels were not lower in men with osteoporosis. The relationship between INSL3, its receptor and bone metabolism requires further study.
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May 2014

Carney Stratakis syndrome in a patient with SDHD mutation.

Endocr Pathol 2012 Sep;23(3):181-6

Department of Diabetes and Endocrinology, Guy's and St Thomas' Foundation Trust, St Thomas' Hospital, London, UK.

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http://dx.doi.org/10.1007/s12022-012-9213-zDOI Listing
September 2012

Pituitary involvement in Wegener's granulomatosis: unusual biochemical findings and severe malnutrition.

BMJ Case Rep 2011 Nov 7;2011. Epub 2011 Nov 7.

Diabetes and Endocrinology Department, Guy and St Thomas Hospital, London, UK.

Wegener's granulomatosis (WG) is a systemic disease with a complex genetic background. It is characterised by inflammation of the small blood vessels leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies against neutrophil proteinase-3 (Antineutrophil Cytoplasmic Antibody, ANCA). Pituitary involvement is a rare complication of this disease and, when it occurs, diabetes insipidus is the most common manifestation. We describe a 38-year-old female with known long-term WG who presented with partial hypopituitarism, severe malnutrition and ANCA negative status, with a favourable response to steroid pulse therapy.
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http://dx.doi.org/10.1136/bcr.02.2011.3850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207734PMC
November 2011

Co-morbidities, management and clinical outcome of auto-immune Addison's disease.

Endocrine 2010 Aug 3;38(1):113-7. Epub 2010 Jul 3.

Department of Endocrinology, Guy's & St Thomas' NHS Foundation Trust, St. Thomas' Hospital, London, UK.

There are no consensus guidelines on the optimum long-term care of patients with primary adrenal failure. Published data suggest increased morbidity and mortality in patients treated with current therapy. Investigations of bone mineral density (BMD) in adults with adrenal failure have reported conflicting results. The objectives of this study were to determine the prevalence of auto-immune and other co-morbidities, describe the treatment regimens and to assess the BMD of adults with auto-immune Addison's disease (AAD). A retrospective, cohort study of adults with primary adrenal failure was used. Electronic and paper records were used to collect demographic, biochemical, BMD data and details of other co-morbidities. 48 patients (35% male; 65% female; 50 ± 16, years, mean ± SD) with primary adrenal failure were identified. There was high prevalence of other auto-immune co-morbidities (hypothyroidism 58%, vitamin B(12) deficiency 29%, type 1 diabetes 10%). The presence of cardiovascular risk factors including dyslipidaemia (65% had total cholesterol >5 mmol/l) and excess weight (65% had a BMI >25 kg/m(2)) were high. Using WHO criteria, 17.9 and 53.5% of patients had spinal osteoporosis and osteopenia, respectively, at the spine. This did not relate to the duration or dose of glucocorticoid replacement. Our data shows a high prevalence of both auto-immune and non-autoimmune co-morbidities in patients with AAD. In addition to common auto-immune diseases, patients should be screened for other cardiovascular risk factors. Further studies are needed to assess the cause of the observed increased prevalence of reduced BMD at the lumbar spine. There is a need for internationally agreed long-term management guidelines.
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http://dx.doi.org/10.1007/s12020-010-9359-8DOI Listing
August 2010

Relaxin-3 and its role in neuroendocrine function.

Ann N Y Acad Sci 2009 Apr;1160:250-5

Department of Investigative Medicine, Division of Investigative Science, Imperial College London, Hammersmith Hospital, London, UK.

The hypothalamus plays a key role in the regulation of energy homeostasis and endocrine function. Relaxin-3 is a hypothalamic neuropeptide that belongs to the insulin superfamily of peptides. It is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus and is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role. RXFP3 and RXFP1 are present in the hypothalamic paraventricular nucleus, an area with a well-characterized role in the regulation of energy balance. The paraventricular nucleus also modulates reproductive function by providing inputs to hypothalamic gonadotropin-releasing hormone neurons. The physiological roles for relaxin-3 remain to be established. Evidence for a role of relaxin-3 as a hypothalamic orexigenic peptide will be reviewed, including its effects on the hypothalamo-pituitary-thyroid axis and energy expenditure. Studies pointing towards a putative role of relaxin-3 in the hypothalamic-pituitary-gonadal axis will be discussed. Central endocrine effects of relaxin-3 will be compared to relaxin. We conclude that relaxin-3 may act as a hypothalamic signal to coordinate appetite, thyroid function, and reproductive status. Further studies will be required to determine whether these are physiological roles for relaxin-3 and to determine the receptors involved.
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http://dx.doi.org/10.1111/j.1749-6632.2008.03796.xDOI Listing
April 2009

Low-dose pancreatic polypeptide inhibits food intake in man.

Br J Nutr 2007 Mar;97(3):426-9

Department of Metabolic Medicine, Faculty of Medicene, Imperial College London, London, UK.

Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to food ingestion and remains elevated for up to 6 h postprandially. Plasma levels are elevated in patients with pancreatic tumours. An intravenous infusion of PP has been reported to reduce food intake in man, suggesting that PP is a satiety hormone. We investigated whether a lower infusion rate of PP would induce significant alterations in energy intake. The study was randomised and double-blinded. Fourteen lean fasted volunteers (five men and nine women) received 90 min infusions of PP (5 pmol/kg per min) and saline on two separate days. The dose chosen was half that used in a previous human study which reported a decrease in appetite but at supra-physiological levels of PP. One hour after the end of the infusion, a buffet lunch was served and energy intake measured. PP infusion was associated with a significant 11 % reduction in energy intake compared with saline (2440 (se 200) v. 2730 (se 180) kJ; P<0 x 05). Preprandial hunger as assessed by a visual analogue score was decreased in the PP-treated group compared to saline. These effects were achieved with plasma levels of PP within the pathophysiological range of pancreatic tumours.
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http://dx.doi.org/10.1017/S0007114507336799DOI Listing
March 2007

Psychosocial interventions for disruptive symptoms of dementia.

J Psychosoc Nurs Ment Health Serv 2006 11;44(11):34-42

Yale New Haven Psychiatric Hospital, New Haven, CT 06504, USA.

An estimated 6% to 8% of the adult population age 65 and older and more than 30% of those age 85 and older are affected by a dementing disorder. The annual direct and indirect cost of caring for the 4.5 million people with Alzheimer's disease in the United States is estimated to be at least $100 billion. By 2030, when the entire Baby Boomer generation is age 65 and older, the increased number of people with Alzheimer's disease could exceed the ability to absorb the added cost. Both professional and familial caregivers should be familiar with the treatment interventions that are most effective in reducing the disruptive behavioral and psychological symptoms of dementia. This article discusses the various kinds of dementia, their associated symptoms, and the psychosocial treatment options that have been found to be effective in alleviating the effects of the disease on both people with dementia and their caregivers. Psychosocial strategies can be divided into four major subgroups: communication techniques, behavioral strategies, environmental modifications, and caregiver education. The ultimate goal is to optimize functioning of people with dementia and minimize caregiver strain.
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http://dx.doi.org/10.3928/02793695-20061101-06DOI Listing
November 2006

Hormonal regulation of food intake.

Physiol Rev 2005 Oct;85(4):1131-58

Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

Our knowledge of the physiological systems controlling energy homeostasis has increased dramatically over the last decade. The roles of peripheral signals from adipose tissue, pancreas, and the gastrointestinal tract reflecting short- and long-term nutritional status are now being described. Such signals influence central circuits in the hypothalamus, brain stem, and limbic system to modulate neuropeptide release and hence food intake and energy expenditure. This review discusses the peripheral hormones and central neuronal pathways that contribute to control of appetite.
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http://dx.doi.org/10.1152/physrev.00015.2004DOI Listing
October 2005

Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.

J Clin Endocrinol Metab 2005 Dec 20;90(12):6609-15. Epub 2005 Sep 20.

Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, London W12 ONN, United Kingdom.

Context: Mutation of the G protein-coupled receptor 54 is associated with a failure of reproductive function. The endogenous neuropeptide agonist for G protein-coupled receptor 54, kisspeptin, potently stimulates the hypothalamic-pituitary-gonadal axis in rodents and primates.

Objective: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH, and testosterone in male volunteers.

Design: This was a double-blind, placebo-controlled, crossover study.

Setting: This was a hospital-based study.

Participants: Male volunteers (n = 6) were recruited.

Interventions: Each volunteer received a 90-min i.v. infusion of kisspeptin-54 (4 pmol/kg x min) and a control infusion of saline (0.9%) in random order.

Main Outcome Measure: Plasma LH, FSH, and testosterone concentrations were measured.

Results: Kisspeptin-54 infusion significantly increased plasma LH, FSH, and testosterone concentrations compared with saline infusion (mean 90-min LH: kisspeptin, 10.8 +/- 1.5 vs. saline, 4.2 +/- 0.5 U/liter, P < 0.001; mean 90-min FSH: kisspeptin, 3.9 +/- 0.7 vs. saline, 3.2 +/- 0.6 U/liter, P < 0.001; mean 180-min testosterone: kisspeptin, 24.9 +/- 1.7 vs. saline, 21.7 +/- 2.2 nmol/liter, P < 0.001). The plasma half-life of kisspeptin-54 was calculated to be 27.6 +/- 1.1 min. The mean metabolic clearance rate was 3.2 +/- 0.2 ml/kg x min, and the volume of distribution was 128.9 +/- 12.5 ml/kg.

Conclusion: Elevation of plasma concentrations of kisspeptin in human males significantly increases circulating LH, FSH, and testosterone levels. Kisspeptin infusion provides a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system.
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http://dx.doi.org/10.1210/jc.2005-1468DOI Listing
December 2005

Appetite control.

J Endocrinol 2005 Feb;184(2):291-318

Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.

Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Brain centres, including the hypothalamus, brainstem and reward centres, signal via neuropeptides which regulate energy homeostasis. Insulin and hormones synthesized by adipose tissue reflect the long-term nutritional status of the body and are able to influence these circuits. Circulating gut hormones modulate these pathways acutely and result in appetite stimulation or satiety effects. This review discusses central neuronal networks and peripheral signals which contribute energy homeostasis, and how a loss of the homeostatic process may result in obesity. It also considers future therapeutic targets for the treatment of obesity.
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http://dx.doi.org/10.1677/joe.1.05866DOI Listing
February 2005