Publications
148 results found
Hughes BM, Holland A, Hödebeck-Stuntebeck N, et al., 2024, Body weight, behaviours of concern, and social contact in adults and adolescents with Prader-Willi syndrome in full-time care services: findings from pooled international archival data, Orphanet Journal of Rare Diseases, Vol: 19, ISSN: 1750-1172
BACKGROUND: Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental condition characterised by a range of debilitating and lifelong symptoms. The many physical and behavioural challenges that arise with adults with PWS often necessitate full-time (i.e., 24-hour) professional care support. However, despite the fact that many clinicians regard full-time PWS-specific care to represent best practice, relatively few studies have directly examined the benefits of such services. The purpose of this paper is to use archival data to investigate the impact of full-time care services on people with PWS, and to assemble a large statistical dataset on which robust analyses of improvements in weight, BMI, and behavioural outcomes can be based. METHODS: Information collated by the International PWS Organisation (IPWSO), an international non-profit membership organisation supporting national PWS associations around the world, was combined into a single anonymised dataset for statistical analysis. Data were supplied by service-providers from several countries who provide full-time support to people with PWS. The dataset included details on the specific services provided, basic demographic information on service recipients, including weight, body mass index (BMI), and observational records relating to behaviours of concern (BOC; consisting of temper outbursts, skin-picking, egocentrism, inflexibility, and striving for dominance). RESULTS: A total of 193 people with PWS (ranging in age from < 10 yrs to > 50 yrs; 93% of whom were > 18 yrs), residing in 11 services across 6 countries, were represented in the dataset. On average, people with PWS showed significant reductions in weight and BMI after joining a full-time care service, with improvements within one year of entering, which were cumulative over time and independent of age or initial weight at entry. Similar cumulative improvements over time were seen for BOC within one year and were unr
Alabdulkader S, Al-Alsheikh AS, Miras AD, et al., 2024, Obesity surgery and neural correlates of human eating behaviour: a systematic review of functional MRI studies, NeuroImage: Clinical, Vol: 41, Pages: 103563-103563, ISSN: 2213-1582
Changes in eating behaviour including reductions in appetite and food intake, and healthier food cue reactivity, reward, hedonics and potentially also preference, contribute to weight loss and its health benefits after obesity surgery. Functional magnetic resonance imaging (fMRI) has been increasingly used to interrogate the neural correlates of eating behaviour in obesity, including brain reward-cognitive systems, changes after obesity surgery, and links with alterations in the gut-hormone-brain axis. Neural responses to food cues can be measured by changes in blood oxygen level dependent (BOLD) signal in brain regions involved in reward processing, including caudate, putamen, nucleus accumbens, insula, amygdala, orbitofrontal cortex, and top-down inhibitory control, including dorsolateral prefrontal cortex (dlPFC). This systematic review aimed to examine: (i) results of human fMRI studies involving obesity surgery, (ii) important methodological differences in study design across studies, and (iii) correlations and associations of fMRI findings with clinical outcomes, other eating behaviour measures and mechanistic measures. Of 741 articles identified, 23 were eligible for inclusion: 16 (69.6%) longitudinal, two (8.7%) predictive, and five (21.7%) cross-sectional studies. Seventeen studies (77.3%) included patients having Roux-en-Y gastric bypass (RYGB) surgery, six (26.1%) vertical sleeve gastrectomy (VSG), and five (21.7%) laparoscopic adjustable gastric banding (LAGB). The majority of studies (86.0%) were identified as having a very low risk of bias, though only six (27.3%) were controlled interventional studies, with none including randomisation to surgical and control interventions. The remaining studies (14.0%) had a low risk of bias driven by their control groups not having an active treatment. After RYGB surgery, food cue reactivity often decreased or was unchanged in brain reward systems, and there were inconsistent findings as to whether reductions in foo
Miller JL, Gevers E, Bridges N, et al., 2024, Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study, Obesity, Vol: 32, Pages: 252-261, ISSN: 1071-7323
OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well-tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.
Pellikaan K, Nguyen NQC, Rosenberg AGW, et al., 2023, Malignancies in Prader-Willi syndrome: results from a large international cohort and literature review, Journal of Clinical Endocrinology and Metabolism, Vol: 108, Pages: e1720-e1730, ISSN: 0021-972X
CONTEXT: Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. OBJECTIVE: To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. METHODS: We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. RESULTS: Seven adults (age range 18-55 years old) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. CONCLUSION: Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged.
Al-Alsheikh AS, Alabdulkader S, Miras AD, et al., 2023, Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies, Obesity Reviews, Vol: 24, ISSN: 1467-7881
This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for 11C-raclopride, 18F-fallypride, 123I-IBZM; one for dopamine transporter, 123I-FP-CIT; one used tracer for serotonin 5-HT2A receptor, 18F-altanserin; two used tracers for serotonin transporter, 11C-DASB or 123I-FP-CIT; two used tracer for μ-opioid receptor, 11C-carfentanil; one used tracer for noradrenaline transporter, 11C-MRB); seven studies assessed glucose uptake using 18F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using 15O-H2O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using 18F-FTHA and one using 11C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies.
Howell TA, Matza LS, Mallya UG, et al., 2023, Health state utilities associated with hyperphagia: data for use in cost-utility models, Obesity Science and Practice, Vol: 9, Pages: 376-382, ISSN: 2055-2238
ObjectiveRare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost-utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels.MethodsFour health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade-off elicitation study in a UK general population sample.ResultsIn total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were −0.08 (0.10) for mild, −0.28 (0.30) for moderate, and −0.77 (0.58) for severe hyperphagia.ConclusionsThese data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost-utility models of treatments for rare genetic diseases of obesity.
Goldstone A, Bhargava R, Luur S, et al., 2023, Post-prandial increases in liver-gut hormone LEAP2 correlate with attenuated eating behaviour in adults without obesity, Journal of the Endocrine Society, Vol: 7, Pages: 1-19, ISSN: 2472-1972
Background: The novel liver-gut hormone LEAP2 is a centrally acting inverse agonist, and competitive antagonist of orexigenic acyl ghrelin (AG), at the growth hormone secretagogue receptor, reducing food intake in rodents. In humans, the effects of LEAP2 on eating behaviour and mechanisms behind the post-prandial increase in LEAP2 are unclear, though this is reciprocal to the post-prandial decrease in plasma AG.Methods: Plasma LEAP2 was measured in a secondary analysis of a previous study. Twenty-two adults without obesity attended after an overnight fast (Fasted-saline), consuming a 730kcal meal without (Fed-saline) or with (Fed-ghrelin) subcutaneous AG administration. Post-prandial changes in plasma LEAP2 were correlated with post-prandial changes in appetite, high-energy (HE) or low-energy (LE) food cue reactivity using functional MRI, ad libitum food intake, and plasma/serum AG, glucose, insulin and triglycerides.Results: Post-prandial plasma LEAP2 increased by 24.5-52.2% at 70-150 min, but was unchanged by exogenous AG administration. Post-prandial increases in LEAP2 correlated positively with post-prandial decreases in appetite, and cue reactivity to HE/LE and HE food in anterior/posterior cingulate cortex, paracingulate cortex, frontal pole, middle frontal gyrus, with similar trend for food intake. Post-prandial increases in LEAP2 correlated negatively with body mass index, but did not correlate positively with increases in glucose, insulin or triglycerides, nor decreases in AG.Conclusions: These correlational findings are consistent with a role for post-prandial increases in plasma LEAP2 in suppressing human eating behaviour in adults without obesity. Post-prandial increases in plasma LEAP2 are unrelated to changes in plasma AG and the mediator(s) remain uncertain.
Ruban A, Aldubaikhi G, Johnson NA, et al., 2023, ENDOBARRIER®, A DUODENAL-JEJUNAL BYPASS LINER DEVICE, ALTERS THE GLOBAL METABOLIC AND THE GUT BACTERIAL PROFILES OF PATIENTS WITH OBESITY AND DIABETES, Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1457-S1457, ISSN: 0016-5085
Kharbanda KK, Farokhnia M, Deschaine SL, et al., 2022, Role of the ghrelin system in alcohol use disorder and alcohol-associated liver disease: a narrative review, Alcoholism: Clinical and Experimental Research, Vol: 46, Pages: 2149-2159, ISSN: 0145-6008
Unhealthy alcohol consumption is a global health problem. Adverse individual, public health, and socioeconomic consequences are attributable to harmful alcohol use. Epidemiological studies have shown that alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) are the top two pathologies among alcohol-related diseases. Consistent with the major role that the liver plays in alcohol metabolism, uncontrolled drinking may cause significant damage to the liver. This damage is initiated by excessive fat accumulation in the liver, which can further progress to advanced liver disease. The only effective therapeutic strategies currently available for ALD are alcohol abstinence or liver transplantation. Any molecule with dual-pronged effects at the central and peripheral organs controlling addictive behaviors and associated metabolic pathways are a potentially important therapeutic target for treating AUD and ALD. Ghrelin, a hormone primarily derived from the stomach, has such properties, and regulates both behavioral and metabolic functions. In this review, we highlight recent advances in understanding the peripheral and central functions of the ghrelin system and its role in AUD and ALD pathogenesis. We first discuss the correlation between blood ghrelin concentrations and alcohol use or abstinence. Next, we discuss the role of ghrelin in alcohol-seeking behaviors and finally its role in the development of fatty liver by metabolic regulations and organ crosstalk. We propose that a better understanding of the ghrelin system could open an innovative avenue for improved treatments for AUD and associated medical consequences, including ALD.
Goldstone AP, Ling YY, Nestor LJ, et al., 2022, Effect of acute desacyl ghrelin administration on eating and addictive behaviours: The gut hormone in addiction study, 2nd World Congress on Alcohol and Alcoholism Joint meeting of ISBRA and ESBRA, Publisher: Wiley, Pages: 72-73, ISSN: 0145-6008
Aldhwayan MM, Al-Najim W, Ruban A, et al., 2022, Does bypass of the proximal small intestine impact food intake, preference, and taste function in humans? An experimental medicine study using the duodenal-jejunal bypass liner, Nutrients, Vol: 14, ISSN: 2072-6643
The duodenal-jejunal bypass liner (Endobarrier) is an endoscopic treatment for obesity and type 2 diabetes mellitus (T2DM). It creates exclusion of the proximal small intestine similar to that after Roux-en-Y Gastric Bypass (RYGB) surgery. The objective of this study was to employ a reductionist approach to determine whether bypass of the proximal intestine is the component conferring the effects of RYGB on food intake and sweet taste preference using the Endobarrier as a research tool. A nested mechanistic study within a large randomised controlled trial compared the impact of lifestyle modification with vs. without Endobarrier insertion in patients with obesity and T2DM. Forty-seven participants were randomised and assessed at several timepoints using direct and indirect assessments of food intake, food preference and taste function. Patients within the Endobarrier group lost numerically more weight compared to the control group. Using food diaries, our results demonstrated similar reductions of food intake in both groups. There were no significant differences in food preference and sensory, appetitive reward, or consummatory reward domain of sweet taste function between groups or changes within groups. In conclusion, the superior weight loss seen in patients with obesity and T2DM who underwent the Endobarrier insertion was not due to a reduction in energy intake or change in food preferences.
Ruban A, Miras A, glaysher M, et al., 2022, Duodenal-jejunal bypass liner for the management of Type 2 diabetes and obesity: a multicenter randomized controlled trial, Annals of Surgery, Vol: 275, Pages: 440-447, ISSN: 0003-4932
Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary Background Data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44–2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8–39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial Registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research
Ruban A, Miras AD, Glaysher MA, et al., 2022, Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity, Annals of Surgery, Vol: 275, Pages: 440-447, ISSN: 0003-4932
<jats:sec> <jats:title>Objective:</jats:title> <jats:p>The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.</jats:p> </jats:sec> <jats:sec> <jats:title>Summary Background Data:</jats:title> <jats:p>This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44–2.0; <jats:italic toggle="yes">P</jats:italic> = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8–39; <jats:italic toggle="yes">P</jats:italic> = .007). The DJBL grou
Al-Alsheikh AS, Alabdulkader S, Johnson B, et al., 2022, Effect of obesity surgery on taste, Nutrients, Vol: 14, Pages: 1-24, ISSN: 2072-6643
Obesity surgery is a highly efficacious treatment for obesity and its comorbidities. The underlying mechanisms of weight loss after obesity surgery are not yet fully understood. Changes to taste function could be a contributing factor. However, the pattern of change in different taste domains and among obesity surgery operations is not consistent in the literature. A systematic search was performed to identify all articles investigating gustation in human studies following bariatric procedures. A total of 3323 articles were identified after database searches, searching references and deduplication, and 17 articles were included. These articles provided evidence of changes in the sensory and reward domains of taste following obesity procedures. No study investigated the effect of obesity surgery on the physiological domain of taste. Taste detection sensitivity for sweetness increases shortly after Roux-en-Y gastric bypass. Additionally, patients have a reduced appetitive reward value to sweet stimuli. For the subgroup of patients who experience changes in their food preferences after Roux-en-Y gastric bypass or vertical sleeve gastrectomy, changes in taste function may be underlying mechanisms for changing food preferences which may lead to weight loss and its maintenance. However, data are heterogeneous; the potential effect dilutes over time and varies significantly between different procedures.
Howell TA, Matza L, Mallya UG, et al., 2022, Health state utilities associated with hyperphagia, Virtual ISPOR Europe 2021, Publisher: Elsevier, Pages: S234-S235, ISSN: 1098-3015
Pellikaan K, Ben Brahim Y, Rosenberg AGW, et al., 2021, Hypogonadism in Women with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion, JOURNAL OF CLINICAL MEDICINE, Vol: 10
- Author Web Link
- Cite
- Citations: 10
Pellikaan K, Ben Brahim Y, Rosenberg AGW, et al., 2021, Hypogonadism in Adult Males with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion, JOURNAL OF CLINICAL MEDICINE, Vol: 10
- Author Web Link
- Cite
- Citations: 11
Guerrero-Hreins E, Goldstone AP, Brown RM, et al., 2021, The therapeutic potential of GLP-1 analogues for stress-related eating and role of GLP-1 in stress, emotion and mood: a review, Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol: 110, ISSN: 0278-5846
Stress and low mood are powerful triggers for compulsive overeating, a maladaptive form of eating leading to negative physical and mental health consequences. Stress-vulnerable individuals, such as people with obesity, are particularly prone to overconsumption of high energy foods and may use it as a coping mechanism for general life stressors. Recent advances in the treatment of obesity and related co-morbidities have focused on the therapeutic potential of anorexigenic gut hormones, such as glucagon-like peptide 1 (GLP-1), which acts both peripherally and centrally to reduce energy intake. Besides its appetite suppressing effect, GLP-1 acts on areas of the brain involved in stress response and emotion regulation. However, the role of GLP-1 in emotion and stress regulation, and whether it is a viable treatment for stress-induced compulsive overeating, has yet to be established. A thorough review of the pre-clinical literature measuring markers of stress, anxiety and mood after GLP-1 exposure points to potential divergent effects based on temporality. Specifically, acute GLP-1 injection consistently stimulates the physiological stress response in rodents whereas long-term exposure indicates anxiolytic and anti-depressive benefits. However, the limited clinical evidence is not as clear cut. While prolonged GLP-1 analogue treatment in people with type 2 diabetes improved measures of mood and general psychological wellbeing, the mechanisms underlying this may be confounded by associated weight loss and improved blood glucose control. There is a paucity of longitudinal clinical literature on mechanistic pathways by which stress influences eating behavior and how centrally-acting gut hormones such as GLP-1, can modify these. (250).
Sjostrom A, Pellikaan K, Sjostrom H, et al., 2021, Hyperprolactinemia in adults with Prader-Willi syndrome, Journal of Clinical Medicine, Vol: 10, ISSN: 2077-0383
Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioural challenges, cognitive dysfunction, and hypogonadism. Psychotic illness is common, particularly in patients with maternal uniparental disomy (mUPD), and antipsychotic medications can result in hyperprolactinemia. Information about hyperprolactinemia and its potential clinical consequences in PWS is sparse. Here, we present data from an international, observational study of 45 adults with PWS and hyperprolactinemia. Estimated prevalence of hyperprolactinemia in a subset of centres with available data was 22%, with 66% of those related to medication and 55% due to antipsychotics. Thirty-three patients were men, 12 women. Median age was 29 years, median BMI 29.8 kg/m2, 13 had mUPD. Median prolactin was 680 mIU/L (range 329–5702). Prolactin levels were higher in women and patients with mUPD, with only 3 patients having severe hyperprolactinemia. Thyroid function tests were normal, 24 were treated with growth hormone, 29 with sex steroids, and 20 with antipsychotic medications. One patient had kidney insufficiency, and one a microprolactinoma. In conclusion, severe hyperprolactinemia was rare, and the most common aetiology of hyperprolactinemia was treatment with antipsychotic medications. Although significant clinical consequences could not be determined, potential negative long-term effects of moderate or severe hyperprolactinemia cannot be excluded. Our results suggest including measurements of prolactin in the follow-up of adults with PWS, especially in those on treatment with antipsychotics
Coupaye M, Pellikaan K, Goldstone AP, et al., 2021, Hyponatremia in Children and Adults with Prader-Willi Syndrome: A Survey Involving Seven Countries, JOURNAL OF CLINICAL MEDICINE, Vol: 10
- Author Web Link
- Cite
- Citations: 3
Herlinger KE, Ling YY, Nestor LJ, et al., 2021, Comparison of monetary reward anticipation and negative emotional processing in obesity, ex-smokers and abstinent alcohol dependence, 44th Annual Meeting Research Society on Alcoholism / International Society for Behavioral Research on Alcoholism, Publisher: Wiley, Pages: 241A-241A, ISSN: 0145-6008
Goldstone AP, Ling YY, Nestor LJ, et al., 2021, EFFECT OF ACUTE DESACYL GHRELIN ADMINISTRATION ON EATING AND ADDICTIVE BEHAVIOURS: THE GUT HORMONE IN ADDICTION STUDY, Publisher: WILEY, Pages: 51A-51A, ISSN: 0145-6008
Glaysher M, Ward J, Aldhwayan M, et al., 2021, The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, Clinical Nutrition, Vol: 40, Pages: 2343-2354, ISSN: 0261-5614
Background & aimsDuodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs).MethodsSub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group.ResultsWeight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group.ConclusionOne year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation.
Ruban A, Glaysher M, Miras A, et al., 2021, SAFETY PROFILE OF THE DUODENAL-JEJUNAL BYPASS LINER (ENDOBARRIER): A MULTICENTRE RANDOMISED CONTROL TRIAL, Publisher: BMJ PUBLISHING GROUP, Pages: A170-A170, ISSN: 0017-5749
Ruban A, Glaysher M, Ashrafian H, et al., 2021, DUODENAL-JEJUNAL BYPASS LINER THERAPY (ENDOBARRIER®) CAUSES REDUCTIONS IN PLASMA TRIMETHYLAMINE-N-OXIDE IN OBESE PATIENTS WITH DIABETES, Publisher: BMJ PUBLISHING GROUP, Pages: A19-A19, ISSN: 0017-5749
Herlinger K, Ling YY, Nestor LJ, et al., 2020, Comparison of food cue reactivity, eating behaviours, mood and impulsivity in obesity, ex-smokers and abstinent alcohol dependence, 33rd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S15-S15, ISSN: 0924-977X
Ruban A, Glaysher MA, Miras AD, et al., 2020, A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT, Efficacy and Mechanism Evaluation, Vol: 7, Pages: 1-130, ISSN: 2050-4365
BackgroundThe EndoBarrier® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up
Alenaini W, Parkinson JRC, McCarthy JP, et al., 2020, Ethnic differences in body fat deposition and liver fat content in two UK-based cohorts, Obesity (Silver Spring, Md.), Vol: 28, Pages: 2142-2152, ISSN: 1071-7323
OBJECTIVE: Differences in the content and distribution of body fat and ectopic lipids may be responsible for ethnic variations in metabolic disease susceptibility. The aim of this study was to examine the ethnic distribution of body fat in two separate UK-based populations. METHODS: Anthropometry and body composition were assessed in two separate UK cohorts: the Hammersmith cohort and the UK Biobank, both comprising individuals of South Asian descent (SA), individuals of Afro-Caribbean descent (AC), and individuals of European descent (EUR). Regional adipose tissue stores and liver fat were measured by magnetic resonance techniques. RESULTS: The Hammersmith cohort (n = 747) had a mean (SD) age of 41.1 (14.5) years (EUR: 374 men, 240 women; SA: 68 men, 22 women; AC: 14 men, 29 women), and the UK Biobank (n = 9,533) had a mean (SD) age of 55.5 (7.5) years (EUR: 4,483 men, 4,873 women; SA: 80 men, 43 women, AC: 31 men, 25 women). Following adjustment for age and BMI, no significant differences in visceral adipose tissue or liver fat were observed between SA and EUR individuals in the either cohort. CONCLUSIONS: Our data, consistent across two independent UK-based cohorts, present a limited number of ethnic differences in the distribution of body fat depots associated with metabolic disease. These results suggest that the ethnic variation in susceptibility to features of the metabolic syndrome may not arise from differences in body fat.
Murphy CF, Stratford N, Docherty NG, et al., 2020, A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy., J Clin Endocrinol Metab
BACKGROUND: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated post-prandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among post-esophagectomy patients with unintentional weight loss. METHODS: This pilot study prospectively studied post-operative patients with ≥10% body weight loss (BWL) beyond one year who were candidates for clinical treatment with long-acting Octreotide (LAR). Before and after four weeks of treatment, gut hormone secretion, food cue reactivity (functional MRI), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. RESULTS: 8 patients (7 male, age: mean±SD 62.8±9.4 years, post-operative BWL: 15.5±5.8%) participated. Octreotide LAR did not significantly suppress total post-prandial plasma GLP-1 response at four weeks (P=0.08). Post-prandial symptom burden improved after treatment (Sigstad score median(range): 12(2-28) vs. 8(3-18), P=0.04), but weight remained stable (Pre:68.6±12.8kg vs. Post:69.2±13.4kg, P=0.13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P=0.41) nor ad libitum food intake(P=0.46). CONCLUSION: The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses four weeks after Octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter inter-dose interval may be required to optimize the intervention.
Rosenberg AGW, Pellikaan K, Poitou C, et al., 2020, Central adrenal insufficiency is rare in adults with prader-willi syndrome (vol 105, pg 1, 2020), Journal of Clinical Endocrinology and Metabolism, Vol: 105, Pages: E3052-E3052, ISSN: 0021-972X
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.