bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of Onset of Adverse Events With Setmelanotide, an MC4R Agonist, in Patients With Severe Obesity Due to LEPR or POMC Deficiency
Authors: Clément Karine , van den Akker Erica L T , Gordon Gregory , Yuan Guojun , Kühnen Peter 
Published: May 2021

Abstract
Introduction: Setmelanotide is a melanocortin 4 receptor agonist indicated for chronic weight management in patients with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. This analysis aimed to assess the timing of the onset of adverse events (AEs) of special interest in patients with POMC/PCSK1 or LEPR deficiency obesity treated with setmelanotide. Methods: The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials. Patients in the Phase 2 investigator-initiated trial (Charité Universitätsmedizin Berlin) received open-label setmelanotide for 12 to 13 weeks followed by an extension study for eligible patients. The Phase 3 trials included a 12-week open-label phase, an 8-week placebo-controlled phase, and a subsequent 32-week open-label phase, for a total treatment length of at least 1 year. AEs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). AEs of special interest were defined as those related to treatment-emergent AEs (TEAEs) commonly occurring with setmelanotide (hyperpigmentation disorders, disturbances in sexual arousal, nausea, vomiting, injection site reactions [ISRs]). Results: As of November 10, 2020, 35 patients (15 POMC, 2 PCSK1, 18 LEPR) were enrolled and included across the 3 trials; 2 patients in the Phase 2 trial were ongoing treatment as of the cutoff. Daily setmelanotide dose ranged from 0.25 to 3.0 mg. All patients experienced ≥1 TEAE, the most common being skin hyperpigmentation (85.7%), injection site erythema (68.6%), nausea (57.1%), and headache (51.4%). For AEs of special interest, hyperpigmentation disorders occurred in 85.7% of patients (30/35), disturbances in sexual arousal in 17.1% (6/35), nausea in 57.1% (20/35), vomiting in 28.6% (10/35), and ISRs in 88.6% (31/35). The onset of most hyperpigmentation disorder (34/53 events; 64.2%) and disturbances in sexual arousal
(6/11 events; 54.6%) AEs were during Month 1 after starting setmelanotide. Onset of nausea and vomiting were most frequent during Month 1 of treatment (nausea: 12/34 events [35.3%]; vomiting: 6/19 events [31.6%]). ISRs occurred throughout the trial, with 41.6% (91/219 events) having an onset within Month 1 of treatment. Eighteen serious AEs occurred, none were interpreted as related to the study drug. Conclusions: In patients with POMC/PCSK1 or LEPR deficiency obesity who received setmelanotide treatment, the onset of AEs of special interest in any month was generally highest during Month 1 of treatment, with fewer events occurring during subsequent months. Apart from hyperpigmentation, all AEs occurred intermittently.
Weight Loss Mobile Apps: Do They Address COVID-19 and Diabetes
Authors: Wu Gloria , Nguyen Brian , Lau Chap-Kay Kendra , Siu Vincent 
Published: May 2021

Abstract
Background: Over 70 million Americans are obese and 99 million are overweight. There are over 3.7 billion ehealth mobile app downloads per year. Weight loss apps offer information on exercise and nutrition as well as weight tracking. Obesity is a risk factor for COVID-19 infection, along with diabetes and hypertension. In addition, obesity plays a role in the increased mortality of COVID patients. In March of 2020, the U.S. government, through the Small Business Administration and through the Small Business Innovation Research program, as well as through Facebook and Google, offered individuals and companies money for public education and/or solutions for the COVID-19 epidemic. Thus, are software app developers adding information about COVID-19 for their audience? Specifically, do weight loss apps mention obesity being a risk factor for DM, Hypertension, and COVID-19? Weight loss apps target a young demographic, and for public health purposes, COVID-19 information needs to reach this demographic since obesity can be a risk factor for COVID-19 infection. Purpose: Do weight loss apps provide information about DM, HTN, and COVID-19 during this pandemic era? Methods: Evaluation of the 10 most popular apps in the Apple (iOS) and Google (Android) stores via the search term “weight loss.” Apps were ranked by downloads/star rating respectively for Android and iOS apps. Apple does not provide information about the number of downloads. App inclusion criteria: 1) Free 2) iOS: star ratings greater than 4 (greater than 10K ratings); Android: greater than or equal to 1 Million downloads; App features: DM, HTN, Race, Gender, COVID-19, BMI, Heart Disease, Calorie Count, and Fitness. Results: DM: 0/20, HTN: 0/20, BMI: 19/20, while Race is 0/20; Gender 19/20; COVID-19: 0/20; Calorie Count 11/20; Fitness 13/20. Conclusion: 1) Weight Loss apps have not ventured in the public education realm of risk factors and comorbidities of COVID-19 despite the pandemic in 2020. 2) As physicians, we should continue to educate our patients with weight issues and other risk factors in the era of a worldwide pandemic.
Weight Loss With a Novel Peptide YY Analogue for Obesity: A Randomised, Placebo-Controlled Phase I Trial
Authors: Tan Tricia , Minnion James , Eu Khoo Bernard Chong , Ball Laura-Jayne , Malviya Reshma , Day Emily , Fiorentino Francesca , Brindley Charlie , Bush Jim , Bloom Stephen R 
Published: May 2021

Abstract
Background: Obesity and its co-morbidities remain a prime driver of global morbidity and mortality. Current therapies for obesity are limited in efficacy and durability, have serious adverse effects or are not scalable to the numbers required to treat this widespread disease. Gut hormones such as peptide YY (PYY) have emerged as candidate therapies for obesity which activate natural satiety pathways, reduce food intake and therefore body weight. We report the results from a Phase I trial of a PYY analogue, Y14, in overweight volunteers. Methods: In a first time in human Phase I randomized placebo-controlled trial, an extended-release formulation of Y14 with zinc chloride for subcutaneous injection, utilizing various Zn:peptide molar ratios, was tested. Part A of the trial was a partially blinded single ascending dose study. Part B was double-blinded and tested multiple ascending doses given at 7–14 day intervals over the course of 28 days with up to 5 doses given per subject. The primary outcome was the safety and tolerability of extended-release Y14; the secondary outcome was to assess its pharmacokinetics. Exploratory outcomes included the assessment of food consumption, body weight and glucose tolerance in response to 75g oral glucose load after multiple doses of Y14. [ClinicalTrials.gov NCT03673111]. Findings: Between Apr 11, 2017, and Dec 24, 2018 44 participants were enrolled into Part A of the trial and 24 into Part B and were included in the full analysis and safety datasets. The multiple doses of Y14 given in Part B led to significant mean placebo-subtracted reductions in body weight of 2.76 to 3.59 kg at 31 days after the first dose, in association with profound reductions in food intake and no evidence of tachyphylaxis. No significant changes in glucose tolerance were detected. The most common adverse events were nausea, vomiting and injection site reactions. No serious adverse events occurred. The pharmacokinetic characteristics of extended-release Y14 were compatible with administration every 7–14 days. Interpretation: Our results support the continued development of Y14 as a novel treatment for obesity. Funding: UK Medical Research Council Developmental Pathway Funding Scheme.
Metabolic Improvements After Gastric Sleeve Surgery in a Patient With Familial Partial Lipodystrophy
Authors: Niaz Azra , Sophia Ali 
Published: May 2021

Abstract
Familial Partial Lipodystrophy (FPLD) is a rare genetic disorder characterized by loss of subcutaneous adipose tissue mainly from peripheral areas but preservation, or increase, of fat in the face, neck, and trunk. This abnormal fat redistribution leads to a characteristic phenotype and severe metabolic derangements that are difficult to manage. FPLD often present with severe insulin resistance causing type 2 diabetes mellitus (DM2), acanthosis nigricans, hypertriglyceridemia (HTG), and non-alcoholic steatohepatitis (NASH). We present a case of FPLD with severe HTG and HTG induced pancreatitis requiring plasmapheresis, with dramatic metabolic improvements after gastric sleeve surgery. Case presentation: Our patient is a 40-year-old Caucasian male who was diagnosed with DM2 and HTG at age 18 when he presented with pancreatitis. He reported eruptive xanthomas with triglyceride (TG) &gt;3000 mg/dl on the initial presentation. He has central obesity with disproportionately thin extremities and NASH. He has a strong family history of HTG and premature coronary artery disease. He was in a leptin trial; however, he was not included in an extended arm due to deterioration of his metabolic profile, specifically NASH. Despite aggressive therapy with dietary changes, fenofibrate, statin, omega-3, and niacin, he had multiple episodes of pancreatitis with TG levels &gt;5000 mg/dl on many occasions. As a result, he was started on biweekly plasmapheresis that was later changed to weekly. His insulin requirement increased to 450 units daily on U-500. A decision was made for him to proceed with bariatric surgery with his history of insulin-resistant DM2 and morbid obesity. He lost 54 lbs in one year with sleeve gastrectomy and his insulin requirement decreased to 120 units daily. Above all, he had only a single incomplete session of plasmapheresis since his bariatric surgery. He has not required plasmapheresis for over a year so far and his TG levels are consistently &lt;500 mg/dl while only on rosuvastatin 40 mg, with the most recent TG level of 182 mg/dl. Discussion: Bariatric surgery has shown tremendous results in terms of reversal of diabetes and other metabolic derangements. These metabolic benefits are attributed mainly to weight loss in restrictive surgeries and proposed increased GLP-1 levels with Roux-en-Y Gastric Bypass Surgery (RYGB). There are a few case reports of FPLD patients with positive outcomes in terms of metabolic profile with RYGB. In our patient, bariatric surgery was decided due to his DM2 and morbid obesity. He had an unexpected dramatic improvement in the metabolic control of his lipodystrophy. To our knowledge, this is the first case of a FPLD patient with severe HTG requiring plasmapheresis with striking metabolic improvements after sleeve gastrectomy. Gastric sleeve surgery may be an important adjunct or alternative treatment option to the current standard of therapy in patients with FPLD.
Novel Heterozygous LMNA Variants Causing Familial Partial Lipodystrophy, Dunnigan Variety
Authors: Wadhwa Akhilesh , Vasandani Chandna , Garg Abhimanyu 
Published: May 2021

Abstract
Familial partial lipodystrophy (FPLD) is a rare, mostly autosomal dominant disorder characterized by selective loss of subcutaneous fat from the extremities. Patients with FPLD are predisposed to insulin resistance, dyslipidemia, diabetes mellitus, cardiac abnormalities (coronary heart disease [CHD], cardiomyopathy and conduction system disorders) and hepatic steatosis. FPLD2 (the Dunnigan variety) is the most common subtype which is caused by heterozygous variants in the lamin A/C (LMNA) gene. Over 50 LMNA causal variants have been reported in patients with FPLD2, with p.R482W and p.R482Q comprising ~75% of the families. We report 5 novel LMNA variants (c.722T&gt;C, p.L241P; c.848A&gt;G, p.N283S; c.1396A&gt;G, p.N466D; c.1543A&gt;G, p.K515E; c.1744C&gt;A, p.R582S) in 5 families, where a female proband presented to us with moderately-severe FPLD, from among a total cohort of 264 FPLD2 families, with 259 families harboring other known pathogenic LMNA variants. The p.L241P variant was found in a 62-year-old female with a body mass index (BMI) of 28 kg/m2. She had hypertriglyceridemia. She is adopted and has two offsprings, who have not yet been examined and genotyped. The p.N283S variant was found in two males and two females from the same family (Age 40–74 y; BMI 18–45 kg/m2). Of these, only the 74-year-old female proband had clinical lipodystrophy, diabetes and hypertriglyceridemia. The other three subjects did not have lipodystrophy. Thus, this variant did not segregate with the phenotype of lipodystrophy in this family likely due to low penetrance or reduced clinical expressivity. The p.N466D variant was found in a 53-year-old female (BMI 26 kg/m2) who had diabetes and hypertriglyceridemia. The p.K515E variant was found in 4 females and 1 male who belonged to the same family (Age 29–62 y; BMI 19–26 kg/m2). All of them had lipodystrophy and hypertriglyceridemia and three of them had diabetes. The p.R582S variant was found in 3 males and one female who belonged to the same family (Age 19–76 y; BMI 16–30 kg/m2). All of them had lipodystrophy but only two of them had diabetes and hypertriglyceridemia. Eight of them had hypertension, three had CHD, one of them had acute pancreatitis and another one had a stroke. None of these patients had cardiomyopathy, cardiac conduction system defects or myopathy. In conclusion, we report genotype-phenotype relationship of 5 novel LMNA variants in patients presenting with FPLD2, with variable prevalence of diabetes, hypertriglyceridemia hypertension and CAD. None of these variants are associated with cardiomyopathy or myopathy or progeroid features. Our report adds to the allelic and clinical heterogeneity associated with LMNA variants.
Obesity Is Associated With Higher odds of Hepatorenal syndrome in Patients Admitted With Alcoholic Hepatitis: Analysis of the National Inpatient Sample (2016–2017)
Authors: Asotibe Jennifer Chiagoziem , Shaka Hafeez , Achebe Ikechukwu , Pudasaini Garima , Akuna Emmanuel , Rashad Essam , Busari Olukayode A , Palomera Emmanuel Tejeda 
Published: May 2021

Abstract
Introduction: Obesity is a significant independent risk factor for the development of liver disease. There is some available data suggesting worse outcomes of alcoholic hepatitis (AH) in obese patients however, national sample data supporting these findings are scarce. The aim of our study was to study the severity of AH in patients with concurrent obesity thus we analyzed data from the national inpatient sample.
Methods: We queried the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for hospitalization of adult patients with alcoholic hepatitis as a principal diagnosis with and without Obesity (BMI = 30 and above) as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality while the secondary outcomes were severe sepsis with shock, hospital length of stay (LOS), NSTEMI, hepatorenal syndrome (HRS) and bleeding esophageal varices (BEV) development. STATA software was used for analysis. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders.
Results: There were over 71 million discharges in the combined 2016 and 2017 NIS database. Out of 32,584 adult AH hospitalizations, 3,720 (11.4%) had a concomitant diagnosis of obesity. There were no differences between mean age, sex and race in both groups of patients. Patients with AH and concurrent obesity had no significant difference in inpatient mortality (aOR= 0.74, P = 0.272, CI = 0.438 -1.261) however, they were found to have higher odds of developing HRS (aOR = 1.54, P= 0.020, CI= 1.069 -2.209) and lower odds of developing BEV(aOR 0.22, P= 0.008, CI= 0.070 -0.670). Patients with AH and concurrent obesity were also found to have similar odds of developing NSTEMI (aOR = 2.29, P= 0.180, CI= 0.680 - 7.762), severe sepsis with shock (aOR = 0.97%, P= 0.945, CI= 0.486 -1.954) and a 0.5 day mean increase in LOS (P =0.045, CI = 0.011 - 0.987) when compared to those without obesity.
Conclusion: In conclusion, patients with obesity admitted with AH have higher odds of developing HRS, lower odds of developing BEV and no statistically significant difference in mortality, development of NSTEMI and severe sepsis with septic shock. It is important to identify these patients at higher risk and provide better surveillance to prevent the development of HRS.
Type 2 Diabetes Mellitus Remission in Obese Patients Under Bariatric Surgery: The Role of Preoperative Triglycerides Levels
Authors: Gonçalves Vanessa Guerreiro , Maia Isabel , Mendonça Fernando , Silva Maria Manuel , Neves João Sérgio , Pedro Jorge Pires , Salazar Cristina Daniela , Ferreira Maria João Silva , Costa Cláudia Fernandes , Canha Marta Borges , Lau Eva , Freitas Paula , Carvalho Davide M 
Published: May 2021

Abstract
Background: There is abundant evidence reporting the relationship between triglycerides levels and type 2 diabetes mellitus, however few studies confirmed the influence of triglycerides levels on the incidence of diabetes. Bariatric surgery may lead to the remission of type 2 diabetes mellitus, but the effect of basal serum triglycerides levels on this reversal is unknown. This study aimed to assess the association between preoperative triglycerides levels and pre- and type 2 diabetes mellitus remission in obese patients one year after bariatric surgery.
Methods: A retrospective study was conducted among 1959 obese patients who underwent bariatric surgery in our entre. Data on socio-demographic and clinical characteristics were used. Pre-diabetes and type 2 diabetes mellitus remission was defined as normal glycaemic measures at least one year’s duration without pharmacological therapy. Logistic regression models, crude and adjusted for sex, age, preoperative serum triglycerides levels and type of bariatric surgery, were used.
Results: The median of preoperative serum triglycerides level was 121.00 (SD=75.00) mg/dL, and 34.7% and 30.0% of patients presented pre- and type 2 diabetes mellitus, respectively, at baseline. Preoperative serum triglycerides levels were higher in type 2 diabetes mellitus patients (139.00 vs. 106.00 mg/dL, in normal glycaemic patients; p&lt;0.001) and showed to be significantly correlated with fasting glycaemia, glycated
haemoglobin, homeostasis model assessment of insulin resistance and homeostasis model assessment of β-cell function. One year after bariatric surgery, 62.5% of patients with pre- or type 2 diabetes at baseline showed remission. Preoperative serum triglycerides levels were negatively associated with this remission (OR: 0.997; 95%CI=0.995–0.998), independently of, sex, age and type of bariatric surgery. Conclusions: One year after bariatric surgery, 62.5% of patients showed pre- or type 2 diabetes mellitus remission, being the preoperative serum triglycerides levels an important clinical parameter for remission.
Keywords: triglycerides, diabetes, remission, obesity, bariatric surgery
Activin A Plays a Critical Role in Adipose Tissue Wasting in the Progression of Cancer Cachexia
Authors: Luan Yi , You Mikyoung , Xu Pauline C , Thompson Tom , Kim So-Youn 
Published: May 2021

Abstract
Background: Nearly 50% of cancer patients suffer from cancer cachexia, a wasting syndrome with atrophy of white adipose tissue (WAT) and skeletal muscle. Cachexia leads to negative energy balance, limits cancer therapies, and reduces survival rate. It is characterized by body weight loss due to negative nutrients and energy balance from involuntary reduced food intake and abnormal metabolic conditions such as insulin resistance and hypertriglyceridemia. Cancer-driven factors such as activin A and IL-6 (interlukein-6) contribute to the occurrence of cachexia symptoms during cancer progression. While the importance of muscle atrophy has been emphasized in cachexia research, the underlying mechanism of adipose tissue wasting remains unclear. One proposed theory is that WAT switches to brown adipose tissue (BAT), characterized by the high expression level of UCP1 (uncoupling protein 1). Hypothesis: We hypothesize that activin A plays a critical role in adipose tissue wasting during cancer cachexia progression. Experiment: GDF9-iCre+; PIK3CA* female mice which shows cachexia symptoms in cancer progression were sacrificed before and after cachexia development. In addition, we injected FST288, an antagonist to activin A, for two weeks during cancer cachexia development. We harvested and analyzed multi-sites adipose tissues (gonadal, subcutaneous, interscapular and perirenal), muscle and liver. Serum activin A and IL-6 were measured using ELISA kits. DEXA and calorimetry analyses were performed, as well as immunohistochemistry, qPCR and western blotting assay. Results:GDF9-iCre+; PIK3CA* female mice started to display bilateral ovarian tumors around postnatal day (PD) 60, lose body weight around PD70 and became cachexia condition around PD80 with an increased level of serum activin A. Along with that, other body organs including liver, pancreas, muscle, and adipose tissues became dramatically small in mass. Our data proved that cachexia progression is correlated with the level of activin A rather than IL-6 in serum of GDF9-iCre+; PIK3CA* female mice. As serum activin A increased, adipocytes lost lipids and had distinct browning phenotypes in some adipocytes within WAT. Interestingly, calorimetry analysis did not display an increase in energy expenditure in cachectic mice although browning was evident in WAT. However, treatment with FST288 during cancer progression kept body weight and WAT in GDF9-iCre+; PIK3CA* female mice. Most of all, FST288 protected the size and lipid droplets of adipose tissues against WAT wasting during cachexia development. Conclusion: The progression of cancer cachexia impacts adipose tissues. Injection of FST288 supports the key role of activin A in the progress of cachexia. FST288 prevented adipose tissue wasting and cachexia development, revealing another evidence of the efficacy of activin A antagonist in preventing cancer cachexia development.
Exposure to the Widely Used Pyrethroid Pesticide Deltamethrin, Does Not Exacerbate High Fat Diet Induced Obesity or Insulin Resistance in C57BL/6J Mice
Authors: Tsakiridis Evangelia Evelyn , Morrow Marisa , Llanos Andrea , Wang Bo , Holloway Alison , Morrison Katherine Mary , Steinberg Gregory R 
Published: May 2021

Abstract
Deltamethrin is a commonly used pesticide for the control of mosquito populations. Despite widespread use, the effects of deltamethrin on adiposity and glucose homeostasis have been equivocal with some studies showing increased, decreased and no effect on adiposity and glycemic control. However, no study to date has investigated the effect of deltamethrin in mice housed at thermoneutral temperatures, which is important for modelling metabolic diseases in rodents due to reduced thermal stress and constitutive activation of brown adipose tissue. In the current study we demonstrate for the first time that deltamethrin reduces uncoupling protein-1 expression in brown adipocytes cultured in vitro at concentrations as low as 1pm. Meanwhile, in-vivo deltamethrin does not appear to alter glycemic control or promote adiposity at exposures equivalent to 0.01, 0.1 or 1.0 mg/kg/day. Together, our study demonstrates environmentally relevant exposure to deltamethrin does not exacerbate diet induced obesity or insulin resistance.