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Objective Clinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis. Design This multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoholic Steato-hepatitis - BRAVES trial); validation cohort, n=150 (Liquid Biopsy for NASH and Liver Fibrosis - LIBRA trial)) with histologically proven non-alcoholic fatty liver (NAFL) or NASH with or without fibrosis. Proteomics was performed in monocytes and hepatic stellate cells (HSCs) with iTRAQ-nano- Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (LC-MS/MS), while flow cytometry measured perilipin-2 (PLIN2) and RAB14 in peripheral blood CD14 + CD16 - monocytes. Neural network classifiers were used to predict presence/absence of NASH and NASH stages. Logistic bootstrap-based regression was used to measure the accuracy of predicting liver fibrosis. Results The algorithm for NASH using PLIN2 mean florescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT) and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively. The area under the receiver operating characteristic (AUROC) for NAS level prediction ranged from 83.7% (CI 75.6% to 91.8%) in the discovery cohort to 97.8% (CI 95.8% to 99.8%) in the validation cohort. The algorithm including RAB14 MFI, age, waist circumference, high-density lipoprotein cholesterol, plasma glucose and ALT levels as covariates to predict the presence of liver fibrosis yielded an AUROC of 95.9% (CI 87.9% to 100%) in the discovery cohort and 99.3% (CI 98.1% to 100%) in the validation cohort, respectively. Accuracy was 99.25%, sensitivity 100% and

Background and rationale: Obesity is associated with the development and progression of many diseases. Understanding and management of obesity have become increasingly important; however, a knowledge gap remains between how healthcare providers (HCPs) consider weight-loss treatment and the importance of weight loss for improving obesity-related diseases. Objective: The objective of this study was to investigate how HCPs assess obesity, how they interpret the relationship between obesity and 12 recognized co-morbidities of obesity (excluding diabetes), and their view about the value of various weight-loss therapies. Methods: This was a cross-sectional, non-interventional, descriptive study. Participants were medical doctors (HCPs) from eight European countries. Results: Eighty-nine percent of the 197 HCPs that completed the survey considered obesity a disease. For most of the 12 obesity-related diseases under consideration, a majority of HCPs agreed that weight loss could reverse the disease or prevent progression. Among HCPs who have recommended weight loss, lifestyle interventions were by far the most common recommendation. However, more than three out of four HCPs stated that they would be likely to prescribe anti-obesity medications if available and reimbursed. Conclusion: Most HCPs in this survey consider obesity a disease that needs to be treated. However, the majority of HCPs appear to prefer recommending lifestyle changes, although it is well documented that weight loss obtained by lifestyle changes is difficult to maintain. These results underscore the need for improved education of HCPs involved in the treatment of obesity-related diseases.

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.

The COVID-19 pandemic has stretched healthcare resources and caused severe knock-on effects on patients with metabolic diseases worldwide. We encourage clinicians and patient-interest groups in the field of diabetes and metabolism to raise their voices to ensure adequate care and admission of patients.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

La scelta di analizzare l’argomento oggetto della presente trattazione, pur deri-vando da un interesse di ricerca personale, sviluppato in particolare negli ultimi anni, presenta alcuni elementi di collegamento con i temi trattati dal Prof. Lucia-no Marchi nella suaLectio Magistralis che si è tenuta a ottobre 2019 presso l’Università di Pisa . L’informazione aziendale non può essere limitata alla di-mensione economico-finanziaria: tale esigenza ormai diventata un “imperativo categorico, è avvertita in misura crescente sia dal business che dalla finanza e ciò si riflette indubbiamente anche nell’ambito dei sistemi di controllo e di revisione. L’analisi, per quanto sommaria, della tematica dell’informativa non finanzia-ria e del controllo richiama inoltre la contrapposizione fra dimensione interna e esterna. Il Prof. Marchi era solito, nelle sue lezioni e spesso anche nei suoi di-scorsi introduttivi in sede di apertura di molti convegni, richiamare e spesso enfa-tizzare la contrapposizione fra controllo “interno” e controllo “esterno” e in gene-rale fra dimensione “interna” ed “esterna” in ambito aziendale. Devo ammettere che tale distinzione mi appariva un po' semplicistica: negli ultimi anni mi sono invece resa conto che stavo commettendo un grande errore non soltanto per l’effettiva rilevanza della distinzione ma anche perché, in riferimento all’informativa non finanziaria, tale contrapposizione assume una particolare ri-levanza tanto da stimolare molteplici ricerche, anche a livello internazionale. Si assiste infatti ad un costante richiamo negli studi, sia di reportistica che di con-trollo aziendale, alla contrapposizione fra dimensione “interna” ed “esterna”, do-ve indubbiamente la crescente importanza degli interessi degli stakeholder esterni ha svolto un ruolo determinante. Richiamando la sua Lectio Magistralis infatti il Prof. Marchi sottolinea quanto l’evoluzione del sistema di controllo interno “nella direzione del risk management, da un lato, e della

Background: No data from randomised controlled trials of metabolic surgery for diabetes are available beyond 5 years of follow-up. We aimed to assess 10-year follow-up after surgery compared with medical therapy for the treatment of type 2 diabetes. Methods: We did a 10-year follow-up study of an open-label, single-centre (tertiary hospital in Rome, Italy), randomised controlled trial, in which patients with type 2 diabetes (baseline duration >5 years; glycated haemoglobin [HbA1c] >7·0%, and body-mass index ≥35 kg/m2) were randomly assigned (1:1:1) to medical therapy, Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD) by a computerised system. The primary endpoint of the study was diabetes remission at 2 years (HbA1c <6·5% and fasting glycaemia <5·55 mmol/L without ongoing medication for at least 1 year). In the 10-year analysis, durability of diabetes remission was analysed by intention to treat (ITT). This study is registered with ClinicalTrials.gov, NCT00888836. Findings: Between April 30, 2009, and Oct 31, 2011, of 72 patients assessed for eligibility, 60 were included. The 10-year follow-up rate was 95·0% (57 of 60). Of all patients who were surgically treated, 15 (37·5%) maintained diabetes remission throughout the 10-year period. Specifically, 10-year remission rates in the ITT population were 5·5% for medical therapy (95% CI 1·0–25·7; one participant went into remission after crossover to surgery), 50·0% for BPD (29·9–70·1), and 25·0% for RYGB (11·2–46·9; p=0·0082). 20 (58·8%) of 34 participants who were observed to be in remission at 2 years had a relapse of hyperglycaemia during the follow-up period (BPD 52·6% [95% CI 31·7–72·7]; RYGB 66·7% [41·7–84·8]). All individuals with relapse, however, maintained adequate glycaemic control at 10 years (mean HbA1c 6·7% [SD 0·2]). Participants in the RYGB and BPD groups had fewer diabetes-related complications than those in the medical therapy group (relative risk 0·07 [95% CI 0·01–0·48] f

There is a bidirectional relationship between Covid-19 and diabetes. On the one hand, diabetes is associated with an increased risk of severe Covid-19. On the other hand, new-onset diabetes and severe metabolic complications of preexisting diabetes, including diabetic ketoacidosis and hyperosmolarity for which exceptionally high doses of insulin are warranted, have been observed in patients with Covid-19.1-3 These manifestations of diabetes pose challenges in clinical management and suggest a complex pathophysiology of Covid-19–related diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver-related mortality. NAFLD is associated with obesity, hepatic fat accumulation, and insulin resistance, all of which contribute to its pathophysiology. Weight-loss is the main therapy for NAFLD, and metabolic surgery is the most effective treatment for morbid obesity and its metabolic comorbidities. Although has been reported that Roux-en-Y gastric bypass can reverse NAFLD, it is unclear whether such effects result from reduced weight, from a lower calorie-intake, or from the direct influence of surgery on mechanisms contributing to NAFLD. We aimed to investigate whether gastrointestinal (GI) bypass surgery could induce direct effects on hepatic fat accumulation and insulin resistance, independently of weight reduction. Twenty Wistar rats on a high-fat diet underwent duodenal-jejunal-bypass (DJB) or sham operation and were pair fed (PF) for 15 wk after surgery to obtain a matched weight. Outcome measures include ectopic fat deposition, expression of genes and proteins involved in fat metabolism, insulin-signaling, and gluconeogenesis in liver and muscle. Despite no differences in body weight and calorie intake, DJB showed lower ectopic fat accumulation, improved peripheral and hepatic insulin sensitivity, and enhanced lipid droplet degradation. In both tissues, DJB increased insulin signaling, whereas hepatic key enzymes involved in gluconeogenesis and de novo lipogenesis were decreased. These findings suggest that DJB can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of NAFLD that share a mutual pathway, in which perilipin-2 (PLIN2) seems to be the main player, supporting further investigation into strategies that target the gut to treat metabolic liver diseases. NEW & NOTEWORTHY Our findings suggest that duodenal-jejunal bypass can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of non

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.

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.