Adipocytes in obesity: A perfect reservoir for SARS-CoV-2?

Research evidence suggests that adipocytes in obesity might facilitate SARS-CoV-2 replication, for it was only found in adipose tissue of individuals with overweight or obesity but not lean individuals who died from COVID-19. As lipid metabolism is key to adipocyte function, and viruses are capable of exploiting and manipulating lipid metabolism of host cells for their own benefit of infection, we hypothesize that adipocytes could not only impair host immune defense against viral infection, but also facilitate SARS-CoV-2 entry, replication and assembly as a reservoir to boost the viral infection in obesity. The latter of which could mainly be mediated by SARS-CoV-2 hijacking the abnormal lipid metabolism in the adipocytes. If these were to be confirmed, an approach to combat COVID-19 in people with obesity by taking advantage of the abnormal lipid metabolism in adipocytes might be considered, as well as modifying lipid metabolism of other host cells as a potential adjunctive treatment for COVID-19.

Economic impacts of overweight and obesity: current and future estimates for 161 countries.

INTRODUCTION: The scope of the challenge of overweight and obesity (OAO) has not been fully realised globally, in part because much of what is known about the economic impacts of OAO come from high-income countries (HICs) and are not readily comparable due to methodological differences. Our objective is to estimate the current and future national economic impacts of OAO globally. METHODS: We estimated economic impacts of OAO for 161 countries using a cost-of-illness approach. Direct and indirect costs of OAO between 2019 and 2060 were estimated from a societal perspective. We assessed the effect of two hypothetical scenarios of OAO prevalence projections. Country-specific data were sourced from published studies and global databases. RESULTS: The economic impact of OAO in 2019 is estimated at 2.19% of global gross domestic product (GDP) ranging on average from US$20 per capita in Africa to US$872 per capita in the Americas and from US$6 in low-income countries to US$1110 in HICs.If current trends continue, by 2060, the economic impacts from OAO are projected to rise to 3.29% of GDP globally. The biggest increase will be concentrated in lower resource countries with total economic costs increasing by fourfold between 2019 and 2060 in HICs, whereas they increase 12-25 times in low and middle-income countries. Reducing projected OAO prevalence by 5% annually from current trends or keeping it at 2019 levels will translate into average annual reductions of US$429 billion or US$2201 billion in costs, respectively, between 2020 and 2060 globally. CONCLUSION: This study provides novel evidence on the economic impact of OAO across different economic and geographic contexts. Our findings highlight the need for concerted and holistic action to address the global rise in OAO prevalence, to avert the significant risks of inaction and achieve the promise of whole-of-society gains in population well-being.

The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review.

Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The 'SGLT2i Prescribing Tool for T2DM Management', previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care.

PARIS: protocol for a prospective single arm, theory-based, group-based feasibility intervention study to increase Physical Activity and reduce sedentary behaviouR after barIatric Surgery.

INTRODUCTION: Increased physical activity and reduced sedentary behaviour can encourage favourable outcomes after bariatric surgery. However, there is a lack of evidence as to how to support patients with behaviour change. The aim of this study is to assess the feasibility of a physiotherapist led, online group-based behaviour change intervention to increase physical activity and reduce sedentary behaviour following bariatric surgery. METHODS AND ANALYSIS: Single arm feasibility study of a theory and evidence-based group behaviour change intervention based on the Behaviour Change Wheel and Theoretical Domains Framework using behaviour change techniques from the Behaviour Change Technique Taxonomy v1. The intervention has eight objectives and specifies behaviour change techniques that will be used to address each of these. Groups of up to eight participants who have had surgery within the previous 5 years will meet weekly over 6 weeks for up to 1½ hours. Groups will be held online led by a physiotherapist and supported by an intervention handbook. Feasibility study outcomes include: rate of recruitment, retention, intervention fidelity, participant engagement and acceptability. Secondary outcomes include: physical activity, sedentary behaviour, body composition, self-reported health status and will be analysed descriptively. Change in these outcomes will be used to calculate the sample size for a future evaluation study. Qualitative interviews will explore participants' views of the intervention including its acceptability. Data will be analysed according to the constant comparative approach of grounded theory. ETHICS AND DISSEMINATION: This study has National Health Service Research Ethics Committee approval; Haydock 20/NW/0472. All participants will provide informed consent and can withdraw at any point. Findings will be disseminated through peer-reviewed journals, conference and clinical service presentations. TRIAL REGISTRATION NUMBER: ISRCTN31524689.

Economic impacts of overweight and obesity: current and future estimates for eight countries.

BACKGROUND: Obesity is a growing public health challenge worldwide with significant health and economic impacts. However, much of what is known about the economic impacts of obesity comes from high-income countries and studies are not readily comparable due to methodological differences. Our objective is to demonstrate a method for estimating current and future national economic impacts of obesity and apply it across a sample of heterogeneous contexts globally. METHODS: We estimated economic impacts of overweight and obesity for eight countries using a cost-of-illness approach. Direct and indirect costs of obesity from 2019 to 2060 were estimated from a societal perspective as well as the effect of two hypothetical scenarios of obesity prevalence projections. Country-specific data were sourced from published studies and global databases. RESULTS: In per capita terms, costs of obesity in 2019 ranged from US$17 in India to US$940 in Australia. These economic costs are comparable to 1.8% of gross domestic product (GDP) on average across the eight countries, ranging from 0.8% of GDP in India to 2.4% in Saudi Arabia. By 2060, with no significant changes to the status quo, the economic impacts from obesity are projected to grow to 3.6% of GDP on average ranging from 2.4% of GDP in Spain to 4.9% of GDP in Thailand. Reducing obesity prevalence by 5% from projected levels or keeping it at 2019 levels will translate into an average annual reduction of 5.2% and 13.2% in economic costs, respectively, between 2020 and 2060 across the eight countries. CONCLUSION: Our findings demonstrate that the economic impacts of obesity are substantial across countries, irrespective of economic or geographical context and will increase over time if current trends continue. These findings strongly point to the need for advocacy to increase awareness of the societal impacts of obesity, and for policy actions to address the systemic roots of obesity.

Realising the full potential of data-enabled trials in the UK: a call for action.

RATIONALE: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. APPROACH: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. REFLECTION: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. DISCUSSION: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

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).

Strengthening resistance to the COVID-19 pandemic and fostering future resilience requires concerted action on obesity.

Initial observations showed that people with chronic noncommunicable diseases were at heightened risk of severe COVID-19 and adverse outcomes. Subsequently, data from various countries have revealed obesity as an independent and significant factor, with people who are overweight/have obesity significantly more likely to be hospitalized, require ICU treatment, and to die. Notably, this additional risk applies to younger people relative to the general COVID-19 risk profile. This paper sets out the evidence of greater risk of poor COVID outcomes for people who are overweight/have obesity, indication of reduced treatment and support for obesity self-management where it existed prior to COVID-19, and highlights the dearth of specific guidance and measures to mitigate the impacts of COVID-19 upon people with obesity. We identify the health, social and economic impacts that this specific vulnerability creates relative to COVID-19 outcomes. Reduced national and global pandemic resilience due to high obesity prevalence should spur governments and funders to provide urgent specific protection and support for people with overweight/obesity, and to commission rapid research to identify effective prevention and reduction measures. We set out priorities for action on obesity to begin compensating for years of underfunding and inadequate policy attention in the face of escalating obesity across countries of all income groups and world regions.