Examining the effects of short-term energy restriction on liver lipid, metabolism and inflammatory status in severely obese adults

A pre-operative energy restrictive diet is common practice prior to bariatric surgery in the United Kingdom. A review of current practice found variability in form, duration and application of the diet used, with little evidence for efficacy beyond patients successfully undergoing surgery. Imperative for best practice was to provide evidence of the efficacy of dietary approaches both in terms of the original aim of the diet to reduce liver size and improve access to enable laparoscopic surgery, but also to investigate the wider effects of the diet on this population. A clinical trial was designed to compare two very low energy dietary approaches applied over two weeks before bariatric surgery, using a) a food-based diet, which is standard practice at the Royal Derby Hospital, and comparing this to b) an alternative meal replacement approach with products supplied by LighterLife. The diets were designed to offer similar energy intakes, 800kcal/d, but with varying macronutrient composition and format. Both diets achieved comparable body weight loss (median -3.4%) and excess body mass index loss (median -1.79kg/m2). The trial found similar results from both diets for the original aim of the diet, which is to enable surgery. Surgeons’ visual assessment of the liver at the time of surgery for operative difficulty was associated to histologically assessed levels of steatosis, with lower levels of steatosis associated to less operative difficulty. Patient evaluation of the diets revealed no significant difference in outcomes between diets, and overall satisfaction of the diets was very high, with 92% and 85% reporting that they were satisfied or very satisfied with their diet respectively. Both diets produced a favourable change in circulating lipids, inflammatory markers and glucose (pooled median LDL -0.4mmol/L, Glucose-0.2mmol/L, CRP -3.6mg/L, IL6 -0.4pg/mL, ELF -0.8). Findings including histology and gene expression data suggest a dynamic lipid environment in both liver and omental adipose tissue post-diet, concurrent with insulin sensitivity, but suggest a less dynamic environment in subcutaneous adipose tissue. Overall the diets could not be separated in terms of effects on circulating biomarkers, Non-Alcoholic Fatty Liver disease outcomes, operative difficulty, gene expression levels, or patient acceptability. Negative associations with diabetes status were found for steatosis and inflammation post-diet and warrant further investigation. Also, childhood weight status was found to be linked to the level of improvement in insulin sensitivity and requires further work. Limitations suggest additional work should incorporate reporting or recording of physical activity levels, pre-diet assessment of liver condition, diabetes duration and habitual dietary intake. Work should also confirm findings and corroborate suppositions regarding physiological changes observed from mRNA transcript expression levels, into protein and onto functional levels. This work informs the format and application of a short-term pre-operative diet in severe obesity. It has established that pre-bariatric surgery patients were satisfied with either format of VLED when applied in clinical practice. It has also extended the existing evidence base on the effects of a short-term VLED, specifically the potential beneficial effects on progressive features of NAFLD, and adipose tissue inflammatory status, which could be of value in the management of the disease

Herschel-ATLAS: Dust temperature and redshift distribution of SPIRE and PACS detected sources using submillimetre colours

We present colour-colour diagrams of detected sources in the Herschel-ATLAS science demonstration field from 100 to 500μm using both PACS and SPIRE. We fit isothermal modified black bodies to the spectral energy distribution (SED) to extract the dust temperature of sources with counterparts in Galaxy And Mass Assembly (GAMA) or SDSS surveys with either a spectroscopic or a photometric redshift. For a subsample of 330 sources detected in at least three FIR bands with a significance greater than 3σ, we find an average dust temperature of (28±8) K. For sources with no known redshift, we populate the colour-colour diagram with a large number of SEDs generated with a broad range of dust temperatures and emissivity parameters, and compare to colours of observed sources to establish the redshift distribution of this sample. For another subsample of 1686 sources with fluxes above 35 mJy at 350μm and detected at 250 and 500μm with a significance greater than 3σ we find an average redshift of 2.2 ±0.6Amblard, Barton, Cooray, Leeuw, Serra and Temi acknowledge support from NASA funds for US participants in Herschel through JPL. Funding for the SDSS and SDSS-II has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, the US Department of Energy, the National Aeronautics and Space Administration, the Japanese Monbukagakusho, the Max Planck Society, and the Higher Education Funding Council for England. The SDSS Web Site is http://www.sdss.org/. The SDSS is managed by the Astrophysical Research Consortium for the Participating Institutions. The UKIDSS project is defined in Lawrence et al. (2007)

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Examining the effects of short-term energy restriction on liver lipid, metabolism and inflammatory status in severely obese adults

A pre-operative energy restrictive diet is common practice prior to bariatric surgery in the United Kingdom. A review of current practice found variability in form, duration and application of the diet used, with little evidence for efficacy beyond patients successfully undergoing surgery. Imperative for best practice was to provide evidence of the efficacy of dietary approaches both in terms of the original aim of the diet to reduce liver size and improve access to enable laparoscopic surgery, but also to investigate the wider effects of the diet on this population. A clinical trial was designed to compare two very low energy dietary approaches applied over two weeks before bariatric surgery, using a) a food-based diet, which is standard practice at the Royal Derby Hospital, and comparing this to b) an alternative meal replacement approach with products supplied by LighterLife. The diets were designed to offer similar energy intakes, 800kcal/d, but with varying macronutrient composition and format. Both diets achieved comparable body weight loss (median -3.4%) and excess body mass index loss (median -1.79kg/m2). The trial found similar results from both diets for the original aim of the diet, which is to enable surgery. Surgeons’ visual assessment of the liver at the time of surgery for operative difficulty was associated to histologically assessed levels of steatosis, with lower levels of steatosis associated to less operative difficulty. Patient evaluation of the diets revealed no significant difference in outcomes between diets, and overall satisfaction of the diets was very high, with 92% and 85% reporting that they were satisfied or very satisfied with their diet respectively. Both diets produced a favourable change in circulating lipids, inflammatory markers and glucose (pooled median LDL -0.4mmol/L, Glucose-0.2mmol/L, CRP -3.6mg/L, IL6 -0.4pg/mL, ELF -0.8). Findings including histology and gene expression data suggest a dynamic lipid environment in both liver and omental adipose tissue post-diet, concurrent with insulin sensitivity, but suggest a less dynamic environment in subcutaneous adipose tissue. Overall the diets could not be separated in terms of effects on circulating biomarkers, Non-Alcoholic Fatty Liver disease outcomes, operative difficulty, gene expression levels, or patient acceptability. Negative associations with diabetes status were found for steatosis and inflammation post-diet and warrant further investigation. Also, childhood weight status was found to be linked to the level of improvement in insulin sensitivity and requires further work. Limitations suggest additional work should incorporate reporting or recording of physical activity levels, pre-diet assessment of liver condition, diabetes duration and habitual dietary intake. Work should also confirm findings and corroborate suppositions regarding physiological changes observed from mRNA transcript expression levels, into protein and onto functional levels. This work informs the format and application of a short-term pre-operative diet in severe obesity. It has established that pre-bariatric surgery patients were satisfied with either format of VLED when applied in clinical practice. It has also extended the existing evidence base on the effects of a short-term VLED, specifically the potential beneficial effects on progressive features of NAFLD, and adipose tissue inflammatory status, which could be of value in the management of the disease

Pragmatic management of low energy diets in people with Type 2 diabetes in primary care: a decision aid for clinicians

Significant weight loss at a level to achieve remission in the short‐term has been achieved through total dietary replacement or a low‐energy diets 1-3. These diets aim for an energy restriction to between 800 and 1600 kcal/day, and could achieve 15% weight loss in 8–12 weeks 4. This is distinct from a very‐low‐energy diet of 5. As observed by Astbury et al. 2, combinations of food, meals and meal replacement products are all effective at achieving a significant level of weight loss in this time. Analysis of the pragmatic intervention utilized in the Diabetes Remission Clinical Trial (DiRECT) indicates that it is a safe and cost‐effective strategy, and appears to result in sustained weight loss in some cases 6

Effects of short-term energy restriction on liver lipid content and inflammatory status in severely obese adults: results of a randomised controlled trial (RCT) using two dietary approaches

Short-term very low energy diets (VLED) are used in clinical practice prior to bariatric surgery, however, regimens vary and outcomes for a short intervention are unclear. We examined the effect of two VLEDs; a food-based diet (FD) and meal replacement plan (MRP) (LighterLife) over two weeks in a randomised controlled trial (RCT). We collected clinical and anthropometric data, fasting blood samples, and dietary evaluation questionnaires. Surgeons took liver biopsies and made a visual assessment of the liver. We enrolled 60 participants and 54 completed (FD n=26, MRP n=28). Baseline demographic features, reported energy intake, dietary evaluation and liver histology were comparable between groups. Both diets induced significant weight loss. Perceived difficulty of surgery correlated significantly with the degree of steatosis on histology. Circulating inflammatory mediators: CRP, Fetuin-A and IL6 reduced pre to post diet. Diets achieved comparable weight loss and reduction in inflammatory biomarkers, perceived operative difficulty, and patient evaluation. NAFLD histology assessments post-diet were also not significantly different between diets. Results indicate effectiveness of short term very low energy diets and energy restriction irrespective of macronutrient composition although small sample size precluded detection of subtle differences between interventions

Efficacy of Low- and Very-Low-Energy Diets in people with Type 2 Diabetes Mellitus: A systematic review and meta-analysis of interventional studies.

AIMS: To systematically review and quantify the weight loss achieved by Low- and Very-Low-Energy Diets in people with type 2 diabetes mellitus. MATERIALS AND METHODS: Studies reporting the effects of diet-only interventions up to 1600kcal/day in people with type 2 diabetes mellitus were searched in MEDLINE, EMBASE, CINAHL until July 2018. Changes in the primary (body weight and body mass index) and secondary (HbA1c, blood lipids) outcomes according to energy restriction and duration of diet were modelled using restricted cubic splines. RESULTS: Forty-four studies (3817 participants) were included. The overall quality of the evidence was moderate and limited to short-term interventions up to four months. Baseline mean weight and body mass index were 92.1kg and 36.6kg/m2 . Very-Low-Energy Diets of 400kcal/day led to 5.4% weight loss at two weeks, increasing to 17.9% at three months. More modest reductions of 7.3% were observed on Low-Energy Diets of 1200kcal/day and 2.0% on 1600kcal/day after three months. No clear patterns emerged for secondary outcomes. Publication bias was significant for primary outcomes. CONCLUSIONS: High-quality studies are required to support evidence-based Low- and Very-Low Energy prescription in people with type 2 diabetes. Available evidence would suggest variable reduction of body weight, ranging from 2% to 18%, after three months of Low- and Very-Low-Energy Diets

Movement through Active Personalised engagement (MAP) — a self-management programme designed to promote physical activity in people with multimorbidity: study protocol for a randomised controlled trial

Abstract Background Multimorbidity, defined as two or more concurrent chronic diseases within the same individual, is becoming the clinical norm within primary care. Given the burden of multimorbidity on individuals, carers and health care systems, there is a need for effective self-management programmes. Promoting active participation within their clinical care and following a healthy lifestyle will help empower patients and target lifestyle factors that are exacerbating their conditions. The aim of this study is to establish whether a tailored, structured self-management programme can improve levels of physical activity at 12 months, in people with multimorbidity. Methods/design This study is a single-centre randomised controlled trial, with follow-up at 6 and 12 months. The primary outcome is change in objectively assessed average daily physical activity at 12 months. Secondary outcomes include medication adherence, lifestyle behaviours, quality of life, chronic disease self-efficacy and self-efficacy for exercise. Anthropometric and clinical measurements include blood pressure, muscle strength, lipid profile, kidney function and glycated haemoglobin (HbA1c). Participants are recruited from primary care. Those between 40 and 85 years of age with multimorbidity, with a good understanding of written and verbal English, who are able to give informed consent, have access to a mobile phone for use in study activities and are able to walk independently will be invited to participate. Multimorbidity is defined as two or more of the chronic conditions listed in the Quality and Outcomes Framework. A total of 338 participants will be randomly assigned, with stratification for gender and ethnicity, to either the control group, receiving usual care, or the intervention group, who are invited to the Movement through Active Personalised engagement programme. This involves attending four group-based self-management sessions aimed at increasing physical activity, mastering emotions, managing treatments and using effective communication. The sessions are delivered by trained facilitators, and regular text messages during the study period provide ongoing support. Changes in primary and secondary outcomes will be assessed, and an economic evaluation of the intervention undertaken. Discussion This study will provide new evidence on whether physical activity can be promoted alongside other self-management strategies in a multimorbid population and whether this leads to improvements in clinical, biomedical, psychological and quality of life outcomes. Trial registration ISRCTN, ISRCTN 42791781. Registered on 14 March 2017

Physical behaviours and chronotype in people with Type 2 diabetes

Introduction Previous investigations have suggested that evening chronotypes may be more susceptible to obesity-related metabolic alterations. However, whether device-measured physical behaviours differ by chronotype in those with T2DM remains unknown. Research design and methods This analysis reports data from the ongoing Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) observational study. Eligible participants were recruited from both primary and secondary care settings in the Midlands area, UK. Participants were asked to wear an accelerometer (GENEActiv, ActivInsights Ltd, Kimbolton, UK) on their non-dominant wrist for 7 days to quantify different physical behaviours (sleep, sedentary, light, moderate-to-vigorous physical activity (MVPA), intensity gradient, average acceleration and the acceleration above which the most active continuous 2, 10, 30 and 60 minutes are accumulated). Chronotype preference (morning, intermediate or evening) was assessed using the Morningness-Eveningness Questionnaire. Multiple linear regression analyses assessed whether chronotype preference was associated with physical behaviours and their timing. Evening chronotypes were considered as the reference group. Results 635 participants were included (age=63.8±8.4 years, 34.6% female, BMI=30.9±5.1kg/m2). 25% (n=159) of the cohort were morning chronotypes, 52% (n=330) intermediate and 23% (n=146) evening chronotypes. Evening chronotypes had higher sedentary time (28.7 minutes/day, 95% CI 8.6, 48.3), and lower MVPA levels (-9.7mins/day, -14.9, -4.6) compared to morning chronotypes. The intensity of the most active continuous 2-60 minutes of the day, average acceleration and intensity gradient were lower in evening chronotypes. The timing of physical behaviours also differed across chronotypes, with evening chronotypes displaying a later sleep onset and consistently later physical activity time. Conclusions People with T2DM lead a lifestyle characterised by sedentary behaviours and insufficient MVPA. This may be exacerbated in those with a preference for ‘eveningness’ (i.e., go to bed late and get up late).</p

Effects of empagliflozin, diet, or both on physical activity and sedentary behaviour in people with type 2 diabetes: analyses from the SEESAW trial [Abstract]

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