Weight outcomes audit in 1.3 million adults during their first 3 months' attendance in a commercial weight management programme

Background: Over sixty percent of adults in the UK are now overweight/obese. Weight management on a national scale requires behavioural and lifestyle solutions that are accessible to large numbers of people. Evidence suggests commercial weight management programmes help people manage their weight but there is little research examining those that pay to attend such programmes rather than being referred by primary care. The objective of this analysis was to evaluate the effectiveness of a UK commercial weight management programme in self-referred, fee-paying participants. Methods: Electronic weekly weight records were collated for self-referred, fee-paying participants of Slimming World groups joining between January 2010 and April 2012. This analysis reports weight outcomes in 1,356,105 adult, non-pregnant participants during their first 3 months’ attendance. Data were analysed by regression, ANOVA and for binomial outcomes, chi-squared tests using the R statistical program. Results: Mean (SD) age was 42.3 (13.6) years, height 1.65 m (0.08) and start weight was 88.4 kg (18.8). Mean start BMI was 32.6 kg/m² (6.3 kg/m²) and 5 % of participants were men. Mean weight change of all participants was −3.9 kg (3.6), percent weight change −4.4 (3.8), and BMI change was −1.4 kg/m² (1.3). Mean attendance was 7.8 (4.3) sessions in their first 3 months. For participants attending at least 75 % of possible weekly sessions (n = 478,772), mean BMI change was −2.5 kg/m² (1.3), weight change −6.8 kg (3.7) and percent weight change −7.5 % (3.5). Weight loss was greater in men than women absolutely (−6.5 (5.3) kg vs −3.8 (3.4) kg) and as a percentage (5.7 % (4.4) vs 4.3 % (3.7)), respectively. All comparisons were significant (p < 0.001). Level of attendance and percent weight loss in the first week of attendance together accounted for 55 % of the variability in weight lost during the study period. Conclusions: A large-scale commercial lifestyle-based weight management programme had a significant impact on weight loss outcomes over 3 months. Higher levels of attendance led to levels of weight loss known to be associated with significant clinical benefits, which on this scale may have an impact on public health

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Evidence of big five and aggressive personalities in gait biomechanics

Behavioral observation techniques which relate action to personality have long been neglected (Furr and Funder in Handbook of research methods in personality psychology, The Guilford Press, New York, 2007) and, when employed, often use human judges to code behavior. In the current study we used an alternative to human coding (biomechanical research techniques) to investigate how personality traits are manifest in gait. We used motion capture technology to record 29 participants walking on a treadmill at their natural speed. We analyzed their thorax and pelvis movements, as well as speed of gait. Participants completed personality questionnaires, including a Big Five measure and a trait aggression questionnaire. We found that gait related to several of our personality measures. The magnitude of upper body movement, lower body movement, and walking speed, were related to Big Five personality traits and aggression. Here, we present evidence that some gait measures can relate to Big Five and aggressive personalities. We know of no other examples of research where gait has been shown to correlate with self-reported measures of personality and suggest that more research should be conducted between largely automatic movement and personality

β-cell function is regulated by metabolic and epigenetic programming of islet-associated macrophages, involving Axl, Mertk, and TGFβ receptor signaling

Summary: We have exploited islet-associated macrophages (IAMs) as a model of resident macrophage function, focusing on more physiological conditions than the commonly used extremes of M1 (inflammation) versus M2 (tissue remodeling) polarization. Under steady state, murine IAMs are metabolically poised between aerobic glycolysis and oxidative phosphorylation, and thereby exert a brake on glucose-stimulated insulin secretion (GSIS). This is underpinned by epigenetic remodeling via the metabolically regulated histone demethylase Kdm5a. Conversely, GSIS is enhanced by engaging Axl receptors on IAMs, or by augmenting their oxidation of glucose. Following high-fat feeding, efferocytosis is stimulated in IAMs in conjunction with Mertk and TGFβ receptor signaling. This impairs GSIS and potentially contributes to β-cell failure in pre-diabetes. Thus, IAMs serve as relays in many more settings than currently appreciated, fine-tuning insulin secretion in response to dynamic changes in the external environment. Intervening in this nexus might represent a means of preserving β-cell function during metabolic disease

<i>Tgm2</i> deletion has no effect on insulin secretion by islets.

<p>Islets were isolated (A) from 6 month-old male B6 WT and TG2^−/− (i) or 129 WT and TG2^−/− (ii) mice fed a normal chow diet (chow) or fed a normal chow diet for 3 months followed by a high-fat diet for 3 months (fat) or (B) from 3 month old male 129 WT and TG2^−/− mice fed a normal chow diet. (A) Isolated islets, 5 per group (n = 7), were incubated in Krebs-Ringer bicarbonate (KRB) buffer containing 2.8 mM glucose or 16.8 mM glucose or 16.8 mM glucose plus 0.1 mM carbachol, 37°C, 1 h. (B) Groups of 70 islets (n = 3 for WT and n = 2 for TG2^−/−) were perifused in KRB containing 2.8 mM glucose for 10 min before a stimulatory period of 60 min with KRB containing 16.8 mM glucose. The perifusate was switched back to 2.8 mM glucose for 30 min to allow insulin secretion to return to basal levels before exposure to 16.8 mM glucose and 100 µM carbachol for 30 min. The perifusate was switched back to 2.8 mM glucose for 10 min before non-metabolic depolarisation with 24 mM KCl to activate voltage-gated Ca²⁺ channel-triggered insulin secretion. One min fractions of the perifusate were collected for the first 10 min, then 2 min fractions were collected at a flow rate of 0.5 ml/min. Insulin content of supernatant and of islets was determined by radioimmunoassay. Data are presented as means ± SEM. Overall <i>P</i> values calculated using 2-way ANOVA are shown at the top; individual Bonferroni <i>post hoc</i> test results are shown above the columns.**<i>P</i><0.01; ***<i>P</i><0.001.</p