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Background: Following consumption of a meal, circulating glucose concentrations can rise and then fall briefly below the basal/fasting concentrations. This phenomenon is known as reactive hypoglycaemia but to date no researcher has explored potential inter-individual differences in response to meal consumption. Objective: We conducted a secondary analysis of existing data to examine inter-individual variability of reactive hypoglycaemia in response to breakfast consumption. Methods: Using a replicate crossover design, 12 healthy, physically active men (age: 18–30 y, body mass index: 22.1 to 28.0 kg⋅m− 2) completed two identical control (continued overnight fasting) and two breakfast (444 kcal; 60% carbohydrate, 17% protein, 23% fat) conditions in randomised sequences. Blood glucose and lactate concentrations, serum insulin and non-esterified fatty acid concentrations, whole-body energy expenditure, carbohydrate and fat oxidation rates, and appetite ratings were determined before and 2 h after the interventions. Inter-individual differences were explored using Pearson's product-moment correlations between the first and second replicates of the fasting-adjusted breakfast response. Within-participant covariate-adjusted linear mixed models and a random-effects meta-analytical approach were used to quantify participant-by-condition interactions. Results: Breakfast consumption lowered 2-h blood glucose by 0.44 mmol/L (95%CI: 0.76 to 0.12 mmol/L) and serum NEFA concentrations, whilst increasing blood lactate and serum insulin concentrations (all p < 0.01). Large, positive correlations were observed between the first and second replicates of the fasting-adjusted insulin, lactate, hunger, and satisfaction responses to breakfast consumption (all r > 0.5, 90%CI ranged from 0.03 to 0.91). The participant-by-condition interaction response variability (SD) for serum insulin concentration was 11 pmol/L (95%CI: 5 to 16 pmol/L), which was consistent with the τ-statistic from the random-effects meta-analysis (11.7 pmol/L, 95%CI 7.0 to 22.2 pmol/L) whereas effects were unclear for other outcome variables (e.g., τ-statistic value for glucose: 0 mmol/L, 95%CI 0.0 to 0.5 mmol/L). Conclusions: Despite observing reactive hypoglycaemia at the group level, we were unable to detect any meaningful inter-individual variability of the reactive hypoglycaemia response to breakfast. There was, however, evidence that 2-h insulin responses to breakfast display meaningful inter-individual variability, which may be explained by relative carbohydrate dose ingested and variation in insulin sensitivity of participants. [ABSTRACT FROM AUTHOR]

Background: Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking. Methods: We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using two-sample Mendelian randomization and mice models. Results: Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7 and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2 hr glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice. Conclusions: Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR). Methods: Genetic variants significantly associated with lifestyle behaviours, abdominal obesity, generalized obesity and diabetic microvascular complications were extracted from the UK Biobank (UKB) and FinnGen. The inverse variance weighted (IVW) method was regarded as the primary method. The main results were presented in odds ratio (OR) per standard deviation (SD) increase, and a series of sensitivity analyses were also conducted to validate the stability of the results. Results: There was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04-1.30; p = 0.01). All of the indicators representing abdominal obesity had a statistically significant causal association with diabetic microvascular complications. Concerning generalized obesity, there were significant causal associations of body mass index (BMI) on diabetic nephropathy (OR = 1.92; 95%CI: 1.58-2.33; p < 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15-1.40; p < 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95-3.45; p < 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications. Conclusion: Our findings suggested that smoking has a genetically causal association with the development of diabetic retinopathy rather than diabetic nephropathy and diabetic neuropathy. In addition, both abdominal obesity and generalized obesity are risk factors for diabetic microvascular complications. To note, abdominal obesity represented by waist circumference (WC) is the most significant risk factor. [ABSTRACT FROM AUTHOR]

Context Among children, evidence on long-term longitudinal associations of accelerometer-measured sedentary time, light physical activity (LPA), and moderate to vigorous PA (MVPA) with lipid indices are few. The mediating role of body composition and other metabolic indices in these associations remains unclear and whether poor movement behavior precedes altered lipid levels is unknown. Objective This study examined the associations of sedentary time, LPA, and MVPA from childhood through young adulthood with increased lipids, the mediating role of body composition, and whether temporal interrelations exist. Methods Data from 792 children (58% female; mean [SD] age at baseline, 11.7 [0.2] years), drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort, who had at least 2 time-point measures of accelerometer-based sedentary time, LPA, and MVPA during clinic visits at ages 11, 15, and 24 years and complete fasting plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol measured during follow-up visits at ages 15, 17, and 24 years were analyzed. Results Total fat mass partly mediated the inverse associations of LPA with low-density lipoprotein cholesterol by 13%, triglyceride by 28%, and total cholesterol by 6%. Total fat mass mediated the inverse associations of MVPA with low-density lipoprotein cholesterol by 37% and total cholesterol by 48%, attenuating the effect on total cholesterol to nonsignificance (P =.077). In the temporal path analyses, higher MVPA at age 15 years was associated with lower low-density lipoprotein cholesterol at 24 years (β = −0.08, SE, 0.01, P =.022) but not vice versa. Conclusion Sedentary time worsens lipid indices, but increased LPA had a 5- to 8-fold total cholesterol-lowering effect and was more resistant to the attenuating effect of fat mass than MVPA. [ABSTRACT FROM AUTHOR]

Objectives: To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank. Methods: PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods. Results: We studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models. Conclusions: The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF. Clinical relevance statement: This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF. Key Points: •PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. •Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. •An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure. [ABSTRACT FROM AUTHOR]

Cancer risk is associated with the widely debated measure body mass index (BMI). Fat mass and fat-free mass measurements from bioelectrical impedance may further clarify this association. The UK Biobank is a rare resource in which bioelectrical impedance and BMI data was collected on ~ 500,000 individuals. Using this dataset, a comprehensive analysis using regression, principal component and genome-wide genetic association, provided multiple levels of evidence that increasing whole body fat (WBFM) and fat-free mass (WBFFM) are both associated with increased post-menopausal breast cancer risk, and colorectal cancer risk in men. WBFM was inversely associated with prostate cancer. We also identified rs615029[T] and rs1485995[G] as associated in independent analyses with both PMBC (p = 1.56E–17 and 1.78E–11) and WBFFM (p = 2.88E–08 and 8.24E–12), highlighting splice variants of the intriguing long non-coding RNA CUPID1 (LINC01488) as a potential link between PMBC risk and fat-free mass. [ABSTRACT FROM AUTHOR]

Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding proteins known to interact with postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors. Loci in/near discs large homolog 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P < 5 × 10-8) for BF% and/or BMI. To further evaluate the functional role of postsynaptic density protein-95 (PSD-95; gene name: DLG4) and PICK1 in energy homeostasis, we used dimeric PSD-95/disc large/ZO-1 (PDZ) domain-targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising therapeutic avenue for sustained weight loss. [ABSTRACT FROM AUTHOR]

Appearance-related interactions with peers, both positive and negative, are commonplace on social media. Using qualitative methods, this study explores U.K. adolescents' shared understandings and experiences of these interactions. Sixty-four adolescents (Age M = 12.56; SD = 0.97; Girls = 33) from a secondary school in Northern England participated in semi-structured focus groups. Using thematic analysis, three themes were developed that encapsulate their shared understandings of appearance-related interactions: (a) positive appearance commentary is the norm, especially if you are popular and attractive; (b) comments to others should be positive, but comments about the self should be modest and self-deprecating; and (c) negative appearance comments are problematic but not always intentionally harmful. Overall, our findings suggest that, to adolescents, the boundaries between positive and negative interactions are blurred, as content, intention, gender, and social rules intersect with social media platform design. Further research is needed to better understand how social media site design alters adolescents' appearance interactions, as well as the role of these interactions in the development and maintenance of peer relationships and body image concerns. [ABSTRACT FROM AUTHOR]

Background Diabetes (regardless of type) and obesity are associated with a range of musculoskeletal disorders. The causal mechanisms driving these associations are unknown for many upper limb pathologies. We used genetic techniques to test the causal link between glycemia, obesity and musculoskeletal conditions. Methods In the UK Biobank's unrelated European cohort (N  = 379 708) we performed mendelian randomisation (MR) analyses to test for a causal effect of long-term high glycaemia and adiposity on four musculoskeletal pathologies: frozen shoulder, Dupuytren's disease, carpal tunnel syndrome and trigger finger. We also performed single-gene MR using rare variants in the GCK gene. Results Using MR, we found evidence that long-term high glycaemia has a causal role in the aetiology of upper limb conditions. A 10-mmol/mol increase in genetically predicted haemoglobin A1C (HbA1c) was associated with frozen shoulder: odds ratio (OR) = 1.50 [95% confidence interval (CI), 1.20–1.88], Dupuytren's disease: OR = 1.17 (95% CI, 1.01–1.35), trigger finger: OR = 1.30 (95% CI, 1.09–1.55) and carpal tunnel syndrome: OR = 1.20 (95% CI, 1.09–1.33). Carriers of GCK mutations have increased odds of frozen shoulder: OR = 7.16 (95% CI, 2.93–17.51) and carpal tunnel syndrome: OR = 2.86 (95% CI, 1.50–5.44) but not Dupuytren's disease or trigger finger. We found evidence that an increase in genetically predicted body mass index (BMI) of 5 kg/m2 was associated with carpal tunnel syndrome: OR = 1.13 (95% CI, 1.10–1.16) and associated negatively with Dupuytren's disease: OR = 0.94 (95% CI, 0.90–0.98), but no evidence of association with frozen shoulder or trigger finger. Trigger finger (OR 1.96 (95% CI, 1.42–2.69) P  =   3.6e-05) and carpal tunnel syndrome [OR 1.63 (95% CI, 1.36–1.95) P  =   8.5e-08] are associated with genetically predicted unfavourable adiposity increase of one standard deviation of body fat. Conclusions Our study consistently demonstrates a causal role of long-term high glycaemia in the aetiology of upper limb musculoskeletal conditions. Clinicians treating diabetes patients should be aware of these complications in clinic, specifically those managing the care of GCK mutation carriers. Upper limb musculoskeletal conditions should be considered diabetes complications. [ABSTRACT FROM AUTHOR]

Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two‐sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome‐wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse‐variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10‐9.99; P = 2.35E‐30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32‐24.72; P =.020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have investigated the association between endocrine and metabolic factors and idiopathic pulmonary fibrosis (IPF), yet have produced inconsistent results. Therefore, it is imperative to employ the Mendelian randomization (MR) analysis method to conduct a more comprehensive investigation into the impact of endocrine and metabolic factors on IPF. Methods: The instrumental variables (IVs) for 53 endocrine and metabolic factors were sourced from publicly accessible genome-wide association study (GWAS) databases, with GWAS summary statistics pertaining to IPF employed as the dependent variables. Causal inference analysis encompassed the utilization of three methods: inverse-variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analysis incorporated the implementation of MR-PRESSO and leave-one-out techniques to identify potential pleiotropy and outliers. The presence of horizontal pleiotropy and heterogeneity was evaluated through the MR-Egger intercept and Cochran's Q statistic, respectively. Results: The IVWmethod results reveal correlations between 11 traits and IPF. After correcting for multiple comparisons, seven traits remain statistically significant. These factors include: "Weight" (OR= 1.44; 95% CI: 1.16, 1.78; P=8.71×10-4), "Body mass index (BMI)" (OR= 1.35; 95% CI: 1.13, 1.62; P=1×10-3), "Whole body fat mass" (OR= 1.40; 95% CI: 1.14, 1.74; P=1.72×10-3), "Waist circumference (WC)" (OR= 1.54; 95% CI: 1.16, 2.05; P=3.08×10-3), "Trunk fat mass (TFM)" (OR=1.35; 95% CI: 1.10,1.65; P=3.45×10-3), "Body fat percentage (BFP)" (OR= 1.55; 95% CI: 1.15,2.08; P=3.86×10-3), "Apoliprotein B (ApoB)" (OR= 0.78; 95% CI: 0.65,0.93; P=5.47×10-3). Additionally, the sensitivity analysis results confirmed the reliability of the MR results. Conclusion: The present study identified causal relationships between seven traits and IPF. Specifically, ApoB exhibited a negative impact on IPF, while the remaining six factors demonstrated a positive impact. These findings offer novel insights into the underlying etiopathological mechanisms associated with IPF. [ABSTRACT FROM AUTHOR]

Featured Application: This opinion piece discusses the limitations of the current cytotoxic dosing methods and how advanced body measurement techniques could be used by oncology practitioners to determine cytotoxic chemotherapy dosages for patients, regardless of their body size. Within chemotherapy, estimates of a patient's body surface area (BSA) are used to calculate drug dosages. However, the use of BSA for calculating chemotherapy dosage has been heavily criticised in previous literature, with potentially significant implications for the effectiveness and toxicity of treatment. BSA has been found to be a poor indicator of optimal drug exposure that does not account for the complex processes of cytotoxic drug distribution and elimination. In addition, differences in BSA estimates between existing formulae have been shown to be so large that they can affect patients' mortality, particularly in patients with atypical body types. This uncertainty associated with BSA prediction may decrease the confidence of practitioners when determining chemotherapy dosages, particularly with regards to the risk of excess toxicity from over-dosing, or a reduced anti-cancer effect due to under-dosing. The use of national dose-banding in the UK may in some cases account for possible inaccuracies, but the threshold of variance in this case is small (+/−6%). Advanced body measurement techniques, utilising digital tools such as three-dimensional (3D) surface imaging, capture accurate external dimensions and detailed shape characteristics of the human body. Measures of body shape describe morphological variations that cannot be identified by traditional anthropometric techniques and improve the prediction of total body fat and distribution. It is our view that the use of advanced body measurement techniques can provide practitioners with tools for prescribing chemotherapy dosages that are valid for individuals, regardless of their body type. [ABSTRACT FROM AUTHOR]

Aim: To investigate the sex‐specific causality of body compositions in type 2 diabetes and related glycaemic traits using Mendelian randomization (MR). Materials and Methods: We leveraged sex‐specific summary‐level statistics from genome‐wide association studies for three adipose deposits adjusted for body mass index and height, including abdominal subcutaneous adipose tissue, visceral adipose tissue (VATadj) and gluteofemoral adipose tissue (GFATadj), measured by MRI (20 038 women; 19 038 men), and fat mass‐adjusted appendicular lean mass (ALMadj) (244 730 women; 205 513 men) in the UK Biobank. Sex‐specific statistics of type 2 diabetes were from the Diabetes Genetics Replication and Meta‐analysis Consortium and those for fasting glucose and insulin were from the Meta‐analyses of Glucose and Insulin‐related Traits Consortium. Univariable and multivariable MR (MVMR) were performed. We also performed MR analyses of anthropometric traits and genetic association analyses using individual‐level data of body composition as validation. Results: Univariable MR analysis showed that, in women, higher GFATadj and ALMadj exerted a causally protective effect on type 2 diabetes (GFATadj: odds ratio [OR] 0.59, 95% confidence interval [CI; 0.50, 0.69]; ALMadj: OR 0.84, 95% CI [0.77, 0.91]) and VATadj to be riskier in glycaemic traits. MVMR showed that GFATadj retained a robust effect on type 2 diabetes (OR 0.57, 95% CI [0.42, 0.77]; P = 2.6 × 10−4) in women, while it was nominally significant in men (OR 0.58, 95% CI [0.35, 0.96]; P = 3.3 × 10−2), after adjustment for ASATadj and VATadj. MR analyses of anthropometric measures and genetic association analyses of glycaemic traits confirmed the results. Conclusions: Body composition has a sex‐specific effect on type 2 diabetes, and higher GFATadj has an independent protective effect on type 2 diabetes in both sexes. [ABSTRACT FROM AUTHOR]

Globally, childhood obesity is on the rise and the effect of objectively measured movement behaviour on body composition remains unclear. Longitudinal and causal mediation relationships of accelerometer-based sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) with dual-energy X-ray absorptiometry-measured fat mass were examined in 6059 children aged 11 years followed-up until age 24 years from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort. Over 13-year follow-up, each minute/day of ST was associated with 1.3 g increase in fat mass. However, each minute/day of LPA was associated with 3.6 g decrease in fat mass and each minute/day of MVPA was associated with 1.3 g decrease in fat mass. Persistently accruing ≥60 min/day of MVPA was associated with 2.8 g decrease in fat mass per each minute/day of MVPA, partly mediated by decrease insulin and low-density lipoprotein cholesterol. LPA elicited similar and potentially stronger fat mass-lowering effect than MVPA and thus may be targeted in obesity and ST prevention in children and adolescents, who are unable or unwilling to exercise. Childhood obesity remains a global epidemic. Here, using objective measurements, the authors show that sedentary time increased from 6 h/day in childhood to 9 h/day in young adulthood, and was cumulatively associated with increased total and trunk fat mass. Both light or moderate-to-vigorous physical activity similarly partly reversed risk. [ABSTRACT FROM AUTHOR]

Background Evidence on body fat distribution shows opposing effects of waist circumference (WC) and hip circumference (HC) for coronary heart disease (CHD). We aimed to investigate the causality and the shape of such associations. Methods UK Biobank is a prospective cohort study of 0.5 million adults aged 40–69 years recruited between 2006 and 2010. Adjusted hazard ratios (HRs) for the associations of measured and genetically predicted body mass index (BMI), WC, HC and waist-to-hip ratio with incident CHD were obtained from Cox models. Mendelian randomization (MR) was used to assess causality. The analysis included 456 495 participants (26 225 first-ever CHD events) without prior CHD. Results All measures of adiposity demonstrated strong, positive and approximately log-linear associations with CHD risk over a median follow-up of 12.7 years. For HC, however, the association became inverse given the BMI and WC (HR per usual SD 0.95, 95% CI 0.93–0.97). Associations for BMI and WC remained independently positive after adjustment for other adiposity measures and were similar (1.14, 1.13–1.16 and 1.18, 1.15–1.20, respectively), with WC displaying stronger associations among women. Blood pressure, plasma lipids and dysglycaemia accounted for much of the observed excess risk. MR results were generally consistent with the observational, implying causality. Conclusions Body fat distribution measures displayed similar associations with CHD risk as BMI except for HC, which was inversely associated with CHD risk (given WC and BMI). These findings suggest that different measures of body fat distribution likely influence CHD risk through both overlapping and independent mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence of 'High Fat Sugar Salt' (HFSS) products and front-of-pack nutrition labelling (FOPNL) characteristics across promoted products in UK online supermarkets. Design: A cross-sectional survey conducted (December 2021–January 2022) on promoted products. Data on ingredients, nutritional composition and display of FOPNL were collected from product webpages. The UK's Nutrient Profiling Model and Multiple Traffic Light criteria were used to determine HFSS status and possession of inherent red traffic lights (iRTL), respectively. Data analysis determined the prevalence (i.e. percentage of products of the total number of products sampled) of HFSS; FOPNL and possession of iRTL. Chi-squared tests explored associations between these. Setting: Three major UK online supermarket retailer websites. Participants: Product 'multibuy' and 'entrance' promotions, from selected product categories. Results: Among the sampled 625 promoted products, the prevalence of HFSS was greater in entrance (73 %) compared with multibuy (41 %) promotions (χ2 (1) = 34, P < 0·05), with variations in the former across retailers (49–92 %). The prevalence of HFSS products in multibuy promotions offered by two retailers varied by category (i.e. Confectionery 94–97 %, Yogurts 20–20 %, Soft Drinks 16–33 %, Ready Meals 1·4–18 %). Not all promoted products displayed FOPNL on webpages (70 %) or images (52 %). A number of iRTL were found to be possessed by both HFSS and non-HFSS-promoted products. Conclusions: Prior to the 2022 implementation of Regulations restricting these, HFSS products were promoted in online supermarkets with varying display of FOPNL and possession of iRTL. Findings support future policy evaluation and mandatory digital FOPNL. [ABSTRACT FROM AUTHOR]

The objectives of this observational cohort study were to assess the effect of body condition score change, back fat depth change, and muscle diameter change on the time to commencement of luteal activity and first estrus in commercial pedigree Holstein cows. A total of 140 of 200 commercial pedigree Holstein cows were enrolled in one dairy herd in Somerset, UK, over 52 wk in 2021 to 2022. The herd used 4 automatic milking machines with in-line progesterone measurement capability to determine commencement of luteal activity and time to first estrus. Cows were followed until at least 60 d postpartum, and milk progesterone was measured daily starting from 10 DIM. Body condition scoring and ultrasound measurements of back fat depth and longissimus dorsi muscle diameter were performed on cows twice, within 7 d of both calving and 60 DIM. Other explanatory variables assessed included parity, 60-d and 305-d milk yield, and subclinical ketosis (β-hydroxybutryate ≥1.2 mmol/L). Occurrence of clinical disease <60 DIM was forced into all models as a binary variable. Data were analyzed using multivariable Cox proportionate survival analyses. Muscle loss was associated with commencement of luteal activity and time to first estrus. A reduction in muscle diameter by 1.5 to 5 mm was associated with the shortest time to the start of luteal activity and first estrus. A reduction in muscle diameter >8 mm was associated with the longest times to luteal activity and first estrus. In addition to being affected by muscle loss, commencement of luteal activity was delayed by subclinical ketosis, clinical disease, and failure to gain body condition to 60 DIM. Cows that had a BCS loss of 0.25 or more between calving and 60 DIM were at least 52 ± 22% less likely to have commenced luteal activity compared with those that gained BCS. Interestingly, cows that had no change in body condition score commenced luteal activity later than those that gained body condition score. Muscle loss was associated with time to first estrus irrespective of clinical disease status. Cows that lost >8 mm of muscle diameter showed estrus behavior later than cows that lost 1.5 to 5 mm. In conclusion, our findings indicate that extensive muscle loss postpartum was associated with a delayed start to luteal activity and first estrus, irrespective of body condition change, clinical disease, and subclinical ketosis. Marginal muscle loss and a gain in body condition, however, were associated with an earlier start to luteal activity and first estrus. [ABSTRACT FROM AUTHOR]

Background: Obesity is a complex, multifactorial disease associated with substantial morbidity and mortality worldwide. Although it is frequently assessed using BMI, many epidemiological studies have shown links between body fat distribution and obesity-related outcomes. This study examined the relationships between body fat distribution and metabolic syndrome traits using Mendelian Randomization (MR). Methods/findings: Genetic variants associated with visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and gluteofemoral adipose tissue (GFAT), as well as their relative ratios, were identified from a genome wide association study (GWAS) performed with the United Kingdom BioBank. GWAS summary statistics for traits and outcomes related to metabolic syndrome were obtained from the IEU Open GWAS Project. Two-sample MR and BMI-controlled multivariable MR (MVMR) were performed to examine relationships between each body fat measure and ratio with the outcomes. Increases in absolute GFAT were associated with a protective cardiometabolic profile, including lower low density lipoprotein cholesterol (β: -0.19, [95% CI: -0.28, -0.10], p < 0.001), higher high density lipoprotein cholesterol (β: 0.23, [95% CI: 0.03, 0.43], p = 0.025), lower triglycerides (β: -0.28, [95% CI: -0.45, -0.10], p = 0.0021), and decreased systolic (β: -1.65, [95% CI: -2.69, -0.61], p = 0.0019) and diastolic blood pressures (β: -0.95, [95% CI: -1.65, -0.25], p = 0.0075). These relationships were largely maintained in BMI-controlled MVMR analyses. Decreases in relative GFAT were linked with a worse cardiometabolic profile, with higher levels of detrimental lipids and increases in systolic and diastolic blood pressures. Conclusion: A MR analysis of ASAT, GFAT, and VAT depots and their relative ratios with metabolic syndrome related traits and outcomes revealed that increased absolute and relative GFAT were associated with a favorable cardiometabolic profile independently of BMI. These associations highlight the importance of body fat distribution in obesity and more precise means to categorize obesity beyond BMI. [ABSTRACT FROM AUTHOR]

Introduction: Biological sex influences both overall adiposity and fat distribution. Further, testosterone and sex hormone binding globulin (SHBG) influence adiposity and metabolic function, with differential effects of testosterone in men and women. Here, we aimed to perform sex-stratified genome-wide association studies (GWAS) of body fat percentage (BFPAdj) (adjusting for testosterone and sex hormone binding globulin (SHBG)) to increase statistical power. Methods: GWAS were performed in white British individuals from the UK Biobank (157,937 males and 154,337 females). To avoid collider bias, loci associated with SHBG or testosterone were excluded. We investigated association of BFPAdj loci with high density cholesterol (HDL), triglyceride (TG), type 2 diabetes (T2D), coronary artery disease (CAD), and MRI-derived abdominal subcutaneous adipose tissue (ASAT), visceral adipose tissue (VAT) and gluteofemoral adipose tissue (GFAT) using publicly available data from large GWAS. We also performed 2-sample Mendelian Randomization (MR) using identified BFPAdj variants as instruments to investigate causal effect of BFPAdj on HDL, TG, T2D and CAD in males and females separately. Results: We identified 195 and 174 loci explaining 3.35% and 2.60% of the variation in BFPAdj in males and females, respectively at genome-wide significance (GWS, p<5x10-8). Although the direction of effect at these loci was generally concordant in males and females, only 38 loci were common to both sexes at GWS. Seven loci in males and ten loci in females have not been associated with any adiposity/cardiometabolic traits previously. BFPAdj loci generally did not associate with cardiometabolic traits; several had paradoxically beneficial cardiometabolic effects with favourable fat distribution. MR analyses did not find convincing supportive evidence that increased BFPAdj has deleterious cardiometabolic effects in either sex with highly significant heterogeneity. Conclusions: There was limited genetic overlap between BFPAdj in males and females at GWS. BFPAdj loci generally did not have adverse cardiometabolic effects which may reflect the effects of favourable fat distribution and cardiometabolic risk modulation by testosterone and SHBG. [ABSTRACT FROM AUTHOR]

Background There may be a bidirectional relationship between cognition and adiposity, whereby poor cognition leads to increased adiposity and vice versa. We aimed to determine whether these findings are causal, by undertaking a bidirectional Mendelian randomization (MR) study. Methods A total of 378 877 UK Biobank participants had three adiposity indicators [body fat percentage (BF%), body mass index (BMI) and waist-hip ratio] and two cognitive function measures (reaction time, visual memory). We examined observational associations between each adiposity indicator and cognitive function and vice versa. Using bidirectional inverse-variance weighted MR, we estimated the strength of the adiposity-cognitive function association using genetic instruments for adiposity indicators as our exposures, and we repeated this in the opposite direction using instruments for cognitive function. Results In the direction adiposity to cognitive function, MR analyses were generally directionally consistent with observational findings, but all confidence intervals contained the null. In the opposite direction, MR estimates for all adiposity measures on reaction time were imprecise and directionally inconsistent. MR estimates for the effects of visual memory on all adiposity measures indicated worse visual memory was associated with lower adiposity. For example, a 1-unit worse visual memory score was associated with a 1.32% [β = −1.32; 95% confidence interval (CI): −0.77,−1.88] and 3.57% (β = −3.64; 95% CI: −1.84,−5.15) lower absolute body fat percentage and relative body mass index, respectively. Conclusions Observational associations of adiposity on cognitive function are likely not causal. In the reverse direction, our consistent findings that worse visual memory is associated with three adiposity indicators provide support for a causal link between worse visual memory and lower adiposity. [ABSTRACT FROM AUTHOR]

Background: In terms of assessing obesity-associated risk, quantification of visceral adipose tissue (VAT) has become increasingly important in risk assessment for cardiovascular and metabolic diseases. However, differences exist in the accuracy of various modalities, with a lack of up-to-date comparison with three-dimensional whole volume assessment. Aims: Using CT or MRI three-dimensional whole volume VAT as a reference, we evaluated the correlation of various commonly used modalities and techniques namely body impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA) as well as single slice CT to establish how these methods compare. Methods: We designed the study in two parts. First, we performed an intraindividual comparison of the 4558 participants from the UK Biobank cohorts with matching data of MRI abdominal body composition, DXA with VAT estimation, and BIA. Second, we evaluated 174 CT scans from the publicly available dataset to assess the correlation of the commonly used single-slice technique compared to three-dimensional VAT volume. Results: Across the UK Biobank cohort, the DXA-derived VAT measurement correlated better (R² 0.94, p<0.0001) than BIA (R² 0.49, p<0.0001) with reference three-dimensional volume on MRI. However, DXA-derived VAT correlation was worse for participants with a BMI of < 20 (R² = 0.62, p=0.0013). A commonly used single slice method on CT demonstrated a modest correlation (R² between 0.51 - 0.64), with best values at L3- and L4 (R2 L3 = 0.63, p<0.0001; L4 = 0.64, p<0.0001) compared to reference three-dimensional volume. Combining multiple slices yielded a better correlation, with a strong correlation when L2- L3 levels were combined (R² = 0.92, p<0.0001). Conclusion: When deployed at scale, DXA-derived VAT volume measurement shows excellent correlation with three-dimensional volume on MRI based on the UK Biobank cohort. Whereas a single slice CT technique demonstrated moderate correlation with three-dimensional volume on CT, with a stronger correlation achieved when multiple levels were combined. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a risk factor for both the development of and mortality from breast cancer in postmenopausal but not in premenopausal women. However, which part of the fat mass is associated with risk remains unclear, and whether the difference in the risk for breast cancer is associated with discrepancy in the distribution of fat with menstrual status requires further study. Methods: A dataset from the UK Biobank, which included 245,009 female participants and 5,402 females who developed breast cancer during a mean follow-up of 6.6 years, was analyzed. Body fat mass was measured according to bioelectrical impedance at baseline by trained technicians. Age- and multivariable-adjusted hazard ratios and corresponding 95% confidence intervals for associations between body fat distribution and the risk for breast cancer were estimated using Cox proportional-hazards regression. Height, age, education level, ethnicity, index of multiple deprivation, alcohol intake, smoking, physical activity, fruit consumption, age at menarche, age at first birth, number of births, hormone replacement therapy, family history of breast cancer, hysterectomy, and ovariotomy were adjusted for potential confounders. Results: Fat distribution differed between pre- and postmenopausal women. After menopause, there was an increase in fat mass in different body segments (arms, legs, and trunk). After age- and multivariable adjustment, fat mass in different segments, BMI, and waist circumference were significantly associated with the risk for breast cancer among postmenopausal but not premenopausal women. Conclusion: Postmenopausal women exhibited more fat in different body segments, which are associated with increased risk for breast cancer, compared to premenopausal women. Fat mass control throughout the body may be beneficial in mitigating the risk for breast cancer and was not limited to abdominal fat alone among postmenopausal women. [ABSTRACT FROM AUTHOR]

Purpose: The geometric patterns of ventricular remodeling are determined using indexed left ventricular mass (LVM), end-diastolic volume (LVEDV) and concentricity, most often measured using the mass-to-volume ratio (MVR). The aims of this study were to validate lean body mass (LBM)-based allometric coefficients for scaling and to determine an index of concentricity that is independent of both volume and LBM. Methods: Participants from the UK Biobank who underwent both CMR and dual-energy X-ray absorptiometry (DXA) during 2014–2015 were considered (n = 5064). We excluded participants aged ≥ 70 years or those with cardiometabolic risk factors. We determined allometric coefficients for scaling using linear regression of the logarithmically transformed ventricular remodeling parameters. We further defined a multiplicative allometric relationship for LV concentricity (LVC) adjusting for both LVEDV and LBM. Results: A total of 1638 individuals (1057 female) were included. In subjects with lower body fat percentage (< 25% in males, < 35% in females, n = 644), the LBM allometric coefficients for scaling LVM and LVEDV were 0.85 ± 0.06 and 0.85 ± 0.03 respectively (R2 = 0.61 and 0.57, P < 0.001), with no evidence of sex–allometry interaction. While the MVR was independent of LBM, it demonstrated a negative association with LVEDV in (females: r = − 0.44, P < 0.001; males: − 0.38, P < 0.001). In contrast, LVC was independent of both LVEDV and LBM [LVC = LVM/(LVEDV0.40 × LBM0.50)] leading to increased overlap between LV hypertrophy and higher concentricity. Conclusions: We validated allometric coefficients for LBM-based scaling for CMR indexed parameters relevant for classifying geometric patterns of ventricular remodeling. [ABSTRACT FROM AUTHOR]

Magnitude-based PDFF (Proton Density Fat Fraction) and R 2 ∗ mapping with resolved water-fat ambiguity is extended to calculate field inhomogeneity (field map) using the phase images. The estimation is formulated in matrix form, resolving the field map in a least-squares sense. PDFF and R 2 ∗ from magnitude fitting may be updated using the estimated field maps. The limits of quantification of our voxel-independent implementation were assessed. Bland-Altman was used to compare PDFF and field maps from our method against a reference complex-based method on 152 UK Biobank subjects (1.5 T Siemens). A separate acquisition (3 T Siemens) presenting field inhomogeneities was also used. The proposed field mapping was accurate beyond double the complex-based limit range. High agreement was obtained between the proposed method and the reference in UK. Robust field mapping was observed at 3 T, for inhomogeneities over 400 Hz including rapid variation across edges. Field mapping following unambiguous magnitude-based water-fat separation was demonstrated in-vivo and showed potential at 3 T. [ABSTRACT FROM AUTHOR]

Objective: Liver fat associates with obesity‐related metabolic disturbances and may precede incident diseases. Metabolomic profiles of liver fat in the UK Biobank were investigated. Methods: Regression models assessed the associations between 180 metabolites and proton density liver fat fraction (PDFF) measured 5 years later through magnetic resonance imaging, as the difference (in SD units) of each log metabolite measure with 1‐SD higher PDFF among those without chronic disease and not taking statins, and by diabetes and cardiovascular diseases. Results: After accounting for confounders, multiple metabolites were associated positively with liver fat (p < 0.0001 for 152 traits), particularly extremely large and very large lipoprotein particle concentrations, very low‐density lipoprotein triglycerides, small high‐density lipoprotein particles, glycoprotein acetyls, monounsaturated and saturated fatty acids, and amino acids. Extremely large and large high‐density lipoprotein concentrations had strong inverse associations with liver fat. Associations were broadly comparable among those with versus without vascular metabolic conditions, although negative, rather than positive, associations were observed between intermediate‐density and large low‐density lipoprotein particles among those with BMI ≥25 kg/m2, diabetes, or cardiovascular diseases. Metabolite principal components showed a 15% significant improvement in risk prediction for PDFF relative to BMI, which was twice as great (but nonsignificant) compared with conventional high‐density lipoprotein cholesterol and triglycerides. Conclusions: Hazardous metabolomic profiles are associated with ectopic hepatic fat and are relevant to risk of vascular‐metabolic disease. [ABSTRACT FROM AUTHOR]

In their book I The Typical Tudor: Reconstructing Everyday 16th Century Dress, i Jane Malcolm-Davies and Ninya Mikhaila make an argument for how working- and middle-class people dressed during the Tudor era in England. Each of these garment chapters provides detailed pattern diagrams, construction instructions, interior and exterior photographs of extant garments or fragments of garments as well as process photographs of reconstructed garments made for modern models of a variety of body types. [Extracted from the article]

Background. Observational studies have shown that obesity is closely associated with leukocyte telomere length (LTL). However, the causal relationship between obesity and LTL remains unclear. This study investigated the causal relationship between obesity and LTL through the Mendelian randomization approach. Materials and Methods. The genome-wide association study (GWAS) summary data of several studies on obesity-related traits with a sample size of more than 600,000 individuals were extracted from the UK Biobank cohort. The summary-level data of LTL-related GWAS (45 6,717 individuals) was obtained from the IEU Open GWAS database. An inverse-variance-weighted (IVW) algorithm was utilized as the primary MR analysis method. Sensitivity analyses were conducted via MR-Egger regression, IVW regression, leave-one-out test, MR-pleiotropy residual sum, and outlier methods. Results. High body mass index was correlated with a short LTL, and the odds ratio (OR) was 0.957 (95% confidence interval [CI] 0.942-0.973, p = 1.17E-07). The six body fat indexes (whole body fat mass, right leg fat mass, left leg fat mass, right arm fat mass, left arm fat mass, and trunk fat mass) were consistently inversely associated with LTL. Multiple statistical sensitive analysis approaches showed that the adverse effect of obesity on LTL was steady and dependable. Conclusion. The current study provided robust evidence supporting the causal assumption that genetically caused obesity is negatively associated with LTL. The findings may facilitate the formulation of persistent strategies for maintaining LTL. [ABSTRACT FROM AUTHOR]

Background: An estimated 55.5% and 37.3% of people globally with type 2 diabetes (T2D) will have concomitant non-alcoholic fatty liver disease (NAFLD) and the more severe fibroinflammatory stage, non-alcoholic steatohepatitis (NASH). NAFLD and NASH prevalence is projected to increase exponentially over the next 20 years. Bayesian Networks (BNs) offer a powerful tool for modelling uncertainty and visualising complex systems to provide important mechanistic insight. Methods: We applied BN modelling and probabilistic reasoning to explore the probability of NASH in two extensively phenotyped clinical cohorts: 1) 211 participants with T2D pooled from the MODIFY study & UK Biobank (UKBB) online resource; and 2) 135 participants without T2D from the UKBB. MRI-derived measures of visceral (VAT), subcutaneous (SAT), skeletal muscle (SMI), liver fat (MRI-PDFF), liver fibroinflammatory change (liver cT1) and pancreatic fat (MRI-PDFF) were combined with plasma biomarkers for network construction. NASH was defined according to liver PDFF >5.6% and liver cT1 >800ms. Conditional probability queries were performed to estimate the probability of NASH after fixing the value of specific network variables. Results: In the T2D cohort we observed a stepwise increase in the probability of NASH with each obesity classification (normal weight: 13%, overweight: 23%, obese: 36%, severe obesity: 62%). In the T2D and non-T2D cohorts, elevated (vs. normal) VAT conferred a 20% and 1% increase in the probability of NASH, respectively, while elevated SAT caused a 7% increase in NASH risk within the T2D cohort only. In those with T2D, reducing HbA1c from the ‘high’ to ‘low’ value reduced the probability of NASH by 22%. Conclusion: Using BNs and probabilistic reasoning to study the probability of NASH, we highlighted the relative contribution of obesity, ectopic fat (VAT and liver) and glycaemic status to increased NASH risk, namely in people with T2D. Such modelling can provide insights into the efficacy and magnitude of public health and pharmacological interventions to reduce the societal burden of NASH. [ABSTRACT FROM AUTHOR]

Obesity remains an unmet global health burden. Detrimental anatomical distribution of body fat is a major driver of obesity-mediated mortality risk and is demonstrably heritable. However, our understanding of the full genetic contribution to human adiposity is incomplete, as few studies measure adiposity directly. To address this, we impute whole-body imaging adiposity phenotypes in UK Biobank from the 4,366 directly measured participants onto the rest of the cohort, greatly increasing our discovery power. Using these imputed phenotypes in 392,535 participants yielded hundreds of genome-wide significant associations, six of which replicate in independent cohorts. The leading causal gene candidate, ADAMTS14, is further investigated in a mouse knockout model. Concordant with the human association data, the Adamts14−/− mice exhibit reduced adiposity and weight-gain under obesogenic conditions, alongside an improved metabolic rate and health. Thus, we show that phenotypic imputation at scale offers deeper biological insights into the genetics of human adiposity that could lead to therapeutic targets. Our understanding of the genetic contribution to human adiposity is incomplete, as few studies measure adiposity directly. Here, the authors impute whole-body imaging adiposity phenotypes in large biobanks, enhancing their power to discover genes driving human adiposity, and further investigate one such gene using a mouse model. [ABSTRACT FROM AUTHOR]

For any given body mass index (BMI), individuals vary substantially in fat distribution, and this variation may have important implications for cardiometabolic risk. Here, we study disease associations with BMI-independent variation in visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) fat depots in 40,032 individuals of the UK Biobank with body MRI. We apply deep learning models based on two-dimensional body MRI projections to enable near-perfect estimation of fat depot volumes (R2 in heldout dataset = 0.978-0.991 for VAT, ASAT, and GFAT). Next, we derive BMI-adjusted metrics for each fat depot (e.g. VAT adjusted for BMI, VATadjBMI) to quantify local adiposity burden. VATadjBMI is associated with increased risk of type 2 diabetes and coronary artery disease, ASATadjBMI is largely neutral, and GFATadjBMI is associated with reduced risk. These results – describing three metabolically distinct fat depots at scale – clarify the cardiometabolic impact of BMI-independent differences in body fat distribution. Different location of adipose tissue may have different consequences to cardiometabolic risk. Here the authors report that deep learning enabled accurate prediction of specific adipose tissue volumes, and that after adjustment for BMI, visceral adiposity was associated with increased risk of cardiometabolic disease, while gluteofemoral adiposity was associated with reduced risk. [ABSTRACT FROM AUTHOR]

Chemical-shift encoded MRI (CSE-MRI) is a widely used technique for the study of body composition and metabolic disorders, where derived fat and water signals enable the quantification of adipose tissue and muscle. The UK Biobank is acquiring whole-body Dixon MRI (a specific implementation of CSE-MRI) for over 100,000 participants. Current processing methods associated with large whole-body volumes are time intensive and prone to artifacts during fat-water separation performed by the scanner, making quantitative analysis challenging. The most common artifacts are fat-water swaps, where the labels are inverted at the voxel level. It is common for researchers to discard swapped data (generally around 10%), which is wasteful and may lead to unintended biases. Given the large number of whole-body Dixon MRI acquisitions in the UK Biobank, thousands of swaps are expected to be present in the fat and water volumes from image reconstruction performed on the scanner. If they go undetected, errors will propagate into processes such as organ segmentation, and dilute the results in population-based analyses. There is a clear need for a robust method to accurately separate fat and water volumes in big data collections like the UK Biobank. We formulate fat-water separation as a style transfer problem, where swap-free fat and water volumes are predicted from the acquired Dixon MRI data using a conditional generative adversarial network, and introduce a new loss function for the generator model. Our method is able to predict highly accurate fat and water volumes free from artifacts in the UK Biobank. We show that our model separates fat and water volumes using either single input (in-phase only) or dual input (in-phase and opposed-phase) data, with the latter producing superior results. Our proposed method enables faster and more accurate downstream analysis of body composition from Dixon MRI in population studies by eliminating the need for visual inspection or discarding data due to fat-water swaps. [ABSTRACT FROM AUTHOR]

This article explores how 'fat shaming' as a practice that encourages open disdain for those living in larger bodies operates as a moralising tool to regulate and manage those who are viewed as 'bad citizens'. It begins by outlining the problematic use of fat shaming language that is often used as a tool to promote 'healthy' lifestyle choices by those who view it as not only an acceptable way of communicating the health risks associated with obesity, but also a productive way of motivating people with overweight and obesity to lose weight. I then go on to discuss how shame as it relates to body image and excess weight is culturally produced through both objective conceptualisations of deviance and subjective judgements about the moral character of those who are living with excess weight. Adopting a feminist theoretical perspective, this article further considers the reciprocal nature of fat shaming by calling attention to how shame as a felt emotion is dependent on understandings of oneself in relation to others, as well as the relationships that one forms with others. In this way, I argue that shame in general, and fat shaming in particular, is performative to the extent that it exists as a relational construct that is iteratively produced through the language and actions that give it meaning. [ABSTRACT FROM AUTHOR]

Objective: To quantify the sector-wide energy and nutritional differences of both adult and children's restaurant menu items in the UK and the USA in 2018. Design: Cross-sectional study. Setting: Energy and nutritional information provided on restaurant websites. Participants: Menu items (n 40 902) served by forty-two large UK chains and ninety-six large USA chains. Results: Mean absolute energy, fat and saturated fat values were higher in USA menu items. For example, the mean adjusted per-item differences of adult menu items between the USA and the UK were 45·6 kcal for energy and 3·2 g for fat. Comparable figures for children's menu items were 43·7 kcal and 4 g. Compared with UK menu items, USA adult menu items also had higher sugar content (3·2 g, 95 % CI (0·5, 6)), and children's menu items had higher Na content (181·1 mg, 95 % CI (108·4, 253·7)). Overall, 96·8 % of UK and 95·8 % of USA menu items exceeded recommended levels for at least one of Na, fat, saturated fat or sugars. Conclusions: Menu items served by large chain restaurants had higher mean absolute levels of energy, fat and saturated fat in the USA compared with the UK. UK adult menu items were also lower in sugars compared with the USA ones and children's items lower in Na. As more than 95 % of all items were considered to have high levels of at least one nutrient of public health concern in the USA and the UK, improvements in restaurant menu items are needed in both countries. [ABSTRACT FROM AUTHOR]

Background: The fatty liver index (FLI) is frequently used as a non-invasive clinical marker for research, prognostic and diagnostic purposes. It is also used to stratify individuals with hepatic steatosis such as non-alcoholic fatty liver disease (NAFLD), and to detect the presence of type 2 diabetes or cardiovascular disease. The FLI is calculated using a combination of anthropometric and blood biochemical variables; however, it reportedly excludes 8.5-16.7% of individuals with NAFLD. Moreover, the FLI cannot quantitatively predict liver fat, which might otherwise render an improved diagnosis and assessment of fatty liver, particularly in longitudinal studies. We propose FLI+ using predictive regression modelling, an improved index reflecting liver fat content that integrates 12 routinely-measured variables, including the original FLI. Methods and findings: We evaluated FLI+ on a dataset from the UK Biobank containing 28,796 individual estimates of proton density fat fraction derived from magnetic resonance imaging across normal to severe levels and interpolated to align with the original FLI range. The results obtained for FLI+ outperform the original FLI by delivering a lower mean absolute error by approximately 47%, a lower standard deviation by approximately 20%, and an increased adjusted R2 statistic by approximately 49%, reflecting a more accurate representation of liver fat content. Conclusions: Our proposed model predicting FLI+ has the potential to improve diagnosis and provide a more accurate stratification than FLI between absent, mild, moderate and severe levels of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Cardiometabolic risk (CMR) factors are associated with accelerated brain aging and increased risk for sex‐dimorphic illnesses such as Alzheimer's disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E‐ϵ4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi‐shell diffusion‐weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist‐to‐hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied (i) between males and females, (ii) according to age at menopause in females, and (iii) across different age groups in males and females. We report sex differences in associations between BAG and all three CMRs, with stronger positive associations among males compared to females. Independent of APOE4 status, higher BAG (older brain age relative to chronological age) was associated with greater BMI, WHR, and BF% in males, whereas in females, higher BAG was associated with greater WHR, but not BMI and BF%. These divergent associations were most prominent within the oldest group of females (66–81 years), where greater BF% was linked to lower BAG. Earlier menopause transition was associated with higher BAG, but no interactions were found with CMRs. In conclusion, the findings point to sex‐ and age‐specific associations between CMRs and brain age. Incorporating sex as a factor of interest in studies addressing CMR may promote sex‐specific precision medicine, consequently improving health care for both males and females. [ABSTRACT FROM AUTHOR]

Previous studies reported associations between obesity measured by body mass index (BMI) and coronavirus disease 2019 (COVID-19). However, BMI is calculated only with height andweight and cannot distinguish between body fat mass and fatfree mass. Thus, it is not clear if one or both of these measures are mediating the relationship between obesity and COVID-19. Here, we used Mendelian randomization (MR) to compare the independent causal relationships of body fat mass and fat-free mass with COVID-19 severity. We identified single nucleotide polymorphisms associated with body fat mass and fat-free mass in 454,137 and 454,850 individuals of European ancestry from the UK Biobank, respectively. We then performed two-sample MR to ascertain their effects on severe COVID-19 (cases: 4,792; controls: 1,054,664) from the COVID-19 Host Genetics Initiative. We found that an increase in body fat mass by one standard deviation was associated with severe COVID-19 (odds ratio (OR)body fat mass = 1.61, 95% confidence interval [CI]: 1.28-2.04, P=5.51Ã--10-5;ORbody fat-free mass=1.31,95%CI:0.99-1.74,P=5.77Ã--10-2). Considering that body fat mass and fat-freemasswere genetically correlated with each other (r = 0.64), we further evaluated independent causal effects of body fat mass and fat-free mass using multivariable MR and revealed that only body fat mass was independently associated with severe COVID-19 (ORbody fat mass = 2.91, 95% CI: 1.71-4.96, P=8.85Ã--10-5 and ORbody fat-free mass = 1.02, 95%CI: 0.61-1.67, P = 0.945). In summary, this study demonstrates the causal effects of body fat accumulation on COVID-19 severity and indicates that the biological pathways influencing the relationship between COVID-19 and obesity are likely mediated through body fat mass. [ABSTRACT FROM AUTHOR]

For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results – using MRI-derived, BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes. The inherited basis of body fat distribution is not fully understood. Here, the authors use genetic data and MRI-derived measures of local adiposity to highlight fat depot-specific genetic architecture with implications for cardiometabolic health. [ABSTRACT FROM AUTHOR]

Objective: This study describes the development of the world's first suite of firefighter body composition centile reference curves which can be used as both academic research tools and clinical references, to plot and track individual firefighter skeletal muscle mass (SMM) and fat mass (FM) measurements against the representative reference sample. Methods: The body composition of 497 white male London (England) firefighters was measured by anthropometry and bioelectrical impedance analysis. Smoothed centile curves were then generated for skeletal muscle mass index (SMMI), fat mass index (FMI), body fat percentage (BF%) and waist-to-height ratio (WHtR). Results: Between 48 and 62 years, firefighter SMMI is greater than the UK white male age-matched general population by a mean of 0.35 units, although SMMI declines 0.006 units/years faster in firefighters between these ages. This is estimated to translate to a mean decline of approximately 0.6% of absolute SMM per year. Between 40 and 49 years, firefighter FMI is 0.1 units greater than the UK white male age-matched general population, which becomes identical (7 units) between 50 and 54 years. At the 50th centile, WHtR exceeds 0.5 by 39 years reaching 0.55 at 62 years. This contrasts with FMI which remains stable from 47 years. Conclusion: Firefighters in this study possess greater FM and SMM compared with the UK general population. SMM appears to decline rapidly within older age ranges. These references offer a novel improvement upon the limitations of BMI and BF% for the benefit of an occupational group at elevated risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations.Research Design and Methods: We used genetic variants associated (P < 5 × 10-8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n = 32,859). We obtained summary-level data for risk of type 1 (9,358 cases) and type 2 (55,005 cases) diabetes from the largest available genome-wide association studies. We performed inverse-variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects.Results: Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27% increased risk and 0.76 [0.62, 0.94] or 24% decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes.Conclusions: Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and type 2 diabetes. [ABSTRACT FROM AUTHOR]

In comparison to fats, oils and grease (FOG) found in commercial and industrial effluents, very little is known about FOG discharged at household level. To address this shortcoming, household FOG production was calculated following a year‐long monthly collection at 2.3 kg/year per household, equivalent to 0.8 kg/year per capita. In the United Kingdom, these numbers translate in an annual estimated FOG production of 62 380 tonnes. Physico‐chemical characterization of household FOG showed promising results for biodiesel production. Biomethane yield was measured at 875 mL CH4/g VSadded, twice as much that of sewage sludge, making it a desirable substrate for anaerobic digestion. It was thus estimated that energy recovery from household FOG through anaerobic co‐digestion or biodiesel production could generate about 490 GWh/year in the United Kingdom. However, insights from participants revealed that most of this waste is currently not recovered, requiring the development of schemes fitting with households' routine to maximize collection rates. [ABSTRACT FROM AUTHOR]

Background: The fat type consumed is considered a risk factor for developing obesity and type 2 diabetes (T2D). However, these associations have not been investigated using a dietary patterns approach, which can capture combinations of foods and fat type consumed.Objectives: This study aimed to investigate associations between dietary patterns with varying proportions of SFAs, MUFAs, or PUFAs and obesity, abdominal obesity, and self-reported T2D incidence.Methods: This study included UK Biobank participants with 2 or more 24-h dietary assessments, free from the outcome of interest at recruitment, and with outcome data at follow-up (n = 16,523; mean follow-up: 6.3 y). Reduced rank regression was used to derive dietary patterns with SFAs, MUFAs, and PUFAs (% of energy intake) as response variables. Logistic regression, adjusted for sociodemographic and health characteristics, was used to investigate the associations between dietary patterns and obesity [BMI (kg/m2) ≥30], abdominal obesity (waist circumference; men: ≥102 cm; women: ≥88 cm) and T2D incidence.Results: Two dietary patterns, DP1 and DP2, were identified: DP1 positively correlated with SFAs (r = 0.48), MUFAs (r = 0.67), and PUFAs (r = 0.56), characterized by higher intake of nuts, seeds, and butter and lower intake of fruit and low-fat yogurt; DP2 positively correlated with SFAs (r = 0.76) and negatively with PUFAs (r = -0.64) and MUFAs (r = -0.01), characterized by higher intake of butter and high-fat cheese and lower intake of nuts and seeds. Only DP2 was associated with higher obesity and abdominal obesity incidence (OR: 1.24; 95% CI: 1.02, 1.45; and OR: 1.19; 95% CI: 1.02, 1.38, respectively). Neither of the dietary patterns was associated with T2D incidence.Conclusions: These findings provide evidence that a dietary pattern characterized by higher SFA and lower PUFA foods is associated with obesity and abdominal obesity incidence, but not T2D. [ABSTRACT FROM AUTHOR]

Fat mass and fat-free mass are found to be associated with different health outcomes in observational studies, but the underlying causality remains unclear. We aimed to investigate the causal relationships between body composition and cardiometabolic traits using a two-sample Mendelian randomization (MR) approach. Independent genetic variants associated with body fat mass, fat-free mass, and fat percentage in UK Biobank population were used as genetic instrumental variables, and their causal effects on circulatory diseases, type 2 diabetes, glycemic traits, and lipid fractions were estimated from large-scale genome-wide association studies (GWAS) in European populations. Univariable, multivariable, and bidirectional MR analyses were performed. Genetically predicted high fat mass and fat percentage significantly increased risks of most cardiometabolic diseases, and high fat-free mass had protective effects on most cardiometabolic diseases after accounting for fat mass. Fat mass, fat-free mass, and fat percentage were all positively associated with higher risks of atrial fibrillation and flutter, varicose veins, and deep vein thrombosis and pulmonary embolism. High fat mass increased fasting glucose, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, decreased high-density lipoprotein cholesterol, and high fat-free mass reduced HOMA-IR, triglycerides, and low-density lipoprotein cholesterol. Genetically predicted fat-free mass was bidirectionally negatively associated with 2-h glucose and total cholesterol. The findings may be helpful in risk stratification and tailoring management of body composition in patients with different cardiometabolic statuses. [ABSTRACT FROM AUTHOR]

1, 2, 3)0-64 0-0010-99NS0-99NS1-09NS1-18NS1-94 0-0011-01NS0-86NS1-19NS 5 (v. 1, 2)0-98NS0-93NS1-14NS1-20NS1-09NS1-410-0290-94NS0-730-0061-10NS 4 (v. 1, 2, 3)0-64 0-0010-99NS0-99NS1-09NS1-18NS1-94 0-0011-02NS0-86NS1-19NS 5 (v. [Extracted from the article]

A variety of materials offering healthy eating advice have been produced in the United Kingdom to encourage people to eat well and avoid diet-related health issues. By applying a Foucauldian discourse analysis, this research aimed to uncover the discourses used in six healthy eating texts (two state-produced and four commercial texts), how people positioned themselves in relation to these discourses, and the power relations between institutions and the U.K. public. Ten discourses including scientific, thermodynamics, natural, family/caring, emotional, medical, and moral discourses were uncovered and offered up subject positions in relation to moral citizenship and personal responsibility. Through the use of biopower, foods appeared to be categorized as "good" or "bad" foods in which bad foods were considered to be risky to health due to their nutritional composition. Most texts assumed people have the agency to follow the advice provided and failed to consider the readers' personal contexts. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that normal weight postmenopausal women with a relative excess of body fat are at increased breast cancer risk. However, little is known about the associations between obesity‐related blood markers and risk of breast cancer among these individuals. In this prospective study comprising 58 629 normal weight postmenopausal women (body mass index between 18.5 kg/m2 and 24.9 kg/m2) who were enrolled in the UK Biobank cohort between 2006 and 2010, we examined the associations of glycated hemoglobin, triglycerides, high‐density lipoprotein cholesterol, C‐reactive protein (CRP), testosterone and sex hormone‐binding globulin (SHBG) with risk of breast cancer. A total of 1268 postmenopausal breast cancer cases were ascertained during a median follow‐up period of 7 years. Women with CRP, total testosterone and free testosterone (FT) levels in the highest quintile had increased risk of breast cancer compared to those in the lowest quintile (HRQ5 vs Q1: 1.35, 95% confidence interval [CI]: 1.12‐1.63, HR Q5 vs Q1: 1.47, 95% CI: 1.20‐1.80 and HR Q5 vs Q1: 1.53, 95% CI: 1.23‐1.90, respectively), whereas those with SHBG in the highest quintile had reduced risk (HR Q5 vs Q1: 0.70, 95% CI: 0.56‐0.88). These associations were attenuated but persisted after additional adjustment for BMI, fat mass index (whole body fat mass [kg]/height [m2]) or waist circumference and after mutual adjustment for testosterone, CRP and/or SHBG. Our study suggests that the risk of postmenopausal breast cancer among normal weight women is increased in association with relatively high levels of CRP and testosterone and with relatively low levels of SHBG. What's new? Excess body fat is positively associated with breast cancer risk in normal weight postmenopausal women. Excess fat is also known to alter cardiometabolic function, producing detectable changes in specific blood markers. Here, the authors investigated potential associations between excess body fat, postmenopausal breast cancer risk, and levels of obesity‐related blood markers, including C‐reactive protein (CRP) and testosterone, in normal weight women. Analyses reveal positive associations between postmenopausal breast cancer risk and CRP and testosterone levels. Meanwhile, risk was inversely associated with sex hormone‐binding globulin. The findings may be valuable in developing prevention strategies for reducing postmenopausal breast cancer risk. [ABSTRACT FROM AUTHOR]

2,4-Dinitrophenol (DNP) is a highly toxic industrial chemical that is sometimes misused to reduce body fat. Toxicity following ingestion of DNP has recently become more common in the United Kingdom. This research was performed to document the frequency of DNP toxicity as reported to poisons centres in the United States (US) and United Kingdom (UK) and to identify the clinical features associated with fatality. Calls to UK and US poisons centres involving systemic exposure to DNP were extracted for the 12 calendar years 2007-2018. These were analysed using univariate and multivariate statistical techniques. There were 204 cases (n = 86, US; n = 118, UK) of systemic DNP exposure identified, of which 86% were under the age of 40 and 71% were males. Over the study period the incidence of reported DNP toxicity was higher in the United Kingdom than the United States (1.78 vs. 0.26 cases per million population) and annual case numbers have increased in both countries since 2011. Case fatality was high and did not differ significantly between countries (US 11.6%; 95% CI: 6.4–20.1%: UK 16.9%; 95% CI: 11.3–24.7%; X2(1) = 1.12, p = 0.29). Univariate analysis demonstrated significant associations between risk of death and the presence of hypoglycaemia (OR = 17.1, 95% CI 1.7–174.3), hypertonia (OR = 12.9, 95% CI 3.5–47.6), acidosis (OR = 12.5, 95% CI 4.8–32.9), raised lactate (OR = 8.3, 95% CI 2.4–28.4), hyperpyrexia (OR = 6.5, 95% CI 2.8–15.2), tachycardia (OR = 6.4, 95% CI 2.5–16.4), agitation or confusion (OR = 6.0, 95% CI 2.6–13.7), hypertension (OR = 5.6, 95% CI 1.9–16.4) and tachypnoea/dyspnoea (OR = 2.8, 95% CI 1.2–6.1). After backwards stepwise logistic regression, the following were retained as significant independent predictors of mortality: acidosis (OR = 5.4, 95% CI: 1.8 − 16.5), tachycardia (OR = 3.6, 95% CI: 1.2 − 11.0), agitation/confusion (OR = 3.4, 95% CI: 1.2 − 9.7) and hyperpyrexia (OR = 2.8, 95% CI: 1.0 − 7.4). DNP toxicity is uncommonly reported to poisons centres but has recently become more frequent in the United States and United Kingdom. Tachycardia, hyperpyrexia, acidosis, and agitation/confusion are independent risk factors for mortality and their presence should prompt rapid escalation to an intensive care environment for aggressive supportive treatment and monitoring. [ABSTRACT FROM AUTHOR]

Background The effects of specific macronutrients on kidney function independent of total calorie intake have rarely been studied, although the composition of macronutrient intake has been reported to affect health outcomes. Objectives We aimed to investigate the effects of macronutrient intake ratios on the risk of chronic kidney disease (CKD) by Mendelian randomization (MR) analysis. Methods The study was an observational cohort study mainly based on the UK Biobank and including MR analysis. First, we evaluated the relative baseline macronutrient composition—that is, the number of calories from each macronutrient divided by total calorie intake—of the diets of UK Biobank participants, and we used Cox regression to assess the incidence of end-stage kidney disease (ESKD) in 65,164 participants with normal kidney function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. We implemented a genetic instrument for relative fat, protein, and carbohydrate intake developed by a previous genome-wide association study (GWAS) and performed MR analysis. Two-sample MR was performed with the summary statistics from independent CKDGen GWAS for kidney function traits (n  = 567,460), including CKD (eGFR <60 mL/min/1.73 m2) and log-transformed eGFR. Results The median relative macronutrient intake composition at baseline was 35% fats, 15% protein, and 50% carbohydrates. Higher relative protein intake in subjects with normal kidney function was significantly associated with a lower risk of incident ESKD (HR: 0.54; 95% CI: 0.30, 0.95) in the observational investigation. Two-sample MR indicated that increased relative fat intake causally increased the risk of kidney function impairment [CKD (OR: 1.94; 95% CI: 1.39, 2.71); log eGFR (β: −0.036; 95% CI: −0.048, −0.024)] and that higher relative protein intake was causally linked to a lower CKD risk [CKD (OR: 0.50; 95% CI: 0.35, 0.72); log eGFR (β: 0.044; 95% CI: 0.030, 0.058)]. Conclusions A desirable macronutrient composition, including high relative protein intake and low relative fat intake, may causally reduce the risk of CKD in the general population. [ABSTRACT FROM AUTHOR]

Purpose: To compare metabolic effects of modified release hydrocortisone (MR-HC) with standard hydrocortisone (HC) therapies in adults with Adrenal Insufficiency (AI). Methods: Adult patients (n = 12) with AI, established on HC therapy, were recruited from Endocrinology clinics at University Hospitals Coventry and Warwickshire (UHCW), UK. Baseline (HC) metabolic assessments included fasting serum HbA1C, lipid and thyroid profiles, accurate measures of body composition (BodPod), and 24-h continuous measures of energy expenditure including Sleeping Metabolic Rate (SMR) using indirect calorimetry within the Human Metabolism Research Unit, UHCW. All participants then switched HC to MR-HC with repeat (MR-HC) metabolic assessments at 3 months. Paired-sample t-tests were used for data comparisons between HC and MR-HC assessments: P-value <0.05 was considered significant. Results: Following exclusion of 2 participants, analyses were based on 10 participants. Compared with baseline HC data, following 3 months of MR-HC therapy mean fat mass reduced significantly by −3.2 kg (95% CI: −6.0 to −0.4). Mean (SD) baseline HC fat mass vs repeat MR-HC fat mass: 31.9 kg (15.2) vs 28.7 kg (12.8) respectively, P = 0.03. Mean SMR increased significantly by +77 kcal/24 h (95% CI: 10–146). Mean (SD) baseline HC SMR vs repeat MR-HC SMR: 1,517 kcal/24 h (301) vs 1,594 kcal/24 h (344) respectively, P = 0.03. Mean body fat percentage reduced significantly by −3.4% (95% CI: −6.5 to −0.2). Other measures of body composition, energy expenditure, and biochemical analytes were equivalent between HC and MR-HC assessments. Conclusions: In adults with AI, switching from standard HC to MR-HC associates with early metabolic benefits of reduced fat mass and increased SMR. [ABSTRACT FROM AUTHOR]

Objective: Differences in the content and distribution of body fat and ectopic lipids may be responsible for ethnic variations in metabolic disease susceptibility. The aim of this study was to examine the ethnic distribution of body fat in two separate UK‐based populations. Methods: Anthropometry and body composition were assessed in two separate UK cohorts: the Hammersmith cohort and the UK Biobank, both comprising individuals of South Asian descent (SA), individuals of Afro‐Caribbean descent (AC), and individuals of European descent (EUR). Regional adipose tissue stores and liver fat were measured by magnetic resonance techniques. Results: The Hammersmith cohort (n = 747) had a mean (SD) age of 41.1 (14.5) years (EUR: 374 men, 240 women; SA: 68 men, 22 women; AC: 14 men, 29 women), and the UK Biobank (n = 9,533) had a mean (SD) age of 55.5 (7.5) years (EUR: 4,483 men, 4,873 women; SA: 80 men, 43 women, AC: 31 men, 25 women). Following adjustment for age and BMI, no significant differences in visceral adipose tissue or liver fat were observed between SA and EUR individuals in the either cohort. Conclusions: Our data, consistent across two independent UK‐based cohorts, present a limited number of ethnic differences in the distribution of body fat depots associated with metabolic disease. These results suggest that the ethnic variation in susceptibility to features of the metabolic syndrome may not arise from differences in body fat. [ABSTRACT FROM AUTHOR]

Background Obesity has been positively associated with upper gastrointestinal cancers, but prospective data by subtype/subsite are limited. Obesity influences hormonal factors, which may play a role in these cancers. We examined anthropometry, body fat and reproductive factors in relation to oesophageal and gastric cancer by subtype/subsite in the UK Biobank cohort. Methods Among 458,713 UK Biobank participants, 339 oesophageal adenocarcinomas, 124 oesophageal squamous cell carcinomas, 137 gastric cardia and 92 gastric non-cardia cancers were diagnosed during a mean of 6.5 years follow-up. Cox models estimated multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Results Body mass index (BMI), hip circumference, waist circumference, waist-to-hip ratio, waist-to-height ratio, total body fat and trunk fat were positively associated with oesophageal adenocarcinoma (highest vs lowest category: HR = 2.33, 95%-CI:1.65-3.28; HR = 1.56, 95%-CI:1.15-2.13; HR = 2.30, 95%-CI:1.47-3.57; HR = 1.71, 95%-CI:1.01-2.90; HR = 2.87, 95%-CI:1.88-4.38; HR = 1.96, 95%-CI:1.30-2.96; HR = 2.34, 95%-CI:1.70-3.22, respectively). Although there were no statistically significant associations in combined sex analyses, BMI (HR = 1.83, 95%-CI:1.00-3.37), waist circumference (HR = 2.21, 95%-CI:1.27-3.84) and waist-to-hip ratio (HR = 1.92, 95%-CI:1.11-3.29) were associated with gastric cardia cancer in men; however, mutual adjustment attenuated the associations for BMI and waist-to-hip ratio. For oesophageal squamous cell carcinoma, statistically significant inverse associations were observed among women for BMI, hip circumference, waist circumference, waist-to-height ratio, total body fat and trunk fat, although they were based on small numbers. In addition, older age at first (HR = 0.44, 95%-CI:0.22-0.88) and last live birth (HR = 0.44, 95%-CI:0.22-0.87) were inversely associated with oesophageal squamous cell carcinoma and having a stillbirth/miscarriage/termination was positively associated (HR = 1.84, 95%-CI:1.10-3.07). Conclusions Obesity and abdominal obesity specifically may be a risk factor for oesophageal adenocarcinoma and gastric cardia cancer in men. Some reproductive factors may be associated with oesophageal squamous cell carcinoma in women. [ABSTRACT FROM AUTHOR]