BACKGROUND AND AIMS:While vigorous physical activity (VPA) is known to provide greater health benefits per unit time than moderate activity, the spectrum of these benefits across different chronic diseases and the relative importance of physical activity (PA) intensity vs volume remain unclear. This study examined associations between the proportion of VPA (%VPA) relative to total volume of PA and the incidence of multiple chronic disease outcomes. METHODS:This prospective population-based cohort study included 96,408 participants (mean age 61.9 years, women: 56.3%) with device-measured data (wrist-worn accelerometers) and 375,730 participants (mean age 56.2 years, women: 52.2%) with self-reported PA data (IPAQ) from the UK Biobank. Main outcomes included incidence of eight chronic diseases: major adverse cardiovascular events (MACE), atrial fibrillation (AFib), type 2 diabetes (T2D), immune-mediated inflammatory diseases, metabolic dysfunction-associated steatotic liver disease (MASLD), chronic respiratory diseases (CRD), chronic kidney disease (CKD), and dementia, as well as all-cause mortality. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence interval. RESULTS:In the device-measured data, non-linear inverse dose-response relationships were observed between %VPA and all outcomes (all P < .001), and these patterns remained consistent across strata of total PA volume. In multivariable models adjusted for total PA volume, participants with >4% VPA had 29%-61% lower risks of these outcomes compared with those with 0% VPA. Joint analyses and population attributable fraction revealed distinct disease-specific patterns: immune-mediated inflammatory diseases showed very strong intensity-dependence with minimal contribution from PA volume (20.3% for intensity vs 1.0% for volume), while MACE (17.8% vs 6.0%), AFib (16.2% vs 5.0%), CRD (21.4% vs 5.6%), and dementia (32.3% vs 8.1%) demonstrated intensity predominance with modest contribution from PA volume, and T2D (26.6% vs 17.7%), MASLD (22.1% vs 16.6%), CKD (23.0% vs 15.3%), and all-cause mortality (31.4% vs 14.2%) showed more balanced contributions from both intensity and volume. CONCLUSIONS:A higher %VPA, independent of total activity volume, is inversely associated with eight major chronic diseases and all-cause mortality. Intensity consistently demonstrated a higher preventive potential than total PA volume. These findings support, whenever possible, prioritizing higher-intensity activities in clinical and public health interventions aimed at preventing non-communicable diseases.

We investigated associations between food liking and risk of health outcomes in a prospective cohort and explored if associations were potentially explained by body mass index (BMI). We included 182,181 participants from UK Biobank. Food liking was measured using a 9-point hedonic scale, covering liking (points 6-9)/disliking (points 1-5) for high fat savoury (HFSa), high fat sweet (HFSw), vegetable, low fat savoury (LFSa), and fruit-based, low fat sweet (LFSw) foods. Cox proportional hazard models assessed associations with health outcomes, as hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant confounders. Compared to disliking, liking HFSa was associated with higher risks of type-2-diabetes (T2D) (HR 1.14; 95% CI: 1.09-1.19) and lung cancer (HR 1.10; 95% CI: 1.01-1.20). Liking HFSw was associated with higher risks of all-cause mortality, and cancer (HR range 1.03-1.07; 95% CI range: 1.00-1.14). Liking LFSa was associated with lower risks of all-cause mortality, T2D, cardiovascular disease (CVD), all-cause cancer, and colorectal cancer (HR range 0.85-0.97; 95% CI range: 0.79-0.99). Liking LFSw was associated with lower risks of T2D, CVD, and colorectal cancer (HR range 0.91-0.96; 95% CI range: 0.86-1.00). Associations between food liking and health outcomes differed between food groups, with most appearing not to be attenuated after adjusting for BMI. The key findings were that associations with adverse health outcomes were strongest for higher-fat containing food preference patterns, while sweet preference alone was not associated with increased risk. Our study highlighted the potential role of food liking in designing and targeting health promotion interventions.

BACKGROUND:Current sedentary behavior (SB) guidelines primarily emphasize total time spent sedentary. We explored differences between interrupted and prolonged SB in relation to a range of cancer outcomes. METHODS AND FINDINGS:This study included 91,292 UK Biobank participants with valid accelerometer data. Participants were followed for a median of 12.38 years (interquartile range 11.56-13.15 years). A two-step approach based on a random forest model was used to classify SB. Multivariable Cox proportional hazards models were applied to overall incident cancers and cancer deaths, plus obesity-related and type-2 diabetes-related cancers, and 23 site-specific cancers. Models were adjusted for demographic, socioeconomic, lifestyle, dietary, and health-status factors, including age, ethnicity, deprivation, education, smoking, alcohol intake, diet, and morbidity count. Isotemporal substitution models were used to estimate the associated cancer risk when replacing prolonged SB with intermittent SB, or physical activity (PA). After adjusting for sociodemographic and lifestyle factors, each additional hour of prolonged SB was associated with a higher risk of overall cancer mortality (hazard ratio [HR] HR1hour 1.09; 95% confidence interval [CI] [1.06, 1.11]; p < 0.001). Replacing 1 hour per day of prolonged SB with light PA (HRLPA 0.88; 95% CI [0.79, 0.99]; p = 0.033) was associated with lower risk of overall cancer mortality. Similarly, replacing 30 min per day of prolonged SB with moderate PA (HRMPA 0.92; 95% CI [0.86, 0.99]; p = 0.024) was associated with a lower risk of overall cancer mortality. The main methodological limitations were observational design, residual confounding, healthy volunteer bias, and measurement imprecision due to having only 7 days of accelerometer wear. CONCLUSION:Cancer risk associated with SB is specific to prolonged SB. Replacing prolonged SB physical activity is associated with lower cancer risk.

Introduction Weight gain in adulthood is a common potentially modifiable breast cancer risk factor. Intermittent 5:2 diets (two low-calorie days/week) have proven efficacy for weight loss among people with overweight or obesity and can promote sustained awareness and mindfulness of diet choice and help appetite control.This trial aims to test whether a less intensive 6:1 intermittent diet programme (one low-calorie day/week) is a feasible intervention to promote healthy eating and prevent weight gain in women at increased risk of breast cancer.Methods and analysis Single arm prospective feasibility trial in 30 healthy weight women aged 18–40 years, at moderate or high risk of breast cancer (≥17% lifetime risk and/or ≥3% 10 year risk at 40 years), body mass index 20–25 kg/m2. Participants will be entered to a 16-week 6:1 diet programme involving 1 day consuming 1000 kcal and healthy eating for 6 days a week. Participants will also be advised to meet physical activity recommendations for health (≥150 min of moderate intensity physical activity/week and resistance exercise two times per week). The programme will be supported remotely by dietitian calls at baseline, week 1, 4, 8, 12 and 16. Participants will also be provided access to a trial-specific private monitored Facebook group which includes information and the opportunity for peer support.Co-primary outcomes are: (a) uptake to the trial, (b) retention rate, (c) adherence to the 6:1 diet and (d) participant feedback on acceptability of the programme. Secondary outcomes include characteristics of those recruited and completing the programme and a preliminary evaluation of benefits and harms. This includes changes in body weight and body composition (bioelectrical impedance), diet quality, physical activity, binge eating, sleep quality (Pittsburgh Sleep Quality Index), menstrual cycle length and potentially diet-related adverse events, that is, fatigue, constipation, dizziness, headache, indigestion. Exploratory outcomes include the impact of low-calorie days on dietary intake and physical activity across the week and any differences in adherence to the low calorie days across the menstrual cycle.Ethics and dissemination This trial has been approved by South Central—Berkshire B Research Ethics committee (rec reference 24/SC/0321). Findings will be disseminated via peer-reviewed journals, national and international cancer prevention and obesity conferences and cancer prevention charitable bodies.Trial registration number ISRCTN14330469.

Purpose: Environments can be designed to be health enhancing. The Govan–Partick Bridge, a new major walking and cycling river bridge in Glasgow (UK), aims to promote active travel, reduce motorised transport and contribute to Glasgow’s net-zero climate goals. A comprehensive two-year evaluation is underway to assess the bridge’s impact on active travel, wellbeing, and transport. This study explores users’ early experiences and how the bridge has influenced their physical activity, wellbeing, and travel behaviour in the initial weeks after opening. Methods: The Govan–Partick Bridge opened on 7th September 2024, with baseline intercept surveys conducted in September and October 2024, and with 12-month and 2-year follow-ups planned. In-person intercept surveys were administered to bridge users via fieldworkers with tablets, gathering data on demographics, transport modes, reasons for use, and its impact on physical activity, wellbeing, and transport. Data were analysed using descriptive statistics. Results: Baseline intercept surveys were conducted with n = 690 respondents (51% male, 77% car owners). When surveyed, 93% of respondents were walking, with 69% reporting their journey was for recreation and 10% for commuting to/from work. Almost two-thirds (64%) stated that the bridge’s opening helped them increase their regular physical activity, for 50% of respondents their wellbeing had improved and for 74% their overall satisfaction with life increased. Respondents reported that if the bridge did not exist, 83% would have used a non-active mode or would not have made the journey. The bridge most frequently provided access to tourist/visitor attractions (67%), retail (36%), greenspace (25%), workplace (20%), and family or friends (20%). The most common factors influencing bridge use was liking the surroundings, getting exercise, improving wellbeing, and feeling safe. Overall sentiment was highly positive, with 78% stating they would ‘very likely’ recommend the route. Conclusion: Initial findings suggest that investments in this type of infrastructure can increase physical activity, encourage active travel, enhance wellbeing, improve access to services, and have positive public reception. The evaluation will triangulate data from mobile phone sensors, resident surveys, counters, observations, and ‘go-along’ interviews to assess the comprehensive and longer-term impact of the bridge as it embeds into the community. Support/Funding Source: Natural Environment Research Council

Background and Aims Maintenance of weight loss is a major challenge. Continuous glucose monitoring (CGM) could provide biofeedback to support lifestyle changes to facilitate weight maintenance. This randomised controlled trial evaluated the feasibility of incorporating CGM into a personalised, dietitian-led, weight loss maintenance programme (PWM), and whether CGM use led to greater improvements in dietary intake, physical activity, body weight, body composition, and cardiometabolic risk biomarkers over 24 weeks. Methods Adults who lost >5kg bodyweight in the past six months were eligible. Of 131 individuals who expressed interest, 99 met eligibility criteria. Forty-nine participants (17 men, 32 women) consented and were randomised to either PWM (n=25) or PWM/CGM (n=24) groups. Average recruitment rate was five participants/month. All participants received five one-to-one personalised dietitian consultations in weeks 1, 2, 4, 8 and 12; the PWM/CGM group also received a CGM for the 24-week intervention period and education on its use to support diet and physical activity behaviours. Results 19 PWM and 22 PWM/CGM participants completed the study (83.7% of randomised participants). All completers attended all dietitian consultations, and PWM/CGM participants wore their CGMs on 92.6% of intervention days. In completers, weight loss at 24-weeks was greater for PWM/CGM than PWM (-2.7±1.1 kg vs +0.5±0.8 kg, p=0.032). This difference remained significant in an intention-to-treat sensitivity analysis (-2.5±1.0 kg vs +0.4±0.6 kg, p=0.012). Change in energy intake from baseline to 24-weeks was greater in PWM/CGM than PWM (-235.0±123.0 kcal.day-1 vs +23.3±201.6 kcal.day-1, p=0.007). There were no differences in changes in physical activity or cardiometabolic risk biomarkers except triglycerides between groups. Conclusions These findings indicate that CGM is a feasible addition to an intensive weight loss maintenance programme and support a future fully-powered randomised controlled trial to determine long-term effectiveness. ClinicalTrials.gov (NCT05890209)

Purpose Adipocyte glucocorticoid (GC) signalling influences lipid storage and insulin sensitivity, and South Asians develop insulin resistance at lower BMI than White Europeans. We tested whether early modest weight gain alters adipocyte GC-related transcripts differently by ancestry and whether within-person transcript changes track dynamic insulin responses. Methods White European (n = 21) and South Asian (n = 14) men underwent ~ 6% diet-induced weight gain. Abdominal subcutaneous adipocytes were sampled at baseline and post–weight gain for RT-qPCR assessment of GC-responsive transcripts ( FKBP5, TSC22D3/GILZ ) and related targets ( HSD11B1, HSD11B2, IL2, IL6 ). Metabolic responses were characterised using a standardised mixed-meal test with 5-hour profiles of glucose, insulin, C-peptide and triglycerides; hepatic triglyceride content was quantified by MRI. Results Weight gain reduced FKBP5 (− 23.65 ± 8.82% in White Europeans; −17.68 ± 11.62% in South Asians; P = 0.007) and GILZ (− 11.40 ± 2.83%; −5.95 ± 4.01%; P = 0.001 for change with weight gain), with no ethnicity×intervention interaction (P ≥ 0.26). HSD11B1/HSD11B2 and IL2/IL6 did not change. At baseline, FKBP5 and GILZ were associated with adiposity, liver fat and adipocyte size. Within-person ΔFKBP5 (post–weight gain minus baseline) correlated with Δpostprandial insulin (r = 0.46, P = 0.006) and ΔC-peptide (r = 0.34, P = 0.049). ΔGILZ correlated with Δfasting glucose (r = − 0.40, P = 0.017) and Δpostprandial insulin (r = 0.34, P = 0.049). In mixed-effects models, change in postprandial insulin remained an independent correlate of both transcripts. Conclusion Early modest weight gain downregulates adipocyte GC-responsive transcripts similarly across ancestries, and dynamic transcript changes track insulin exposure. These findings implicate insulin dynamics as a potential driver of adipocyte GC signalling adaptations during early weight gain, linking adipocyte transcriptional responses to clinically relevant postprandial insulin physiology.

Purpose: Cycling offers health and environmental benefits, yet levels are low in the United Kingdom (UK). Effective cycling interventions in the community are therefore essential. Cycle Nation (CN) is a 9-week group-based intervention incorporating cycling skills, bicycle maintenance, behaviour change techniques, and provision of equipment. CN was originally rigorously developed as a workplace-based intervention and was adapted for the community setting. The aim of this project was to assess the feasibility of delivering the CN intervention in different community settings. Methods: The CN programme was delivered by local cycling organisations in Manchester with South Asian women and with residents in Glasgow, UK. Participants completed pre- and post-intervention self-report questionnaires including number of cycling rides and minutes per week cycling, cycling confidence and motivation, self-esteem, and vitality. Attendance and programme completion were recorded, and interviews conducted with CN participants and facilitators. Observations were conducted of sessions. Quantitative data were analysed descriptively; qualitative data were analysed thematically. Results: Across the two settings, 49 participants were recruited (n = 19 in Manchester and n = 30 in Glasgow) (40 female, 7 male, and 2 other) and only five withdrew in total. At post-intervention, participants in Manchester reported an increase in cycling by 3.1 rides and 89.3 minutes per week, and participants in Glasgow reported an increase of 5.2 rides and 144.3 minutes per week. In both settings this was mainly attributed to leisure cycling. CN enhanced cycling confidence, motivation for cycling, and self-esteem. In participant interviews, women highlighted the value of group-based cycling sessions, describing them as inspiring and empowering. They reported feeling increased confidence, physical and mental benefits, and higher levels of physical activity. Conclusion: This study demonstrates that delivering CN in community settings is highly feasible and was positively received by participants and facilitators. Cycling levels increased and there was high recruitment and retention rates. Findings suggest CN has potential to be effective in different contexts and can support cycling in underrepresented population sub-groups. Future research will include a randomised controlled trial of CN to provide robust longer-term evidence of its effectiveness and cost-effectiveness, with an embedded process evaluation. Support/Funding Source: Natural Environment Research Council & British Cycling.

Introduction Cycling can be beneficial for health, well-being and the environment; however, cycling participation in the UK remains low. Effective and cost-effective strategies are needed to support people in the community to increase cycling. The Cycle Nation Communities randomised controlled trial (RCT) will evaluate whether a 9 week multi-component cycling programme (Cycle Nation) is more effective and cost-effective than an existing national cycle training session on cycling participation, transport use and health and well-being.Methods and analysis This pragmatic, single-blinded, two-arm RCT will recruit ≥268 adults who cycle infrequently. Participants will be randomised to the 9 week multi-component individual/social-level group-based Cycle Nation programme or an existing national standard single group-based cycle training session. Both arms will be delivered by community-based cycling organisations in Glasgow. Participants will complete self-reported measurements at baseline, 12 weeks and 12 months. The primary outcome is the proportion of participants cycling at least weekly at 12 months. Secondary outcomes include proportion of participants cycling at least weekly at 12 weeks; change in weekly number of rides and minutes of cycling and use of private car, taxi, public transport and walking at 12 weeks and 12 months; change in motivation, perceptions of cycling safety, confidence to cycle, self-esteem, vitality, health-related quality of life and perceived general physical health at 12 weeks and 12 months. A within-trial economic evaluation from a National Health Service/personal social service and a broader societal perspective will be undertaken. Pending within-trial results, a long-term model may be developed. An embedded process evaluation will use participant and facilitator interviews, participant acceptability questionnaires, facilitator delivery proforma and session observations.Ethics and dissemination Ethical approval has been obtained from the University of Glasgow Medical, Veterinary and Life Sciences Ethics Committee (11 April 25). Findings will be published in peer-reviewed journals and communicated to stakeholders and the public.Trial registration number NCT07005674.

Background South Asians (SA) have higher risk of cardiometabolic disease compared to other ethnicities. However, detailed analyses of body compositional profile (BCP) in large cohorts with inclusion of ectopic fat depots and muscle composition is lacking. Methods Using MRI data from UK biobank, we compared body compositional data in South Asians (n = 397) relative to age, sex, height, and weight-matched white Europeans (EUR) (matched 5:1 to SA group). We also compared BCP in 66 SAs with type 2 diabetes (T2D) versus matched EUR (matched 3:1 to SA group). Results SAs had higher overall levels of fat compared to EUR (mean difference in: visceral adipose tissue 0·20 L; subcutaneous adipose tissue 0·93 L; liver fat 0·92 pp; muscle fat infiltration (MFI) 0·59 pp, all p < 0·001) and lower muscle volume (mean difference -0·61 L, p < 0·001) (all adjusted for sex, age, height, and weight). The higher MFI and lower muscle volume resulted in a higher prevalence of adverse muscle composition in the SA group (19·9 % vs 7·9 %). Differences remained significant with further adjustment for lifestyle and socioeconomic factors. Notably, SA participants with T2D had similar BCP to sex-, age-, height-, and weight-matched EUR participants with T2D. Conclusion SAs have greater visceral, liver, and muscle fat accumulation, but lower muscle volume compared to EUR. These findings may underlie their greater risk for T2D and atherothrombotic outcomes. Lifestyle changes to prevent or reduce weight gain can help offset cardiometabolic risks in SAs by facilitating favorable changes in body composition.

Short sleep duration and poor sleep quality are associated with higher energy intake and increased preference for sweet foods. The aim was to determine whether cognitive behaviour therapy for insomnia (CBTi) i) improved sleep duration and quality and ii) altered dietary behaviours and food preferences. Participants (sleep duration <7 h; Pittsburgh Sleep Quality Index (PSQI) > 5; BMI ≥25 kg m-2) were randomised to 8 weeks of CBTi (n = 14) or Control (n = 13). Sleep characteristics, dietary intake (3-day food diaries), food cravings (Control of Eating Questionnaire), and explicit liking, explicit wanting, and implicit wanting of foods (Leeds Food Preference Questionnaire) were assessed pre- and post-intervention. Self-reported sleep duration increased by 49.2 min more in the CBTi intervention compared with the Control group (+1.11 ± 0.21 h vs +0.29 ± 0.30 h, p = 0.01), self-reported sleep quality (PSQI) improved more (-5.86 ± 0.73 vs -0.62 ± 0.92, p = 0.00002), and daytime sleepiness (Epworth Sleepiness Scale) decreased more (-2.64 ± 0.80 vs +1.54 ± 0.66, p = 0.00004) in the Intervention group. However, there were no differences accelerometer-measured sleep duration and sleep efficiency between groups. The Intervention group had greater increases in food craving control (+21.9 ± 4.7 mm vs -3.0 ± 4.3 mm, p = 0.002), and greater reductions in craving for sweet (-16.4 ± 6.0 mm vs +3.3 ± 4.2 mm, p = 0.01) and savoury (-15.0 ± 3.0 mm vs +0.8 ± 4.8 mm, p = 0.003) foods. Implicit wanting of low-fat savoury foods increased (+12.3 ± 3.2 vs -2.1 ± 3.1, p = 0.006) and implicit wanting of high-fat sweet foods decreased (-15.8 ± 7.4 vs +9.8 ± 4.4, p = 0.001) more in the Intervention group. There was substantial under-reporting of dietary intake with 19 participants reporting energy intake <1.1 x basal metabolic rate. Amongst those with valid dietary measures, there were no significant differences in changes in energy or macronutrient intake between groups, but statistical power to detect effects was limited. In conclusion, this study demonstrates that a CBTi intervention leads to improvements in food craving control and changes in food preference. Future research is needed to determine whether this translates into differences in dietary intake.

BACKGROUND:Few middle-aged and older adults engage in regular leisure-time exercise. Incidental physical activity (IPA) encompasses activities of daily living outside the leisure-time domain. No dose-response study is available to guide IPA-focused interventions and guidelines. We examined the associations of device-assessed IPA intensities (vigorous [VIPA], moderate [MIPA], light [LIPA]) with major adverse cardiovascular events (MACE) and mortality, and we estimated the "health equivalence" of LIPA and MIPA against 1 minute of VIPA. METHODS:A total of 24 139 nonexercisers from the 2013 to 2015 UK Biobank accelerometry substudy (56.2% women) with a mean±SD age of 61.9±7.6 years were analyzed using a prospective cohort design. IPA energy expenditure and daily durations of VIPA, MIPA, and LIPA were calculated with a validated machine learning-based intensity classifier. MACE included incident stroke, myocardial infarction, and heart failure; CVD death; CVD mortality; and all-cause mortality. RESULTS:Analyses included 22 107 (MACE), 22 174 (CVD mortality), and 24 139 (all-cause mortality) participants, corresponding to 908/223/1071 events over 7.9 years of follow-up. IPA volume exhibited an L-shaped association with a nadir at ≈35 to 38 kJ·kg-1·d-1, corresponding to hazard ratios of 0.49 (95% CI, 0.39-0.61) for MACE, 0.33 (95% CI, 0.22-0.52) for CVD mortality, and 0.31 (95% CI, 0.25-0.38) for all-cause mortality. Any amounts of VIPA or MIPA were associated with lower risk, with a plateau of ≈14 minutes per day (VIPA) and 34 to 50 minutes per day (MIPA). The median VIPA (4.6 min/d) and MIPA (23.8 min/d) durations were associated with CVD mortality hazard ratio of 0.62 (95% CI, 0.46-0.83) and 0.50 (95% CI, 0.31-0.80), respectively. LIPA showed a subtle inverse gradient which was statistically significant only for CVD mortality at levels >130 minutes per day. One minute of VIPA was equivalent to 2.8 (MACE) to 3.4 (CVD mortality) minutes of MIPA and 34.7 (CVD mortality) to 48.5 (MACE) minutes of LIPA. CONCLUSIONS:Any daily IPA amount of vigorous or moderate intensity was associated with lower CVD risk in a dose-response manner. LIPA had weak associations with all outcomes. One minute of vigorous or ≈3.0 to 3.5 minutes of moderate IPA was associated with a similar degree of lower CVD risk. Our findings highlight the potential cardiovascular health value of incidental physical activity, especially for people who struggle to do structured exercise.

South Asians (SAs) in the UK are at an increased risk of cardiovascular disease (CVD), develop type 2 diabetes mellitus at a lower age and body mass index, and have a lower high-density lipoprotein cholesterol (HDL-C) concentration than their white European (EU) counterparts. The failure of HDL-C raising therapies for CVD risk reduction has turned attention to its composition and function. A previous study comparing the effect of moderate weight gain on SA and EU men found baseline and weight gain-induced ethnic differences in body composition, adipocyte function and insulin resistance (ClinicalTrials.gov registration: NCT02399423). This study investigated differences in HDL protein composition, subclass distribution and in vitro vascular functions at baseline and after weight gain in the same cohort of men. HDL protein composition was determined by nano liquid chromatography tandem mass spectrometry using label-free quantification. HDL subclass distribution was measured by native gel electrophoresis. HDL in vitro paraoxonase-1 (PON-1) activity was measured by monitoring the PON-1 mediated hydrolysis of phenylacetate. In vitro HDL anti-inflammatory function was assessed in an endothelial cell assay of adhesion molecule inhibition. SAs had higher levels of immunity- and inflammation-related proteins and a detrimental profile of lipid metabolism-related proteins at baseline and with weight gain (including lower apolipoprotein (apo) A-IV and apoF and higher apoC-III) compared with EU. HDL subclass distribution and in vitro vascular function were not different between EUs and SAs. HDL protein composition reflects systemic physiology and acts as a mechanistic marker of impaired lipid metabolism in SAs.

Background: Vigorous (VILPA) and moderate to vigorous (MVILPA) intermittent lifestyle physical activity refer to brief bouts of physical activity (<1 and <3 minutes, respectively) embedded in daily routines. Evidence suggests that 4 to 6 daily bursts of VILPA/MVILPA can significantly reduce the risk of cardiovascular disease and some cancers. These micropatterns of activity may offer a time-efficient and accessible alternative to structured exercise, particularly for women from socioeconomically diverse backgrounds who face intersecting barriers to traditional forms of physical activity. This study aimed to explore womens perspectives and experiences of VILPA/MVILPA and co-design a micropatterns intervention to promote these behaviours among socioeconomically diverse women. Methods: The study involved a series of three co-design workshops with women in Glasgow (N=19) and Sydney (N=31). Workshops incorporated participatory activities, education, training, discussion, and reflection to explore the concept of micropatterns, related facilitators and barriers and co-design the intervention. This study was guided by the Behaviour Change Wheel and MRC and 6SQuID intervention development frameworks. Data were audio-recorded, transcribed, and analysed using thematic framework analysis. Results: Participants identified a range of barriers (e.g. concerns about ability and safety, low mood, sociocultural norms) and facilitators (e.g. adaptability, dual-purpose activities, minimal time commitment) to engaging in micropatterns. Following reflection on the barriers and facilitators, six modifiable factors were identified to be addressed in the intervention, these included: lack of knowledge and awareness, concerns about ability and safety, low mood and poor mental health, sociocultural norms and environmental constraints. Participants identified thirteen intervention components that utilized seven intervention functions (education, persuasion, training, environmental restructuring, modelling, incentivisation, and enablement) to promote VILPA/MVILPA activities. Participants emphasised the importance of educational content, social support, and inclusive delivery formats (e.g. short videos, visual materials). Terminology such as Mindful Movement and Boosting Everyday Movement were preferred over technical acronyms and jargon. Conclusions: The final intervention involved a six-week programme of education, training, goal setting and VILPA/MVILPA tracking. Due to the popularity of social components and mixed perceptions of the accessibility of digital technology, the intervention was designed with three different delivery mechanisms:1) a smartphone application, 2) a smartphone application and a wearable device (e.g. Fitbit) and 3) workshops, a smartphone application and a wearable device. With further testing, this co-designed intervention could offer a feasible approach to promoting physical activity micropatterns among women from diverse socioeconomic backgrounds. ### Competing Interest Statement ES is a paid consultant and holds equity in Complement 1, a US-based company whose products and services relate to healthy lifestyles. All other authors disclose no conflict of interest for this work. ### Funding Statement This study was funded by The University of Glasgow and University of Sydney Health Inequalities Initiative (227213) and an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (APP1194510). The funders had no specific role in any of the following study aspects: the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The College of Medicine, Veterinary & Life Sciences Ethics Committee of the University of Glasgow (200240234) and Human Research Ethics Committee of the University of Sydney(HEOO1729) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All qualitative data relating to the findings are included in the manuscript in the form of quotations.

BACKGROUND:Vigorous intermittent lifestyle physical activity (VILPA) refers to brief bouts of intense physical activity embedded into daily life. OBJECTIVE:To examine sex differences in the dose-response association of VILPA with major adverse cardiovascular events (MACE) and its subtypes. METHODS:Using multivariable-adjusted cubic splines, we examined the associations of daily VILPA duration with overall MACE and its subtypes (incident myocardial infarction, heart failure and stroke) among non-exercisers (individuals self-reporting no leisure-time exercise and no more than one recreational walk per week) in the UK Biobank. We also undertook analogous analyses for vigorous physical activity among exercisers (individuals self-reporting participation in leisure-time exercise and/or recreational walking more than once a week). RESULTS:Among 13 018 women and 9350 men, there were 331 and 488 all MACE, respectively, over a 7.9-year follow-up. In women, daily VILPA duration exhibited a near-linear dose-response association with all MACE, myocardial infarction and heart failure. In men, dose-reponse curves were less clear with less evidence of statistical signifigance. Compared with women with no VILPA, women's median daily VILPA duration of 3.4 min was associated with hazard ratios (HRs; 95% confidence intervals) of 0.55 (0.41 to 0.75) for all MACE and 0.33 (0.18 to 0.59) for heart failure. Women's minimum doses of 1.2-1.6 min of VILPA per day were associated with HRs of 0.70 (0.58 to 0.86) for all MACE, 0.67 (0.50 to 0.91) for myocardial infarction, and 0.60 (0.45 to 0.81) for heart failure. The equivalent analyses in UK Biobank's accelerometry sub-study exercisers suggested no appreciable sex differences in dose-response. CONCLUSIONS:Among non-exercising women, small amounts of VILPA were associated with a substantially lower risk of all MACE, myocardial infarction and heart failure. VILPA may be a promising physical activity target for cardiovascular disease prevention, particularly in women unable or not willing to engage in formal exercise.

The aim of this work was to investigate tissue-specific insulin resistance in South Asian and Nordic women with previous gestational diabetes mellitus (pGDM) and to evaluate potential ethnic differences contributing to type 2 diabetes risk. A cross-sectional study using a two-step hyperinsulinaemic–euglycaemic clamp with a glucose tracer was conducted to assess insulin sensitivity in muscle, liver and adipose tissue in 19 South Asian and 16 Nordic women with pGDM and prediabetes (impaired glucose tolerance and/or impaired fasting glucose), along with 16 ethnicity-specific control women. We assessed inflammation and mitochondrial genes by mRNA sequencing of adipose tissue. Both South Asian and Nordic women with pGDM showed reduced total glucose disposal (mainly due to muscle insulin resistance) and hyperinsulinaemia compared with the control group. Endogenous glucose production (mainly due to hepatic insulin resistance) was elevated in Nordics with pGDM, while South Asians with pGDM showed pronounced adipose tissue insulin resistance (reduced suppression of glycerol during clamp). mRNA sequencing of adipose tissue indicated increased tissue inflammation in South Asian women compared with Nordic women with pGDM. Furthermore, we observed a differential response to hyperinsulinaemia in South Asians vs Nordics related to mitochondrial mRNA, such as thymidine kinase 2 (TK2). Correlations between adiposity markers and insulin sensitivity also differed by ethnicity, suggesting that the pathways leading to type 2 diabetes may vary across populations. South Asian and Nordic women with pGDM exhibited differences in insulin resistance profiles, with South Asians showing greater adipose tissue insulin resistance and inflammation.

Objective: To synthesise current evidence on knowledge, perceptions and practices towards type 2 diabetes risk in sub-Saharan AfricaDesign: Mixed-methods scoping review, which included 101 studies (seventy-three quantitative, twenty qualitative and eight mixed methods) from seven electronic databases.Setting: Sub-Saharan Africa, 2000-2023.Participants: Men and women without diabetes with mean ages ranging from 20 to 63 years.Results: The majority of participants in most studies knew the three main diabetes modifiable risk factors - excess weight, unhealthy diet and physical inactivity. However, most people with excess weight in almost all studies underestimated their weight. Further, the self-described ideal body weight was between midpoint of normal weight and the upper limits of overweight in most quantitative studies and was described as not too skinny but not too fat in qualitative studies. In the majority of studies, participants reported low engagement in weight control, high regular sugar intake, and low regular fruit and vegetable intake but moderate to high engagement in physical activity. Barriers to reducing diabetes risk were social (e.g. societal perceptions promoting weight gain) and environmental (e.g. limited affordability of healthy foods, high accessibility of Western diets and lack of physical activity facilities).Conclusion: There is a need for multicomponent type 2 diabetes prevention interventions that increase knowledge of identifying diabetes risk (e.g. what constitutes excess weight) and create social and physical environments that support healthy lifestyles (e.g. societal perceptions that promote healthy living, increased availability and affordability of healthy foods and physical activity facilities).

Aim: Elevated C-reactive protein (CRP), a marker of inflammation, is common in many chronic conditions. We aimed to examine to what extent elevated CRP in chronic conditions could be explained by concurrent adiposity. Materials and Methods: This cross-sectional study analysed UK Biobank data on 10 chronic conditions reported at baseline. Linear regression models explored the extent to which CRP concentrations were elevated in each condition, unadjusted; adjusted for sociodemographic confounders and lifestyle and body mass index (BMI) in a series of models; or adjusted for BMI and waist circumference together or for adiposity alone. Results: After exclusion of participants with a potential acute infection at baseline, we tested the association in 292 772 UK Biobank participants. Linear regression showed that elevated CRP concentration was associated with all included conditions. After adjustment for sociodemographic confounders, lifestyle and BMI, chronic kidney disease, heart failure, liver disease, psoriasis, rheumatoid arthritis and chronic obstructive pulmonary disease were still associated with elevated CRP. In contrast, the association between prevalent diabetes, prior myocardial infarction (MI), hypertension and sleep apnoea and CRP could be mostly explained by adiposity alone. For example, the 42% higher CRP concentrations in diabetes compared to those without diabetes in the unadjusted model (lnCRP (3: 0.35; 95% confidence interval [CI]: 0.32- 0.37, p <0.001) were completely attenuated after adjustment for BMI (lnCRP (3:-0.07; 95% CI:-0.09-0.05, p < 0.001). Conclusions/Interpretation: In diabetes, MI, hypertension and sleep apnoea and elevated CRP appears to be accounted for by the greater adiposity typically evident in these conditions. However, for the other conditions, systemic inflammation cannot be explained by excess adiposity alone.

South Asians (SAs) develop type 2 diabetes at lower body mass index values than white Europeans (WEs). This basic human experimental study aimed to compare the metabolic consequences of weight gain in SA and WE men without overweight or obesity. Fourteen SAs and 21 WEs had assessments of body composition, metabolic responses to mixed-meal ingestion, cardiorespiratory fitness and physical activity, and a subcutaneous abdominal adipose tissue biopsy, before and after 4-6 weeks of overfeeding to induce 5-7% weight gain. Here we show that body mass index and whole-body adipose tissue volume increases similarly between ethnic groups, but SAs gain less lean tissue. SAs experience a substantially greater decrease in insulin sensitivity compared with WEs (38% versus 7% decrease, P = 0.009), have fewer small (37.1% versus 60.0%, P = 0.003) and more large (26.2% versus 9.1%, P = 0.005) adipocytes at baseline and have a smaller decrease in very small adipocytes with weight gain (-0.1% versus -1.9%, P < 0.0001). Ethnic differences in adipocyte morphology are associated with SA's greater adverse metabolic changes with weight gain. ClinicalTrials.gov registration: NCT02399423 .

South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1–3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.