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To investigate the association between self-reported walking pace and type 2 diabetes (T2D) incidence and whether it differed by physical activity levels and walking time.There were 162,155 participants (mean age, 57.1 years; 54.9% women) from the UK Biobank prospective study, recruited between 2006 and 2010, included in the study. Walking pace was self-reported and classified as brisk, average, or slow. Total physical activity and walking time were self-reported using the International Physical Activity Questionnaire. Association between walking pace and T2D incidence and the potential moderating role of physical activity and walking time were investigated using Cox proportional hazards models.The median follow-up was 7.4 (interquartile range, 6.7 to 8.2) years. There were 4442 participants in whom T2D developed during the follow-up period. In the fully adjusted model (sociodemographic factors, diet, body mass index, and physical activity), average walking pace (hazard ratio [HR], 1.28; 95% CI, 1.14 to 1.44) and slow walking pace (HR, 1.91; 95% CI, 1.62 to 2.24) were associated with a higher T2D risk compared with brisk walking among women. Among men, average walking pace (HR, 1.28; 95% CI, 1.17 to 1.40) and slow walking pace (HR, 1.73; 95% CI, 1.50 to 1.99) were also associated with higher T2D risk. Compared with slow walkers, brisk walkers have the same diabetes incidence rate 18.6 and 16.0 years later, for women and men, respectively.Average and slow walking pace was associated with a higher risk of incident T2D in both men and women, independent of major confounding factors. The associations were consistent across different physical activity levels and walking time.

Background Active passive trainers are frequently used as a safe, feasible way for people with neurological disabilities to exercise. However, evidence regarding their efficacy is limited. The aim of this study was to review the literature investigating the effects of lower limb active passive trainer cycling, with or without functional electrical stimulation, on spasticity, cardiovascular fitness, function and quality of life in people with neurological conditions Methods Five electronic databases were searched from inception to June 2021. Studies included: randomised controlled trials using lower limb active passive trainers as a cycling intervention; participants with neurological conditions, such as multiple sclerosis, spinal cord injury, stroke and Parkinson's disease; and at least one outcome related to spasticity, cardiovascular fitness, physical function or quality of life. Results A total of 12 articles were included (n=423 participants, 52% male). Of these, six used functional electrical stimulation-assisted active passive trainer interventions, and the remaining six used active passive trainer interventions alone. A meta-analysis demonstrated statistically significant improvement in walking endurance; however, this only included stroke studies (6-Minute Walk Test performance, P Conclusions The included studies featured heterogeneous designs, outcome measures, exercise prescriptions and participant disability levels, which made comparison difficult. Active passive trainer interventions appear to improve walking endurance in people with stroke; however, the effect on other outcomes and in other conditions remains unclear. It also remains uncertain as to whether functional electrical stimulation-assisted cycling is more beneficial than active passive trainer cycling alone.

To investigate the associations between types of diet and incident type 2 diabetes and whether adiposity mediated these associations.In total, 203 790 participants from UK Biobank (mean age 55.2 years; 55.8% women) without diabetes at baseline were included in this prospective study. Using the dietary intake data self-reported at baseline, participants were categorized as vegetarians (n = 3237), fish eaters (n = 4405), fish and poultry eaters (n = 2217), meat eaters (n = 178 004) and varied diet (n = 15 927). The association between type of diet and incident type 2 diabetes was investigated using Cox-proportional hazards models with a 2-year landmark analysis. The mediation role of adiposity was tested under a counterfactual framework.After excluding the first 2 years of follow-up, the median follow-up was 5.4 (IQR: 4.8-6.3) years, during which 5067 (2.5%) participants were diagnosed with type 2 diabetes. After adjusting for lifestyle factors, fish eaters (HR 0.52 [95% CI: 0.39-0.69]) and fish and poultry eaters (HR 0.62 [95% CI: 0.45-0.88]) had a lower risk of incident type 2 diabetes compared with meat eaters. The association for vegetarians was not significant. Varied diet had a higher risk of type 2 diabetes. Obesity partially mediated the association of fish (30.6%), fish and poultry (49.8%) and varied (55.2%) diets.Fish eaters, as well as fish and poultry eaters, were at a lower risk of incident type 2 diabetes than meat eaters, partially attributable to lower obesity risk.

Background Most studies investigating the association between physical activity (PA) and the risk of type 2 diabetes are derived from self-reported questionnaires, with limited evidence using device-based measurements. Therefore, this study aimed to investigate the dose–response relationship between device-measured PA and incident type 2 diabetes. Methods This prospective cohort study included 40,431 participants of the UK Biobank. Wrist-worn accelerometers were used to estimate total, light, moderate, vigorous and moderate-to-vigorous PA. The associations between PA and incident type 2 diabetes were analysed using Cox-proportional hazard models. The mediating role of body mass index (BMI) was tested under a causal counterfactual framework. Results The median follow-up period was 6.3 years (IQR: 5.7–6.8), with 591 participants developing type 2 diabetes. Compared to those achieving 600 min/week were at 49% (95% CI 62–32%), 62% (95% CI 71–50%) and 71% (95% CI 80–59%) lower risk of type 2 diabetes, respectively. For vigorous PA, compared to those achieving 75 min/week were at 38% (95% CI 48–33%), 48% (95% CI 64–23%) and 64% (95% CI 78–42%) lower type 2 diabetes risk, respectively. Twelve per cent and 20% of the associations between vigorous and moderate PA and type 2 diabetes were mediated by lower BMI, respectively. Conclusions PA has clear dose-response relationship with a lower risk of type 2 diabetes. Our findings support the current aerobic PA recommendations but suggest that additional PA beyond the recommendations is associated with even greater risk reduction. Trial registration The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Ref 11/NW/0382 on June 17, 2011).

This is a pre-copyedited, author-produced version of an article accepted for publication in the European Journal of Preventive Cardiology following peer review. The version of record Hansen, K.W., Peytz, N., Blokstra, A., Bojesen, S.E., Celis-Morales, C., Chrysohoou, C, ... Prescott, E. (2021). Association of fatal myocardial infarction with past level of physical activity: a pooled analysis of cohort studies. European Journal of Preventive Cardiology, zwaa146, is available online at: https://doi.org/10.1093/eurjpc/zwaa146. Aims: To assess the association between past level of physical activity (PA) and risk for death during the acute phase of myocardial infarction (MI) in a pooled analysis of cohort studies. Methods and results: European cohorts including participants with a baseline assessment of PA, conventional cardiovascular (CV) risk factors, and available follow-up on MI and death were eligible. Patients with an incident MI were included. Leisure-time PA was grouped as sedentary (32 MET-hours) based on calculated net weekly energy expenditure. The main outcome measures were instant and 28-day case fatality of MI. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate random-effects models. Adjustments for age, sex, CV risk factors, alcohol consumption, and socioeconomic status were made. From 10 cohorts including a total of 1 495 254 participants, 28 140 patients with an incident MI comprised the study population. A total of 4976 (17.7%) died within 28 days—of these 3101 (62.3%) were classified as instant fatal MI. Compared with sedentary individuals, those with a higher level of PA had lower adjusted odds of instant fatal MI: low PA [OR, 0.79 (95% CI, 0.60–1.04)], moderate PA [0.67 (0.51–0.89)], and high PA [0.55 (0.40–0.76)]. Similar results were found for 28-day fatal MI: low PA [0.85 (0.71–1.03)], moderate PA [0.64 (0.51–0.80)], and high PA [0.72 (0.51–1.00)]. A low-to-moderate degree of heterogeneity was detected in the analysis of instant fatal MI (I2 = 47.3%), but not in that of 28-day fatal MI (I2 = 0.0%). Conclusion: A moderate-to-high level of PA was associated with a lower risk of instant and 28-day death in relation to a MI.

BackgroundRegular participation in resistance exercise is known to have broad-ranging health benefits and for this reason is prominent in the current physical activity guidelines. Recovery after such exercise is important for several populations across the age range and nutritional strategies to enhance recovery and modulate post-exercise physiological processes are widely studied, yet effective strategies remain elusive. Vitamin K2 supplementation has emerged as a potential candidate, and the aim of the current study, therefore, is to test the hypothesis that vitamin K2 supplementation can accelerate recovery, via modulation of the underlying physiological processes, following a bout of resistance exercise in young and older adults.MethodsThe current study is a two-arm randomised controlled trial which will be conducted in 80 (40 young (≤40 years) and 40 older (≥65 years)) adults to compare post-exercise recovery in those supplemented with vitamin K2 or placebo for a 12-week period. The primary outcome is muscle strength with secondary outcomes including pain-free range of motion, functional abilities, surface electromyography (sEMG) and markers of inflammation and oxidative stress.DiscussionEthical approval has been granted by the College of Medical Veterinary and Life Sciences Ethical Committee at the University of Glasgow (Project No 200190189) and recruitment is ongoing. Study findings will be disseminated through a presentation at scientific conferences and in scientific journals.Trial registrationClinicialTrials.gov NCT04676958. Prospectively registered on 21 December 2020.

BackgroundThe aim of the current study was to determine the prevalence of low muscle strength and to evaluate physical activity and sleep characteristics in people with type 2 diabetes in Kuwait. Additionally, equivalent data from the UK Biobank cohort were compared.MethodsPeople with type 2 diabetes from the UK Biobank (n = 23,570) and Kuwaiti cohorts (n = 3,135) were included in this cross-sectional study. Self-reported sleep, physical activity, and muscle strength were compared between the cohorts, using linear and logistic regression, with adjustments for age, sex, and duration of diabetes.ResultsPhysical activity levels (−937 (−1,097, −851) Met-min/week: standardized B-coefficient −0.42 (−0.47, −0.37)) and grip strength (3.2 (−3.58, −2.82) kg: standardized B-coefficient (−0.29 (−0.32, −0.26)) were lower in the Kuwaiti cohort, and the odds of having short sleep (OR 1.32 (1.19,1.46), being classed as inactive (OR 8.70 (7.59, 9.98), and having muscle weakness (OR 1.88 (1.69, 2.09) were higher. These analyses were adjusted for age, sex, and duration of diabetes.ConclusionsThe aim of the current study was to determine the prevalence of low muscle strength and to evaluate physical activity and sleep characteristics in people with type 2 diabetes in Kuwait. Additionally, equivalent data from the UK Biobank cohort were compared.

Background: Chronic fatigue is a poorly managed problem in people with inflammatory rheumatic diseases. Cognitive behavioural approaches (CBA) and personalised exercise programmes (PEP) can be effective, but they are not often implemented because their effectivenesses across the different inflammatory rheumatic diseases are unknown and regular face-to-face sessions are often undesirable, especially during a pandemic. We hypothesised that remotely delivered CBA and PEP would effectively alleviate fatigue severity and life impact across inflammatory rheumatic diseases. Methods: LIFT is a multicentre, randomised, controlled, open-label, parallel-group trial to assess usual care alongside telephone-delivered CBA or PEP against usual care alone in UK hospitals. Patients with any stable inflammatory rheumatic disease were eligible if they reported clinically significant, persistent fatigue. Treatment allocation was assigned by a web-based randomisation system. CBA and PEP sessions were delivered over 6 months by trained health professionals in rheumatology. Coprimary outcomes were fatigue severity (Chalder Fatigue Scale) and impact (Fatigue Severity Scale) at 56 weeks. The primary analysis was by full analysis set. This study was registered at ClinicalTrials.gov (NCT03248518). Findings: From Sept 4, 2017, to Sept 30, 2019, we randomly assigned and treated 367 participants to PEP (n=124; one participant withdrew after being randomly assinged), CBA (n=121), or usual care alone (n=122), of whom 274 (75%) were women and 92 (25%) were men with an overall mean age of 57·5 (SD 12·7) years. Analyses for Chalder Fatigue Scale included 101 participants in the PEP group, 107 in the CBA group, and 107 in the usual care group and for Fatigue Severity Scale included 101 in PEP, 106 in CBA, and 107 in usual care groups. PEP and CBA significantly improved fatigue severity (Chalder Fatigue Scale; PEP: adjusted mean difference −3·03 [97·5% CI −5·05 to −1·02], p=0·0007; CBA: −2·36 [–4·28 to −0·44], p=0·0058) and fatigue impact (Fatigue Severity Scale; PEP: −0·64 [–0·95 to −0·33], p

Objective To develop a score from cumulative dietary risk factors and examine its nonlinear associations with cardiovascular disease (CVD) and cancer incidence and mortality, as well as all-cause mortality. Patients and Methods There were 422,702 participants from UK Biobank included in this prospective study. Cumulative dietary risk factors were represented using a score ranging from 0 (healthiest) to 9 (least healthy). This was derived from 9 food items based on current UK guidelines using baseline data. Associations between the cumulative score and health outcomes were investigated using nonlinear penalized cubic splines fitted in Cox proportional hazard models. Follow-up was conducted until June 2020 for mortality, and for incidence, up to June 2020 in England and March 2017 in Wales and Scotland. Results The median follow-up period was 9.0 years for incidence outcomes and 9.3 years for mortality outcomes. Each 1-point increment in the cumulative dietary risk factors score was associated with higher risk for incidence and mortality of the outcomes studied. The highest risks were identified for mortality due to heart failure (8.0% higher), CVD, and ischemic heart disease (both 7.0% higher). In addition, a higher diet score accounted for 18.8% of all deaths, 4.47% of incident cases of CVD, 25.5% of CVD deaths, 7.7% of incident cancers, and 18.2% of all cancer deaths. Conclusion Our findings show that dietary risk factors contributed to a large proportion of CVD and cancer events, as well as deaths, among those who did not meet most dietary recommendations.

Supplemental Digital Content is available in the text., Background: Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA. Methods: United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401 820, 54.6% women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83 816). Incident AAA was defined as first hospital inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines. Results: In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI, 0.678–0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837–0.878). In the validation cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the USPSTF model +0.176 (95% CI, 0.120–0.232). A combined model, whereby risk scoring was combined with the USPSTF model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055–0.147]). Conclusions: In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation of risk scores to detect asymptomatic AAA are needed.

Background: Studies of objectively measured physical activity (PA) have investigated acute cardiovascular outcomes but not heart failure (HF), an emerging chronic condition. This study aimed to investigate the dose-response relationship between device-measured PA and HF by intensity of PA. Methods: This was a prospective cohort study of 94 739 UK Biobank participants who had device-measured PA in 2013 to 2015 and were free from myocardial infarction and HF. PA was measured with a wrist-worn accelerometer, and time spent on light-, moderate-, and vigorous-intensity PA was extracted. Incident HF was ascertained from linked hospital and death records. Cox proportional hazard models with cubic penalized splines were used to study the associations, which were adjusted for sociodemographic and lifestyle factors. Competing risk was handled with cause-specific hazard ratios. Results: The overall incidence of HF was 98.5 per 10 000 person-years over a median 6.1 years of follow-up. Compared with participants who undertook no moderate- to vigorous-intensity PA, those who performed 150 to 300 min/wk of moderate-intensity PA (hazard ratio, 0.37 [95% CI, 0.34–0.41]) and 75 to 150 min/wk of vigorous-intensity PA (hazard ratio, 0.34 [95% CI, 0.25–0.46]) were at lower HF risk. The association between vigorous-intensity PA and HF was reverse-J shaped with a potentially lower risk reduction above 150 min/wk. Conclusions: Device-measured PA, especially moderate-intensity PA, was associated with a lower risk of HF. Current vigorous-intensity PA recommendations should be encouraged but not increased. In contrast, increasing moderate-intensity PA may be beneficial even among those meeting current recommendations.

Introduction Resistance training (RT) is the most effective way to increase muscle mass and function in older adults both with/without sarcopenia/frailty. In younger adults, when RT is performed to muscle failure the load lifted does not mediate the magnitude of response, but there are no studies in older adults. We aimed to determine the feasibility of recruitment to a RT intervention working to muscle failure at different loads in frail and healthy older adults. Methods We performed an 8-week randomised feasibility trial of lower limb RT to volitional muscular failure, at high and low load. Participants were recruited via hospital outpatient clinics and newspaper advertisements. Outcomes included: frailty assessment (Fried criteria); muscle strength (maximum voluntary contraction/one-repetition maximum); functional abilities (Short Physical Performance Battery); safety/adverse events were recorded via a log, and patient experiences from focus groups. Results 110 people were assessed for eligibility, and 58 randomised (frail n = 6, prefrail n = 20, robust n = 32) to either high (n = 30) or low load (n = 28) groups. Mean age of participants was 72 years (range 65–93), 36 were female, 22 male. Session attendance was 95% (high load) and 90.4% (low load). Most participants were recruited via advertisements. All participants reported feeling safe and reassured in the RT sessions. Two participants had a serious adverse event, one related to RT (hypotension) and several had adverse events (three intervention-related). Pain was reported at both loads (high n = 9, low n = 8) yet all completed. There were no differences (P > 0.05) in effects of RT outcome variables between low and high load groups. Conclusion In this feasibility trial the recruitment of frail patients via clinics was limited. Performing supervised RT to muscle failure in older adults was safe/acceptable and the load at which RT was performed did not influence its efficacy. Future research into the effectiveness of such RT is warranted.

Objective To inform potential guideline development, we investigated nonlinear associations between television viewing time (TV time) and adverse health outcomes. Methods From 2006 to 2010, 490,966 UK Biobank participants, aged 37 to 73 years, were recruited. They were followed from 2006 to 2018. Nonlinear associations between self-reported TV time (hours per day) and outcomes explored using penalized cubic splines in Cox proportional hazards adjusted for demographics and lifestyle. Population-attributable and potential impact fractions were calculated to contextualize population-level health outcomes associated with different TV time levels. Nonlinear isotemporal substitution analyses were used to investigate substituting TV time with alternative activities. Primary outcomes were mortality: all-cause, cardiovascular disease (CVD) and cancer; incidence: CVD and cancer; secondary outcomes were incident myocardial infarction, stroke, and heart failure and colon, lung, breast, and prostate cancer. Results Those with noncommunicable disease (109,867 [22.4%]), CVD (32,243 [6.6%]), and cancer (37,81 [7.7%]) at baseline were excluded from all-cause mortality, CVD, and cancer analyses, respectively. After 7.0 years (mortality) and 6.2 years (disease incidence) mean follow-up, there were 10,306 (2.7%) deaths, 24,388 (5.3%) CVD events, and 39,121 (8.7%) cancer events. Associations between TV time and all-cause and CVD mortality were curvilinear (Pnon-linear ≤.003), with lowest risk observed Conclusion TV time is associated with numerous adverse health outcomes. Future guidelines could suggest limiting TV time to less than 2 hours per day to reduce most of the associated adverse health events.

Introduction\ud It is unclear what combinations of physical capability markers used to define sarcopenia have the strongest associations with health outcomes.\ud \ud Aim\ud To compare the associations between different combinations of physical capability markers of sarcopenia with cardiovascular and respiratory outcomes and all-cause mortality.\ud \ud Study design\ud 469,830 UK Biobank participants were included in this prospective study. Four groups were derived based on combinations of three physical capability markers used to define sarcopenia or severe sarcopenia: gait speed, grip strength and muscle mass. Outcomes studied were all-cause mortality, as well as incidence and mortality from cardiovascular disease (CVD), respiratory disease and chronic obstructive pulmonary disease (COPD).\ud \ud Results\ud All combinations of physical capability markers used to define sarcopenia or severe sarcopenia identified individuals at increased risk of respiratory disease and all-cause mortality. However, the definition most strongly associated with a wide range of adverse health outcomes was the combination of slow gait speed plus low muscle mass, followed by severe sarcopenia, and the combination of slow gait speed plus low grip strength. The current definition of sarcopenia (low grip strength plus low muscle mass) had the weakest associations with all-cause (HR: 1.35 [95% CI: 1.07 to 1.71]) and respiratory mortality (HR: 1.88 [95% CI: 1.15 to 3.10]), as well as respiratory disease (HR: 1.38 [95% CI: 1.11 to 1.73]) and COPD incidence (HR: 2.08 [95% CI: 1.14 to 3.79]).\ud \ud Conclusions\ud Associations of sarcopenia with adverse outcomes were strongest when sarcopenia was defined as slow gait speed plus low muscle mass, followed by severe sarcopenia, suggesting that this combination of physical capability markers should be still considered in the diagnosis of sarcopenia.

To investigate whether the excess risk of adverse health outcomes associated with a lower physical capability in adulthood differs by deprivation levels.279,030 participants from the UK Biobank were included. Handgrip strength and walking pace were the exposures. All-cause mortality, CVD mortality and incidence were the outcomes. Townsend deprivation index was treated as a potential effect modifier. The associations were investigated using Cox-regression models with years of follow-up as the time-varying covariate.A significant interaction between deprivation and handgrip strength was found for all-cause mortality (p = 0.024), CVD mortality (p = 0.006) and CVD incidence (p = 0.001). The hazard ratio for all-cause mortality was 1.18 [1.09; 1.29] per 1-tertile higher level of grip strength in the least deprived group, whereas it was 1.30 [1.18; 1.43] in the most deprived individuals. Similar results were found for CVD mortality and incidence per tertile increment in handgrip strength in the least and most deprived quintiles, respectively. No significant interactions between deprivation and walking pace were found for any of the outcomes.Low handgrip strength is a stronger predictor of morbidity and mortality in individuals living in more deprived areas.

Background: Muscle–bone deficits are common in pediatric Crohn’s disease; however, few studies have assessed long-term musculoskeletal outcomes in adults with childhood-onset Crohn’s disease. This study assessed the prevalence of musculoskeletal deficits in young adults with childhood-onset Crohn’s disease compared with healthy controls. Methods: High-resolution MRI and MR spectroscopy were used to assess bone microarchitecture, cortical geometry and muscle area, and adiposity at distal femur and bone marrow adiposity (BMA) at lumbar spine. Muscle function and biomarkers of the muscle-bone unit were also assessed. Results: Twenty-seven adults with Crohn’s disease with median (range) age 23.2 years (18.0, 36.1) and 27 age and sex-matched controls were recruited. Trabecular microarchitecture, cortical geometry and BMA were not different between Crohn’s disease and controls (P > 0.05 for all). Muscle area was lower (P = 0.01) and muscle fat fraction was higher (P = 0.04) at the distal femur in Crohn’s disease compared to controls. Crohn’s disease participants had lower grip strength [-4.3 kg (95% confidence interval (CI), -6.8 to -1.8), P = 0.001] and relative muscle power [-5.0 W/kg (95% CI, -8.8 to -1.2), P = 0.01]. Crohn’s disease activity scores negatively associated with trabecular bone volume (r = -0.40, P = 0.04) and muscle area (r = -0.41, P = 0.03). Conclusion: Young adults with well-controlled Crohn’s disease managed with contemporary therapies did not display abnormal bone microarchitecture or geometry at the distal femur but exhibited muscle deficits. The observed muscle deficits may predispose to musculoskeletal morbidity in future and interventions to improve muscle mass and function warrant investigation.

Background Resistance exercise is known to be effective in reducing glycated haemoglobin (HbA1c) in people with type 2 diabetes. However, studies, so far, have employed supervised resistance exercise in a laboratory or gym facility which limits the future translation of such exercise in to clinical practice and recommendations. Our primary aim, therefore, is to test the hypothesis, in a randomized controlled trial, that home-based resistance exercise training and gym-based resistance exercise training both reduce HbA1c levels in people with type 2 diabetes compared to control. We will also investigate the effects of home- and gym-based resistance exercise training on muscle strength and body composition. Methods The current study is a three-arm randomised controlled trial which will be conducted with 150 eligible people with type 2 diabetes to compare home-and gym-based resistance exercise training with usual care in Kuwait. The interventions will be delivered by exercise specialists and last for 32 weeks. The primary outcomes are HbA1c with secondary outcomes measuring muscle function, body composition, physical activity and quality of life. Discussion Ethical approval has been granted by the Dasman Diabetes Institute ethical review committee (RA/197/2019). Study findings will be disseminated through presentation at scientific conferences and in scientific journals. Trial registration NCT04136730: Retrospectively registered on 21 October 2019

Background This study aimed to study the association between shift work and incident and fatal cardiovascular disease (CVD), and to explore modifying and mediating factors. Methods This is a population-based, prospective cohort study with a median follow-up of 11 years; 238 661 UK Biobank participants who were in paid employment or self-employed at baseline assessment were included. Results Shift workers had higher risk of incident [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.06–1.19] and fatal (HR 1.25, 95% CI 1.08–1.44) CVD compared with non-shift workers, after adjusting for socio-economic and work-related factors. The risk was higher with longer duration of shift work, in women and in jobs with little heavy manual labour. Current smoking, short sleep duration, poor sleep quality, adiposity, higher glycated haemoglobin and higher cystatin C were identified as the main potentially modifiable mediators. Mediators collectively explained 52.3% of the associations between shift work and incident CVDs. Conclusions Shift workers have higher risk of incident and fatal CVD, partly mediated through modifiable risk factors such as smoking, sleep duration and quality, adiposity and metabolic status. Workplace interventions targeting these mediators have the potential to alleviate shift workers’ CVD risk.

Objectives: Fatigue is a challenging feature of all inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) included remotely delivered personalised exercise programme (PEP) or cognitive-behavioural approach (CBA) interventions. The aim of this nested qualitative evaluation was to understand rheumatology health professionals (therapists’) perspectives of delivering the interventions in the LIFT trial. Methods: A subgroup of therapists who had delivered the personalized exercise programme (PEP) and cognitive-behavioural approach (CBA) interventions took part in semi-structured telephone interviews.Results: Seventeen therapists (13 women and 4 men) who delivered PEP (n = 8) or CBA (n = 9) interventions participated. Five themes were identified. In ‘The benefits of informative, structured training’, therapists described how they were able to practice their skills, and the convenience of having the LIFT manual for reference. When ‘Getting into the swing of it’, supporting patients gave therapists the confidence to tailor the content of the manual to each patient. Clinical supervision supported therapists to gain feedback and request assistance when required. In ‘Delivering the intervention’, therapists reported that patients valued the opportunity to talk about their fatigue and challenge their beliefs. In ‘Challenges in delivering the LIFT intervention’, therapists struggled to work in partnership with patients who lacked motivation or stopped engaging. Finally, in ‘LIFT developing clinical skills’, therapists gained confidence and professional satisfaction, seeing patients’ fatigue improve over time.Conclusion: The findings support the provision of training for rheumatology health professionals to remotely deliver fatigue-management interventions. Insights from these trials can be used to better improve clinical practice and service provision.Lay summary What does this mean for patients ? Fatigue can be a challenge in inflammatory rheumatic diseases (IRDs). The LIFT study (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) explored interventions to support people with fatigue. These were: a cognitive-behavioural approach (CBA), a personalized exercise programme (PEP), or usual care. People with IRDs were chosen randomly to take part in seven sessions of CBA, seven sessions of PEP or usual care. All sessions (aside from the first PEP session) were delivered over the phone. The aim of this study was to explore therapists' experiences of delivering the intervention. Seventeen therapists (13 women and 4 men) took part; eight had delivered the PEP intervention, and 9 delivered the CBA intervention. Therapists who delivered LIFT told us they enjoyed the chance to practice their skills, and that the LIFT manual gave them the confidence to tailor the intervention to each patient. Clinical supervision was valued. Therapists also shared that LIFT improved their skills and they were happy to see patients' fatigue improve over time. These new results can inform clinical practice, and how services are provided.

Objectives Fatigue can be a disabling symptom of inflammatory rheumatic diseases (IRD). LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) is a randomised trial of remotely delivered cognitive-behavioural approach (CBA) or personalised exercise programme (PEP) interventions, compared with usual care. The aim of this nested qualitative study was to evaluate participants’ experiences of taking part in the intervention, including their ideas about future service delivery. Methods Semi-structured telephone interviews with a subgroup of LIFT participants to discuss their views and experiences of the interventions. Results Forty-three participants (30 women) from six sites who had participated in CBA (n = 22) or PEP (n = 21) interventions took part. Five themes were identified in the thematic analysis: In ‘Not a miracle cure, but a way to better manage fatigue’, LIFT could not cure fatigue, however, most felt better able to manage after participating. Participants valued ‘Building a therapeutic relationship’ with the same therapist throughout the intervention. In ‘Structure, self-monitoring and being accountable’, participants liked the inclusion of goal setting techniques, and were motivated by reporting back to the therapist. After taking part in the interventions, participants felt ‘Better equipped to cope with fatigue’; more confident and empowered. Lastly, participants shared ideas for ‘A tailored programme delivered remotely’, including follow-up sessions; video calling; and group-based sessions for social support. ConclusionMany participants engaged with the LIFT interventions and reported benefits of taking part. This suggests an important future role for the remote delivery of fatigue self-management. Lay summary What does this research mean for patients? Fatigue can be a disabling symptom in inflammatory rheumatic diseases (IRDs). The LIFT Study (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) looked at different interventions; a cognitive-behavioural approach (CBA), Personalised Exercise Programme (PEP), or usual care. CBA sessions addressed unhelpful thoughts and feelings. The PEP sessions supported people with IRDs to gradually increase their exercise levels. People with IRDs were randomly selected to take part in seven sessions of CBA, seven sessions of PEP, or usual care. All sessions except the first PEP session were delivered remotely by phone. The aim of this study was to explore people’s experiences of taking part. Forty-three people with IRDs (30 women, 13 men) were interviewed from six UK locations. Twenty-two took part in the CBA sessions, and twenty-one took part in PEP. People with IRDs who took part in LIFT told us about a range of benefits. These included feeling less fatigue and more confidence. Those in PEP told us they felt stronger. People with IRDs shared that they liked being able to talk about their fatigue with a supportive therapist. These are encouraging results for remotely-delivered research to support people with fatigue.

Background Previous cohort studies have investigated the relationship between self-reported physical activity (PA) and dementia. Evidence from objective device-measured PA data is lacking. This study aimed to explore the association of device-measured PA with the risk of dementia incidence and common subtypes (Alzheimer’s disease [AD] and vascular dementia) using the UK Biobank study. Methods 84,854 participants (55.8% women), invited to participate in the device-measured PA between 2013 and 2015, were included in this prospective cohort study. Wrist accelerometers were used to measure light, moderate, vigorous, moderate-to-vigorous PA (MVPA) and total PA intensity and duration (MET/min/week). Incident dementia (fatal and non-fatal) was extracted from hospital episodes records for incidence and death register for mortality. Incidence follow-up was carried out until the end of March 2021in England and Scotland and the end of March 2018 in Wales. Mortality data were available until February 2021. Nonlinear associations were first investigated using penalised cubic splines fitted in the Cox proportional hazard models. In addition, using MVPA, five categories were created. Associations of these categories with the outcomes were investigated using Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. Results After a median follow-up of 6.3 years, 678 individuals were diagnosed with dementia. Evidence of nonlinearity was observed for all PA modes and all-cause dementia. For categories of MVPA, there was a significant trend towards a low risk of overall dementia when higher levels of MVPA were achieved (HRtrend 0.66 [95% CI 0.62 to 0.70]. The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed Conclusions Participants with higher PA levels had a lower risk of incident dementia than those less active, independently of sociodemographic, lifestyle factors and comorbidity. Considering that the majority of previous studies have reported this association using self-reported data, our findings highlight the strong inverse association between PA objectively measured and incident dementia.

Background: \ud Understanding the mental health consequences of child maltreatment at different life stages is important in accurately quantifying the burden of maltreatment. This study investigated the association between child maltreatment and incident mental disorders in middle and older age as well as the potential mediators and moderators.\ud \ud Methods: \ud This is a retrospective cohort study of 56,082 participants from UK Biobank. Child maltreatment was recalled using the Childhood Trauma Screener. Incident mental disorders, including depressive, anxiety and affective disorders, behavioural syndromes, post-traumatic stress disorder (PTSD), schizophrenia, substance abuse, and dementia, after baseline assessment were ascertained through linkage to primary care records.\ud \ud Findings: \ud There was a dose-response relationship between child maltreatment and mental disorder. Those who experienced three or more maltreatment types had the highest risk of all mental disorders (HR 1.85, 95% CI: 1.67-2.06) followed by those who experienced two (HR 1.48, 95% CI: 1.35-1.63) and then one (HR 1.26, 95% CI: 1.19-2.35). Child maltreatment was most strongly associated with PTSD (HR 1.59, 95% CI: 1.20-2.10 P=0.001). The excess risk was largely unexplained by the included mediators. The association between child maltreatment and all mental disorders were stronger among participants who binge drank (Pinteraction=0.003) or had few social visits (Pinteraction=0.003).\ud \ud Interpretation: \ud The mental health consequence of child maltreatment could last decades, even among those who had no recorded mental disorders in early adulthood. In the absence of strong mediators, prevention of child maltreatment remains the priority.\ud \ud Funding: \ud Wellcome Trust Institutional Strategic Support Fund.

Regular participation in resistance exercise is known to have broad-ranging health benefits and for this reason is prominent in the current physical activity guidelines. Recovery after such exercise is important for several populations across the age range and nutritional strategies to enhance recovery and modulate post-exercise physiological processes are widely studied, yet effective strategies remain elusive. Vitamin K2 supplementation has emerged as a potential candidate, and the aim of the current study, therefore, is to test the hypothesis that vitamin K2 supplementation can accelerate recovery, via modulation of the underlying physiological processes, following a bout of resistance exercise in young and older adults.The current study is a two-arm randomised controlled trial which will be conducted in 80 (40 young (≤40 years) and 40 older (≥65 years)) adults to compare post-exercise recovery in those supplemented with vitamin K2 or placebo for a 12-week period. The primary outcome is muscle strength with secondary outcomes including pain-free range of motion, functional abilities, surface electromyography (sEMG) and markers of inflammation and oxidative stress.Ethical approval has been granted by the College of Medical Veterinary and Life Sciences Ethical Committee at the University of Glasgow (Project No 200190189) and recruitment is ongoing. Study findings will be disseminated through a presentation at scientific conferences and in scientific journals.ClinicialTrials.gov NCT04676958. Prospectively registered on 21 December 2020.

Introduction The aim of this study was to determine risk of being SARS‐CoV‐2 positive and severe infection (associated with hospitalization/mortality) in those with family history of diabetes. Methods We used UK Biobank, an observational cohort recruited between 2006 and 2010. We compared the risk of being SARS‐CoV‐2 positive and severe infection for those with family history of diabetes (mother/father/sibling) against those without. Results Of 401,268 participants in total, 13,331 tested positive for SARS‐CoV‐2 and 2282 had severe infection by end of January 2021. In unadjusted models, participants with ≥2 family members with diabetes were more likely to be SARS‐CoV‐2 positive (risk ratio‐RR 1.35; 95% confidence interval‐CI 1.24–1.47) and severe infection (RR 1.30; 95% CI 1.04–1.59), compared to those without. The excess risk of being tested positive for SARS‐CoV‐2 was attenuated but significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions. The excess risk for severe infection was no longer significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions, and was absent when excluding incident diabetes. Conclusion The totality of the results suggests that good lifestyle and not developing incident diabetes may lessen risks of severe infections in people with a strong family of diabetes., Our aim was to determine risk of severe SARS‐CoV‐2 (infection associated with hospitalization/mortality) in those with family history of diabetes. Using UK Biobank data, the findings suggest that having ≥2 family members with diabetes is associated with higher risk of SARS‐CoV‐2 infection and severe infection, but that such risk may be attenuated by better lifestyle, and by avoiding development of diabetes.

Objectives This trial aimed to determine the feasibility of recruitment, retention, adherence, and safety of a resistance training (RT) intervention to skeletal muscle failure in both frail and non-frail older adults. Design An 8-week randomised feasibility trial. Setting and participants Older adults, with and without frailty, recruited from both clinics and community. Methods Recruitment was based on the number of participants enrolled from those provided with a Patient Information Sheet (PIS). Retention was based on the number of participants who completed the trial. Adherence was based on the number of RT sessions attended out of 16. Outcomes included frailty (Fried criteria), muscle strength (maximal voluntary contraction), functional abilities (Short Physical Performance battery), quality of life (EQ-5D-5L), activities of daily living (LIADL) and safety (diary). Results Recruitment target (n = 60) was achieved within 15 months, 58 were randomised to high (n = 30) or low repetition-load (n = 28) groups. Mean age of participants was 72 years (range 65–93). Adherence and retention rate for the RT intervention was ≥70%. There was one serious adverse experience due to the RT intervention. There were no differences (P > 0.05) in effects of RT on outcome variables between low and high repetition-load groups. Conclusions and implications Recruitment of frail people was challenging. Older adults performing supervised RT to skeletal muscle failure was feasible and safe, with appropriate caution, and the repetition-load did not appear to influence its efficacy. Future research into the effectiveness of this simplified model of RT is warranted., Highlights • Resistance exercise is the most effective way to increase muscle mass. • This is particularly important in older adults. • Recruitment of older adults, particularly with frailty, is challenging. • We found recruitment of older adults feasible, but less so for those with frailty. • The load for exercise did not appear to influence efficacy of exercise.

Background: \ud Sarcopenia often co-occurs with osteoporosis in cross-sectional studies. However, this association has rarely been studied in prospective studies. This study aimed to investigate the association between sarcopenia categories—along with its individual components—and incident osteoporosis in both middle-aged and older men and women from the UK Biobank study.\ud \ud Methods: \ud A total of 168,682 participants (48.8% women, aged 37 to 70 years at baseline) were included in this prospective study. Categories of sarcopenia (pre-sarcopenia and sarcopenia), and its individual components, were defined according to the EWGSOP2 criteria (2019). Associations with incident osteoporosis by sex were investigated using Cox-proportional hazard models adjusted for socio-demographic, lifestyle and health-related factors, and morbidity count. Associations between categories of sarcopenia and incident osteoporosis were also investigated by age-groups and subtype of osteoporosis (with and without pathological fractures).\ud \ud Results: \ud After a median follow-up of 7.4 years, 6296 participants were diagnosed with osteoporosis. When the analyses were adjusted for a range of relevant confounding factors, pre-sarcopenia was associated with 1.3-times higher risk of osteoporosis in men (HR: 1.30 [95% CI: 1.03 to 1.63]) but not in women, and sarcopenia was associated with 1.66-times increased osteoporosis risk in women (HR: 1.66 [95% CI: 1.33 to 2.08]) but not in men compared with people without sarcopenia or pre-sarcopenia. A similar magnitude of associations was found in osteoporosis without pathological fractures but weaker for those with pathological fractures. Within the individual components, low muscle mass (HRwomen: 1.36 [95% CI: 1.22 to 1.51] and HRmen: 3.07 [95% CI: 1.68 to 5.59]), followed by slow gait speed (HRwomen: 1.30 [95% CI: 1.17 to 1.45] and HRmen: 1.70 [95% CI: 1.43 to 2.02]), were associated with a higher risk of incident osteoporosis in both sexes. Low grip strength was associated with a higher risk of incident osteoporosis in men (HR: 1.38 [95% CI: 1.15 to 1.65]), but not in women. No significant interaction between the exposures and incident osteoporosis by age groups were identified.\ud \ud Conclusions: \ud Our findings demonstrated that pre-sarcopenic men and sarcopenic women had a higher risk of developing osteoporosis even after adjustment for a large range of potential confounders. Considering that sarcopenia could be prevented, health interventions to improve physical capability may delay or prevent the onset of osteoporosis.

Objective To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data. Patients and Methods Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders. Results During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1–metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72). Conclusion Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.

Background higher grip strength is associated with better health outcomes. The optimal way to report grip strength (i.e. absolute vs. relative) for prediction, however, remains to be established. Methods in participants (aged 37–73 at baseline) from the UK Biobank, we examined the associations of grip strength, expressed in absolute terms (kilograms) and relative to anthropometric variables, with mortality and disease incidence, after exclusion of the first 2 years of follow-up, and compared risk predictions scores of handgrip strength when differentially expressed. Results of the 356 721 participants included in the analysis 6,234 died (1.7%) and 4,523 developed CVD (1.3%) over a mean follow-up of 5.0 years (ranging from 3.3 to 7.8) for mortality and 4.1 years (ranging from 2.4 to 7.0) for disease incidence data. As expected, baseline higher grip strength was associated with lower risk of all-cause and cause specific mortality and incidence. These associations did not meaningfully differ when grip-strength was expressed in absolute terms, vs. relative to height, weight, fat-free mass, BMI, fat-free mass index and fat-free mass, or as z-scores. Similarly the different ways of expressing grip strength had little effect on the ability of grip strength to improve risk prediction, based on C-index change, of an office-based risk score. Conclusions the ability of grip strength to predict mortality is not altered by changing how it is expressed.

Background Driving is a common type of sedentary behaviour; an independent risk factor for poor health. The study explores whether driving is also associated with other unhealthy lifestyle factors. Methods In a cross-sectional study of UK Biobank participants, driving time was treated as an ordinal variable and other lifestyle factors dichotomized into low/high risk based on guidelines. The associations were explored using chi-square tests for trend and binary logistic regression. Results Of the 386 493 participants who drove, 153 717 (39.8%) drove Conclusions Sedentary behaviour, such as driving, is known to have an independent association with adverse health outcomes. It may have additional impact mediated through its effect on other aspects of lifestyle. People with long driving times are at higher risk and might benefit from targeted interventions.

Background: Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction. Methods: Participants from UK Biobank without baseline CVD and not taking statins, with relevant lipid measurements (n=346 686), were included in the primary analysis. An incident fatal or nonfatal CVD event occurred in 6216 participants (1656 fatal) over a median of 8.9 years. Associations of nonfasting lipid measurements (total cholesterol, HDL-C, non–HDL-C, direct and calculated low-density lipoprotein cholesterol [LDL-C], and apolipoproteins [Apo] A1 and B) with CVD were compared using Cox models adjusting for classical risk factors, and predictive utility was determined by the C-index and net reclassification index. Prediction was also tested in 68 649 participants taking a statin with or without baseline CVD (3515 CVD events). Results: ApoB, LDL-C, and non–HDL-C were highly correlated ( r >0.90), while HDL-C was strongly correlated with ApoA1 ( r =0.92). After adjustment for classical risk factors, 1 SD increase in ApoB, direct LDL-C, and non–HDL-C had similar associations with composite fatal/nonfatal CVD events (hazard ratio, 1.23, 1.20, 1.21, respectively). Associations for 1 SD increase in HDL-C and ApoA1 were also similar (hazard ratios, 0.81 [both]). Adding either total cholesterol and HDL-C, or ApoB and ApoA, to a CVD risk prediction model (C-index, 0.7378) yielded similar improvement in discrimination (C-index change, 0.0084; 95% CI, 0.0065, 0.0104, and 0.0089; 95% CI, 0.0069, 0.0109, respectively). Once total and HDL-C were in the model, no further substantive improvement was achieved with the addition of ApoB (C-index change, 0.0004; 95% CI, 0.0000, 0.0008) or any measure of LDL-C. Results for predictive utility were similar for a fatal CVD outcome, and in a discordance analysis. In participants taking a statin, classical risk factors (C-index, 0.7118) were improved by non–HDL-C (C-index change, 0.0030; 95% CI, 0.0012, 0.0048) or ApoB (C-index change, 0.0030; 95% CI, 0.0011, 0.0048). However, adding ApoB or LDL-C to a model already containing non–HDL-C did not further improve discrimination. Conclusions: Measurement of total cholesterol and HDL-C in the nonfasted state is sufficient to capture the lipid-associated risk in CVD prediction, with no meaningful improvement from addition of apolipoproteins, direct or calculated LDL-C.

Hypertension is a risk factor for cardiovascular disease. Increased urinary sodium excretion, representing dietary sodium intake, is associated with hypertension. Low sodium intake has been associated with increased mortality in observational studies. Further studies should assess whether confounding relationships explain associations between sodium intake and outcomes. We studied UK Biobank participants (n=457 484; mean age, 56.3 years; 44.7% men) with urinary electrolytes and blood pressure data. Estimated daily urinary sodium excretion was calculated using Kawasaki formulae. We analyzed associations between sodium excretion and blood pressure in subjects without cardiovascular disease, treated hypertension, or diabetes mellitus at baseline (n=322 624). We tested relationships between sodium excretion, incidence of fatal and nonfatal cardiovascular disease, heart failure, and mortality. Subjects in higher quintiles of sodium excretion were younger, with more men and higher body mass index. There was a linear relationship between increasing urinary sodium excretion and blood pressure. During median follow-up of 6.99 years, there were 11 932 deaths (1125 cardiovascular deaths) with 10 717 nonfatal cardiovascular events. There was no relationship between quintile of sodium excretion and outcomes. These relationships were unchanged after adjustment for comorbidity or excluding subjects with events during the first 2 years follow-up. No differing risk of incident heart failure (1174 events) existed across sodium excretion quintiles. Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. No pattern of increased cardiovascular disease, heart failure, or mortality risk was demonstrated with either high or low sodium intake.

Background Intake of macronutrients and its components are associated with mortality and morbidity. Isocaloric substitution analysis is a tool to examine how changing the source of energy intake (e.g. from saturated to monounsaturated fat) is associated with health. However, conventional methods assume linearity, which may be untrue in many cases. This paper presents a nonlinear alternative, using UK Biobank data as an example data set. Methods Nonlinear isocaloric substitution analysis was conducted using penalised cubic splines in Cox proportional hazard models. In the UK Biobank, 195,658 participants completed at least one dietary questionnaire and were included in the analyses. Diet was assessed using the Oxford WebQ, a web-based 24-hour recall questionnaire. Prospective all-cause mortality was derived from on linked death records. Results More than half of the associations between macronutrient intake and all-cause mortality were nonlinear. Nonlinear isocaloric substitution analysis provides effect sizes conditional on the current intake, while conventional analysis provides an average over the whole range of intake. For example, conventional isocaloric substitution estimated no effect of replacing sugar with starch. However, the nonlinear method revealed that replacing sugar with starch was associated with a higher risk when the current starch intake was greater than 30% of total energy, and with a lower risk when current intake was less than 25%. Conclusions Nonlinear isocaloric substitution provides an alternative to conventional isocaloric substitution analysis when the underlying association is nonlinear. Key messages Nonlinear associations are common in nutritional epidemiology. In such cases, nonlinear isocaloric substitution analyses should be used.

PurposeThe aims of the current study, therefore, were to compare 1) free-living MPS and 2) muscle and metabolic adaptations to resistance exercise in South Asian and white European adults.MethodsEighteen South Asian and 16 White European men were enrolled in the study. Free-living muscle protein synthesis was measured at baseline. Muscle strength, body composition, resting metabolic rate, VO2max and metabolic responses (insulin sensitivity) to a mixed meal were measured at baseline and following 12 weeks of resistance exercise training. Results Free-living muscle protein synthesis was not different between South Asians (1.48 ± 0.09 %/day) and White Europeans (1.59 ± 0.15 %/day) (p=0.522). In response to resistance exercise training there were no differences, between South Asians and White Europeans, muscle mass, lower body strength or insulin sensitivity. However, there were differences between the ethnicities in response to resistance exercise training in body fat, resting carbohydrate and fat metabolism, blood pressure, VO2max and upper body strength with responses less favourable in South Asians. ConclusionIn this exploratory study there were no differences in muscle protein synthesis or anabolic and metabolic responses to resistance exercise, yet there were less favourable responses in several outcomes. These findings require further investigation.