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Aims/hypothesis The aim of this study was to describe the long-term trends in cancer mortality rates in people with type 2 diabetes based on subgroups defined by sociodemographic characteristics and risk factors. Methods We defined a cohort of individuals aged ≥35 years who had newly diagnosed type 2 diabetes in the Clinical Practice Research Datalink between 1 January 1998 and 30 November 2018. We assessed trends in all-cause, all-cancer and cancer-specific mortality rates by age, gender, ethnicity, socioeconomic status, obesity and smoking status. We used Poisson regression to calculate age- and calendar year-specific mortality rates and Joinpoint regression to assess trends for each outcome. We estimated standardised mortality ratios comparing mortality rates in people with type 2 diabetes with those in the general population. Results Among 137,804 individuals, during a median follow-up of 8.4 years, all-cause mortality rates decreased at all ages between 1998 and 2018; cancer mortality rates also decreased for 55- and 65-year-olds but increased for 75- and 85-year-olds, with average annual percentage changes (AAPCs) of –1.4% (95% CI –1.5, –1.3), –0.2% (–0.3, –0.1), 1.2% (0.8, 1.6) and 1.6% (1.5, 1.7), respectively. Higher AAPCs were observed in women than men (1.5% vs 0.5%), in the least deprived than the most deprived (1.5% vs 1.0%) and in people with morbid obesity than those with normal body weight (5.8% vs 0.7%), although all these stratified subgroups showed upward trends in cancer mortality rates. Increasing cancer mortality rates were also observed in people of White ethnicity and former/current smokers, but downward trends were observed in other ethnic groups and non-smokers. These results have led to persistent inequalities by gender and deprivation but widening disparities by smoking status. Constant upward trends in mortality rates were also observed for pancreatic, liver and lung cancer at all ages, colorectal cancer at most ages, breast cancer at younger ages, and prostate and endometrial cancer at older ages. Compared with the general population, people with type 2 diabetes had a more than 1.5-fold increased risk of colorectal, pancreatic, liver and endometrial cancer mortality during the whole study period. Conclusions/interpretation In contrast to the declines in all-cause mortality rates at all ages, the cancer burden has increased in older people with type 2 diabetes, especially for colorectal, pancreatic, liver and endometrial cancer. Tailored cancer prevention and early detection strategies are needed to address persistent inequalities in the older population, the most deprived and smokers. Graphical abstract

To describe sociodemographic, lifestyle, environmental and traditional clinical risk factor differences between ethnic groups and to investigate the extent to which such differences confound the association between ethnic groups and the risk of cardiovascular disease (CVD) METHODS AND RESULTS: A total of 440,693 white European (55.9% women), 7305 South Asian (48.6%) and 7628 black African or Caribbean (57.7%) people were included from UK Biobank. Associations between ethnicity and cardiovascular outcomes (composite of non-fatal stroke, non-fatal myocardial infarction and CVD death) were explored using Cox-proportional hazard models. Models were adjusted for sociodemographic, lifestyle, environmental and clinical risk factors. Over a median (IQR) of 12.6 (11.8, 13.3) follow-up years, there were 22,711 (5.15%) cardiovascular events in white European, 463 (6.34%) in South Asian and 302 (3.96%) in black African or Caribbean individuals. For South Asian people, the cardiovascular hazard ratio (HR) compared to white European people was 1.28 (99% CI [1.16, 1.43]). For black African or Caribbean people, the HR was 0.80 (0.66, 0.97). The elevated risk of CVD in South Asians remained after adjusting for differences in sociodemographic, lifestyle, environmental and clinical factors, whereas the lower risk in black African or Caribbean was largely attenuated.South Asian, but not black African or Caribbean individuals, have a higher risk of CVD compared to white European individuals. This higher risk in South Asians was independent of sociodemographic, lifestyle, environmental and clinical factors.

Aims The interplay between physical activity (PA) volume and intensity is poorly understood in relation to cardiovascular disease (CVD) risk. This study aimed to investigate the role of PA intensity, over and above volume, in relation to incident CVD. Methods and results Data were from 88 412 UK Biobank middle-aged adults (58% women) without prevalent CVD who wore accelerometers on their dominant wrist for 7 days, from which we estimated total PA energy expenditure (PAEE) using population-specific validation. Cox proportional hazards regressions modelled associations between PAEE (kJ/kg/day) and PA intensity (%MVPA; the fraction of PAEE accumulated from moderate-to-vigorous-intensity PA) with incident CVD (ischaemic heart disease or cerebrovascular disease), adjusted for potential confounders. There were 4068 CVD events during 584 568 person-years of follow-up (median 6.8 years). Higher PAEE and higher %MVPA (adjusted for PAEE) were associated with lower rates of incident CVD. In interaction analyses, CVD rates were 14% (95% confidence interval: 5–23%) lower when MVPA accounted for 20% rather than 10% of 15 kJ/kg/d PAEE; equivalent to converting a 14 min stroll into a brisk 7 min walk. CVD rates did not differ significantly between values of PAEE when the %MVPA was fixed at 10%. However, the lowest CVD rates were observed for combinations of both higher PAEE and %MVPA. Conclusion Reductions in CVD risk may be achievable through higher PA volume and intensity, with the role of moderately intense PA appearing particularly important. This supports multiple approaches or strategies to PA participation, some of which may be more practical or appealing to different individuals.

Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once-weekly subcutaneous semaglutide 2.4 mg (a glucagon-like peptide-1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%-17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%-79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%-27% with placebo) and 51%-64% achieved ≥15% weight loss (vs. 5%-13% with placebo). In STEP 5, mean weight loss was −15.2% with semaglutide 2.4 mg versus −2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was −9.6% with semaglutide 2.4 mg versus −3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity-related diseases.

This review aims to summarize key methods for estimating years of life lost (YLL), highlighting their differences and how they can be implemented in current software, and applies them in a real-world example.We investigated the common YLL methods: (1) Years of potential life lost (YPLL); (2) Global Burden of Disease (GBD) approach; (3) Life tables; (4) Poisson regression; and (5) Flexible parametric Royston-Parmar regression. We used data from UK Biobank and multimorbidity as our example.For the YPLL and GBD method, the analytical procedures allow only to quantify the average YLL within each group (with and without multimorbidity) and, from them, their difference; conversely, for the other methods both the remaining life expectancy within each group and the YLL could be estimated. At 65 years, the YLL in those with vs. without multimorbidity was 1.8, 1.2, and 2.7 years using the life tables approach and the Poisson, and Royston-Parmar regression, respectively; corresponding values were -0.73 and -0.05 years for YPLL and using the GBD approach.While deciding among different methods to estimate YLL, researchers should consider the purpose of the research, the type of available data, and the flexibility of the model.

High physical activity levels during wake are beneficial for health, while high movement levels during sleep are detrimental to health. Our aim was to compare the associations of accelerometer-assessed physical activity and sleep disruption with adiposity and fitness using standardized and individualized wake and sleep windows. People (N = 609) with type 2 diabetes wore an accelerometer for up to 8 days. Waist circumference, body fat percentage, Short Physical Performance Battery (SPPB) test score, sit-to-stands, and resting heart rate were assessed. Physical activity was assessed via the average acceleration and intensity distribution (intensity gradient) over standardized (most active 16 continuous hours (M16h)) and individualized wake windows. Sleep disruption was assessed via the average acceleration over standardized (least active 8 continuous hours (L8h)) and individualized sleep windows. Average acceleration and intensity distribution during the wake window were beneficially associated with adiposity and fitness, while average acceleration during the sleep window was detrimentally associated with adiposity and fitness. Point estimates for the associations were slightly stronger for the standardized than for individualized wake/sleep windows. In conclusion, standardized wake and sleep windows may have stronger associations with health due to capturing variations in sleep durations across individuals, while individualized windows represent a purer measure of wake/sleep behaviors.

OBJECTIVE Sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS Liraglutide (mean −1,144 steps/day; 95% CI −2,069 to −220), empagliflozin (−1,132 steps/day; −1,739, −524), and sitagliptin (−852 steps/day; −1,625, −78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.

Structured self-management education has been shown to be effective in type 2 diabetes (T2DM) but more research is needed to look at culturally appropriate programmes in ethnic minority groups, where prevalence of T2DM is higher and diagnosis earlier. The study tested the effectiveness of a group education programme for people with established T2DM in a multi-ethnic primary care population.Cluster randomised trial conducted in two multi-ethnic UK sites. Practices were randomised (1:1) to a structured T2DM group education programme or to continue with routine care. A culturally-adapted version was offered to South Asians, who formed the majority of ethnic minority participants. Other ethnic minority groups were invited to attend the standard programme. Primary outcome was change in HbA1c at 12 months. All analyses accounted for clustering and baseline value.367 participants (64(SD 10.8) years, 36% women, 34% from minority ethnic groups) were recruited from 31 clusters. At 12 months, there was no difference in mean change in HbA1c between the two groups (-0.10%; (95% CI: -0.37, 0.17). Subgroup analyses suggested the intervention was effective at lowering HbA1c in White European compared with ethnic minority groups. The intervention group lost more body weight than the control group (-0.82 kg at 6 months and -1.06 kg at 12 months; both p = 0.03).Overall, the programme did not result in HbA1c improvement but in subgroup analysis, a beneficial effect occurred in White Europeans. Findings emphasise a need to develop and evaluate culturally-relevant programmes for ethnic minority groups.

PHOSP-COVID is a national UK multi-centre cohort study of patients who were hospitalised for COVID-19 and subsequently discharged.PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalisation, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term effects of COVID-19 treatments, and to serve as a platform to enable future studies, including clinical trials.Data collected covered a wide range of physical measures, biological samples, and Patient Reported Outcome Measures (PROMs).Participants could join the cohort either in Tier 1 only with remote data collection using hospital records, a PROMs app and postal saliva sample for DNA, or in Tier 2 where they were invited to attend two specific research visits for further data collection and biological research sampling. These research visits occurred at five (range 2-7) months and 12 (range 10-14) months post-discharge. Participants could also participate in specific nested studies (Tier 3) at selected sites.All participants were asked to consent to further follow-up for 25 years via linkage to their electronic healthcare records and to be re-contacted for further research.In total, 7935 participants were recruited from 83 UK sites: 5238 to Tier 1 and 2697 to Tier 2, between August 2020 and March 2022.Cohort data are held in a Trusted Research Environment and samples stored in a central biobank. Data and samples can be accessed upon request and subject to approvals.

Background and Aims We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity. Methods and Results We used the Clinical Practice Research Datalink database in England (UK), linked to the Hospital Episode Statistics information, to identify individuals with and without T2D who survived a first CVD event between 1st Jan 2007 and 31st Dec 2017; subsequent death events were extracted from the Office for National Statistics database. Ethnicity was categorised as White, South Asian (SA), Black, or other. Flexible parametric survival models were used to estimate survival and predict life expectancy. 59,939 individuals with first CVD event were included: 7,596 (12.7%) with T2D (60.9% men; mean age at event: 69.7 years [63.2 years in SA, 65.9 in Black, 70.2 in White]) and 52,343 without T2D (56.7% men; 65.9 years [54.7 in Black, 58.2 in SA, 66.3 in White]). Accounting for potential confounders (sex, deprivation, lipid-lowering medication, current smoking, and pre-existing hypertension), comparing individuals with vs without T2D the mortality rate was 53% higher in White (hazard ratio [HR]: 1.53 [95% CI: 1.44, 1.62]), corresponding to a potential loss of 3.87 (3.30, 4.44) life years at the age of 50 years in individuals with T2D. No evidence of a difference in life expectancy was observed in individuals of SA (HR: 0.82 [0.52, 1.29]; -1.36 [-4.58, 1.86] life years), Black (HR: 1.26 [0.59, 2.70]; 1.21 [-2.99, 5.41] life years); and other (HR: 1.64 [0.80, 3.39]; 3.89 [-2.28, 9.99] life years) ethnic group. Conclusion Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups.

Most trials leading to the approval of glucagon-like peptide receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) were primarily designed to confirm their non-inferiority to placebo (commonly using an upper 95% confidence limit threshold of 1.3) and, if confirmed, superiority (threshold 1): this asymmetry of margins (1 vs. 1.3) favours the active intervention. We aimed to quantify the probability of clinical superiority of the active treatment by applying the same threshold used to claim non-inferiority.We searched PubMed and Cochrane CENTRAL for cardiorenal outcome trials in subjects with type 2 diabetes published before 5 December 2021, to reconstruct from Kaplan-Meier plots individual-level data for the primary outcome or all-cause mortality. We calculated Bayesian posterior densities to obtain the probability for a treatment effect (hazard ratio)0.769, which is symmetric to the 1.3 threshold (i.e. its reciprocal 1/1.3), emulating a scenario where the active treatment is placebo and placebo is the active treatment.We extracted data from 27 Kaplan-Meier plots (18 for the primary outcome, nine for mortality). Probabilities of clinical superiority to placebo varied significantly: for GLP-1RAs, from a minimum of 0% to a maximum of 69% for the primary outcome and from 0% to 8% for mortality; corresponding estimates for SGLT2is were 0% to 96% and 0% to 93%. Probabilities were on average greater for SGLT2is, particularly in trials investigating kidney or heart failure outcomes.The probability of clinical superiority to placebo varies widely across trials previously reported as showing superiority of GLP-1RAs or SGLT2is compared with placebo. These results showed within- and between-class differences, highlight the drawbacks of a binary interpretation of the results, particularly in the context of the current designs of non-inferiority trials, and have implications for decision makers and future clinical recommendations.

Background It is uncertain if initial combination therapy with glucose-lowering agents provides longer-term beneficial cardio-renal outcomes compared to stepwise therapy in patients with newly diagnosed type 2 diabetes (T2D). Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated the efficacy and safety of the initial combination therapy vs a stepwise approach in newly diagnosed T2D.Methods Studies were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to January 2022. Study-specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of the evidence was assessed using GRADE.Results Eight articles comprising 4 unique RCTs (n=5,527 participants) and one observational cohort study (n=200) that compared initial combination therapy vs stepwise therapy were included. The RR (95% CI) for myocardial infarction comparing initial combination therapy vs stepwise therapy was 1.21 (0.74-2.00). Initial combination therapy reduced levels of fasting plasma glucose and HbA1c: mean differences (95% CIs) of -0.97 mmol/l (-1.41, -0.53) and -0.13 % (-0.20, -0.07), respectively. Initial combination therapy vs stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition parameters, neuropathy, retinopathy, and adverse events. Single study results showed initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low.Conclusions Except for improving cardiometabolic and glycaemic parameters, a limited number of studies characterised by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio-renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose-lowering agents in newly diagnosed T2D. Definitive RCTs are warranted.

Aims Diabetes can significantly impact quality of life and mental health. However, inconsistencies have been reported in the prevalence of depression in those with Type 1 and Type 2 diabetes, and those without. Systematic reviews also included studies without adequate control subjects. We update existing literature, by comparing depression prevalence between individuals with and without Type 1 and Type 2 diabetes. Methods A systematic review and meta-analysis. We searched MEDLINE, EMBASE and PSYCHINFO, from January 1985 to August 2021. Studies were excluded if they failed to have an adequate control group, specified type of diabetes, or reported depression prevalence by type of diabetes. Results 44 studies were selected for inclusion. The prevalence of depression was significantly higher in people with Type 1 (22% vs 13%, OR = 2.10 (95% CI: 1.23, 3.52)), or Type 2 diabetes (19% vs 11%, OR = 1.76 (1.55, 2.01)) compared to those without diabetes. There was no association between study effect size and mean age or gender. Findings did not significantly differ between methods of depression assessment. Prevalence of depression in people with diabetes was higher in studies carried out in specialist care (36%, OR = 3.14 (2.12, 4.63)) compared to those in community or primary care (12%, OR = 1.51 (1.35, 1.70) and in low- and middle-income countries (OR = 2.58 (1.91, 3.50) compared to countries with high income economies (OR = 1.59 (1.39, 1.82)). Conclusions Depression prevalence remains significant in those with type 1 and type 2 diabetes. Effective chronic disease management in people with diabetes is important, particularly screening and managing depression and diabetes distress in specialist care settings.

The focus in diabetes care has traditionally been around the optimisation of the glycaemic control and prevention of complications. However, the prevention of frailty and improvement in physical function have now emerged as new targets of diabetes management. This is mainly driven by the significant adverse impact that early onset frailty and decline in physical function have on health outcomes, functional independence, and quality of life in people with type 2 diabetes (T2D). There is an increasing emphasis in the expert consensus and management algorithms to improve physical function in people with T2D, predominantly through lifestyle interventions, including exercise and the control of modifiable risk factors. Trials of novel glucose-lowering therapies (GLTs) also now regularly assess the impact of these novel agents on measures of physical function within their secondary outcomes to understand the impact that these agents have on physical function. However, challenges remain as there is no consensus on the best method of assessing physical function in clinical practice, and the recognition of impaired physical function remains low. In this review, we present the burden of a reduced physical function in people with T2D, outline methods of assessment used in healthcare and research settings, and discuss strategies for improvement in physical function in people with T2D.

Fasting during the holy month of Ramadan is one of the five pillars of Islam. Fasting is not meant to create excessive hardship on the Muslim individual according to religious tenets. It is important that health professionals are aware of potential risks associated with fasting during the month of Ramadan (mainly hypoglycemia and hyperglycemia) AIM: to explore the impact of applying the principles of our 2020 recommendation for the management of type 2 diabetes (T2D) during the month of Ramadan.A multinational randomized controlled trial (RCT) was conducted in five Muslim majority countries. 660 participants were deemed eligible for the study, however, 23% declined to participate later for various reasons. In total, 506 participants were enrolled and were equally randomized to the intervention or the control group. By the end of the study, data from 231 participants in the intervention group and 221 participants from the control group were collected after 12.6% and 8.7% were respectively lost to follow up Participants randomized to receive a Ramadan focused education with treatment for diabetes adjusted as per our 2020 recommendation update compared with the local usual care (control group). Results are presented using mean, standard deviation, odds ratio and percentages.By the end of the study the number of hypoglycemic episodes in the intervention group were less than in participants who received usual care. The intervention group had significantly lower severe hypoglycemia compared to the control group with Odds ratios (OR) of 0.2 [0.1-0.8]. Compared to baseline both groups had a significant reduction in glycated hemoglobin (HbA1c) but the improvements were significantly greater in the intervention group. Whilst body weight reduced and HDL cholesterol increased with the intervention these changes were not significantly different to usual care.A pre-Ramadan assessment of people with T2D coupling with a pre-Ramadan education and an adjustment of glucose-lowering treatment as per our updated 2020 recommendations can prevent acute complications and allow a safer fast for people withT2D. We have shown that such an approach reduces the risk of developing severe hypoglycemia and improves the metabolic outcomes in people with T2D. This article is protected by copyright. All rights reserved.

Exercise is recommended for those with, or at risk of non-alcoholic fatty liver disease (NAFLD), owing to beneficial effects on hepatic steatosis and cardiometabolic risk. Whilst exercise training reduces total intra-hepatic lipid in people with NAFLD, accumulating evidence indicates that exercise may also modulate hepatic lipid composition. This metabolic influence is important as the profile of saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) dramatically affect the metabolic consequences of hepatic lipid accumulation; with SFA being especially lipotoxic. Relatedly, obesity and NAFLD are associated with hepatic PUFA depletion and elevated SFA. This review summarises the acute (single bout) and chronic (exercise training) effects of exercise on hepatic lipid composition in rodents (acute studies: n=3, chronic studies: n=13) and humans (acute studies: n=1, chronic studies: n=3). An increased proportion of hepatic PUFA after acute and chronic exercise is the most consistent finding of this review. Mechanistically, this may relate to an enhanced uptake of adipose-derived PUFA (reflecting habitual diet), particularly in rodents. A relative decrease in the proportion of hepatic MUFA after chronic exercise is also documented repeatedly, particularly in rodent models with elevated hepatic MUFA. This outcome is related to decreased hepatic stearoyl-CoA desaturase-1 activity in some studies. Findings regarding hepatic SFA are less consistent and limited by the absence of metabolic challenge in rodent models. These findings require confirmation in well-controlled interventions in people with NAFLD. These studies will be facilitated by recently validated magnetic resonance spectroscopy techniques, able to precisely quantify hepatic lipid composition in vivo.

AIMS To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol). MATERIALS AND METHODS The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening. RESULTS The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2-hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c -1.9% vs. -1.6% or -1.0% [-20 vs. -17 or -10 mmol/mol; 2-hour PPG -7.2 vs. -4.6 or -5.5 mmol/L). Greater proportions of participants achieved HbA1c

Background: Identifying clusters of physical activity (PA) from accelerometer data is important to identify levels of sedentary behaviour and physical activity associated with risks of serious health conditions and time spent engaging in healthy PA. Unsupervised machine learning models can capture PA in everyday free-living activity without the need for labelled data. However, there is scant research addressing the selection of features from accelerometer data. The aim of this systematic review is to summarise feature selection techniques applied in studies concerned with unsupervised machine learning of accelerometer-based device obtained physical activity, and to identify commonly used features identified through these techniques. Feature selection methods can reduce the complexity and computational burden of these models by removing less important features and assist in understanding the relative importance of feature sets and individual features in clustering. Method: We conducted a systematic search of Pubmed, Medline, Google Scholar, Scopus, Arxiv and Web of Science databases to identify studies published before January 2021 which used feature selection methods to derive PA clusters using unsupervised machine learning models. Results: A total of 13 studies were eligible for inclusion within the review. The most popular feature selection techniques were Principal Component Analysis (PCA) and correlation-based methods, with k-means frequently used in clustering accelerometer data. Cluster quality evaluation methods were diverse, including both external(e.g. cluster purity) or internal evaluation measures (silhouette score most frequently). Only four of the 13studies had more than 25 participants and only four studies included two or more datasets. Conclusion: There is a need to assess multiple feature selection methods upon large cohort data consisting of multiple (3 or more) PA datasets. The cut-off criteria e.g. number of components, pairwise correlation value, explained variance ratio for PCA, etc. should be expressly stated along with any hyperparameters used in clustering. Refereed/Peer-reviewed

This study aimed to a) determine whether wrist acceleration varies by accelerometer brand, wear location, and age for self-paced “slow”, “normal” and “brisk” walking; b) develop normative acceleration values for self-paced walking and running for adults. One-hundred-and-three adults (40–79 years) completed self-paced “slow”, “normal” and “brisk” walks, while wearing three accelerometers (GENEActiv, Axivity, ActiGraph) on each wrist. A sub-sample (n = 22) completed a self-paced run. Generalized estimating equations established differences by accelerometer brand, wrist, and age-group (walking only, 40–49, 50–59, 60–69, 70–79 years) for self-paced walking and running. Brand*wrist interactions showed ActiGraph dominant wrist values were ~10% lower than GENEActiv/Axivity values for walking and running, and non-dominant ActiGraph values were ~5% lower for running only (p < 0.001). Acceleration during brisk walking was lower in those aged 70–79 (p < 0.05). Normative acceleration values (non-dominant wrist, all brands; dominant wrist GENEActiv/Axivity) for slow and normal walking were 140 mg and 210 mg. Brisk walking, values were 350 mg in those aged 40–69 years, but 270 mg in those aged 70–79 years. Accelerations >600 mg approximated running. These values facilitate user-friendly interpretation of accelerometer-determined physical activity in large cohort and epidemiological datasets. Refereed/Peer-reviewed

Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of cardiovascular disease. Prevention and management strategies should focus on lifestyle modification, education and awareness, systematic screening for early complications, and intensive management of modifiable risk factors. This review discusses the microvascular complications of diabetes, including diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy, and provides best practice clinical care recommendations to guide health care professionals to better manage people with these conditions.

IntroductionMany people living with chronic kidney disease (CKD) are expected to self-manage their condition. Patient activation is the term given to describe the knowledge, skills and confidence a person has in managing their own health and is closely related to the engagement in preventive health behaviours. Self-management interventions have the potential to improve remote disease management and health outcomes. We are testing an evidence-based and theory-based digital self-management structured 10-week programme developed for peoples with CKD called ‘My Kidneys & Me’. The primary aim of the study (Self-Management Intervention through Lifestyle Education for Kidney health (SMILE-K)) is to assess the effect on patient activation levels.Methods and analysisA single-blind randomised controlled trial (RCT) with a nested pilot study will assess the feasibility of the intervention and study design before continuation to a full RCT. Individuals aged 18 years or older, with established CKD stage 3–4 (eGFR of 15–59 mL/min/1.73 m2) will be recruited through both primary and secondary care pathways. Participants will be randomised into two groups: intervention group (receive My Kidneys & Me in addition to usual care) and control group (usual care). The primary outcome of the nested pilot study is feasibility and the primary outcome of the full RCT is the Patient Activation Measu (PAM-13). The full RCT will assess the effect of the programme on online self-reported outcomes which will be assessed at baseline, after 10 weeks, and then after 20 weeks in both groups. A total sample size of N=432 participants are required based on a 2:1 randomisation. A substudy will measure physiological changes (eg, muscle mass, physical function) and patient experience (qualitative semi-structured interviews).Ethics and disseminationThis study was fully approved by the Research Ethics Committee-Leicester South on the 19 November 2020 (reference: 17/EM/0357). All participants are required to provide informed consent obtained online. The results are expected to be published in scientific journals and presented at clinical research conferences. This is protocol version 1.0 dated 27 January 2021.Trial registration numberISRCTN18314195.

To evaluate the criterion validity of an automated sleep detection algorithm applied to data from three research-grade accelerometers worn on each wrist with concurrent laboratory-based polysomnography (PSG). A total of 30 healthy volunteers (mean [SD] age 31.5 [7.2] years, body mass index 25.5 [3.7] kg/m

Sedentary behaviours continue to increase and are associated with heightened risks of morbidity and mortality. We assessed the cost-effectiveness of SMART Work & Life (SWAL), an intervention designed to reduce sitting time inside and outside of work, both with (SWAL-desk) and without (SWAL-only) a height-adjustable workstation compared to usual practice (control) for UK office workers. Health outcomes were assessed in quality-adjusted life-years (QALY) and costs in pound sterling (2019–2020). Discounted costs and QALYs were estimated using regression methods with multiply imputed data from the SMART Work & Life trial. Absenteeism, productivity and wellbeing measures were also evaluated. The average cost of SWAL-desk was £228.31 and SWAL-only £80.59 per office worker. Within the trial, SWAL-only was more effective and costly compared to control (incremental cost-effectiveness ratio (ICER): £12,091 per QALY) while SWAL-desk was dominated (least effective and most costly). However, over a lifetime horizon, both SWAL-only and SWAL-desk were more effective and more costly than control. Comparing SWAL-only to control generated an ICER of £4985 per QALY. SWAL-desk was more effective and costly than SWAL-only, generating an ICER of £13,378 per QALY. Findings were sensitive to various worker, intervention, and extrapolation-related factors. Based on a lifetime horizon, SWAL interventions appear cost-effective for office-workers conditional on worker characteristics, intervention cost and longer-term maintenance in sitting time reductions.

Foot ulcers and amputations are common conditions in people with diabetes and can considerably impact quality of life, necessitate a lengthy hospital stay and increase mortality. Preventative foot care and examination can prevent or delay ulceration, and individuals may seek information from publicly available social media resources such as YouTube. Therefore, the purpose of this study is to evaluate the educational quality and reliability of publicly available YouTube videos on diabetes foot examinations.A YouTube search for "diabetic foot examination" was conducted, and the first 100 relevant English videos focused on examining the diabetic foot were included for evaluation. The Journal of the American Medical Association (JAMA) standards were used to measure video reliability. The Global Quality Score (GQS) and the Diabetes UK Annual Foot Check (DUK-C) checklist were used to assess video educational quality. Differences in JAMA, GQS, and DUK-C ratings were analysed after videos were sorted by topic and source.The mean number of views per video was 101,311.9 ± 348,383.6, and the mean video power index was 41.6 ± 170.0. The most common upload source was from physicians (28%) and, the most popular material category was diabetes foot examination (58 videos). In terms of video reliability, 36% of videos scored 0. According to the GQS standards, only 5% of the videos are of excellent quality, while 34% are of poor quality, with 24 videos scoring between 0 and 1 on the DUK-C scale.While foot care examination videos have a substantial audience, the majority are considered low in quality and reliability. Videos on comprehensive diabetic foot examination should be accessed on reputable sources that guarantee standardisations of video quality and take into account the simplification of information transmission in order to reach lay audiences.

Background Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 dia...

Aims/Introduction The aim of this study was to examine ethnicity‐specific associations between type 2 diabetes mellitus and the risk of a cardiovascular disease (CVD) event as well as risk of specific CVD phenotypes in England. Methods We obtained data from the Clinical Practice Research Datalink for adults with and without type 2 diabetes mellitus diagnosed 2000–2006. The outcome was the first CVD event during 2007–2017 and the following components: aortic aneurysm, cerebrovascular accidents, heart failure, myocardial infarction, peripheral vascular disease and other CVD‐related conditions. Flexible parametric survival models were used to estimate ethnicity‐specific adjusted hazard ratios. Results A total of 734,543 people with and without type 2 diabetes mellitus (29,847; 4.1%) were included; most were of white ethnicity (93.0% with and 92.3% without type 2 diabetes mellitus) followed by South Asian (3.2 and 4.6%). During a median follow‐up period of 11.0 years, 67,218 events occurred (6,156 in individuals with type 2 diabetes mellitus). Type 2 diabetes mellitus was associated with a small increase in CVD events (adjusted hazard ratio 1.06, 95% confidence interval 1.02–1.09) in individuals of white ethnicity; whereas the adjusted hazard ratios were considerably higher in individuals of South Asian ethnicity (1.28, 95% confidence interval 1.09–1.51), primarily due to an increased risk of myocardial infarction (1.53, 95% confidence interval 1.08–2.18). Conclusions Despite universal access to healthcare, there are large disparities in CVD outcomes in people with and without type 2 diabetes mellitus. Other non‐traditional risk factors might play a role in the higher CVD risk associated with type 2 diabetes mellitus in individuals of South Asian ethnicity., Despite universal access to healthcare, there are large ethnic disparities in cardiovascular disease outcomes in people with and without type 2 diabetes mellitus. Type 2 diabetes mellitus was associated with a small increase in cardiovascular disease events (adjusted hazard ratio 1.06, 95% confidence interval 1.02–1.09) in individuals of white ethnicity; whereas the adjusted hazard ratio was considerably higher in individuals of South Asian ethnicity (1.28, 95% confidence interval 1.09–1.51), primarily due to an increased risk of myocardial infarction (adjusted hazard ratio 1.53, 95% confidence interval 1.08–2.18).