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In a randomised controlled trial (RCT), the between-arm difference in the average probability of an event per unit of time (i.e., yearly incidence risk difference, YIRD) is an easy-to-interpret treatment effect metric. We aimed to quantify the YIRD in cardiorenal RCTs of GLP-1RAs or SGLT-2is. We digitally searched for RCTs published up to March 1st, 2023, including subjects with type 2 diabetes randomised to GLP-1RAs or SGLT-2is and investigating cardiorenal outcomes or death. We extracted information from Kaplan-Meier (KM) plots to obtain time-to-event individual data and estimate within-arm yearly incidence risk and YIRD. Data from 19 RCTs (28 kM plots) were analysed: comparing treatment to placebo, in GLP-1RA RCTs the YIRD ranged from 0.2 % (95 % CI: −0.7 %, 1.1 %) to −1.9 % (−3.1, −0.7), for primary outcome; and from −0.2 % (−0.5, 0.2) to −0.4 % (−0.7 %, −0.0 %), for mortality. With the exception of SOLOIST-WHF (YIRD 11.9 % for primary outcome), corresponding estimates in SGLT-2is RCTs were: from −0.1 % (−0.4, 0.1) to −5.0 % (−7.7, −2.6), for primary outcome; and from −0.1 % (−0.2, 0.1) to −1.9 % (−4.4 %, 0.6 %), for mortality. The YIRD metric complements other relative treatment effect estimates and helps quantify the absolute benefit of GLP-1RAs and SGLT-2is. • Yearly incidence risk difference (YIRD) can help interpreting treatment effect. • Using reconstructed time-to-event data, we estimated YIRD in cardiorenal trials. • YIRDs was estimated for primary outcomes and death in GLP1-RAs and SGLT2-is trials. • YIRD is easy-to-interpret and could add insights in clinical decision-making. [ABSTRACT FROM AUTHOR]

To investigate associations of self-reported walking pace (SRWP) with relative and absolute risks of cause-specific mortality. In 391,652 UK Biobank participants recruited in 2006–2010, we estimated sex- and cause-specific (cardiovascular disease [CVD], cancer, other causes) mortality hazard ratios (HRs) and 10-year mortality risks across categories of SRWP (slow, average, brisk), accounting for confounders and competing risk. Censoring occurred in September 30, 2021 (England, Wales) and October 31, 2021 (Scotland). Over a median follow-up of 12.6 years, 22,413 deaths occurred. In women, the HRs comparing brisk to slow SRWP were 0.74 (95% CI: 0.67, 0.82), 0.40 (0.33, 0.49), and 0.29 (0.26, 0.32) for cancer, CVD, and other causes of death, respectively, and 0.71 (0.64, 0.78), 0.38 (0.33, 0.44), and 0.29 (0.26, 0.32) in men. Compared to CVD, HRs were greater for other causes (women: 39.6% [6.2, 72.9]; men: 31.6% [9.8, 53.5]) and smaller for cancer (−45.8% [−58.3, −33.2] and − 45.9% [−54.8, −36.9], respectively). For all causes in both sexes, the 10-year mortality risk was higher in slow walkers, but varied across sex, age, and cause, resulting in different risk reductions comparing brisk to slow: the largest were for other causes of death at age 75 years [women: −6.8% (−7.7, −5.8); men: −9.5% (−10.6, −8.4)]. Compared to slow walkers, brisk SRWP was associated with reduced cancer (smallest reduction), CVD, and other (largest) causes of death and may therefore be a useful clinical predictive marker. As absolute risk reductions varied across age, cause, and SRWP, certain groups may particularly benefit from interventions to increase SRWP. [ABSTRACT FROM AUTHOR]

In the STEP-HFpEF trial, 2.4 mg semaglutide produced marked improvements in heart failure-related symptoms, physical limitations, and exercise function, and reduced inflammation and body weight in individuals with obesity HFpEF phenotype. These data usher in a new paradigm of targeting obesity as a therapeutic strategy in HFpEF. [ABSTRACT FROM AUTHOR]

To implement a diabetes prevention programme in primary care The programme was implemented for 12 months in two neighbouring towns, served by eight general practices. Practices requested a referral pathway involving an external administrator running electronic searches and sending postal invitations. If interested, people called and booked a place on the programme. Practices were also provided with resources to refer people directly. Six Educators were trained to deliver the programme. The RE-AIM constructs "Adoption", "Reach" and "Uptake" were assessed. All practices engaged in the searches and postal invitations. Overall, 3.9 % of those aged ≥ 25 years had an HbA1c level indicative of non-diabetic hyperglycaemia (NDH) and were invited. Overall uptake (attended as percentage of invited) was 16 % (practice range 10.5–26.6 %) and was highest in two practices where the invitation was followed by a telephone call. Four people were referred directly by their practice. Groups at risk of being excluded were the Bengali population and those unable to attend because of issues such as health, mobility and frailty. Comprehensive electronic searches meant everyone previously diagnosed with NDH was invited to attend. Follow-up telephone call improved uptake and providing practices with resources to make these calls themselves would likely increase uptake further. • General practices supported to implement diabetes prevention programme. • Practices requested support from external referral pathway. • 3.9 % of ≥ 25 y had HbA1c indicative of non-diabetic hyperglycaemia. • 16 % uptake to postal invitation, increased if followed by phone call. • Closer involvement by health care professionals likely to improve uptake. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity. 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: 7596 (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. Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups. • Limited evidence for the prognosis of individuals with cardiovascular disease (CVD) by type 2 diabetes (T2D) and ethnicity. • After first CVD, the largest life expectancy difference was in White ethnicity, (loss of 3.9 years) with vs without T2D. • Differences were non-significant in other ethnicity (3.9 years), Black (1.2 y), South Asian (-1.4 y) with vs without T2D. • Study shows the heterogeneous impact of T2D on life expectancy among individuals of different ethnicity who survived a CVD. [ABSTRACT FROM AUTHOR]

Background and Aims: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Aims: To estimate rates and identify determinants of post-partum glucose screening attendance in women with a history of gestational diabetes mellitus (GDM).Methods: Retrospective cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics, to identify women diagnosed with GDM between 01/01/2000 and 05/11/2018. Age adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models.Results: In 10,868 women with GDM, with an average follow-up of 5.38 years (95% CI 5.31,5.45), there was an average of 3.79 (95% CI 3.70,3.89) screening episodes per individual, with a mean time to first screening test of 1.22 (95% CI 1.18, 1.25) years. South Asian women had a significantly greater likelihood of being screened compared to White women within the first 5 years post-partum, aOR: 1.89 95% CI (1.20,2.98). A low proportion of women received at least one test per year of follow-up (23.87%). Older age at GDM diagnosis, polycystic ovary syndrome, prescribed medication for GDM, and living in England, were all associated with a greater likelihood of being screened.Conclusion: While the majority of women with previous GDM receive at least one glucose screening test within the first 5 years post-partum, fewer than a quarter of them receive on average one test per year of follow-up. Developing strategies to motivate more women to attend screening in primary care is essential. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

STEP-HFpEF, a 52 week trial conducted in patients with obesity phenotype of heart failure with preserved ejection fraction (HFpEF) and no type 2 diabetes, examined the effects of once-weekly semaglutide 2.4 mg versus placebo on HF-related symptoms, physical limitations, and exercise function, as well as inflammation and body weight (BW). Except for sodium-glucose co-transporter 2 inhibitors, previous HF therapies have shown differential effects across the spectrum of left ventricular ejection fraction (LVEF). In this pre-specified analysis, we investigated the effects of semaglutide on the primary and key secondary endpoints across the range of LVEF in the STEP-HFpEF Trial. STEP-HFpEF randomized 529 participants with symptomatic HF, LVEF ≥45% and body mass index of ≥30 kg/m2 to receive once weekly semaglutide 2.4 mg or placebo. Key exclusion criteria were prior or planned bariatric surgery, self-reported change in BW >11 pounds (5 kilograms) within 90 days prior to randomization, and a HbA1c level ≥6.5% or prior medical history of diabetes. Dual primary endpoints were change from baseline in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and BW. Confirmatory secondary endpoints included change in 6-minute walk distance (6MWD), hierarchical composite endpoint (death, HF events and change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP). For this analysis, patients were stratified based on baseline LVEF of 45-49%, 50-59%, and ≥60%. The effects of semaglutide versus placebo on the dual primary and confirmatory secondary endpoints were examined across these LVEF categories. Overall, the median LVEF in STEP-HFpEF was 57%; 16.1, 40.6, and 43.3% of participants had LVEF of 45-49%, 50-59%, and ≥60%, respectively. Baseline characteristics of patients in the three LVEF based sub-groups are shown in the Table. The effects of semaglutide compared with placebo on the dual primary and confirmatory secondary outcomes across these LVEF categories will be presented. STEP-HFpEF is the first clinical trial of pharmacotherapy to specifically target the obesity phenotype of HFpEF. In this pre-specified analysis, we will examine whether the effects of semaglutide on symptoms, physical limitations, exercise function, as well as inflammation and BW in this patient population are consistent across the range of LVEF. [ABSTRACT FROM AUTHOR]

Background: Trimethylamine N-oxide (TMAO), a metabolite generated by the gut in response (in part) to meat consumption, is linked to poor cardiometabolic health.Objectives: We investigate the effect of an 8-week vegan diet, followed by a 4-week period of unrestricted diet, on glucose tolerance and plasma TMAO in human omnivores with obesity or dysglycemia.Methods: This interventional single-group prospective trial involved 23 regular meat eaters with dysglycemia [glycated hemoglobin ≥ 5.7% and ≤8% (39-64 mmol/mol)], or obesity (ΒΜΙ ≥ 30 kg/m2) aged 57.8 ± 10.0 years. Participants [14 men (60.9%) and 9 women (39.1%)] were supported in following a vegan diet for 8 weeks, followed by 4 weeks of unrestricted diet. The primary outcomes (plasma TMAO and glucose) were assessed at baseline, during the vegan diet (weeks 1 and 8), and after the unrestricted diet period (week 12). TMAO was assessed after fasting and glucose was measured as a time-averaged total AUC using a 180-minute oral-glucose-tolerance test. Generalized estimating equation models with an exchangeable correlation structure were used to assess changes from baseline, adjusting for age, sex, ethnicity, and weight.Results: TMAO levels (marginal mean) were reduced after weeks 1 and 8 of a vegan diet compared to baseline, from 10.7 (97.5% CI, 6.61-17.3) μmol/L to 5.66 (97.5% CI, 4.56-7.02) μmol/L and 6.38 (97.5% CI, 5.25-7.74) μmol/L, respectively; however, levels rebounded at week 12 after resumption of an unrestricted diet (17.5 μmol/L; 97.5% CI, 7.98-38.4). Postprandial glucose levels (marginal means) were reduced after weeks 1 and 8 compared to baseline, from 8.07 (97.5% CI, 7.24-8.90) mmol/L to 7.14 (97.5% CI, 6.30-7.98) mmol/L and 7.34 (97.5% CI, 6.63-8.04) mmol/L, respectively. Results for glucose and TMAO were independent of weight loss. Improvements in the lipid profile and markers of renal function were observed at week 8.Conclusions: These findings suggest that a vegan diet is an effective strategy for improving glucose tolerance and reducing plasma TMAO in individuals with dysglycemia or obesity. This study was registered at clinicaltrials.gov as NCT03315988. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes, which contributes 90% of all cases of diabetes mellitus is now mostly managed in the primary care settings in the UK and other advanced health care systems. The UK National Health Service as a whole could potentially benefit if more patients were managed in primary care settings since primary care-based care is likely to be more cost-effective. We initially compared eight larger general practices (Enhanced practices) in Leicester, UK with neighbouring smaller practices (Core practices) matched for comparable demographic characteristics. Even though this initial study did not find any statistically significant differences in terms of clinical outcomes there was trend in favour of the enhanced practices. In this current study, we conducted a cost comparison of enhanced practice model of diabetes care, to standard care delivered in the core practices.Methods: Data and information were combined from a number of sources and a cost comparison evaluation was carried out in WinBUGs. A probabilistic approach was taken, to allow uncertainty to be included around analysis parameters where appropriate. The analysis evaluated a straight-forward cost comparison of enhanced versus standard care.Results: The cost per person with diabetes per year was £255 (95% CrI 175, 380) in the core practices and £173 (95% CrI 96, 291) in the enhanced practices, resulting in an annual cost saving of -£83 (95% CrI -148, -28) per patient. If the enhanced model of diabetes care were delivered across all the practices in the UK, the cost would be £575,100,000 (95% CrI 320,700,000, 970,700,000), resulting in an annual cost saving of -276,200,000 (95% CrI -495,400,000, -94,480,000).Conclusion: A cost comparison analysis of our larger enhanced primary care based diabetes service confirms significant cost saving, probably driven by economies of scale. These benefits could be multiplied manifold if the service was implemented nationally. [ABSTRACT FROM AUTHOR]

To investigate in women with prior gestational diabetes mellitus (GDM), differences by ethnicity and socioeconomic status in the incidence of recurrent GDM, type 2 diabetes (T2D), hypertension, and depression. This was a retrospective cohort study including 10,868 women diagnosed with GDM in the Clinical Practice Research Datalink (CPRD GOLD) between January 01, 2000 and November 05, 2018. Linked data were obtained for Hospital Episode Statistics and the Index of Multiple Deprivation. We estimated incidence rates and hazard ratios, by ethnicity and socioeconomic status. During a follow-up of 58,479 person years (mean (SD): 5.38 (3.67) years), the crude incidence was 9.67 (95 % confidence interval: 9.30–10.00) per 100 person years for recurrent GDM, 3.86 (3.70–4.02) for depression, 2.15 (2.03–2.27) for T2D and 0.89 (0.81–0.97) for hypertension. South Asian ethnicity was associated with an increased risk of T2D compared to White (adjusted hazard ratio: 1.65; 1.34–2.05) and Black ethnicity was associated with a greater risk of hypertension (2.93; 1.93–4.46). Black and South Asian ethnicity were associated with a reduced risk of depression compared to White: 0.23 (0.13–0.39) and 0.37 (0.29–0.46), respectively. Incidence rates were higher for all conditions with increasing deprivation level. The risk of health complications in women with a prior history of GDM differs by ethnicity and socio-economic status, suggesting the opportunity for targeted assessment in the years following pregnancy. These findings may inform future guidelines on screening for health outcomes in women with GDM. • Gestational diabetes (GDM) is increasingly prevalent and is associated with serious adverse maternal health outcomes. • South Asian women with prior GDM had a greater risk of developing type 2 diabetes compared to White. • Black women were found to have a greater risk of hypertension, compared to White women, following GDM. • There is an opportunity for targeted screening and preventative interventions following pregnancy complicated by GDM. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality, when implementing a multifactorial optimal control approach in primary care in the United Kingdom (UK), in individuals with newly diagnosed type 2 diabetes.Materials and Methods: A retrospective cohort of 53 942 patients were stratified into 1 of the 8 groups according to whether glycated haemoglobin (HbA1c), blood pressure (BP) and total cholesterol (TC) target values were achieved or not from baseline to the date of last follow-up. Those with single or combinations of risk factor control targets achieved, were compared to those who achieved no targets in any of the risk factor. Hazard ratios from the Cox proportional hazards models were estimated against patients who achieved no targets.Results: Of 53 942 patients with newly diagnosed type 2 diabetes, 28%, 55%, and 68% were at target levels for HbA1c <48mmol/mol (<6.5%), BP<140/85mm Hg, and TC<5mmol/L respectively, 36%, 40%, and 12% were at target levels for any one, two, or all three risk factors respectively. Being at HbA1c, BP, and TC targets was associated with an overall 47%, 25%, 42%, 55% and 42% reduction in the risk of ischemic heart disease, cerebrovascular disease, ESRD, cardiovascular-mortality, and all-cause-mortality respectively. Among all subgroups, the risk reduction of study outcome events was greater in the subgroups of patients with microalbuminuria, males, smokers, and patients with BMI≥30kg/m2.Conclusions: Optimal levels of HbA1c, BP, and TC occurring together in patients with newly diagnosed type 2 diabetes are uncommon. Achieving multiple risk factor control targets could substantially reduce the risk of CVD, ESRD and mortality. [ABSTRACT FROM AUTHOR]

Aim: Whether the relative risk of cancer incidence and mortality associated with diabetes has changed over time is unknown.Data Synthesis: On August 12th, 2020, we electronically searched for observational studies reporting on the association between diabetes and cancer. We estimated temporal trends in the relative risk of cancer incidence or mortality associated with diabetes and calculated the ratio of relative risk (RRR) comparing different periods. As many as 193 eligible articles, reporting data on 203 cohorts (56,852,381 participants; 3,735,564 incident cancer cases; 185,404 cancer deaths) and covering the period 1951-2013, were included. The relative risk of all-site cancer incidence increased between 1980 and 2000 [RRR 1990 vs.1980: (1.24; 95% CI: 1.16, 1.34); 2000 vs.1990: (1.23; 1.15, 1.31)] and stabilised thereafter at a relative risk of 1.2; the relative risk of all-site cancer mortality was constant at about 1.2 from 1980 to 2010. Both magnitudes and trends in relative risk varied across cancer sites: the relative risk of colorectal, female breast, and endometrial cancer incidence and pancreatic cancer mortality was constant during the observed years; it increased for bladder, stomach, kidney, and pancreatic cancer incidence until 2000; and decreased for liver while increased for prostate, colon and gallbladder cancer incidence after 2000.Conclusions: Alongside the increasing prevalence of diabetes, the temporal patterns of the relative risk of cancer associated with diabetes may have contributed to the current burden of cancer in people with diabetes. [ABSTRACT FROM AUTHOR]

Background and Aims: Intake of red and processed meat has been associated with a higher risk of morbidity and mortality; it is unknown whether these associations are modified by overall physical health. This study examined the associations of red and processed meat consumption with all-cause, cardiovascular, and cancer mortality and investigated whether markers of physical function modified the associations.Methods and Results: This observational cohort study used UK Biobank data derived from 419,075 participants free from cancer and cardiovascular disease. Cox models assessed the association of red and processed meat consumption (obtained from a baseline food frequency questionnaire) with mortality, adjusted for potential confounders. Objectively measured handgrip strength and self-reported walking pace were used as interaction terms. The median age was 57 (interquartile range, 49-63) years and 54.9% were women. Over 7 years of follow-up, 8586 all-cause, 1660 cardiovascular, and 4812 cancer deaths occurred. Each additional serving per week of red and processed meat was associated with a hazard ratio (HR) of 1.037 (95% CI: 1.028-1.047) for all-cause; 1.030 (1.009-1.051) for cardiovascular; and 1.029 (1.016-1.042) for cancer mortality. The association of red and processed meat consumption was modified by walking pace, with brisk walkers having the lowest risk per additional serving for all-cause and cancer mortality (HR 1.025; 1.006-1.045 and 1.015; 0.990-1.040, respectively); no interaction was observed for handgrip strength.Conclusion: The known risk of mortality associated with red and processed meat consumption may be lower in those with high physical function. [ABSTRACT FROM AUTHOR]

In randomized controlled trials (RCTs), treatment effects are commonly reported as hazard ratio, a measure often misinterpreted as a relative risk reduction. The acceleration factor (AF) indicates the extent to which a treatment increases/decreases the time before the occurrence of an outcome and gives useful insights in the interpretation of trials' results. Using individual time-to-event data reconstructed from Kaplan-Meier plots, we estimated AFs for the primary outcomes (POs) and all-cause mortality in glucagon-like peptide-1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2-is) cardiorenal outcome trials in subjects with type 2 diabetes. AFs were estimated from 28 Kaplan-Meier plots of 19 RCTs. Compared to placebo, most GLP1-RAs increased the time before the onset of POs (from 9 % to 59 %) and all-cause mortality (from 8 to 13 %). Similarly, SGLT2-is increased time before the onset of POs (from 19 % to 87 %) and all-cause mortality (from 13 % to 42 %). The AFs provide a complementary and easier-to-interpret measure of treatment effect that could be useful to improve the shared decision-making. • The acceleration factor (AF) – how the time before an outcome is increased/decreased – can help interpret trial's result. • Using reconstructed time-to-event data, we estimated AFs for primary outcomes and death in GLP1-RAs and SGLT2-is trials. • AFs provide an easy-to-interpret measure of treatment effect, adding actionable information in clinical decision-making. SUMMARY In a randomised controlled trial, the acceleration factor (AF) indicates the extent to which the occurrence of an outcome is accelerated or delayed by an intervention, providing a complementary, easy-to-interpret measure of treatment effect. We estimated AFs for primary outcomes and all-cause mortality in type 2 diabetes cardiorenal outcome trials. [ABSTRACT FROM AUTHOR]

Our aim is to demonstrate how a data-driven accelerometer metric, the acceleration above which a person's most active minutes are accumulated, can (a) quantify the prevalence of meeting current physical activity guidelines for global surveillance and (b) moving forward, could inform accelerometer-driven physical activity guidelines. Unlike cut-point methods, the metric is population-independent (e.g. age) and potentially comparable across datasets. Cross-sectional, secondary data analysis. Analyses were carried out on five datasets using wrist-worn accelerometers: children (N = 145), adolescent girls (N = 1669), office workers (N = 114), pre- (N = 1218) and post- (N = 1316) menopausal women, and adults with type 2 diabetes (N = 475). Open-source software (GGIR) was used to generate the magnitude of acceleration above which a person's most active 60, 30 and 2 min are accumulated: M60 ACC ; M30 ACC and M2 ACC , respectively. The proportion of participants with M60 ACC (children) and M30 ACC (adults) values higher than accelerations representative of brisk walking (i.e., moderate-to-vigorous physical activity) ranged from 17 to 68% in children and 15 to 81% in adults, tending to decline with age. The proportion of pre-and post-menopausal women with M2 ACC values meeting thresholds for bone health ranged from 6 to 13%. These metrics can be used for global surveillance of physical activity, including assessing prevalence of meeting current physical activity guidelines. As accelerometer and corresponding health data accumulate it will be possible to interpret the metrics relative to age- and sex- specific norms and derive evidence-based physical activity guidelines directly from accelerometer data for use in future global surveillance. This is where the potential advantages of these metrics lie. [ABSTRACT FROM AUTHOR]

Background and Aims: Meta-analyses of randomised controlled trials (RCTs) and observational studies indicate a lower risk of venous thromboembolism (VTE) associated with statin treatment. We aimed to compare the effect of statin therapy in these two settings and to identify and quantify potential factors to explain statin efficacy and effectiveness.Methods and Results: We electronically searched on December 11th, 2018, articles reporting on first VTE events in RCTs (statin vs placebo) and in observational studies (participants exposed vs non-exposed to statin). We performed Knapp-Hartung random-effect meta-analyses to calculate pooled relative risks (RRs) of VTE events associated with statin treatment, separately for RCTs and observational studies; and estimated the ratio of the relative risk (RRR) comparing RCTs and observational studies using meta-regressions, progressively adjusted for study-level characteristics. Twenty-one RCTs (115,107 participants; 959 events) and 8 observational studies (2,898,096 participants; 19,671 events) were included. Pooled RRs for RCTs and observational studies were 0.82 (95% confidence interval (CI): 0.67-1.00; I2 19.2%) and 0.60 (95% CI: 0.42-0.86; I2 86.3%), respectively. In meta-regressions, the unadjusted RRR indicated a nonsignificant 23% smaller benefit in RCTs (RRR 0.77; 95% CI: 0.52-1.13); accounting for age, sex, geographical region, and duration of follow-up, there was a sensible change of the RRR which resulted 0.30 (95% CI: 0.13-0.68).Conclusion: Differences in the characteristics between patients included in RCTs and those in observational studies may account for the differential effect of statins in preventing VTE in the two settings. [ABSTRACT FROM AUTHOR]

Routine care for chronic disease is an ongoing major challenge. We aimed to evaluate the global impact of COVID-19 on routine care for chronic diseases. An online survey was posted 31 March to 23 April 2020 targeted at healthcare professionals. 202 from 47 countries responded. Most reported change in routine care to virtual communication. Diabetes, chronic obstructive pulmonary disease, and hypertension were the most impacted conditions due to reduction in access to care. 80% reported the mental health of their patients worsened during COVID-19. It is important routine care continues in spite of the pandemic, to avoid a rise in non-COVID-19-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Currently, there is uncertainty as to whether blood pressure control in patients with type 2 diabetes should be treated to standard recommended levels or more intensively. Medline, EMBASE, CENTRAL, and Clinicaltrials.gov were searched between January 1, 2000 and April 20th, 2023. Outcomes considered were all-cause mortality, stroke, heart failure, cardiovascular disease, albuminuria, coronary heart disease, and renal outcomes. Random-effects meta-analyses estimated pooled relative risks and mean differences. Nine trials enrolling 11,005 participants with type 2 diabetes were included. The pooled mean difference between the intensive and standard treatment groups at follow-up were −7.98 mmHg (95% CI: 12.19 to −3.76) in systolic blood pressure, and −5.08 mmHg (−7.00 to −3.17) in diastolic blood pressure; although between study heterogeneity was high for both meta-analyses (I 2 >85%). Intensive blood pressure lowering resulted in a reduction in risk of stroke (risk ratio 0.64; 0.52 to 0.79), and macro-albuminuria (0.77; 0.63 to 0.93). More intensive blood pressure control did not result in a statistically significant reduction in risk of all-cause mortality, heart failure, cardiovascular death, cardiovascular events, renal outcomes, and micro-albuminuria; although the direction of estimated effect was beneficial for all outcomes. The use of intensive compared with standard blood pressure targets resulted in a significant reduction in blood pressure, stroke, and macro-albuminuria in patients with type 2 diabetes. The post-treatment blood pressure level in the intensive group was 125/73 mmHg, suggesting the current recommendations of 130/80 mmHg blood pressure or lower if tolerated, could be reduced further. • Aiming for a low blood pressure target in participants with T2DM results in a reduced risk of stroke and macro-albuminuria. • No significant difference was found for CVD events or mortality, heart failure, micro-albuminuria, or renal outcomes. • The post-treatment BP level in the intensive group was 125/73 mmHg, suggesting the current recommendations could be reduced. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the prevalence of accurate self-knowledge of a patient's own HbA1c level (HbA1cSK), as a component of structural education (University Hospital's of Leicester (UHL), 2013) and its association with glycaemic control.Methods: Data from the GUIDANCE study, a cross-sectional study involving 7597 participants from eight European countries was used. HbA1cSK was evaluated and compared with laboratory measured HbA1c levels (HbA1cLAB), which represented the measure of glycaemic control. Accuracy of the self-reported HbA1c was evaluated by using agreement statistical methods.Results: The prevalence of HbA1cSK was 49.4%. Within this group, 78.3% of the participants had accurately reported HbA1cSK. There was good level of agreement between HbA1cSK and HbA1cLAB (intra-class correlation statistic=0.84, p<0.0001). Participants with accurately reported HbA1cSK were found to have a statistically significantly lower HbA1cLAB compared to participants with inaccurately reported HbA1cSK (7.0% versus 7.3%, p<0.001).Conclusion: Nearly half of the patients had self-knowledge of their own HbA1c level. Moreover, the participants with accurately reported HbA1cSK were found to have associated better glycaemic control. [ABSTRACT FROM AUTHOR]

Aims: Weight loss-induced serum creatinine reduction may increase creatinine-based estimated glomerular filtration rate (eGFR) producing incorrect estimates of kidney function. We investigated whether weight changes in the SCALE program with liraglutide 3.0mg were associated with changes in serum creatinine.Methods: Post hoc analysis of two 56-week, randomized, double-blind trials: SCALE Obesity and Prediabetes (n=3731, without type 2 diabetes [T2D], randomized [2:1] to liraglutide 3.0mg [n=2487] or placebo [n=1244]); SCALE Diabetes (n=846 with T2D, randomized [2:1:1] to liraglutide 3.0mg [n=423], 1.8mg [n=211, excluded from this analysis] or placebo [n=212]). NCT01272219/NCT01272232.Results: In SCALE Obesity and Prediabetes, mean (±SD) weight loss (baseline to week 56) with liraglutide was 8.0±6.7% (2.6±6.9% with placebo); baseline creatinine with liraglutide was 76±15μmol/L and 74±15μmol/L after 56weeks (similar across treatment groups). In SCALE Diabetes, weight loss with liraglutide was 5.9±5.5% (2.0±4.3% with placebo); baseline creatinine was 79±19μmol/L (77±16μmol/L, placebo) and 79±20μmol/L after 56weeks (76±15μmol/L, placebo). No association between changes in weight and changes in serum creatinine was observed (P≥0.05, both trials, all tests).Conclusions: Moderate gradual body weight reductions observed in the SCALE program were not associated with changes in serum creatinine. [ABSTRACT FROM AUTHOR]

The global epidemic of type 2 diabetes (T2DM) continues largely unabated due to an increasingly sedentary lifestyle and obesogenic environment. A cost-effective patient-centred approach, incorporating glucose-lowering therapy and modification of cardiovascular risk factors, could help prevent the inevitable development and progression of macrovascular and microvascular complications. Glycaemic optimization requires patient structured education, self-management and empowerment, and psychological support along with early and proactive use of glucose lowering therapies, which should be delivered in a system of care as shown by the Chronic Care Model. From diagnosis, intensive glycaemic control and individualised care is aimed at reducing complications. In older people, the goal is maintaining quality of life and minimizing morbidity, especially as overtreatment increases hypoglycaemia risk. Maintaining durable glycaemic control is challenging and complex to achieve without hypoglycaemia, weight gain and other significant adverse effects. Overcoming patient and physician barriers can help ensure adequate treatment initiation and intensification. Cardiovascular safety studies with newer glucose-lowering agents are now mandatory, with a sodium glucose co-transporter-2 inhibitor (empagliflozin), and two glucagon like peptide-1 receptor agonists (liraglutide and semaglutide) being the first to demonstrate superior CV outcomes compared with placebo. [ABSTRACT FROM AUTHOR]

Aims We investigated whether a continuous quality improvement programme in primary care for people with type 2 diabetes led to better care and outcomes in hard to reach groups. Methods GEDAPS was implemented in Catalonia, Spain between 1993 ( n = 2239) and 2002 ( n = 5819). Process (e.g. education), intermediate (e.g. HbA1c) and final (e.g. retinopathy) outcomes were compared between urban and rural areas, and between younger (≤74 years) and older (≥75 years) individuals as examples of harder to reach groups. Results In 1993, people in urban areas had significantly better or similar outcomes to rural areas; by 2002, most outcomes improved in urban and rural areas. For all outcomes, the improvement in rural areas was similar to or better than urban areas. Similarly, for most outcomes, the younger and older group improved, with the older group experiencing similar or better improvements than the younger group for all indicators, except coronary artery disease. Conclusions A quality improvement programme was associated with equivalent or better outcomes in hard to reach groups, regardless of whether they were specifically targeted. The ability to apply one programme to all populations could save time and money. [ABSTRACT FROM AUTHOR]

Diabetes is a chronic and progressive metabolic disorder characterized by hyperglycaemia. The two main types of diabetes are type 1 diabetes (T1DM) where there is complete lack of insulin and type 2 diabetes (T2DM) which may be due to a combination of insulin resistance and relative insulin deficiency due to impaired β-cell function. Good control of blood glucose near physiological limits is vital to reduce long-term microvascular and macrovascular complications of diabetes. Insulin replacement is a life-saving measure in individuals with T1DM whereas the mainstay of therapy in T2DM includes oral agents, non-insulin injectables (incretin mimetics) and insulin. In T2DM, the incretin mimetics and sodium glucose co-transporter 2 inhibitors have revolutionized recent treatment options by reducing blood glucose, promoting weight loss and improving β-cell function with improved cardiovascular outcomes associated with some of these agents. Despite the availability of several drugs to treat this chronic debilitating condition, the management of hyperglycaemia remains challenging. The role of diet, lifestyle changes and patient education is of paramount importance and should be pursued aggressively. This review will look at drugs currently used to optimize blood glucose control and briefly discuss the role of newer therapeutic agents. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To describe and evaluate risk assessment tools which detect those with pre-diabetes defined as either impaired glucose tolerance or impaired fasting glucose using an OGTT or as a raised HbA1c. Methods: Tools were identified through a systematic search of PubMed and EMBASE for articles which developed a risk tool to detect those with pre-diabetes. Data were extracted using a standardised data extraction form. Results: Eighteen tools met the inclusion criteria. Eleven tools were derived using logistic regression, six using decision trees and one using support vector machine methodology. Age, body mass index, family history of diabetes and hypertension were the most frequently included variables. The size of the datasets used and the number of events per variable considered were acceptable in all the tools. Missing data were not discussed for 8 (44%) of the tools, 10 (91%) of the logistic tools categorised continuous variables, external validation was carried out for only 7 (39%) of the tools and only 3 tools reported calibration levels. Conclusions: Several risk scores are available to identify those with pre-diabetes. Before these are used in practice, the level of calibration and validity of the tools in the population of interest should be assessed. [Copyright &y& Elsevier]

Abstract: Objective: The cardiometabolic risk cluster metabolic syndrome (MS) includes ≥3 of elevated fasting glucose, hypertension, elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-c), and increased waist circumference. Each can be affected by physical activity and diet. Our objective was to determine whether determine whether baseline physical activity and/or diet behavior impact MS in the course of a large pharmaceutical trial. Materials/Methods: This was an observational study from NAVIGATOR, a double-blind, randomized (nateglinide, valsartan, both, or placebo), controlled trial between 2002 and 2004. We studied data from persons (n=9306) with impaired glucose tolerance and cardiovascular disease (CVD) or CVD risk factors; 7118 with pedometer data were included in this analysis. Physical activity was assessed with 7-day pedometer records; diet behavior was self-reported on a 6-item survey. An MS score (MSSc) was calculated using the sum of each MS component, centered around the Adult Treatment Panel III threshold, and standardized according to sample standard deviation. Excepting HDL-c, assessed at baseline and year 3, MS components were assessed yearly. Follow-up averaged 6 years. Results: For every 2000-step increase in average daily steps, there was an associated reduction in average MSSc of 0.29 (95% CI -0.33 to -0.25). For each diet behavior endorsed, there was an associated reduction in average MSSc of 0.05 (95% CI -0.08 to -0.01). Accounting for the effects of pedometer steps and diet behavior together had minimal impact on parameter estimates with no significant interaction. Relations were independent of age, sex, race, region, smoking, family history of diabetes, and use of nateglinide, valsartan, aspirin, antihypertensive, and lipid-lowering agent. Conclusions: Baseline physical activity and diet behavior were associated independently with reductions in MSSc such that increased attention to these lifestyle elements provides cardiometabolic benefits. Thus, given the potential to impact outcomes, assessment of physical activity and diet should be performed in pharmacologic trials targeting cardiometabolic risk. [Copyright &y& Elsevier]

Abstract: Aims: This paper focuses mainly on explanations and lessons from a research-based programme for identifying undiagnosed type 2 diabetes and high risk. In addition to outlining key quantitative findings, we specifically aim to explore reasons for low uptake from the perspective of primary care staff involved. Methods: The MY-WAIST study was conducted in UK primary care and included the use of oral glucose tolerance tests (OGTTs) and waist measurement. Qualitative data from interviews with healthcare providers and records of meetings were analysed thematically. Results: The key quantitative finding was low uptake of the assessments offered (8.6% overall, 2.6% in inner-city locations with high South Asian residency). In addition to confirming patient-reported barriers including those associated with OGTTs, qualitative findings highlighted a number of primary care provider barriers, including limited staff capacity. Interviewees suggested that those who attended were typically the ‘worried well’ rather than those from hard-to-reach groups. Conclusions: Implications discussed include the impact of low uptake on the usefulness of the quantitative data obtained, and lessons relevant to research design. Relevance to current guidance regarding early identification strategies is discussed and the importance of addressing the needs of less accessible groups is highlighted. [Copyright &y& Elsevier]

Abstract: Aims: To report the characteristics and treatment of individuals requiring emergency ambulance services for severe hypoglycaemia and estimate associated provider costs. Methods: Retrospective analysis of routinely collected data collected by the East Midlands Ambulance Trust, UK, of episodes of severe hypoglycaemia attended by emergency ambulance services during a four-month period. Standard clinical measures, response time, on-site treatment and transportation were recorded and ambulance services costs calculated. Results: 90,435 emergency calls were recorded, 523 (0.6%) for severe hypoglycaemia, equating to an incidence of to 2.76 per 100 patient years; 74% of individuals were insulin-treated, 28% of events occurred nocturnally (00:00–07:59), and 32% were transported to hospital. Higher respiratory rate was a positive predictor (p =0.03), whereas higher post treatment blood glucose (p =0.05) and insulin treatment (p <0.01) were negative predictors of transport to hospital. Median treatment costs for individuals transported and not transported to hospital were £92 and £176 respectively. Conclusions: Most cases of severe hypoglycaemia requiring assistance from emergency ambulance services are successfully treated at the scene. Individuals not responding to treatment or were non insulin-treated were more likely to be transported to hospital. Further studies are needed to evaluate the effect of prehospital ambulance care by treatment and diabetes type on subsequent outcomes. [Copyright &y& Elsevier]