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Remarkable progress has been made in some aspects of diabetes care over the last 15 years, but there have also been a rising number of challenges that differ between high and low-income countries. In high-income countries, a substantial increase in the use of preventative drugs for cardiovascular disease has lowered vascular complications and improved diabetes survival. More recently, new classes of diabetes drugs have emerged that can variably lower cardiovascular outcomes, new-onset heart failure and slow renal decline, thereby meaningfully increasing the diabetes armoury that should help patients to live even longer lives and with fewer complications. At the other end of the disease spectrum, we can now better prevent diabetes in people who are at elevated risk of developing it, whereas other new research has shown that diabetes remission is possible when lifestyle changes are made in the early years after diagnosis. The downside is that more people than ever before have type 2 diabetes, so despite such progress in high-income countries, the absolute burden of disease is rising. Furthermore, it is rising even faster in low and middle-income countries, where rising adiposity is driving a tidal wave of new diabetes cases; yet, healthcare systems are less able to cope, lacking sufficient drugs, trained personnel and integrated care systems. Thus, despite advances, the future challenges from rising diabetes rates worldwide are daunting.

Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled tirzepatide groups and control groups. A stratified Cox proportional hazards model, with treatment as a fixed effect and trial-level cardiovascular risk as the stratification factor, was used for the estimation of hazard ratios (HRs) and confidence intervals (CIs) comparing tirzepatide to control. Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed. Overall, 142 participants, 109 from the trial with high cardiovascular risk and 33 from the six trials with lower cardiovascular risk, had at least one MACE-4 event. The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57–1.11) for MACE-4; 0.90 (95% CI, 0.50–1.61) for cardiovascular death; and 0.80 (95% CI, 0.51–1.25) for all-cause death. No evidence of effect modifications was observed for any subgroups, although the evidence was stronger for participants with high cardiovascular risk. Tirzepatide did not increase the risk of major cardiovascular events in participants with T2D versus controls. Meta-analysis of cardiovascular secondary outcomes from the SURPASS program, testing efficacy of a new novel dual GIP/GLP-1 receptor agonist tirzepatide, demonstrates cardiovascular safety in patients with type 2 diabetes.

Purpose Low blood 25-hydroxyvitamin D (25(OH)D) concentration has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether baseline serum 25(OH)D concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants. Methods UK Biobank recruited 502,624 participants aged 37–73 years between 2006 and 2010. Baseline exposure data, including serum 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and Poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection. Results Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. 25(OH)D concentration was associated with severe COVID-19 infection and mortality univariably (mortality per 10 nmol/L 25(OH)D HR  0.92; 95% CI 0.86–0.98; p  = 0.016), but not after adjustment for confounders (mortality per 10 nmol/L 25(OH)D HR 0.98; 95% CI = 0.91–1.06; p  = 0.696). Vitamin D insufficiency or deficiency was also not independently associated with either COVID-19 infection or linked mortality. Conclusions Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality. Randomised trials are needed to prove a beneficial role for vitamin D in the prevention of severe COVID-19 reactions or death.

In an observational study, patients with type 2 diabetes who had glycated hemoglobin, LDL cholesterol, albuminuria, and blood pressure in target ranges and did not smoke had minimal excess risk of death, myocardial infarction, and stroke as compared with a general population.

There is a growing burden of cardiometabolic disease in many parts of the world. Despite some progress in its prevention, more can be done to tackle risks of its development in the community and in different specialty clinics. Currently, the identification and management of those at elevated risk of developing cardiovascular disease or diabetes or with conditions such as fatty liver disease remains fragmented and is not linked to constructive lifestyle advice. In this Perspective, we argue for a more consistent weight-management approach, alongside a holistic assessment of the risk for developing cardiometabolic diseases, offering patients a range of simple or more-intensive evidence-based lifestyle options in an empathetic manner, with encouragement for repeated attempts and a willingness to embrace failure. The authors argue for a consistent weight-management approach, alongside an assessment of the risk for developing cardiometabolic diseases as a prevention strategy.

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C -statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment. Analysis of data from over 400,000 UK Biobank participants shows that eGFR measured by cystatin C, but not serum creatinine, is strongly associated with cardiovascular disease outcomes and mortality.

Aims/hypothesisThe aim of this work was to determine how weight patterns together with blood glucose, BP and lipids vary at diagnosis of diabetes by age, sex and ethnicity.MethodsUsing the UK Clinical Practice Research Datalink, we identified people with type 2 diabetes (n = 187,601) diagnosed in 1998–2015 and compared their weights, HbA1c, BP and lipid levels at diagnosis with age-matched people without diabetes (n = 906,182), by sex and ethnic group.ResultsYounger age at diagnosis was associated with greater adjusted mean difference (95% CI) in weight between those with vs without type 2 diabetes: 18.7 (18.3, 19.1) kg at age 20–39 years and 5.3 (5.0, 5.5) kg at age ≥ 80 years. Weight differentials were maximal in white women, and were around double in white people compared with South Asian and black people. Despite lower absolute values, BP differences were also greater at younger age of diabetes onset: 7 (6, 7) mmHg at age 20–39 years vs −0.5 (−0.9, −0.2) at age ≥ 80 years. BP differences were greatest in white people, and especially in women. Triacylglycerol level differences were greatest in younger men. Finally, HbA1c levels were also higher with younger onset diabetes, particularly in black people.Conclusions/interpretationAt diagnosis of type 2 diabetes, when compared with people without diabetes, weight and BP differentials were greater in younger vs older people, in women vs men and in white vs South Asian and black people. These differences were observed even though South Asian and black people tend to develop diabetes a decade earlier with either similar or greater dysglycaemia. These striking patterns may have implications for management and prevention.

Patients with type 1 or type 2 diabetes in Sweden were studied to examine trends in mortality and cardiovascular disease incidence between 1998 and 2014. Both outcomes declined substantially, although fatal outcomes declined less among patients with type 2 diabetes than among controls. Diabetes mellitus is a complex and heterogeneous group of chronic metabolic diseases that are characterized by hyperglycemia. Type 1 diabetes occurs predominantly in young people (diagnosis at 30 years of age or younger) and is generally thought to be precipitated by an immune-associated destruction of insulin-producing pancreatic beta cells, leading to insulin deficiency and an absolute need for exogenous insulin replacement. 1 Type 2 diabetes is a progressive metabolic disease that is characterized by insulin resistance and eventual functional failure of pancreatic beta cells. 2 The prevalence of type 2 diabetes has been increasing dramatically over the past few decades, 3 with projections . . .

Cardiometabolic comorbidities present a considerable burden for patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Both RA and PsA are associated with an increased risk of cardiovascular disease (CVD). PsA more often exhibits an increased risk of metabolically linked comorbidities such as obesity, insulin resistance, type 2 diabetes mellitus and non-alcoholic fatty liver disease. Although both RA and PsA are characterized by a state of chronic inflammation, the mechanisms that contribute to CVD risk in these conditions might not be identical. In RA, systemic inflammation is thought to directly contribute to CVD risk, whereas in PsA, adiposity is thought to contribute to a notable metabolic phenotype that, in turn, contributes to CVD risk. Hence, appropriate management strategies that consider the increased risk of cardiometabolic comorbidities in patients with inflammatory arthropathy are important. In RA, such strategies should focus on the prediction of CVD risk and its management through targeting chronic inflammation and traditional CVD risk factors. In PsA, management strategies should additionally focus on targeting metabolic components, including weight management, which might not only help improve disease activity in the joints, entheses and skin, but also reduce the risk of metabolic comorbidities and improve the quality of life of patients.

Among patients with heart failure and a reduced ejection fraction, those who received the SGLT2 inhibitor empagliflozin had a significantly lower incidence of cardiovascular death or hospitalization for heart failure than those who received placebo.