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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.

PurposeLow 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.MethodsUK 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.ResultsComplete 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.ConclusionsOur 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.

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.

Metabolic Syndrome and Incident Diabetes Current state of the evidence Earl S. Ford , MD, MPH 1 , Chaoyang Li , MD, PHD 1 and Naveed Sattar , MD, PHD 2 1 Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia 2 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland Corresponding author: Earl Ford, eford{at}cdc.gov Abstract OBJECTIVE —Our objective was to perform a quantitative review of prospective studies examining the association between the metabolic syndrome and incident diabetes. RESEARCH DESIGN AND METHODS —Using the title terms “diabetes” and “metabolic syndrome” in PubMed, we searched for articles published since 1998. RESULTS —Based on the results from 16 cohorts, we performed a meta-analysis of estimates of relative risk (RR) and incident diabetes. The random-effects summary RRs were 5.17 (95% CI 3.99–6.69) for the 1999 World Health Organization definition (ten cohorts); 4.45 (2.41–8.22) for the 1999 European Group for the Study of Insulin Resistance definition (four cohorts); 3.53 (2.84–4.39) for the 2001 National Cholesterol Education Program definition (thirteen cohorts); 5.12 (3.26–8.05) for the 2005 American Heart Association/National Heart, Lung, and Blood Institute definition (five cohorts); and 4.42 (3.30–5.92) for the 2005 International Diabetes Federation definition (nine cohorts). The fixed-effects summary RR for the 2004 National Heart, Lung, and Blood Institute/American Heart Association definition was 5.16 (4.43–6.00) (six cohorts). Higher number of abnormal components was strongly related to incident diabetes. Compared with participants without an abnormality, estimates of RR for those with four or more abnormal components ranged from 10.88 to 24.4. Limited evidence suggests fasting glucose alone may be as good as metabolic syndrome for diabetes prediction. CONCLUSIONS —The metabolic syndrome, however defined, has a stronger association with incident diabetes than that previously demonstrated for coronary heart disease. Its clinical value for diabetes prediction remains uncertain. Footnotes Published ahead of print at http://care.diabetesjournals.org on 30 June 2008. The findings and conclusions in this article are those of the authors and do not represent the official position of the Centers for Disease Control and Prevention. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact. Accepted June 12, 2008. Received February 28, 2008. DIABETES CARE

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.