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.
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.
The changing face of diabetes complications Gregg, Edward W; Sattar, Naveed; Ali, Mohammed K
The lancet. Diabetes & endocrinology,
06/2016, Volume:
4, Issue:
6
Journal Article
Peer reviewed
The global increase in type 2 diabetes prevalence is well documented, but international trends in complications of type 2 diabetes are less clear. The available data suggest large reductions in ...classic complications of type 2 diabetes in high-income countries over the past 20 years, predominantly reductions in myocardial infarction, stroke, amputations, and mortality. These trends might be accompanied by less obvious, but still important, changes in the character of morbidity in people with diabetes. In the USA, for example, substantial reductions in macrovascular complications in adults aged 65 years or older mean that a large proportion of total complications now occur among adults aged 45-64 years instead, rates of renal disease could persist more than other complications, and obesity-related type 2 diabetes could have increasing effect in youth and adults under 45 years of age. Additionally, the combination of decreasing mortality and increasing diabetes prevalence has increased the overall mean years lived with diabetes and could lead to a diversification of diabetes morbidity, including continued high rates of renal disease, ageing-related disability, and cancers. Unfortunately, data on trends in diabetes-related complications are limited to only about a dozen countries, most of which are high income, leaving the changing character for countries of low and middle income ambiguous.
Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients ...with type 2 diabetes could be reduced or eliminated.
In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes.
The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range. Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval CI, 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death.
Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.).
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.
South Asians, particularly when living in high-income countries, are at a substantially elevated risk of type 2 diabetes compared with white Europeans, and typically develop the disease 5-10 years ...earlier and at a lower BMI. Migrant south Asians seem to be more insulin resistant than white Europeans across the life course and potentially experience β-cell exhaustion at a younger age. Differences in adiposity (high percentage of body fat and high proportion of deep subcutaneous and visceral fat) and skeletal muscle (low percentage of lean mass and low cardiorespiratory fitness) are likely to contribute these factors. No clear evidence is available suggesting genetic factors make a major contribution to the increased risk of diabetes in south Asians, but epigenetic factors might have a role. Irrespective of future mechanistic discoveries, south Asians need to be encouraged and helped-by various culturally appropriate methods--to maintain a high physical activity level and low bodyweight across the life course to prevent diabetes. In clinical terms, cardiovascular risks have attenuated over time in migrant south Asians with diabetes but retinopathy and renal complication risks remain high because of the high levels of glycaemia and rapid glycaemic deterioration noted in this population. We review these aspects and suggest areas for future research.
Men are well known to have a higher risk than women for cardiovascular disease. In recent years, however, studies show adult men also have higher risk for type 2 diabetes, an observation which has ...important clinical implications, particularly in the public health arena. This chapter explores the relevant data underlying this observation, examines potential mechanisms including life course changes in insulin resistance and role of adiposity, and discusses relevant clinical implications and solutions.
Data from basic science experiments is overwhelmingly supportive of the causal role of immune‐inflammatory response(s) at the core of atherosclerosis, and therefore, the theoretical potential to ...manipulate the inflammatory response to prevent cardiovascular events. However, extrapolation to humans requires care and we still lack definitive evidence to show that interfering in immune‐inflammatory processes may safely lessen clinical atherosclerosis. In this review, we discuss key therapeutic targets in the treatment of vascular inflammation, placing basic research in a wider clinical perspective, as well as identifying outstanding questions.
Linked Articles
This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc
Abstract
Aims
Little is known about the long-term association between low-carbohydrate diets (LCDs) and mortality. We evaluated the link between LCD and overall or cause-specific mortality using both ...individual data and pooled prospective studies.
Methods and results
Data on diets from the National Health and Nutrition Examination Survey (NHANES; 1999–2010) were analysed. Multivariable Cox proportional hazards were applied to determine the hazard ratios and 95% confidence intervals (CIs) for mortality for each quartile of the LCD score, with the lowest quartile (Q1—with the highest carbohydrates intake) used as reference. We used adjusted Cox regression to determine the risk ratio (RR) and 95% CI, as well as random effects models and generic inverse variance methods to synthesize quantitative and pooled data, followed by a leave-one-out method for sensitivity analysis. Overall, 24 825 participants from NHANES study were included (mean follow-up 6.4 years). After adjustment, participants with the lowest carbohydrates intake (quartile 4 of LCD) had the highest risk of overall (32%), cardiovascular disease (CVD) (50%), cerebrovascular (51%), and cancer (36%) mortality. In the same model, the association between LCD and overall mortality was stronger in the non-obese (48%) than in the obese (19%) participants. Findings on pooled data of nine prospective cohort studies with 462 934 participants (mean follow-up 16.1 years) indicated a positive association between LCD and overall (RR 1.22, 95% CI 1.06–1.39, P < 0.001, I2 = 8.6), CVD (RR 1.13, 95% CI 1.02–1.24, P < 0.001, I2 = 11.2), and cancer mortality (RR 1.08, 95% CI 1.01–1.14, P = 0.02, I2 = 10.3). These findings were robust in sensitivity analyses.
Conclusion
Our study suggests a potentially unfavourable association of LCD with overall and cause-specific mortality, based on both new analyses of an established cohort and by pooling previous cohort studies. Given the nature of the study, causality cannot be proven; we cannot rule out residual bias. Nevertheless, further studies are needed to extend these important findings, which if confirmed, may suggest a need to rethink recommendations for LCD in clinical practice.
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.
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