Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European ...League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.
Aims/hypothesis
Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether ...cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance.
Methods
A cross-sectional study of non-diabetic and diabetic men and women (
n
= 7,529) aged 60–79 years with no previous myocardial infarction who underwent an examination was conducted. Measurements of anthropometry, blood pressure and fasting measurements of lipids, insulin, glucose and haemostatic and inflammatory markers were taken.
Results
Non-diabetic women tended to have more favourable risk factors and were less insulin resistant than non-diabetic men, but this was diminished in the diabetic state. Levels of waist circumference, BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR), diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA) and factor VIII differed more between diabetic and non-diabetic women than between diabetic and non-diabetic men (test for diabetes × sex interaction
p
< 0.05). The more adverse effect of diabetes on these risk markers in women was associated with, and thereby largely attenuated by, insulin resistance.
Conclusions/interpretation
The greater adverse influence of diabetes per se on adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial dysfunction and systemic inflammation in women compared with men may contribute to their greater relative risk of coronary heart disease.
Circumstantial evidence suggests that the innate immune system and coagulation system share a common evolutionary origin, which explains the extensive crosstalk between inflammatory cytokines and ...coagulation factors, with many components being important for both systems. This crosstalk has been extensively studied in sepsis, an acute state of high-grade inflammation. However, rheumatoid arthritis (RA) as well as many other autoimmune diseases can also be considered as a prothrombotic state. More and more studies show that autoimmune diseases, including RA, are a risk factor for cardiovascular disease, and also for venous thromboembolic events, such as pulmonary embolism and deep vein thrombosis. Inflammation and its effect on the haemostatic system is probably the link between these diseases. This viewpoint gives an update of the current literature on thromboembolic risk in RA, but also documents important knowledge gaps. This viewpoint will therefore help to focus on further research topics to improve diagnostic and therapeutic options which may relieve both the proinflammatory and the prothrombotic burden of autoimmune diseases.
Aims
To quantify the extent to which ethnic differences in muscular strength might account for the substantially higher prevalence of diabetes in black and South‐Asian compared with white European ...adults.
Methods
This cross‐sectional study used baseline data from the UK Biobank study on 418 656 white European, black and South‐Asian participants, aged 40–69 years, who had complete data on diabetes status and hand‐grip strength. Associations between hand‐grip strength and diabetes were assessed using logistic regression and were adjusted for potential confounding factors.
Results
Lower grip strength was associated with higher prevalence of diabetes, independent of confounding factors, across all ethnicities in both men and women. Diabetes prevalence was approximately three‐ to fourfold higher in South‐Asian and two‐ to threefold higher in black participants compared with white European participants across all levels of grip strength, but grip strength in South‐Asian men and women was ~ 5–6 kg lower than in the other ethnic groups. Thus, the attributable risk for diabetes associated with low grip strength was substantially higher in South‐Asian participants (3.9 and 4.2 cases per 100 men and women, respectively) than in white participants (2.0 and 0.6 cases per 100 men and women, respectively). Attributable risk associated with low grip strength was also high in black men (4.3 cases) but not in black women (0.4 cases).
Conclusions
Low strength is associated with a disproportionately large number of diabetes cases in South‐Asian men and women and in black men. Trials are needed to determine whether interventions to improve strength in these groups could help reduce ethnic inequalities in diabetes prevalence.
What's new?
In participants in the UK Biobank study, grip strength was significantly associated with odds of diabetes, independent of major confounding factors in all ethnic groups.
Grip strength was lower (by ˜ 5–6 kg) in South‐Asian men and women compared with black and white European men and women.
Lower grip strength combined with higher diabetes prevalence resulted in the attributable risk for diabetes associated with low grip strength being substantially higher in South‐Asian people (3.9 and 4.2 cases per 100 men and women) than in white people (2.0 and 0.6 cases). Attributable risk was also high in black men (4.3 cases) but not in black women (0.4 cases).
Aim
To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial).
Methods
Participants were aged 20–65 years, with type 2 diabetes ...duration of <6 years and BMI 27–45 kg/m2, and were not receiving insulin. Weight loss was initiated by total diet replacement (825–853 kcal/day, 3–5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions (HbA1c <48 mmol/mol <6.5%, without antidiabetes medications) in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m2) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss.
Results
Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma‐glutamyl transferase levels, and reporting better quality of life with less anxiety/depression. Lower baseline HbA1c was a predictor at 12 months, and older age and male sex were predictors at 24 months. Being prescribed antidepressants predicted non‐remission. Some, but not all effects were explained by weight loss. Weight loss was the strongest predictor of remission at 12 months (adjusted odds ratio per kg weight loss 1.24, 95% CI 1.14, 1.34; P < 0.0001) and 24 months (adjusted odds ratio 1.23, 95% CI 1.13, 1.35; P <0.0001). Weight loss in kilograms and percentage weight loss were equally good predictors. Early weight loss and higher programme attendance predicted more remissions. Baseline BMI, fasting insulin, fasting C‐peptide and diabetes duration did not predict remission.
Conclusions
Other than weight loss, most predictors were modest, and not sufficient to identify subgroups for which remission was not a worthwhile target.
Objective: Much has been written on the metabolic syndrome and related recent criteria. However, it remains unclear whether such criteria help clinical practice. This review will evaluate the ...usefulness of metabolic syndrome criteria to enhance risk prediction for either cardiovascular disease or diabetes. Design: This is a narrative review that is based on the author's experience from relevant publications from his group and from other related research. Results: Although the presence of metabolic syndrome, however defined, is clearly associated with higher risk for vascular disease, the criteria do not enhance coronary heart disease (CHD) prediction from simpler Framingham-based risk scores. The dichotomous nature of metabolic syndrome criteria--either you have it or you do not--combined with the lack of age, low-density lipoprotein cholesterol and smoking account for their inferior predictive value. Metabolic syndrome criteria are, in fact, more strongly associated with incident diabetes, an observation demonstrated in the West of Scotland Coronary Prevention Study (WOSCOPS). This is because three of the five parameters within metabolic syndrome criteria (waist, glucose and triglyceride) are more closely linked to risk for diabetes than risk for CHD. However, screening for prevalent or high risk of incident diabetes is a complex and debated issue and is by no means guaranteed to be widely adopted. Conclusions: Metabolic syndrome criteria do not offer benefits beyond established methods of vascular risk assessment. Thus, the focus in clinical practice should remain on established risk factors (for example, smoking, lipids, blood pressure) both to determine CHD risk, through established charts, and to reduce it.
Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an ...antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum.
We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire.
A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference -0.14 s.d., 95% confidence interval -0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (-0.49 to -0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (-35.34; -48.0 to -22.67; P<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; P<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet.
This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.
Aims
To evaluate the effects of dulaglutide vs placebo on liver and glycaemic/metabolic measurements in a population with Type 2 diabetes and in a subgroup with non‐alcoholic fatty ...liver/non‐alcoholic steatohepatitis.
Methods
A total of 1499 participants from AWARD‐1, AWARD‐5, AWARD‐8 and AWARD‐9 clinical trials were included in this analysis (dulaglutide 1.5 mg, n=971 and placebo, n=528). Thresholds of alanine aminotransferase levels ≥30 IU/l in men and ≥19 IU/l in women were used to determine the subgroup who had non‐alcoholic fatty liver/non‐alcoholic steatohepatitis. Objectives included changes from baseline to 6 months in: (1) alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels in the overall population and (2) alanine aminotransferase, aspartate transaminase, gamma‐glutamyl transpeptidase and glycaemic/metabolic measurements (e.g. HbA1c, fasting serum glucose, body weight, lipids and homeostatic model assessment) in the non‐alcoholic fatty liver/non‐alcoholic steatohepatitis subgroup.
Results
In the overall population at 6 months, dulaglutide significantly reduced alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels vs placebo least squares mean treatment differences: –1.7 IU/l (95% CI –2.8, –0.6), P=0.003; –1.1 IU/l (95% CI –2.1, –0.1), P=0.037; –6.6 IU/l (95% CI –12.4, –0.8), P=0.025, respectively. In the subgroup with non‐alcoholic fatty liver/non‐alcoholic steatohepatitis (alanine aminotransferase levels greater than or equal to the upper limit of normal), mean baseline liver enzyme values were 38.0 IU/l, 27.8 IU/l and 43.9 IU/l for alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase, respectively. In this population, more pronounced reductions from baseline in alanine aminotransferase were observed with dulaglutide vs placebo (–8.8 IU/l vs –6.7 IU/l). In the subgroup of people with alanine aminotransferase levels less than the upper limit of normal, changes from baseline in alanine aminotransferase did not significantly differ between treatment groups (0.0 IU/l vs 0.7 IU/l).
Conclusions
Once‐weekly dulaglutide improved alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels compared with placebo in a pattern consistent with liver fat reductions. Our results add further weight to the notion that glucagon‐like peptide‐1 receptor agonists may provide benefit in lowering liver fat in addition to their other metabolic actions.
What's new?
Non‐alcoholic fatty liver disease is present in >75% of people with Type 2 diabetes.
Dulaglutide is a once‐weekly glucagon‐like peptide‐1 receptor agonist approved for the treatment of Type 2 diabetes.
This analysis evaluated the effects of dulaglutide on liver and glycaemic/metabolic measurements in a subgroup of people with non‐alcoholic fatty liver/non‐alcoholic steatohepatitis and Type 2 diabetes.
Treatment response of dulaglutide in the subgroup was similar to that in the overall population.
Dulaglutide improved plasma aminotransferases and gamma‐glutamyl transpeptidase in a pattern consistent with liver fat reductions.
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