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Corticosteroids increase the risk of diabetes mellitus in RA and contribute to the risk of myocardial infarction and heart failure
... Among these risk factors is insulin resistance, which is reported to be associated with inflammation and glucocorticoid therapy in RA (2,(4)(5)(6). In addition, RA patients experience a diabetes prevalence of 10-20% (7)(8)(9), and diabetes predicts increased rates of cardiovascular events in this disease (8,9). ...
... Among these risk factors is insulin resistance, which is reported to be associated with inflammation and glucocorticoid therapy in RA (2,(4)(5)(6). In addition, RA patients experience a diabetes prevalence of 10-20% (7)(8)(9), and diabetes predicts increased rates of cardiovascular events in this disease (8,9). ...
... Cumulative doses of glucocorticoids were strongly associated with enhanced beta cell function in the present cohort. In a longitudinal investigation, glucocorticoid therapy accounted for the increased incidence of diabetes in RA (8). These apparently contrasting findings may again relate to differences in glucocorticoid use. ...
To identify factors that regulate glucose metabolism in rheumatoid arthritis (RA).
We evaluated the homeostatic model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in 94 RA patients. We investigated the relationship between characteristics known to affect glucose metabolism in the general population (age, abdominal obesity [waist circumference], hypertension, antihypertensive therapy) as well as characteristics of RA (disease activity, glucocorticoid therapy) and insulin resistance and beta cell function.
Patients with high-grade inflammation (high-sensitivity C-reactive protein value >1.92 mg/liter) (n = 81) were more insulin resistant than patients with low-grade inflammation (n = 13), whereas beta cell function was similar in both groups. Insulin resistance and beta cell function were similar in both groups after adjustment for waist circumference. All recorded characteristics except for age were associated with HOMA-IR or/and HOMA-B in univariate analyses. In mixed regression models, abdominal obesity and patient's assessment of disease activity (by visual analog scale) were predictors of insulin resistance. The Disease Activity Score assessed using 28-joint counts for swelling and tenderness, tender joint count, and patient's assessment of disease activity were associated with reduced beta cell function, and the cumulative dose of glucocorticoids was associated with enhanced beta cell function. The cumulative glucocorticoid dose in all study patients was a mean of only 536 mg (95% confidence interval 239-1,173). In patients with high-grade inflammation, age was further associated with impaired beta cell function, whereas use of angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers was associated with enhanced beta cell function.
The modifiable factors of abdominal obesity, antihypertensive therapy, disease activity, and use of glucocorticoids appear to affect glucose metabolism in RA.
... Recently some studies have shown an increased presence of IR in patients with RA [15,16]. RA patients also experience a prevalence of impaired glucose tolerance (IGT) of 10e20% [17,18]. ...
... The increased atherosclerotic risk in RA have been explained by various factors including lipid profiles [19] and prolong steroid therapy [17,18] which have been elucidated as the reasons for continued risk of CVD in these RA patients with disease progression. Till date, only a few studies have reported the concurrent presence of IR and increased risk of CVD in RA patients [20e22]. ...
Background:
The continued atherosclerotic risk in rheumatoid arthritis (RA) has been inadequately explained by conventional factors. Chronic inflammation and endothelial activation seems responsible for developing insulin resistance (IR). The study was aimed to assess the role of inflammation and endothelial activation causing IR in long term RA patients leading to increased atherosclerotic risk.
Methods:
Fifty (25 long-duration and 25 short-duration) RA patients and twenty-three healthy controls were recruited excluding potential confounding co-morbidities. Fasting insulin, proinflammatory cytokines, endothelial stress markers and adipokines were quantified by ELISA. Homeostasis Model Assessment (HOMA)-IR calculated using glucose and insulin values. Atherosclerotic indices were measured using ultrasound.
Results:
Lipid profile was comparable among groups. Mean carotid intima media thickness (cIMT) was significantly higher in both RA groups (p = 0.0062) compared to controls. HOMA-IR was significantly higher in long-duration RA (p = 0.005); it showed significant associations with DAS 28 (p = 0.01) and hsCRP (p = 0.03) in this subset. Mean cIMT for short-duration RA (p = 0.02) and long-duration RA (p = 0.0006) respectively was also significantly associated with HOMA-IR. Pro-inflammatory markers like TNF-α, resistin and leptin were highest in long-duration RA, higher in short-duration RA when compared to control group respectively. HOMA-IR was significantly dependent on TNF-α (p = 0.008), resistin (p = 0.031), leptin (p = 0.0054). Mean cIMT showed association with all parameters mainly with TNF-α (p = 0.001), iNOS (p = 0.001), resistin (p = 0.008) and leptin (p = 0.04).
Conclusions:
Persistent inflammation leads to altered adipokine secretion promoting IR in RA patients with long disease duration. Treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) is incomplete to control chronic inflammation and limit progression of atherosclerosis.
... Also, the glucocorticoid therapy which is widely used for the treatment of RA have also the potential to adversely affect beta cell function and predispose to insulin resistance [10][11][12]. In addition, RA patients experience a diabetes prevalence of 10-20% [13][14][15], and diabetes predicts increased rates of cardiovascular events in this disease [14,15]. ...
... Also, the glucocorticoid therapy which is widely used for the treatment of RA have also the potential to adversely affect beta cell function and predispose to insulin resistance [10][11][12]. In addition, RA patients experience a diabetes prevalence of 10-20% [13][14][15], and diabetes predicts increased rates of cardiovascular events in this disease [14,15]. ...
Background
Insulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.
Aim of the work
To study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.
Patients and Methods
Forty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.
Results
RA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.
Conclusions
In RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.
... Subsequently, an adjusted model was made including indication, type of bDMARD (ADA/ETN), gender, and the most common combination therapies, i.e. MTX and/or corticosteroids, as independent variables [18][19][20][21][22]. Due to limited data, other variables like comorbidities could not be included in this analysis. ...
Background
Previous studies showed a discrepancy between health care professionals’ (HCPs’) and patients’ perspective on adverse drug reaction (ADR) burden. However, it is unclear which factors make an ADR burdensome. We aimed to give insight in why ADRs are perceived as burdensome by inflammatory rheumatic disease (IRD) patients, and whether this differs from the HCPs’ perspective.
Research design and methods
A qualitative study was conducted using XXX. Participants received bimonthly questionnaires on experienced ADRs attributed to biological DMARDs and were asked to elaborate on ADR burden using a Likert-type scale and an open-ended question for clarification. Data of 440 IRD patients were analysed following thematic analysis. Similar analysis was done with semi-structured interviews with 13 HCPs.
Results
We identified seven themes associated with ADR burden: ‘effect on medication prescription’, ‘impact on appearance’, ‘impact on autonomy’, ‘impact on daily life’, ‘psychological consequences’, ‘distressing aspects of ADR’, and ‘physical consequences’. Identical themes were identified by HCPs, although they identified most subthemes in ‘psychological consequences’, and less subthemes in ‘impact on daily life’ and ‘impact on autonomy’.
Conclusion
Patients describe perceived ADR burden in both physical and psychological themes. The HCPs’ perspective is comparable, but mostly focuses on psychological impact.
... Subsequently, an adjusted model was made including indication, type of bDMARD (ADA/ETN), gender, and the most common combination therapies, i.e. MTX and/or corticosteroids, as independent variables [18][19][20][21][22]. Due to limited data, other variables like comorbidities could not be included in this analysis. ...
Background
The extent to which adverse drug reactions (ADRs) of biologics differ per immune-mediated inflammatory disease (IMID), and the relevance of tailoring ADR information per IMID is not fully investigated. We aimed to compare patient-reported ADRs attributed to adalimumab and etanercept between different inflammatory rheumatic diseases (IRDs).
Research design and methods
ADR reports from IRD patients were extracted from the Dutch Biologic Monitor. ADR frequencies were compared using Fischer–Freeman–Halton exact test and the influence of covariates was assessed using binomial logistic regression.
Results
A total, of 729 participants were included, of which 354 participants reported 887 unique ADRs. ADR frequencies were not significantly different between the IRDs. Rheumatoid arthritis and ankylosing spondylitis including axial spondyloarthritis patients had an increased risk of ADRs related to ‘Respiratory, thoracic and mediastinal disorders’ and as compared to psoriatic arthritis patients. Etanercept use, combination therapy with methotrexate and/or corticosteroids, and age also influenced the risk of reporting specific ADRs.
Conclusions
There were no differences in frequencies and nature of patient-reported ADRs attributed to adalimumab and etanercept between different IRDs. However, more research is needed to align patients’ and health-care professionals’ perspectives to improve knowledge on disease-specific ADRs.
... Apart from systemic inflammation, continuous glucocorticoid use also independently predicts insulin resistance in RA 46 . In keeping with the latter, Wolfe and Michaud showed that prednisone use predicts the development of diabetes mellitus, a metabolic syndrome feature that was complicated by an increased risk for CV events in RA 47 . Overt or subclinical hypothyroidism was found to occur in 24% of RA patients and untreated subclinical hypothyroidism was independently associated with insulin resistance 48 . ...
Rheumatoid arthritis (RA) is an autoimmune, symmetrical polyarticular disease that affects primarily the diarthrodial joints, which is characterized by chronic inflammation of the synovial joints. Microalbuminuria occur leakage of small amounts of albumin into the urine, when there is an abnormal high permeability for albumin in the renal glomerulus of kidney. Microalbuminuria is generally associated with elevated levels of several inflammatory factors in the presence or absence of hypertension or diabetes. It is clear that kidney is involved in RA with both glomerular and tubular damage. Renal disease in RA however is usually asymptomatic and is detected only on laboratory investigations. It is often difficult to differentiate between damage due to disease activity and that due to drugs used to treat RA. Microalbuminuria is one of the important biomarker involved in various disorders in related to RA. The present review work bounces limelight on role of microalbuminuria in RA as well as in relation with other disorders.
... Epidemiological studies investigating the relationship between GC exposure and CVD burden in RA patients have provided conflicting results. Most of the studies support an harmful effect of GC: it has been shown that patients receiving GC are at increased risk of heart failure, AMI, stroke, early atherosclerosis and overall CVD mortality [26][27][28][29]. It has also been suggested that GC may interact with RF status to modulate the occurrence of CV events: in a 2007 study on 603 RA patients, RF positive but not RF negative patients were at increased CVD risk after exposure to GC [30]. ...
Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis with increased mortality largely attributable to cardiovascular disease. There is extensive evidence that patients with RA experience accelerated atherosclerosis, which is considered as the main responsible of this increased cardiovascular burden. Nowadays atherosclerosis is regarded as an inflammatory condition: hence, the cumulative inflammation of RA, with the abundant synthesis of proinflammatory cytokines, contributes directly to the early formation of the atheromatic plaque. It is therefore reasonable to postulate that, by alleviating inflammation, drugs commonly used in RA treatment may ameliorate the cardiovascular profile of these patients. Here we provide an extensive review of the literature, focusing on the effects of the available anti-rheumatic agents on cardiovascular mortality, and morbidity among RA sufferers.
... 15 In retrospective studies in patients with RA, GC exposure was shown to correlate with insulin resistance, 16 and to predict diabetes. 17 On the other hand, the use of GCs in chronic infl ammatory states may improve glucose tolerance by their anti-infl ammatory effects, as was demonstrated in a number of short-term studies using GC treatment; 18 19 this was also shown in a study using methotrexate. 20 In addition, confounding by indication should be kept in mind when evaluating the relation between GC use and glucose tolerance in patients with RA in observational studies. ...
To compare glucose tolerance and parameters of insulin sensitivity and β-cell function between chronic glucocorticoid (GC)-using and GC-naive patients with rheumatoid arthritis (RA).
Frequently sampled 75 g oral glucose tolerance tests were performed in 58 chronic GC-using and 82 GC-naive patients with RA with established disease, with no known type 2 diabetes mellitus (T2DM), and 50 control subjects of comparable age with normal glucose tolerance. The associations between cumulative GC dose and disease characteristics and glucose tolerance state, insulin sensitivity and β-cell function were tested using multivariate linear and logistic regression models, correcting for patient characteristics.
Glucose tolerance state, insulin sensitivity and β-cell function did not differ between the two RA populations; de novo T2DM was detected in 11% and impaired glucose metabolism in 35% of patients with RA. In patients with RA, cumulative GC dose was associated with T2DM, which seemed mostly driven by the effects of cumulative GC dose on insulin resistance; however, the association decreased when corrected for current disease activity. Patients with RA had decreased insulin sensitivity and impaired β-cell function compared with controls, and multivariate regression analyses showed a negative association between the presence of RA and insulin sensitivity.
GC-using and GC-naive patients with RA had comparable metabolic parameters, and had decreased insulin sensitivity and β-cell function as compared with healthy controls. Although cumulative GC dose was shown to have a negative impact on glucose tolerance state and insulin sensitivity, confounding by indication remains the main challenge in this cross-sectional analysis.
... Corticosteroids have been used as bridge therapy in combination therapy trials to control inflammation until DMARD therapy takes effect [11, 53] . However, corticosteroids are associated with an increased incidence of acute myocardial infarction, heart failure, diabetes mellitus, herpes, and osteoporosis54555657 . Implementation of measures to prevent osteoporosis and close monitoring of the patient are critical during use of these agents. ...
Early, aggressive disease management is critical for halting disease progression and joint destruction in patients with rheumatoid arthritis. Combination therapy with at least two disease-modifying antirheumatic drugs, such as methotrexate (MTX), sulfasalazine, or hydroxychloroquine, is often more effective than monotherapy in reducing disease activity. Biologic therapies represent more effective and tolerable treatment options that, when combined with MTX, have been shown to dramatically reduce inflammation, inhibit radiographic progression, and induce remission. Although several types of treatment strategies are used in clinical practice, the most aggressive approaches that target early disease have shown the most promise in reversing disease progression and reducing disease-related costs.
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