Non-diabetic Rheumatoid Arthritis Patients Research Articles

Changes in metabolic parameters and serum YKL-40 levels in Chinese rheumatoid arthritis patients during tocilizumab therapy.

To investigate the metabolic changes during therapy of tocilizumab (TCZ) and methotrexate (MTX) in non-diabetic rheumatoid arthritis (RA) patients and for the first time explore the associations between metabolic parameters and serum YKL-40 (sYKL-40) levels. We enrolled active non-diabetic RA patients who were refractory to MTX. Patients received intravenous TCZ (8mg/kg) once every 4weeks combined with MTX for 24weeks. Metabolic parameters and sYKL-40 levels were measured before TCZ infusion at baseline, week 4, week 12, and week 24. Correlations were assessed by the Spearman's rank correlation analysis. A total of 91 non-diabetic RA patients were enrolled in this study. At week 24, we observed a significant elevation in body mass index (BMI), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels. In contrast, there was a significant decrease in TC/HDL‑C ratio. No apparent changes in insulin resistance were found. Additionally, we detected a significant reduction in sYKL-40 levels during the study. At week 24, changes in sYKL-40 levels showed a significant negative correlation (r = -0.334, p = 0.002) with changes in TC levels. The combined therapy of TCZ and MTX resulted in a significant increase in BMI and lipid levels, while an evident decrease in the TC/HDL‑C ratio and sYKL-40 levels in RA patients. Additionally, there was a significant correlation between the decrease in sYKL-40 levels and the increase in TC levels during treatment with TCZ and MTX. Key Points • Lipid levels elevated significantly and sYKL-40 levels decreased obviously after therapy of TCZ combined with MTX in Chinese RA patients. • There was a significant correlation between the increase in TC levels and the decrease in sYKL-40 levels during treatment with TCZ and MTX in RA patients.

Clinical Features of Diabetes Mellitus on Rheumatoid Arthritis: Data from the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group.

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are linked by underlying inflammation influencing their development and progression. Nevertheless, the profile of diabetic RA patients and the impact of DM on RA need to be elucidated. This cross-sectional study includes 1523 patients with RA and no episodes of cardiovascular events, followed up in 10 Italian University Rheumatologic Centers between 1 January and 31 December 2019 belonging to the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group of the Italian Society of Rheumatology. The demographic and clinical features of DM RA patients were compared to non-diabetic ones evaluating factors associated with increased risk of DM. Overall, 9.3% of the RA patients had DM, and DM type 2 was more common (90.2%). DM patients were significantly older (p < 0.001), more frequently male (p = 0.017), with a significantly higher BMI and mean weight (p < 0.001) compared to non-diabetic patients. DM patients were less likely to be on glucocorticoids (p < 0.001), with a trend towards a more frequent use of b/ts DMARDs (p = 0.08), and demonstrated higher HAQ (p = 0.001). In around 42% of patients (n = 114), DM diagnosis preceded that of RA. Treatment lines were identical in diabetic and non-diabetic RA patients. DM is a comorbidity that may influence RA management and outcome. The association between DM and RA supports the theory of systemic inflammation as a condition underlying the development of both diseases. DM may not have a substantial impact on bDMARDs resistance, although further investigation is required to clarify the implications of biological therapy resistance in RA patients.

Role of adiponectin in non-diabetic patients with rheumatoid arthritis undergoing anti-IL-6 therapy.

Adiponectin is an adipokine that plays a relevant role in the development of metabolic syndrome (MetS), a complication that increases the risk of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). Accordingly, we assessed for the first time the short-term effect of anti-IL-6 receptor tocilizumab (TCZ) administration on adiponectin serum levels in RA patients and explored the potential association of adiponectin levels with MetS features, other CV risk factors and demographic and clinical characteristics of these patients. Adiponectin serum levels were evaluated in 50 non-diabetic RA patients, undergoing TCZ treatment, immediately prior to (pre-infusion) and 60 minutes after the end of a TCZ intravenous infusion (post-infusion). No significant differences in adiponectin levels pre- and post-TCZ infusion were found in RA patients (p=0.69). Patients with obesity exhibited decreased basal levels of adiponectin with respect to those non-obese (p=0.03). Additionally, a negative association of adiponectin basal levels with body mass index, insulin, insulin/glucose index, C-peptide and leptin levels (p<0.01; p=0.02; p=0.03; p=0.03 and p=0.01, respectively), as well as a positive correlation with HDL-cholesterol levels (p<0.001) was seen. Our results support the claim that low adiponectin may contribute to the development of MetS and, consequently, CV disease in RA. Anti-IL-6 therapy does not seem to exert a short-term effect on adiponectin levels.

The Performance of Vascular Age in the Assessment of Cardiovascular Risk of Patients with Rheumatoid Arthritis.

Background. Cardiovascular (CV) disease risk prediction models developed for use in the general population have suboptimal performance in patients with rheumatoid arthritis (RA). Vascular age (VA) is a new concept that has been proposed as a measure of CV ‘relative’ risk instead of the ‘absolute’ risk that current prediction models provide. In the present study we aim to study the performance of vascular age (VA) in the assessment of CV risk in patients with RA. We additionally aimed to analyze its relation with subclinical atherosclerosis as measured through carotid plaque ultrasound. Methods. A total of 1173 non-diabetic RA patients without previous CV events were included. Disease characteristics, SCORE, VA determined on SCORE and on carotid intima media thickness (cIMT), and the presence of plaque through carotid ultrasound were assessed. The interrelations of VA with SCORE, and its associations with subclinical carotid atherosclerosis were studied. Results. On average, RA patients had both a SCORE determined VA (4.7 years) and a cIMT-based VA (2.4 years) significantly higher than the chronological age. When these differences were analyzed in different age intervals, while VA based on SCORE was significantly higher compared to chronological age in all age ranges, VA determined on cIMT was significantly elevated only in RA patients younger than 60 years. The area under the curve analysis for the association of SCORE and VA with the presence of carotid plaque disclosed no differences between both parameters. VA was associated with the presence of carotid plaque after multivariable regression analysis in patients younger than 60 years old. Conclusion. VA is significantly higher than chronological age in patients with RA. The performance of VA in its relation to carotid plaque is similar to that of the SCORE.

Glycated albumin (GA) and inflammation: role of GA as a potential marker of inflammation.

Abnormal levels of glycated albumin (GA) are associated with the onset of both diabetes and inflammation. Although inflammation has long been associated with diabetes, this article aims to explore the underlying mechanisms of this relationship as it pertains to the role of GA. We have reviewed 52 research articles since the year 2000. Common search terms used were "(inflammatory mediator) and GA" or "inflammation and GA". The findings have been organized according to diabetic complications with respect to the interactions of GA and inflammatory mediators. Glycated albumin and specific inflammatory mediators have been reported to play various roles in the pathogenesis of insulin resistance, atherosclerosis, coronary artery disease, retinopathy, and nephropathy. In the case of nephropathy and recently retinopathy, there is considerable evidence for GA in concert with inflammation playing a direct role in organ pathology. There is copious literature detailing GA's involvement in stimulating inflammatory markers and certain pro-inflammatory cytokines. A recent clinical study has shown GA to be a marker for inflammation in non-diabetic rheumatoid arthritis patients with the significance of standard inflammatory markers. The clinical utility of GA measurement may likely reside in its versatility as both a mediator of inflammation as well as a marker to track hyperglycemia and other diabetes complications. Further understanding of the role GA plays in glycemic and inflammatory diseases could lead to its acceptance as an independent bio-inflammatory marker.

Prevalence of Undiagnosed Diabetes in Rheumatoid Arthritis: an OGTT Study.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an excess of cardiovascular disease (CVD) risk, estimated to be at least 50% greater when compared to the general population. Although the widespread diffusion of type 2 diabetes mellitus (T2DM) awareness, there is still a significant proportion of patients with T2DM that remain undiagnosed. Aim of this cross-sectional study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in RA patients.For the present study, 100 consecutive nondiabetic RA patients were recruited. Age- and sex-matched subjects with noninflammatory diseases (osteoarthritis or fibromyalgia) were used as controls. After overnight fasting, blood samples were obtained for laboratory evaluation including serum glucose, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, uric acid, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (ACPA). A standard Oral Glucose Tolerance Test (OGTT) with 75 g of glucose was performed and blood samples were collected at time 0, 30, 60, 90, and 120 minutes, for measurement of plasma glucose concentrations.The prevalence of impaired fasting glucose (IFG) (9/100 vs 12/100, P = 0.49), impaired glucose tolerance (IGT) (19/100 vs 12/100, P = 0.17), and concomitant IFG/IGT (5/100 vs 9/100, P = 0.27) was similar between groups, whereas the prevalence of diabetes was significantly higher in RA patients (10/100 vs 2/100, P = 0.02). In a logistic regression analysis, increasing age (OR = 1.13, 95% CI 1.028–1.245, P = 0.01) and disease duration (OR = 1.90, 95% CI 1.210–2.995, P = 0.005) were both associated with an increased likelihood of being classified as prediabetes (i.e. IFG and/or IGT) or T2DM. A ROC curve was built to evaluate the predictivity of disease duration on the likelihood of being diagnosed with T2DM. The area under the ROC curve was 0.67 (95% CI: 0.56–0.78, P = 0.004). We identified the best cut-off of 33 months that yielded a sensitivity of 61% and a specificity of 70% for classification of T2DM patients.According to our data, RA seems to be characterized by an elevated prevalence of undiagnosed diabetes, especially in patients with longer disease duration.

Prevalence of Atherosclerosis in diabetic and non-diabetic patients with rheumatoid arthritis.

Objectives:(1) To compare the prevalence of preclinical atherosclerosis in diabetic vs. non-diabetic rheumatoid arthritis (RA) patients; (2) to determine the influence of classical and RA-related factors on atherosclerosis; (3) to assess the usefulness of combined carotid and femoral ultrasonography in detecting atherosclerosis.Methods:The study comprised 42 non-diabetic RA patients, 42 diabetic RA patients and 42 controls. Intima media thickness (IMT) was measured in the common carotid and superficial femoral arteries. These vessels were screened for atherosclerotic plaque.Results:Plaque was more prevalent in diabetic RA patients than in non-diabetic RA patients or controls. Carotid IMT and femoral IMT were higher in diabetic RA patients compared to controls. So was femoral IMT in diabetic compared to non-diabetic RA patients. The prevalence of increased IMT and plaque was comparable in carotid ultrasonography and combined carotid and femoral ultrasonography in all groups.Conclusions:Subclinical atherosclerosis was found to be higher in diabetic RA patients than in non-diabetic RA patients. The combination of carotid and femoral artery ultrasonography did not improve the detection of atherosclerosis in RA.

FRI0138 The importance of cystatin c as a predictor of accelerated atherosclerosis in premenopausal non-diabetic patients with rheumatoid patients

BackgroundLife expectancy in rheumatoid arthritis (RA) patients is reduced by 3-10 years mainly due to cardiovascular diseases. Cystatin C is a basic microprotein, widely distributed in human tissues and body...

THU0056 Impaired beta cell signaling is present in non diabetic rheumatoid arthritis patients

ObjectivesIt has been suggested that resistance to insulin action is a feature that accompanies rheumatoid arthritis (RA), a disease where chronic inflammation predominates and classical triggers for insulin resistance (IR)...

Impaired beta cell function is present in nondiabetic rheumatoid arthritis patients

IntroductionTo investigate how markers of β-cell secretion (proinsulin-processing metabolites) are expressed in rheumatoid arthritis (RA) patients and their potential relation with the insulin resistance (IR) observed in these patients.MethodsThe 101 RA patients and 99 nondiabetic sex- and age-matched controls were included. IR by homeostatic model assessment (HOMA2), and β-cell secretion, as measured by insulin, split and intact proinsulin, and C-peptide levels were determined for both groups. Multiple regression analysis was performed to compare IR between groups and to explore the interrelations between RA features, proinsulin metabolites, and IR. Data were adjusted for glucocorticoids intake and for IR classic risk factors.ResultsCompared with controls, RA patients showed higher HOMA-IR (β coef., 0.40 (95% CI, 0.20 to 0.59); P = 0.00). When data were adjusted for glucocorticoids intake, noncorticosteroid patients maintained a higher IR index (β, 0.14 (0.05 to 0.24); P = 0.00). Impaired insulin processing in RA patients was detected by the onset of elevated split proinsulin levels (β, 0.70 pmol/L (0.38 to 1.02); P = 0.00). These data remained significant also when adjusted for prednisone intake (β, 0.19 (0.00 to 0.36) pmol/L; P = 0.04). Split proinsulin-to-C-peptide ratios were higher in RA patients undergoing corticosteroid therapy (β, 0.25 (0.12 to 0.38); P = 0.03) and were nearly significant in comparison between noncorticosteroids patients and controls (β, 0.16 (-0.02 to 0.34); P = 0.08). Interestingly, the impact of HOMA-IR on the ratio of intact proinsulin to C-peptide was higher in controls compared with patients (β, 6.23 (1.41 to 11.06) versus 0.43 (-0.86 to 1.71); P = 0.03).Conclusionsβ-Cell function is impaired in nondiabetic and in RA patients not taking corticoids by a mechanism that seems to be, at least in part, independent of IR.

Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: a longitudinal study

IntroductionRheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to both classical risk factors and chronic inflammation. We assessed longitudinally the factors associated with new carotid plaques in nondiabetic RA patients and apparently healthy individuals.MethodsIn our present prospective observational study, carotid plaques were identified by ultrasonography at baseline and follow-up end, separated by an average of 3.6 ± 0.2 years, in 64 patients (mean age 59.2 ± 12.0 and disease duration at baseline 7.8 ± 6.2 years, 83% women, clinical and laboratory evaluation every 3 to 6 months). In a substudy, 35 of the patients were matched 1:1 for traditional cardiovascular risk factors with 'healthy' controls and were studied in parallel.ResultsNew atherosclerotic plaques formed in 30% of patients (first plaque in 9%) who were significantly older than the remaining patients. Tobacco use, blood pressure, body mass index, average cumulative low-density lipoprotein, high-sensitivity C-reactive protein, erythrocyte sedimentation rate level, RA stage, functional class, disease duration and treatment modalities during follow-up did not differ significantly between subgroups after application of the Bonferroni correction. RA was in clinical remission, on average, for approximately 70% of the follow-up time and was not different between subgroups. Multivariate analysis including all the above parameters revealed that age (P = 0.006), smoking (P = 0.009) and duration of low-dose corticosteroid use (P = 0.016) associated independently with new plaque formation. RA patients displayed similar numbers of newly formed carotid plaques to the tightly matched for traditional cardiovascular risk factors 'healthy' controls, although more patients than controls had carotid plaques at baseline.ConclusionsFormation of new atherosclerotic plaques in this small cohort of patients with well-controlled RA depended mainly on traditional cardiovascular risk factors and corticosteroid use, whereas an adverse effect of residual systemic inflammation was not readily detectable.

Increased fructosamine in non-diabetic rheumatoid arthritis patients: role of lipid peroxides and glutathione

Modification of proteins by non-enzymatic glycation is one of the underlying factors known to play a major role in the pathogenesis of many clinical disorders. Glycation of plasma proteins is enhanced by elevated glucose concentrations. However, increased fructosamine has been documented in rheumatoid arthritis patients without any history of diabetes. Collective evidence reveals that malondialdehyde and reduced glutathione can modulate the glycation process. This study was undertaken to unravel the possible association of malondialdehyde and glutathione with fructosamine in rheumatoid arthritis patients. A case-control study was performed on 15 rheumatoid arthritis patients and 15 control subjects. Whole blood glutathione, plasma malondialdehyde, fructosamine and fasting glucose were analyzed in both groups. Partial correlation analysis was performed to predict the independent association of malondialdehyde, glutathione and fasting glucose on fructosamine. In rheumatoid arthritis patients, while fructosamine and malondialdehyde levels were significantly increased, glutathione levels were significantly decreased compared with controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with malondialdehyde and a negative correlation with glutathione. These data suggest that plasma fructosamine levels are closely associated with malondialdehyde and glutathione in rheumatoid arthritis patients, warranting extra precaution in interpreting fructosamine as a measure of glycemic control in these patients.

The advanced glycation end product pentosidine correlates to IL-6 and other relevant inflammatory markers in rheumatoid arthritis

Oxidative stress and inflammatory processes accelerate the formation of advanced glycation end products (AGE), e.g. of pentosidine. The aim of this study was to investigate the relationships between levels of pentosidine in serum and synovial fluid, proinflammatory cytokines, other markers of inflammatory activity, and the state of radiologically visible bone destruction in patients with rheumatoid arthritis (RA). One hundred thirty-three nondiabetic RA patients and 56 age-matched, healthy subjects were included. Serum and synovial fluid pentosidine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor levels were determined. In 30 patients, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha and the soluble receptors sIL-2R, sIL-6R, sTNF-alpha, and RI/RII were also measured. Serum levels of pentosidine were on average significantly higher in RA patients than in healthy subjects and correlated significantly to ESR, CRP, and serum levels of IL-6. Serum and synovial fluid pentosidine did not show any differences. Rheumatoid factor-positive RA patients had higher pentosidine levels in the synovial fluid than rheumatoid factor-negative patients. Correlations could not be found between pentosidine and the other cytokines or cytokine receptors measured. The binding of AGE on cell receptors induces activation of nuclear factor kappa B, resulting in enhanced synthesis of proinflammatory cytokines. Moreover, AGE generation may also lead to the formation of new, immunologically relevant epitopes at synovial proteins. Both mechanisms could contribute to initiation and perpetuation of the inflammatory and destructive processes in RA.