Impact of disease activity on impaired glucose metabolism in patients with rheumatoid arthritis.

OBJECTIVE: To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). METHODS: This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of ß-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. RESULTS: RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient's global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (ß = 0.206, P = 0.014; ß = 0.192, P = 0.009; ß = 0.121, P = 0.005; ß = 0.148, P = 0.007; ß = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (ß = 0.090, P = 0.022; ß = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2-2.5) vs. 1.2 (0.8-1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9-1.9) vs. 1.2 (0.8-1.4), P = 0.375]. CONCLUSIONS: RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.

Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity.

BACKGROUND: To evaluate association between von Willebrand factor (vWF) activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA) and low cardiovascular risk. METHODS: Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years). Intima-media thickness (IMT) was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%), none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately. RESULTS: RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05). Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP), modified Health Assessment Questionnaire (p<0.01 for all), duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all), and anti-CCP antibodies (p<0.01). In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05) or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05) than in those without. Duration of smoking was significantly associated with vWF activity (ß 0.026, p = 0.039). CONCLUSIONS: We demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of early atherosclerosis in RA patients.