Fibromyalgia is a chronic disorder of uncertain etiology, characterized by widespread pain, muscle tenderness, and decreased pain threshold to pressure and other stimuli. Obesity is a well-known aggravating factor for certain rheumatologic conditions, such as knee osteoarthritis. Emerging evidences are exploring the link between obesity and other rheumatic diseases, such as fibromyalgia. Epidemiological data show that fibromyalgia patients have higher prevalence of obesity (40%) and overweight (30%) in multiple studies compared with healthy patients. Several mechanisms have been proposed to explain "the hidden link", but at this time is not possible to ascertain whether obesity is cause or consequence of fibromyalgia. Among mechanisms proposed, there are the following: impaired physical activity, cognitive and sleep disturbances, psychiatric comorbidity and depression, dysfunction of thyroid gland, dysfunction of the GH/IGF-1 axis, impairment of the endogenous opioid system. In this article, we review the scientific evidence supporting a possible link between obesity and fibromyalgia, how obesity influences fibromyalgia symptoms and how fibromyalgia severity can be improved by weight loss. In addition, we analyze the possible mechanisms by which fibromyalgia and obesity interrelate.

Allergic rhinitis can be associated with bronchial hyperresponsiveness (BHR), and carries an increased risk for the development of asthma. The aim of this study was to evaluate the ability of specific immunotherapy (SIT) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR. Forty-four subjects monosensitized to Dermatophagoides pteronyssinus, with perennial rhinitis and BHR to methacholine, were randomly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr. After 1 yr of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV(1) (PD(20)FEV(1)) was recorded in the SIT-treated group (95% confidence interval [CI]: 3.98- to 2.09-fold; p < 0.001), with a further increase to fourfold at the end of Year 2 (95% CI: 2.9- to 5.7-fold; p < 0.001). At the end of the study, the methacholine PD(20)FEV(1) was within the normal range in 50% of treated subjects (p < 0.0001), and was significantly higher in this group than in the group receiving placebo (p < 0.0001). In contrast, no changes in methacholine PD(20)FEV(1) were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with SIT did. This study suggests that SIT, when administered to carefully selected, monosensitized patients with perennial allergic rhinitis, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.

Rheumatoid arthritis (RA) is characterized by increased insulin resistance, a well-known risk factor for diabetes and cardiovascular diseases. The aim of the present study was to evaluate the effect of abatacept on insulin sensitivity in RA patients with moderate to severe disease despite treatment with methotrexate.Fifteen RA patients were recruited for the present study. Patients were evaluated at time 0 and after 6 months of the treatment with i.v. abatacept at the dosage recommended for weight range. Evaluation included oral glucose tolerance test (OGTT) at both time points. Insulin sensitivity was estimated with insulin sensitivity index (ISI) by Matsuda, a measure of whole-body insulin sensitivity.ISI significantly increased after the treatment with abatacept from 3.7 ± 2.6 to 5.0 ± 3.2 (P = 0.003) with a mean difference of 1.23. Analysis of glucose and insulin values during OGTT revealed a reduction of both glucose (303.9 ± 73.4 mg/dL min versus 269.2 ± 69.5 mg/dL min, P = 0.009) and insulin (208.4 ± 119.7 mg/dL min versus 158.0 ± 95.3 mg/dL min, P = 0.01) area under the curves (AUCs). Accordingly also glycated hemoglobin significantly improved (5.5 ± 0.4% versus 5.3 ± 0.3%, P = 0.04). No significant differences were found for measures of β-cell function insulinogenic index (1.11 ± 1.19 versus 1.32 ± 0.82, P = 0.77) and oral disposition index (2.0 ± 5.4 versus 6.0 ± 6.0, P = 0.25).Treatment with abatacept seems to be able to improve whole-body insulin sensitivity in RA patients without affecting β-cell function.

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 = .49), impaired glucose tolerance (IGT) (19/100 vs 12/100, P = .17), and concomitant IFG/IGT (5/100 vs 9/100, P = .27) was similar between groups, whereas the prevalence of diabetes was significantly higher in RA patients (10/100 vs 2/100, P = .02). In a logistic regression analysis, increasing age (OR = 1.13, 95% CI 1.028–1.245, P = .01) and disease duration (OR = 1.90, 95% CI 1.210–2.995, P = .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 = .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.

Methotrexate (MTX) is a nonbiological disease-modifying antirheumatic drug that has shown both a good control of clinical disease and a good safety. Usually drug-drug interactions (DDIs) represent the most limiting factor during the clinical management of any disease, in particular when several drugs are coadministered to treat the same disease. In this paper, we report the interactions among MTX and the other drugs commonly used in the management of rheumatoid arthritis. Using Medline, PubMed, Embase, Cochrane libraries, and Reference lists, we searched for the articles published until June 30, 2012, and we reported the most common DDIs between MTX and antirheumatic drugs. In particular, clinically relevant DDIs have been described during the treatment with MTX and NSAIDs, for example, diclofenac, indomethacin, or COX-2 inhibitors, and between MTX and prednisone or immunosuppressant drugs (e.g., leflunomide and cyclosporine). Finally, an increase in the risk of infections has been recorded during the combination treatment with MTX plus antitumor necrosis factor-α agents. In conclusion, during the treatment with MTX, DDIs play an important role in both the development of ADRs and therapeutic failure.

The objective of this cross-sectional study is to investigate the relationship between inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, and complement C3) and insulin resistance (estimated with the surrogate measure homeostasis model assessment of insulin resistance (HOMA-IR)) in Psoriatic arthritis (PsA) patients. Sixty-seven patients with PsA and 138 age- and sex-matched controls were recruited from the Rheumatology Outpatient Clinic of the University of Catanzaro, Catanzaro (Italy). Plasma glucose, insulin, triglycerides, total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol were measured after at least 12-h fasting. CRP was measured by a high-sensitivity turbidimetric immunoassay. ESR was measured by capillary photometry. Serum C3 and C4 were measured by nephelometry. Insulin resistance was estimated using the original HOMA as reported by Matthews et al. (Diabetologia 28(7):412-419, 1985) from overnight fasting insulin and glucose values, with the following formula: HOMA-IR = glucose (in milligrams per deciliter) × insulin (in micro units per milliliter)/405. Patients and controls had similar body mass index (BMI), blood pressure, and fasting glucose, but fasting serum insulin was higher in PsA patients (median (interquartile range (IQR)) 12.96 (6.35-24.65) for PsA and 10.37 (6.97-15.11) for controls; p = 0.005). Consequently, also the surrogate measure of insulin resistance HOMA-IR was significantly higher in patients (median (IQR) 3.77 (1.58-5.18) for PsA and 2.33 (1.67-3.62) for controls; p = 0.008). In univariate analysis, ln(HOMA-IR) correlated positively with BMI, systolic blood pressure (sBP), dBP, ln(TG), WBC, ln(ESR), ln(CRP) and C3, while correlated negatively with total and HDL cholesterol. In multiple linear regression analysis including age, sex and BMI, serum C3 reached the higher standardized β coefficient, while among other variables only ln(ESR) maintained a weak correlation with ln(HOMA-IR) when sBP was added to the model. When all variables were inserted in a single model, only C3 was independently correlated with ln(HOMA-IR). In a stepwise multiple regression model, serum C3 was selected as the strongest single contributing variable. The model explained 61 % of the variance in ln(HOMA-IR) (R (2) = 0.61). Insulin resistance, estimated with the surrogate measure HOMA-IR, is higher in PsA patients compared to age- and sex-matched controls. Serum C3 could represent a simple marker of insulin resistance in psoriatic arthritis patients.

ObjectivesTo evaluate the correlation between inflammatory measures and whole-body insulin sensitivity in psoriatic arthritis (PsA) patients.MethodsFor the present study, 40 nondiabetic PsA patients were recruited. A standard oral glucose tolerance test (OGTT) was performed. The insulin sensitivity index (ISI), insulinogenic index (IGI) and oral disposition index (ODI) were calculated from dynamic values of glucose and insulin obtained during OGTT.ResultsIn our study population, mean ISI was 3.5 ± 2.5, median IGI was 1.2 (0.7–1.8), mean ODI 4.5 ± 4.5. In univariate correlation analysis, ISI correlated inversely with systolic blood pressure (sBP) (R = -0.52, p = 0.001), diastolic blood pressure (dBP) (R = -0.45, p = 0.004) and complement C3 (R = -0.43, p = 0.006) and ODI correlated inversely with sBP (R = -0.38, p = 0.02), dBP (R = -0.35, p = 0.03) and complement C3 (R = -0.37, p = 0.02). No significant correlations were found between analyzed variables and IGI. In a stepwise multiple regression, only complement C3 entered in the regression equation and accounted for approximately 50% of the variance of ISI. Using a receiver operating characteristic (ROC) curve we identified the best cut-off for complement C3 of 1.32 g/L that yielded a sensitivity of 56% and a specificity of 96% for classification of insulin resistant patients.ConclusionsIn conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients.

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