Caterina Bruno

Abatacept Improves Whole-body Insulin Sensitivity in Rheumatoid Arthritis: An Observational Study

AbstractRheumatoid 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 &bgr;-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 &bgr;-cell function.

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

AbstractRheumatoid 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.

Complement C3 Is the Strongest Predictor of Whole-Body Insulin Sensitivity in Psoriatic Arthritis.

Objectives To evaluate the correlation between inflammatory measures and whole-body insulin sensitivity in psoriatic arthritis (PsA) patients. Methods For 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. Results In 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. Conclusions In conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients.

Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy

Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a 36-year-old male patient presenting lesions on the right hand and arm. The infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Different clinical syndromes are described as a direct consequence of S. schenckii infection, including lymphocutaneous and disseminated forms, although extracutaneous presentations are reported most frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis under stable treatment with adalimumab monotherapy (40 mg every other week). During a routine follow-up visit in March 2013, he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm. After diagnostic aspiration of the lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy started.

Role of positron emission tomography for central nervous system involvement in systemic autoimmune diseases: status and perspectives.

In the last years, an increasing interest in molecular imaging has been raised by the extending potential of positron emission tomography [PET]. The role of PET imaging, originally confined to the oncology setting, is continuously extending thanks to the development of novel radiopharmaceutical and to the implementation of hybrid imaging techniques, where PET scans are combined with computed tomography [CT] or magnetic resonance imaging[MRI] in order to improve spatial resolution. Early preclinical studies suggested that 18F-FDG PET can detect neuroinflammation; new developing radiopharmaceuticals targeting more specifically inflammation-related molecules are moving in this direction. Neurological involvement is a distinct feature of various systemic autoimmune diseases, i.e. Systemic Lupus Erythematosus [SLE] or Behcets disease [BD]. Although MRI is largely considered the gold-standard imaging technique for the detection of Central Nervous System [CNS] involvement in these disorders. Several patients complain of neuropsychiatric symptoms [headache, epilepsy, anxiety or depression] in the absence of any significant MRI finding; in such patients the diagnosis relies mainly on clinical examination and often the role of the disease process versus iatrogenic or reactive forms is doubtful. The aim of this review is to explore the state-of-the-art for the role of PET imaging in CNS involvement in systemic rheumatic diseases. In addition, we explore the potential role of emerging radiopharmaceutical and their possible application in aiding the diagnosis of CNS involvement in systemic autoimmune diseases.

High Prevalence of Achilles Tendon Enthesopathic Changes in Patients with Type 2 Diabetes Without Peripheral Neuropathy.

BACKGROUND Metabolic disorders are known to alter the mechanical properties of tendons. We sought to evaluate the prevalence of asymptomatic Achilles tendon enthesopathic changes in patients with type 2 diabetes mellitus (T2DM) without peripheral neuropathy. METHODS We recruited 43 patients with T2DM and 40 controls. Neuropathy was excluded with the Michigan Neuropathy Scoring Instrument. Bilateral ultrasonography of the Achilles tendon enthesis was performed. RESULTS Patients with T2DM had a higher prevalence of hypoechogenicity (26.7% versus 2.5%; P = .0001), entheseal thickening (24.4% versus 8.7%; P = .007), and enthesophytes (74.4% versus 57.5%; P = .02). No differences were found in the number of patients with erosions (1.2% versus 0%; P > .99), cortical irregularities (11.6% versus 3.7%; P = .09), bursitis (5.8% versus 3.7%; P = .72), or tears (2.3% versus 1.2%; P > .99). The mean ± SD sum of abnormalities was higher in patients with T2DM (1.5 ± 1.1 versus 0.7 ± 0.6; P < .0001), as was the percentage of bilateral involvement (72.1% versus 45.0%; P = .01). Mean ± SD thickness did not differ between patients and controls (4.4 ± 1.1 mm versus 4.2 ± 0.8 mm; P = .07). CONCLUSIONS According to our data, there is an elevated prevalence of asymptomatic Achilles tendon enthesopathic changes in patients with T2DM independent of peripheral neuropathy.

Old But Good: Modified-Release Prednisone in Rheumatoid Arthritis

BACKGROUND Since more than 50 years glucocorticoids represent the milestone in the treatment of inflammatory diseases, including rheumatoid arthritis (RA). However, many patients with RA present a circadian rhythm in symptoms severity with a significant worsening in the morning, that correlates with cyclic changes in circulating hormones and cytokines. Classical steroid therapy given in the morning fails to intercept this pathophysiological phenomenon. In the last years, a novel formulation of prednisone has been developed in order to better fit these variations, improve efficacy and minimize adverse events (chronotherapy). This modified-release (MR) prednisone is administered in the evening at 10.00 p.m. and absorbed after about 4 hours. METHODS In this article, we reviewed the recent clinical trials evaluating the efficacy of MR prednisone in RA patients, including two randomized controlled double-blind clinical trials Circadian Administration of Prednisone in Rheumatoid Arthritis - 1 (CAPRA-1) and CAPRA-2 and other nonrandomized observational studies. RESULTS According to the available evidence, MR prednisone seems effective in ameliorating morning stiffness in RA patients. CONCLUSION In conclusion, the use of MR prednisone in the treatment regimen could be a costeffective choice in a significant proportion of RA patients, particularly in those with a clinical phenotype characterized by morning stiffness or morning recrudescence of pain. With regards to the safety, MR prednisone adverse events profile does not differ from that of IR glucocorticoids.

Plantar fascia enthesopathy is highly prevalent in diabetic patients without peripheral neuropathy and correlates with retinopathy and impaired kidney function

Background Aim of this study was to evaluate the prevalence of plantar fascia (PF) enthesopathy in Type 2 diabetes mellitus (T2DM) patients without distal peripheral neuropathy (DPN). Methods We recruited 50 T2DM patients without DPN and 50 healthy controls. DPN was excluded using the Michigan Neuropathy Screening Instrument (MNSI). All patients underwent a bilateral sonographicevaluation of the enthesealportion of the PF. Results PF thickness was significantly higher in T2DM patients (p<0.0001). T2DM patients presented a higher prevalence of entheseal thickening (p = 0.002), enthesophyte (p = 0.02) and cortical irregularity (p = 0.02). The overall sum of abnormalities was higher in T2DM patients (p<0.0001), as was the percentage of bilateral involvement (p = 0.005). In a logistic regression analysis, retinopathy predicted entheseal thickening (OR 3.5, p = 0.05) and enthesophytes (OR 5.13, p = 0.001); reduced eGFR predicted enthesophytes (OR 2.93, p = 0.04); body mass index (BMI) predicted cortical irregularity (OR 0.87, p = 0.05); mean glucose predicted enthesophyte (OR 1.01, p = 0.03); LDL cholesterol predicted cortical irregularity (OR 0.98, p = 0.02). Conclusions Our data suggest that T2DM is associated with PF enthesopathyindependently of DPN.

Serum Complement C3 and Type 2 Diabetes in Rheumatoid Arthritis: A Case-Control Study

BACKGROUND Recent evidence demonstrated a potential role of complement C3 as a candidate biomarker of cardiometabolic risk in the general population. OBJECTIVE Aim of the present study was to investigate the correlation between complement C3 levels and comorbid Type 2 Diabetes (T2DM) in Rheumatoid Arthritis (RA) patients. METHODS For the present study, 40 consecutive diabetic RA patients (RA/T2DM+ group) and 80 consecutive RA patients without diabetes (RA/T2DM- group) were recruited. RESULTS Patients in the RA/T2DM+ group were significantly older (p < 0.0001), had a longer RA duration (p < 0.0001) and higher disease activity (p = 0.006) compared to controls. Moreover, patients in the RA/T2DM+ group had significantly higher levels of ESR (p < 0.0001), CRP (p < 0.0001) and complement C3 (p < 0.0001). A logistic regression model was built to ascertain the effect of selected variables (age, RA duration, BMI, ESR, C3, lnCRP, corticosteroid use) on the likelihood that patients have T2DM. Longer RA duration, ESR and C3 were associated with an increased likelihood of being classified as T2DM. Finally, we built ROC curves to evaluate the predictivity of RA duration, complement C3 and the combination of both variables on the likelihood of being diagnosed with T2DM. The area under the ROC curve was 0.79 (p < 0.0001) for RA duration, 0.71 (p < 0.0001) for complement C3 and 0.89 (p < 0.0001) for the combination of both variables. CONCLUSION According to our data complement C3 levels can predict the presence of T2DM in RA patients.