Date Published: July 12, 2017
Publisher: Public Library of Science
Author(s): Piero Ruscitti, Francesco Ursini, Paola Cipriani, Vasiliki Liakouli, Francesco Carubbi, Onorina Berardicurti, Giovambattista De Sarro, Roberto Giacomelli, Masataka Kuwana.
Despite of the European League Against Rheumatism (EULAR) provided different sets of recommendations for the management of cardiovascular risk in inflammatory arthritis patients, it must be pointed out that cardiometabolic comorbidity, such as type 2 diabetes (T2D), remains still underdiagnosed and undertreated in patients affected by rheumatoid arthritis (RA).
In this work, we designed a single centre, prospective study in order to better investigate the occurrence of T2D during the course of 1 year of follow-up. Furthermore, we evaluated the role of both traditional cardiovascular and RA-specific related risk factors to predict the occurrence of new T2D.
In this study, we evaluated 439 consecutive RA patients and we observed that 7.1% of our patients (31/439) developed T2D, after 12 month of prospective follow-up. The regression analysis showed that the presence of high blood pressure, the impaired fasting glucose (IFG) at the first observation and the poor EULAR-DAS28 response, after 12 months of follow–up, were significantly associated with an increased likelihood of being classified as T2D. Similarly, we observed that 7.7% of our patients (34/439) showed IFG after 12 months of prospective follow-up. The regression analysis showed that the presence of high blood pressure and the poor EULAR-DAS28 response after 12 months of follow-up, were significantly associated with an increased likelihood of showing IFG.
Our study supports the hypothesis of a significant short-term risk of T2D in RA patients and of a close associations between uncontrolled disease activity and glucose metabolism derangement. Further multicentre, randomised-controlled studies are surely needed in order to elucidate these findings and to better ascertain the possible contribution of different therapeutic regimens to reduce this risk.
Rheumatoid arthritis (RA) is a systemic, inflammatory, autoimmune disorder, mainly affecting the joints and associated with a reduction of quality of life . During RA, the therapeutic strategies are aimed at preventing joint destruction by using synthetic disease modifying antirheumatic drugs (sDMARDs) as well as biologic agents [2–5]. In addition, a growing body of evidence is focused on the development of associated comorbidities and their management in rheumatic patients [6–8]. In this context, it has been shown that a large percentage of RA patients can be affected by T2D, as reported by meta-analytic data [9,10]. This clinical phenotype may result from a sinergy between an elevated prevalence of traditional risk factors and pro-inflammatory milieu [11,12]. Furthermore, some well-known pathogenic pro-inflammatory mediators in RA, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), may play a pivotal role in the development of T2D, contributing to beta-cells disfunction and distruction and insulin resistance as observed in bone damage [13,14]. To date, early reports suggest that biologic agents commonly used to treat RA patients may be effective in controlling comorbid T2D in both preclinical and clinical settings [13–17].
Several studies showed the close relationship between RA and risk of cardiovascular disease (CVD) to a similar extent of that observed in T2D [33,34]. RA and T2D are independent risk factors for CVD and, therefore, patients affected by both these diseases may be considered at very higher risk of CVD and related mortality . On this background, identifying risk factors for T2D, which shows and increased incidence and prevalence during RA , could represent an attractive strategy contributing to overall CVD risk reduction and management of RA patients. On these bases, we planned the present study in order to evaluate the occurrence of new-onset T2D in RA patients in the short-term and to identify the possible predictors of T2D development, thus suggesting a possible synergistic interaction in determining a worse cardiovascular phenotype of RA patients with comorbid T2D [33–36].