The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

Ursini, Francesco; Russo, Emilio; Ruscitti, Piero; Giacomelli, Roberto; Sarro, Giovambattista De

doi:10.1016/j.autrev.2017.11.030

Cited by 25 publications

(20 citation statements)

References 58 publications

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“…[21,22] The optimal management of both inflammatory disease and metabolic comorbidity may lead to a beneficial impact on CVD and on management of these patients. [23,24] Insulin resistance is a key pathophysiological process leading to the development and progression of T2D and we observed that the IL-1 blocking agent improved IR in RA patients with comorbid T2D. Conversely, we did not observe a similar effect in a matched population treated with TNFis.…”

Section: Discussioncontrasting

confidence: 56%

IL-1 inhibition improves insulin resistance and adipokines in rheumatoid arthritis patients with comorbid type 2 diabetes

et al. 2019

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Recently, it has been shown that some well-known pathogenic mediators in rheumatoid arthritis (RA), such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), could play a pathogenic role in insulin resistance and (IR) and type 2 diabetes (T2D). In this 6-month longitudinal study, we aimed at investigating if the inhibition of IL-1 or TNF is associated with an improvement of IR in RA patients with comorbid T2D and the possible effects on selected serum adipokines. RA patients with comorbid T2D were recruited among those undergoing treatment with anakinra (ANA) or with TNF inhibitor (TNFi). The 1998-updated version of the Homeostasis Model Assessment (HOMA2) was used to calculate surrogate indexes of IR (HOMA2-IR) and steady-state beta cell function (%B) from fasting values of glucose and C-peptide. Glucagon, adiponectin, adipsin, leptin, and resistin were also measured. All these parameters were collected at baseline, after 3 and 6 months of treatment. ANA-treated patients showed a significant improvement in HOMA2-%β, HOMA2-IR, and glucagon. In TNFi-treated patients, no significant difference was observed analyzing these metabolic parameters. Adipsin and resistin decreased after 6 months in ANA-treated patients whereas, no difference was recognized analyzing adiponectin and leptin. In TNFi-treated patients, leptin and resistin significantly increased, whereas no difference was found analyzing adiponectin and adipsin, during the follow-up. Our data may suggest a beneficial effect of IL-1 inhibition on measures of metabolic derangement in RA-associated T2D. If further confirmed by larger studies, IL-1 targeting therapies may represent a tailored approach in these patients.

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Section: Discussioncontrasting

confidence: 56%

IL-1 inhibition improves insulin resistance and adipokines in rheumatoid arthritis patients with comorbid type 2 diabetes

et al. 2019

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“…Insulin resistance and T2D were shown as being highly prevalent in RA and to enhance the CV burden [51, 52]. Furthermore, T2D and RA could share pathogenic inflammatory pathways suggesting possible common therapeutic targets [53–55]. We also observed that participants with comorbid HBP were associated with enhanced risk of subclinical atherosclerosis.…”

Section: Discussionmentioning

confidence: 68%

Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study

et al. 2019

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Background: Rheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA. Methods: From January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical atherosclerosis and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis, and regression analyses exploited the ORs for the occurrence of those comorbidities. Results: We analysed 841 participants, mostly female (82.2%) and with median age of 60 years (range 21-90). The remission was achieved and maintained by 41.8% of participants during the follow-up. We observed an increased rate of subclinical atherosclerosis at the end of follow-up (139 vs 203 participants, p < 0.0001), particularly in participants with a disease duration less than 5 years at baseline (70 participants vs 133 participants, p < 0.0001). Type 2 diabetes (T2D) (OR 4.50, 95%CI 1.74-11.62, p = 0.002), high blood pressure (OR 2.03, 95%CI 1.04-4.14, p = 0.042), ACPA (OR 2.36, 95%CI 1.19-4.69, p = 0.014) and mean values of CRP during the follow-up (OR 1.07, 95%CI 1.03-1.14, p = 0.040) were significantly associated with higher risk of subclinical atherosclerosis. We observed an increased rate of clinical atherosclerosis at the end of follow-up (48 vs 76 participants, p < 0.0001). T2D (OR 6.21, 95%CI 2.19-17.71, p = 0.001) was associated with a significant risk of clinical atherosclerosis. The achievement and the maintenance of remission reduced the risk of subclinical (OR 0.25, 95%CI 0.11-0.56, p = 0.001) and clinical atherosclerosis (OR 0.20, 95%CI 0.09-0.95, p = 0.041).

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“…The authors found that active patients with RA with concomitant T2DM could achieve their treatment goals for both diseases (DAS28 <2.6 and HbA1c <7%) after taking anakinra 36. Evidence from another study showed that some non-tumour necrosis factor targeting biologics and small molecules (such as tocilizumab and abatacept) may have a role in improving insulin sensitivity 37. Under the setting of limited healthcare budgets, these targeted molecules with additional therapeutic effects for comorbidities are a strongly perceived need 38.…”

Section: Discussionmentioning

confidence: 99%

Dose–response associations between metabolic indexes and the risk of comorbid type 2 diabetes mellitus among rheumatoid arthritis patients from Northern China: a case–control study

Chi

Bai

et al. 2019

BMJ Open

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ObjectiveTo investigate whether there were any differences in the patterns of metabolic abnormalities between patients with rheumatoid arthritis (RA) with comorbid type 2 diabetes mellitus (T2DM) and other populations, and to plot the dose–response relationships between metabolic indexes and the risk of comorbid T2DM among patients with RA.Design and settingThis is a retrospective case–control study using electronic medical records (EMRs). Patients with RA and/or T2DM or controls who were admitted to the First Affiliated Hospital of China Medical University between April 2008 and December 2016 were retrospectively recruited through the EMR system. After age-matching and sex-matching, 261 controls, 274 patients with T2DM, 276 patients with RA and 151 patients with RA+T2DM were eventually recruited.ResultsPatients with RA+T2DM exhibited higher levels of systolic blood pressure (SBP), fasting plasma glucose (FPG) and triglyceride (TG) than the RA only patients. Moreover, the proportions of impaired fasting glucose (IFG), and total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) dyslipidaemia in the RA+T2DM group were higher than those in the RA alone group (for IFG: 28.48% vs 18.84%, p=0.02; for TC: 25.17% vs 15.22%, p=0.01; for LDL-C: 25.83% vs 17.03%; p=0.03). Rheumatoid factor (RF) positivity and IFG were independent risk indicators for comorbid T2DM among patients with RA (for RF positivity: OR=0.45; 95% CI: 0.29 to 0.69; p<0.001; for IFG: OR=1.70; 95% CI: 1.04 to 2.76; p=0.03).ConclusionLinear dose–response associations between SBP, TC, TG and the risk of comorbid T2DM among patients with RA were observed, whereas a non-linear dose–response association between FPG and the risk of comorbid T2DM was found. Patients with RA+T2DM were more likely to exhibit metabolic abnormalities than RA only patients. Patients with RA+T2DM with metabolic abnormalities deserve more attention from rheumatologists and endocrinologists.

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The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

Cited by 25 publications

References 58 publications

IL-1 inhibition improves insulin resistance and adipokines in rheumatoid arthritis patients with comorbid type 2 diabetes

IL-1 inhibition improves insulin resistance and adipokines in rheumatoid arthritis patients with comorbid type 2 diabetes

Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study

Dose–response associations between metabolic indexes and the risk of comorbid type 2 diabetes mellitus among rheumatoid arthritis patients from Northern China: a case–control study

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