Abatacept Improves Whole-Body Insulin Sensitivity in Rheumatoid Arthritis

Abstract

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.

Risk of diabetes mellitus associated with disease-modifying antirheumatic drugs and statins in rheumatoid arthritis

“…Immunologically, ABA may slow the decline of pancreatic β-cell functions in type 1 DM,41 though its effects on type 2 DM are unknown. Our results, along with evidence from a recent study reporting improvement in insulin sensitivity with 6 months ABA treatment in 15 patients with RA,42 suggest ABA has favourable effects on insulin resistance. Nevertheless, considering the relatively lower number of patients taking ABA (N=839), investigation in a larger sample is needed.…”

Complement C3 and fatty liver disease in Rheumatoid arthritis patients: a cross-sectional study

“…Complement system activation [22] has been shown in liver biopsies from patients with NAFLD compared to healthy controls [23]. Moreover, our group previously demonstrated a significant association between complement C3 and insulin resistance (IR) in psoriatic arthritis (PsA) [26,27] and RA patients [28][29][30]. Moreover, our group previously demonstrated a significant association between complement C3 and insulin resistance (IR) in psoriatic arthritis (PsA) [26,27] and RA patients [28][29][30].…”

“…More recently, circulating C3 levels have been demonstrated to predict the presence of NAFLD in large cohorts from general population independently of the most plausible confounders such as MS and obesity [24,25]. Moreover, our group previously demonstrated a significant association between complement C3 and insulin resistance (IR) in psoriatic arthritis (PsA) [26,27] and RA patients [28][29][30].…”

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“…Hence, insulin resistance could be considered as an important marker of excess adipose tissue-related inflammation. Of interest, anti-TNF-α agents were ineffective in reducing insulin resistance in obese RA patients 28 . In contrast, rituximab therapy was successfully used for treating patients with type B syndrome of severe insulin resistance 29 .…”