Insulin resistance in patients with rheumatoid arthritis:: effect of anti-TNFα therapy

Objectives: We undertook this study to test the hypotheses that patients with active rheumatoid arthritis (RA) are insulin resistant and that anti-tumour necrosis factor-alpha (TNF alpha) therapy improves not only the clinical state of these patients but also their glucose metabolism. Methods: Nine RA patients with active disease and nine healthy subjects, matched for sex, age, and body mass index (BMI), underwent a hyperinsulinaemic euglycaemic clamp. The RA patients received anti-TNF alpha therapy with Humira (R)(adalimumab) and had the insulin clamp re-evaluated after 8 weeks of treatment. Results: Patients with RA had marked insulin resistance (glucose infusion rate (GIR) area under the curve (AUC) was 499 +/- 55 mg/kg in the RA group compared to 710 +/- 77 mg/kg in the control group; p < 0.05). However, insulin sensitivity did not differ before and after 8 weeks of adalimumab therapy. The RA patients demonstrated a reduction in C-reactive protein (CRP) and interleukin-6 (IL-6) levels after the therapy as compared to pretreatment values, but there was no concomitant effect on plasma levels of TNF alpha. Conclusion: RA patients with active disease showed marked insulin resistance that was not influenced by anti-TNF alpha therapy despite a reduction in systemic inflammation during the treatment.