Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis

Background: Free fatty acids (FFAs) affect insulin signaling and are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines such as interleukin-6 (IL-6) increase lipolysis and thus levels of FFAs. We hypothesized that increased IL-6 concentrations are associated with increased FFAs resulting in insulin resistance and atherosclerosis in rheumatoid arthritis (RA). Methods: Clinical variables, serum FFAs and inflammatory cytokines, homeostasis model assessment for insulin resistance (HOMA-IR), and coronary artery calcium were measured in 166 patients with RA and 92 controls. We compared serum FFAs in RA and controls using Wilcoxon rank sum tests and further tested for multivariable association by adjusting for age, race, sex and BMI. Among patients with RA, we assessed the relationship between serum FFAs and inflammatory cytokines, HOMA-IR, and coronary artery calcium scores using Spearman correlation and multivariable regression analyses. Results: Serum FFAs did not differ significantly in patients with RA and controls (0.56. mmol/L [0.38-0.75] and 0.56. mmol/L [0.45-0.70] respectively, p= 0.75). Presence of metabolic syndrome was associated with significantly increased serum FFAs in both RA and controls (p= 0.035 and p= 0.025). In multivariable regression analysis that adjusted for age, race, sex and BMI, serum FFAs were associated with HOMA-IR (p= 0.011), CRP (p= 0.01), triglycerides (p= 0.005) and Framingham risk score (p= 0.048) in RA, but not with IL-6 (p= 0.48) or coronary artery calcium score (p= 0.62). Conclusions: Serum FFAs do not differ significantly in patients with RA and controls. FFAs may contribute to insulin resistance, but are not associated with IL-6 and coronary atherosclerosis in RA.