Understanding the Role of the Complement System in Insulin Resistance and Metabolic Syndrome in Patients With Rheumatoid Arthritis.

Objective: The complement system has been associated with the etiopathogenesis of rheumatoid arthritis (RA). Insulin resistance (IR) and metabolic syndrome (MetS) are prevalent among patients with RA. The aim of this study was to explore the relationship between a comprehensive evaluation of the complement system and IR, as well as MetS, in patients with RA.

Methods: A total of 339 nondiabetic patients with RA were recruited. Functional assays of the 3 complement pathways were assessed. Additionally, serum levels of the following individual components of the complement system were measured: C1q (classical); lectin (lectin); C2, C4, and C4b (classical lectin); factor D and properdin (alternative); C3 and C3a (common); C5, C5a, and C9 (terminal); as well as the factor I and C1 inhibitor regulators. IR and β cell function indices were calculated using the homeostatic model assessment. Criteria for MetS were applied. Multivariable linear regression analysis was performed to investigate the association between the complement system and IR in patients with RA.

Results: Many elements of the upstream and common complement pathways, but not the functional tests of the 3 routes, correlated positively with higher levels of IR and β cell function. However, after multivariable adjustment for factors associated with IR, these relationships were lost. Conversely, the presence of MetS in patients with RA maintained a relationship with higher levels of C1q, C4, C3, properdin, and factor I after adjusting for confounders.

Conclusion: There is a positive correlation between the complement system and MetS among nondiabetic patients with RA. This association is independent of traditional IR factors.