Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms

Abstract

Objective: Insulin resistance is increased by inflammation, but the mechanisms are unclear. The present study was undertaken to test the hypothesis that decreased insulin sensitivity is differentially associated with mediators of inflammation by studying 2 chronic inflammatory diseases of different pathogenesis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods: We measured fasting insulin, glucose, and lipid levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and coronary artery calcification in 103 patients with SLE and in 124 patients with RA. Insulin sensitivity was measured using the homeostasis model assessment (HOMA) index.

Results: The HOMA value was higher in RA patients (median 2.05 [interquartile range (IQR) 1.05-3.54]) than in SLE patients (1.40 [0.78-2.59]) (P = 0.007). CRP and ESR did not differ significantly in RA and SLE patients. Body mass index (BMI) was significantly correlated with the HOMA index in both RA (rho = 0.20) and SLE (rho = 0.54), independently of age, sex, race, and current use of corticosteroids. In RA patients, the HOMA index was also significantly positively correlated with IL-6 (rho = 0.63), TNFalpha (rho = 0.50), CRP (rho = 0.29), ESR (rho = 0.26), coronary calcification (rho = 0.26), and Disease Activity Score in 28 joints (rho = 0.21); associations adjusted for age, sex, race, BMI, and current use of corticosteroids remained significant (P < 0.05). In SLE patients, the HOMA index was also significantly correlated with ESR (rho = 0.35) and CRP (rho = 0.25), but not with other variables. The association between the ESR and the HOMA value in patients with SLE remained significant after adjustment for confounding covariates (P = 0.008). In multivariable models, the major contributing factors to the HOMA index were the BMI in SLE patients, and IL-6 and TNFalpha levels in RA patients.

Conclusion: The pathogenesis of insulin resistance and its contribution to atherogenesis varies in different inflammatory settings.

Figures

Figure 1

Relationship between body mass index (BMI) (A), interleukin-6 (IL-6) (B), and tumor necrosis factor α (TNFα) (C) and the homeostasis model assessment (HOMA) index in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A is adjusted for age, sex, race, and current use of corticosteroids, TNFα, IL-6, and C-reactive protein (CRP). P < 0.001 for SLE slope, P = 0.02 for RA slope, and P = 0.04 for interaction. B is adjusted for age, sex, race, BMI, current use of corticosteroids, TNFα, and CRP. P = 0.17 for SLE slope, P < 0.001 for RA slope, and P < 0.01 for interaction. C is adjusted for age, sex, race, BMI, current use of corticosteroids, IL-6, and CRP. P = 0.21 for SLE slope, P < 0.001 for RA slope, and P = 0.16 for interaction.