Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis

Abstract

Objective: Obesity protects against radiographic joint damage in rheumatoid arthritis (RA) through poorly defined mechanisms. Adipocytokines are produced in adipose tissue and modulate inflammatory responses and radiographic joint damage in animal models. The purpose of this study was to examine the hypothesis that adipocytokines modulate inflammation and radiographic joint damage in patients with RA.

Methods: We compared serum concentrations of leptin, resistin, adiponectin, and visfatin in 167 RA patients and 91 control subjects. The independent association between adipocytokines and body mass index (BMI), measures of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNFalpha]), and radiographic joint damage (Larsen score; n = 93 patients) was examined in RA patients by multivariable regression analysis first controlling for age, race, and sex, and then for obesity (BMI) and inflammation (TNFalpha, IL-6, and CRP).

Results: Concentrations of all adipocytokines were significantly higher in RA patients than in controls; for visfatin and adiponectin, this association remained significant after adjusting for BMI, inflammation, or both. Visfatin concentrations were associated with higher Larsen scores, and this association remained significant after adjustment for age, race, sex, disease duration, BMI, and inflammation (odds ratio [OR] 2.38 [95% confidence interval (95% CI) 1.32-4.29], P = 0.004). Leptin concentrations showed a positive association with the BMI (rho = 0.58, P < 0.01) and showed a negative association with the Larsen score after adjustment for inflammation (OR 0.32 [95% CI 0.17-0.61], P < 0.001), but not after adjustment for BMI (OR 0.86 [95% CI 0.42-1.73], P = 0.67).

Conclusion: Concentrations of adipocytokines are increased in patients with RA and may modulate radiographic joint damage. Visfatin is associated with increased, and leptin with reduced, levels of radiographic joint damage.

Conflict of interest statement

Disclosures: None of the authors has a conflict of interest related to this work.

Figures

Figure 1. The Association between RA and Adipocytokines (n=167)

The association between RA and each individual adipocytokine was assessed using linear regression adjusted with a base model (age, sex and race), with BMI (base + BMI), inflammation (base + TNF-α, IL-6, and CRP), and both (base + BMI + inflammation). 10b: Exponentiated linear regression coefficient of disease status (RA vs. controls). 10b denotes the ratio of the mean adjusted serum adipocytokine concentrations of RA vs. controls. The translated percent difference with 95% CI is depicted on the figure.

Figure 2. The Association between Larsen Score and Adipocytokines (n=93)

OR: Odds ratio per IQR change of adipocytokine. The association of each individual adipocytokine with Larsen Score was assessed using proportional odds logistic regression adjusted with a base model (age, sex, race and disease duration), with BMI (base + BMI), inflammation (base + TNF-agr;, IL-6, and CRP), and both (base + BMI + inflammation).