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Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis.

ABSTRACT: Recent reports have suggested that increasing adiposity may protect against radiographic damage in rheumatoid arthritis (RA). We explored the role of serum adipokines (adiponectin, resistin, and leptin) in mediating this association.Patients with RA underwent total-body dual x-ray absorptiometry for measurement of total and regional body fat and lean mass, abdominal computed tomography for measurement of visceral fat area, and radiographs of the hands and feet scored according to the modified Sharp/van der Heijde (SHS) method. Serum levels of adipokines were measured and cross-sectional associations with radiographic damage were explored, adjusting for pertinent confounders. The associations of measures of adiposity with radiographic damage were explored with the introduction of adipokines into multivariable modeling as potential mediators.Among the 197 patients studied, adiponectin demonstrated a strong association with radiographic damage, with the log SHS score increasing by 0.40 units for each log unit increase in adiponectin (P = 0.001) after adjusting for pertinent predictors of radiographic damage. Adiponectin independently accounted for 6.1% of the explainable variability in SHS score, a proportion comparable with rheumatoid factor, and greater than HLA-DRB1 shared epitope alleles or C-reactive protein levels. Resistin and leptin were not associated with radiographic damage in adjusted models. An inverse association between visceral fat area and radiographic damage was attenuated when adiponectin was modeled as a mediator. The association of adiponectin with radiographic damage was stronger in patients with longer disease duration.Adiponectin may represent a mechanistic link between low adiposity and increased radiographic damage in RA. Adiponectin modulation may represent a novel strategy for attenuating articular damage.

SUBMITTER: Giles JT

PROVIDER: S-EPMC2759038 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis.

Giles Jon T JT Allison Matthew M Bingham Clifton O CO Scott William M WM Bathon Joan M JM

Arthritis and rheumatism 20090901 9

<h4>Objective</h4>Recent reports have suggested that increasing adiposity may protect against radiographic damage in rheumatoid arthritis (RA). We explored the role of serum adipokines (adiponectin, resistin, and leptin) in mediating this association.<h4>Methods</h4>Patients with RA underwent total-body dual x-ray absorptiometry for measurement of total and regional body fat and lean mass, abdominal computed tomography for measurement of visceral fat area, and radiographs of the hands and feet s ...[more]

PMID: 19714593

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Project description:INTRODUCTION: Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA. METHODS: In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n?=?632) or had undifferentiated arthritis (UA) (n?=?159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ? 5 in total Sharp-van der Heijde Score (?SHS) between inclusion and 1 year (?SHS ?1 or rapid radiographic progression: ?SHS ?5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion). RESULTS: Adiponectin level was independently associated with baseline total SHS (adjusted ??=?0.12; P?=?0.006). It was also associated with ?SHS ?1 (adjusted odds ratio (aOR)?=?1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR?=?1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ?SHS ?5 (aOR?=?2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ?SHS >0 (aOR?=?1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 ?g/ml for ?SHS ?1 and 6.04 ?g/ml for ?SHS ?5, with a good specificity (58% and 75% for ?SHS ?1 and ?SHS ?5, respectively) and high negative predictive values (75% and 92% for ?SHS ?1 or ?SHS ?5, respectively). CONCLUSION: Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status.

Dataset Information

Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis.

Publications

Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis.

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