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


CONCLUSIONS
The pathogenesis of insulin resistance and its contribution to atherogenesis varies in different inflammatory settings.
Chung
Cecilia P
CP
Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA.
Oeser
Annette
A
Solus
Joseph F
JF
Gebretsadik
Tebeb
T
Shintani
Ayumi
A
Avalos
Ingrid
I
Sokka
Tuulikki
T
Raggi
Paolo
P
Pincus
Theodore
T
Stein
C Michael
CM
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology; D001786:Blood Glucose; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis / Q000276:immunology; D002114:Calcinosis / Q000097:blood / Q000276:immunology; D003324:Coronary Artery Disease / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein