Resistin Levels in Lupus and Associations with Disease-specific Measures, Insulin Resistance, and Coronary Calcification

Division of Rheumatology, Department of Medicine
The Journal of Rheumatology (Impact Factor: 3.19). 09/2011; 38(11):2369-75. DOI: 10.3899/jrheum.110237
Source: PubMed


To evaluate levels of resistin in female subjects with systemic lupus erythematosus (SLE) compared to age and race-matched controls and to determine the relationship between resistin and systemic inflammation, disease measures, and coronary artery calcification (CAC).
Resistin levels were measured on stored samples from 159 women with SLE and 70 controls as an extension of a previous cross-sectional study. Spearman correlations and multivariable regressions were used to examine whether resistin levels were associated with SLE, disease-specific and inflammatory markers, insulin resistance, and CAC.
In a multivariable linear regression model, a diagnosis of SLE was significantly associated with higher resistin levels independent of age, race, renal function, body mass index (BMI), high-sensitivity CRP (hsCRP), hypertension, diabetes, and steroid use. In SLE, resistin levels correlated positively with Systemic Lupus International Collaborating Clinics Damage Index, glomerular filtration rate (GFR), hsCRP, erythrocyte sedimentation rate, homocysteine, and disease duration (all p < 0.03). Resistin level did not correlate with markers of insulin resistance or body adiposity, including homeostatic model assessment or BMI. Resistin levels were significantly elevated in SLE cases with CAC compared to cases without CAC (16.58 vs 13.10 ng/ml, respectively; p = 0.04). In multivariate logistic regression, the association was not present after adjustment for age, race, and GFR.
SLE was independently associated with higher resistin levels. Among subjects with SLE, higher resistin level correlated positively with renal dysfunction, inflammatory markers, and disease damage but not with insulin resistance or BMI. SLE cases with CAC had higher resistin levels than cases without CAC; however, this relationship was dependent on other established risk factors.

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    • "In contrast, high levels of adiponectin were observed in adult SLE and other inflammatory states. However, there has been no consistent correlation between adipokine levels and early markers of atherosclerosis in adult SLE [66-69]. A prospective study of pSLE patients found no significant difference in adiponectin levels between 105 pSLE patients and a group of healthy controls, although seven pSLE subjects had elevated levels [70]. "
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    ABSTRACT: Cardiovascular morbidity and mortality are becoming major health concerns for adults with inflammatory rheumatic diseases. The enhanced atherogenesis in this patient population is promoted by the exposure to traditional risk factors as well as nontraditional cardiovascular insults, such as corticosteroid therapy, chronic inflammation and autoantibodies. Despite definite differences between many adult-onset and pediatric-onset rheumatologic diseases, it is extremely likely that atherosclerosis will become the leading cause of morbidity and mortality in this pediatric patient population. Because cardiovascular events are rare at this young age, surrogate measures of atherosclerosis must be used. The three major noninvasive vascular measures of early atherosclerosis - namely, flow-mediated dilatation, carotid intima-media thickness and pulse wave velocity - can be performed easily on children. Few studies have explored the prevalence of cardiovascular risk factors and even fewer have used the surrogate vascular measures to document signs of early atherosclerosis in children with pediatric-onset rheumatic diseases. The objective of this review is to provide an overview on cardiovascular risk and early atherosclerosis in pediatric-onset systemic lupus erythematosus, juvenile idiopathic arthritis and juvenile dermatomyositis patients, and to review cardiovascular preventive strategies that should be considered in this population.
    Full-text · Article · May 2013 · Arthritis research & therapy
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    • "Although resistin was initially associated with metabolic disorders, increased levels of resistin and its positive correlation with inflammatory markers and disease activity have been previously demonstrated in patients with rheumatoid arthritis (RA) [4,18-20]. In a study by Almehed and colleagues, serum resistin levels did not differ between patients with systemic lupus erythematosus (SLE) and healthy controls [21]; whereas in another study, SLE was independently associated with higher resistin levels [22]. Moreover, in both studies, the levels of resistin positively correlated with inflammatory markers, disease-specific measures and renal dysfunction. "
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    ABSTRACT: The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. The results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies.
    Full-text · Article · May 2012 · Arthritis research & therapy
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    • "In another study, Krysiak et al. (2011) reported that plasma resistin was higher in normotensive CAD patients, particularly in the subgroup with reduced insulin sensitivity, than in the control group. Systemic lupus erythematosus subjects with coronary artery calcification had higher resistin levels than those without calcification, implying that resistin may be involved in coronary artery calcification (Baker et al. 2011). Four clinical studies evaluated the association of resistin with disease severity (Hu et al. 2007, Ohmori et al. 2005, Wang et al. 2009) and occurrence (Krecki et al. 2011). "
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    ABSTRACT: Resistin has been implicated in coronary atherosclerotic disease and congestive heart failure. Recent studies have extended its involvement in peripheral artery disease. Despite some controversial data, the mainstream clinical literature supports that resistin is associated with both coronary and peripheral artery diseases including ischemic stroke. In this review, the multiple roles of resistin as screening, diagnostic, and prognostic marker for cardiovascular disease are discussed. The independence of resistin in disease prediction and diagnosis appears complicated by its confounders, such as C-reactive protein. A clear-cut biomarker function of resistin in cardiovascular disease needs be clarified by additional large-scale, well-designed prospective studies.
    Full-text · Article · Jan 2011 · Trends in cardiovascular medicine
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