Publications

OBJECTIVE

To determine the prevalence of obesity and how accurately standard anthropometric measures identify obesity among men and women with rheumatoid arthritis (RA).

METHODS

Dual x-ray absorptiometry (DXA) was performed for 141 persons with RA (56 men and 85 women). Two anthropometric proxies of obesity (body mass index [BMI] and waist circumference [WC]) were compared to a DXA-based obesity criterion. Receiver operating characteristic curves determined optimal cut points for each anthropometric measure, relative to DXA. The association of body fat and anthropometric obesity measures with disease status and cardiovascular risk was assessed in multiple regression analyses, controlling for age and glucocorticoid use. All analyses were performed separately for men and women.

RESULTS

A total of 20%, 32%, and 44% of women and 41%, 36%, and 80% of men were classified as obese by BMI, WC, and DXA, respectively. Cut points were identified for anthropometric measures to better approximate DXA estimates of percent body fat (BMI ≥26.1 kg/m(2) for women and ≥24.7 kg/m(2) for men; WC ≥83 cm for women and ≥96 cm for men). For women and men, higher percent fat was associated with poorer RA status. Anthropometric measures were more closely linked to RA status for women, but identified cardiovascular risk for both women and men.

CONCLUSION

A large percentage of this RA sample was overfat; DXA-defined obesity was twice as common in men as in women. Utility of revised BMI and WC cut points compared to traditional cut points remains to be examined in prospective studies, but results suggest that lower, sex-specific cut points may be warranted to better identify individuals at risk for poor RA and/or cardiovascular outcomes.

Airway obstruction is a hallmark of allergic asthma and is caused primarily by airway smooth muscle (ASM) hypercontractility. Airway inflammation leads to the release of cytokines that enhance ASM contraction by increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms that prevent or attenuate the increase in RhoA activity have not been well studied. Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8(-/-)) develop exaggerated airway hyperresponsiveness in experimental models of asthma. Mfge8(-/-) ASM had enhanced contraction after treatment with IL-13, IL-17A, or TNF-α. Recombinant Mfge8 reduced contraction in murine and human ASM treated with IL-13. Mfge8 inhibited IL-13-induced NF-κB activation and induction of RhoA. Mfge8 also inhibited rapid activation of RhoA, an effect that was eliminated by an inactivating point mutation in the RGD integrin-binding site in recombinant Mfge8. Human subjects with asthma had decreased Mfge8 expression in airway biopsies compared with healthy controls. These data indicate that Mfge8 binding to integrin receptors on ASM opposes the effect of allergic inflammation on RhoA activity and identify a pathway for specific inhibition of ASM hypercontractility in asthma.