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Background  The aims of this study were to investigate whether circulating irisin is associated with favorable metabolic parameters and how the association differs according to body composition in humans.    Methods  A total of 424 subjects (233 men and 191 women), aged 23–73 years (mean age 47.1 years), were enrolled from the Seoul Metro City Diabetes Prevention Program. Body composition was determined using an impedance body composition analyzer, and serum irisin level was measured using a commercial kit.    Results  Serum irisin was correlated with favorable metabolic parameters including less obese, lower blood pressure and glucose levels and healthy lipid parameters. The skeletal muscle mass to visceral fat area ratio (SVR) was positively correlated with the serum irisin concentration ( r  = 0.10,  P  = 0.04). When the study subjects were divided into tertiles according to their SVR, serum irisin was correlated with favorable metabolic phenotypes in those subjects in the upper tertile. However, there were no such correlations in the lower tertile. In addition, serum irisin was inversely related to pre-diabetes/type 2 diabetes (T2D) independent of other risk factor for T2D and insulin resistance [OR (95 % CI); 0.66 (0.49–0.90),  P  = 0.009].    Conclusions  The compositions of skeletal muscle and visceral fat play key roles in the association between circulating irisin and a patient’s metabolic phenotype.    Electronic supplementary material  The online version of this article (doi:10.1186/s12933-015-0319-8) contains supplementary material, which is available to authorized users.

The ratio of skeletal muscle mass to visceral fat area is a main determinant linking circulating irisin to metabolic phenotype