The association between circulating irisin and cardiometabolic risk is nonlinear and age-group-dependent in Japanese adults

Circulating irisin levels have been associated with a lower cardiometabolic risk (CMR); however, this association may be nonlinear, with a breakpoint that differs across age groups. Therefore, this study examined the association between circulating irisin levels and CMR in 487 Japanese adults aged 18-88 years. Participants were classified as young (<40 years), middle-aged (40-59 years), or older adults (≥60 years). Body fat percentage, blood pressure, high-density lipoprotein (HDL) cholesterol, triglyceride levels, glycated hemoglobin (HbA1c), and circulating irisin levels were assessed, and a composite CMR score was calculated from standardized z-scores. Circulating irisin levels were inversely associated with mean blood pressure, HbA1c, body fat percentage, triglycerides, and CMR score and positively associated with HDL cholesterol in the overall cohort. Segmented regression analysis identified significant breakpoints for body fat percentage, mean blood pressure, HbA1c, and CMR score in both the overall cohort and the young adult group (which additionally showed a breakpoint for HDL cholesterol). Conversely, no significant breakpoints were detected in the middle-aged group, and only body fat percentage showed a significant breakpoint in the older group. Moreover, for the CMR score, the slopes before and after the breakpoint differed significantly within the young group, and both slopes differed significantly from those in the middle-aged and older groups. These findings demonstrate that the association between circulating irisin levels and CMR is nonlinear and characterized by a distinct breakpoint. Furthermore, this relationship is age-group dependent, exhibiting a clear, threshold-like pattern in young adults that becomes attenuated with age.