Abstract

Background: Growth differentiation factor 15 is a stress-responsive cytokine, which increases in the mitochondrial dysfunction and with age, and it has been suggested as a circulating biomarker of sarcopenia. The results have been incredibly varied with some studies showing a definite increase in the sarcopenic range and others showing no relationship, a mystery which has not yet been totally understood. The aim of the present study was to pool the published cohorts and ascertain via the meta-regression analysis the strength of the association and the factors which caused the heterogeneity. Methods: Randomeffects meta-analysis of the standardized mean difference in serum growth differentiation factor 15 (sGDF15) between sarcopenic and non-sarcopenic individuals was performed for the 20 cohort studies that included 8526 participants. Meta-regression using prespecified study-level moderators, funnel plot and trim-and-fill were used to check for heterogeneity and publication bias. Results: A pooled standardized mean difference of 0.45 (small to moderate level of increase) was obtained, with high heterogeneity. Meta-regression revealed that correction for renal function was the main moderator; studies without correction for renal function reported almost three times higher effects. The marker was found to be in inverse relation (shown but not strongly) with muscle mass, grip strength and gait speed. Conclusions: There is only a weak relationship between growth differentiation factor 15 and sarcopenia, and their association is significantly influenced by the renal function, thereby limiting the usefulness of this factor as an individual diagnostic marker.

Keywords: GDF-15, Growth differentiation factor 15, Sarcopenia, Biomarker, Metaregression, Heterogeneity, Renal function