Temporal variation in circulating GDF15 over 24 h in healthy young males

The functions of Growth Differentiation Factor 15 (GDF15) include actions on metabolism, cell survival, immune response, inflammation, and inhibition of food intake. Temporal variations in circulating GDF15 over 24 h have been reported in two small cohorts: one during fasted conditions and one during an overfeeding regimen. Here, 22 healthy young men were studied over 24 h in a controlled setting approximating normal daily life with blood sampling every third hour. Plasma GDF15 concentrations were analyzed using cosinor rhythmometry and one-way repeated measures ANOVA. In the full cohort, cosinor analysis did not show a statistically significant 24-h rhythm of GDF15 (p = 0.0944), but the ANOVA revealed a significant modest effect of time on plasma GDF15 concentrations (p < 0.001). Exploratory post hoc cosinor analysis of a subgroup of 14 subjects with evening-peaking profiles indicated modest rhythmic fluctuations (p = 0.0467), but the effect was small compared with the fluctuations of other metabolic hormones and plasma changes in GDF15 due to, for example, cancer and pregnancy. These findings do not provide definitive evidence for a 24-h rhythm of GDF15, but post hoc results suggest that some individuals may exhibit modest 24-h fluctuations. Larger, prospectively powered studies are required to confirm these observations and clarify their clinical significance.