Objective: Growth differentiation factor-15 (GDF15), a key metabolic regulator, is associated with obesity and diabetes in which sex-specific differences have been reported. Thus, we assessed whether GDF15 could be dependent on sex in diabetes and/or obesity groups.

Methods: We measured serum GDF15 levels by ELISA in eight lean women and men (N = 16), eight women and eight men having obesity (N = 16), eight women and eight men with type 2 diabetes (T2D, N = 16), and seven women and nine men with both diabetes and obesity (N = 16). Estimation of the difference in the means of each group was performed by two-way ANOVA. The interdependence of the different variates was addressed by multivariate analysis. Correlations between GDF15 levels and HOMA-IR, HbA1c, triglycerides, HDL, and LDL were explored by linear regression.

Results: Being a woman and having obesity alone or with diabetes decreased GDF15 serum levels (β =-0.47, CI = [-0.95, 0.00], p = 0.052; β =-0.45, (β =-0.45, CI = [-0.94, 0.05], p = 0.075). Diabetes independently of metformin treatment and obesity was not predictive of low GDF15 levels (β = 0.10, CI = [-0.36, 0.57], p = 0.7). Correlation analysis showed that HOMA-IR (r = 0.45, p = 0.008) and triglycerides (r = 0.41, p = 0.017) were positively and HDL (r =-0.48, p = 0.005), negatively correlated with GDF15 levels in men.

Conclusions/interpretation: GDF15 level was significantly different between men and women, as well as between the groups. Sex-group interaction revealed that being a woman and having obesity alone or in combination with diabetes decreased GDF15 levels.