The effect of exercise on GDF-15 levels in individuals with prediabetes: A randomized controlled trial

Abstract

Aims: Growth differentiation factor-15 (GDF-15) is an inflammatory cytokine that increases in prediabetes and is known for its anorexigenic effects. This study aims to evaluate the effects of a 12-week exercise program on GDF-15 in individuals with prediabetes. Materials and Methods: In this multicenter, parallel-group, randomized-controlled trial, 64 patients aged 18–60 diagnosed with prediabetes were randomized in a 1:1 ratio into the exercise group (E) and the control group (C). Additionally, 32 patients who were planned to start metformin were included in the metformin group (M). Participants in the exercise group engaged in aerobic exercise at 50–70% of their maximum heart rate for 60 min, 3 days a week. Serum GDF-15 levels were evaluated at the beginning and the end of the 12th week. Results: The mean age of the 91 participants who completed the study was 46.13 ± 8.52 years, and 23.1% were male. Basal GDF-15 levels were similar among the groups (E = 668.6 ± 415.1, C = 651.8 ± 352.5, M = 603.6 ± 387.2, P = 0.47). At the 12th week, GDF-15 levels were lower in the E compared to the C, while higher in the M compared to the C (E = 383.1 ± 215.6, C = 556.4 ± 285.6, M = 810.8 ± 498.0, P < 0.001). In inter-group comparisons, no significant change was observed in the C between the 0th and 12th weeks, while GDF-15 decreased in the E (P < 0.001) and increased in the M (P < 0.001). Conclusions: It was determined that in individuals with prediabetes, GDF-15, which serves both as a biomarker of metabolic disorder and has a negative regulatory effect on appetite, decreased with 12 weeks of aerobic exercise and increased with metformin administration. © 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.