Metformin May Blunt Beneficial Effects Of Exercise Training On Cancer-related Biomarkers In Women With Prediabetes

Abstract

Prediabetes and obesity are associated with increased breast cancer risk, and this may be partly due to circulating adipokines. Exercise training and metformin are two interventions that typically improve adipokine profiles, however the effects of a combined metformin and exercise training intervention on adipokines and breast cancer risk is unclear. PURPOSE: To assess changes to leptin, adiponectin and the leptin:adiponectin ratio in women at risk for breast cancer undergoing a 12-week exercise training and/or metformin intervention. METHODS: Twenty-two overweight, sedentary women with prediabetes were randomly assigned to 4 groups: placebo (P, N=6), metformin (M, N=5), exercise training plus placebo (E+P, N=5) or exercise training plus metformin (E+M, N=6). Exercise training consisted of 3x/wk (225’ total) of combined aerobic and resistance exercise training. Metformin consisted of 1000 mg metformin twice daily. Fasted blood samples were taken following 24-hour dietary and physical activity control. Leptin and adiponectin were measured using commercially available radioimmunoassay (Millipore, Billerica MA). Within- and between-group differences were assessed using paired t-tests and 2-way ANOVA. Significance was accepted at p<0.05 and data are presented as percent change from baseline or mean±SEM. RESULTS: There were no baseline differences between the four groups. Leptin levels significantly increased in the placebo group (+17.1%, p=0.02) but were unchanged in M (+9.8%), E+P (-17.4%) and E+M (-23.7%). There were no significant pre- to post-intervention changes in adiponectin (P=-11.2%; M= -0.18%; E+P=+24.47%; E+M=+9.8%), however there were significant pre- to post differences in the Leptin:Adiponectin ratio in E+P (5.59 ± 1.15 vs. 3.83 ± 1.31 p=0.02) but not in P (3.40 ± 0.56 vs. 4.32 ± 0.84), M (5.23 ± 1.08 vs. 7.10 ± 2.46) or E+M (4.94 ± 2.39 vs. 2.76 ± 0.96). CONCLUSION: Exercise training, but not exercise plus metformin, significantly improved the Leptin:Adiponectin ratio, further supporting research that metformin may blunt exercise-induced improvements in cardiometabolic health (e.g. increased insulin sensitivity, reduced hs-CRP concentrations) relevant to breast cancer prevention. Supported by: NIH 5-R56-DK-081038 and Rays of Hope Center for Breast Cancer Research