The role of exosomes for sustained specific cardiorespiratory and metabolic improvements in males with type 2 diabetes after detrainingResearch in context

Summary: Background: High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (V˙O2 max) but may ameliorate insulin sensitivity only in insulin-resistant humans. It is yet unclear whether these benefits persist after detraining and to which extent duration and effectiveness of metabolic improvements differ between individuals without and with prediabetes or type 2 diabetes (T2D). Understanding these differences is relevant for developing targeted exercise training modes for individuals with different stages of dysglycemia. Methods: Men with (20 T2D) and without T2D (12 insulin-sensitive, IS-NDM; 10 insulin-resistant, IR-NDM) underwent hyperinsulinemic-euglycemic clamps, spiroergometry, ectopic lipid quantification and muscle biopsies at baseline, after 12-week HIIT and after 4-week detraining. Findings: After detraining, the HIIT-stimulated V˙O2 max declined in T2D and IR-NDM, but remained higher compared to baseline in all groups. The HIIT-induced changes in hepatic insulin sensitivity and ectopic lipid content were sustained after detraining in T2D and IR-NDM, whereas improvements of whole-body insulin sensitivity were abolished in T2D. T2D and IR-NDM showed persistent increases in the number of small extracellular vesicles, which carry among others antioxidant proteins. The ratio of reduced-to-oxidized glutathione further decreased after detraining in all groups, whereas changes in proteins involved in mitochondrial turnover were dependent on insulin sensitivity, with some evidence for upregulation of fusion and mitophagy in T2D and IR-NDM and upregulation of fission in IS-NDM. Levels of different lipolytic proteins were reduced in all participants after detraining. Interpretation: HIIT offers sustained improvement of energy metabolism and hepatic insulin sensitivity in insulin-resistant humans, but long-term adherence is required to maintain these benefits. Funding: Funding bodies that contributed to this study are listed in the Acknowledgements section.