Exercise-induced miR-126 expression improves vascular health in prediabetes: A randomized controlled trial

In this study, we investigated whether a structured aerobic exercise programme could enhance microRNA-126 (miR-126) expression and improve subclinical atherosclerosis markers [carotid intima-media thickness (CIMT) and ankle-brachial index (ABI)] in individuals with prediabetes. In this 12 week, multicentre, assessor-blinded, randomized controlled trial, 64 adults aged 18-60 years with newly diagnosed prediabetes were randomized into exercise and control groups. The exercise group performed supervised moderate-intensity aerobic exercise programme three times per week (treadmill and cycling, 50%-70% of maximum heart rate), and both groups received standard lifestyle advice. Circulating miR-126 expression was assessed via ΔCt using qPCR at baseline and week 12. The mean age was 46.82 ± 7.94 years, and 75.0% were female. Within- and between-group comparisons of ΔCt miR-126 were evaluated using a two-way repeated-measures ANOVA, demonstrating a significant main effect of time (P < 0.001) and a significant group × time interaction (P = 0.007). A significant group × time interaction was observed for both ABI and CIMT, with the exercise group showing an increase in ABI and a reduction in CIMT compared with the control group (ABI, P = 0.017; CIMT, P = 0.007). Correlation analysis revealed a positive association between change in ΔCt and CIMT (r = 0.260, P = 0.045) and a negative correlation with ABI (r = -0.275, P = 0.034). A 12 week aerobic exercise intervention significantly increased miR-126 expression and was associated with improvements in vascular markers of subclinical atherosclerosis, as evidenced by reduced CIMT and increased ABI. These vascular changes might be influenced, in part, by miR-126-related endothelial pathways among multiple mechanisms, highlighting the potential of miR-126 as a biomarker and therapeutic target for early vascular protection in prediabetes.