In the following study, we examined if the plasma sEVs can enter into cardiomyocytes, first, we labeled the sEVs with PKH67, which is a membrane fluorescence agent, and added the labeled sEVs into culture media of human origin cell line AC16, the results showed that sEVs from plasma can enter into cardiac cells (Figure 5A), and sEVs from DM‐CAD patients can diminish insulin sensitivity in normal AC16 cells, as indicated in Figure 5B, both ser473 and thr308 phosphorylation of AKT response to insulin stimuli are decreased by sEVs‐DM‐CAD treatment, but not by sEVs‐control treatment. Here, AKT1 is linked to diabetes mellitus.