 This study investigates the characteristics and dynamics of circulating extra chromosomal circular DNA, ECCDNA, in newly diagnosed type 2 diabetes mellitus, T2DM, patients undergoing short-term intensive insulin therapy, SIIT. The results show an increase in plasma ECCDNA load following SIIT. A correlation between ECCDNA profiles and glycemia in T2DM and the frequent presence of metabolism-related genes within T2DM plasma ECCDNAs. These findings highlight the potential of ECCDNAs as crucial players in the context of T2DM and glycemic control. This article was authored by Jashu, Junyu He, Peng Han, and others.