Abstract
We measured high mobility group box 1 protein (HMGB1) and platelet-derived microparticles (PDMP) in blood samples from patients with untreated type 2 diabetes mellitus (T2DM). We examined the effects of a combination of sodium/glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Multiple regression analysis of HMGB1 was conducted on data from 252 patients in our previously reported T2DM-related clinical study. The results revealed significant correlations between HMGB1 and PDMP, soluble CD40 ligand, plasminogen activator inhibitor-1, and soluble E-selectin in multivariate analysis. Based on the HMGB1 levels before treatment with combination, 46 T2DM patients in the study were classified into two groups, high and low. The high HMGB1 group showed a significantly lower adiponectin level and higher PDMP production than the low HMGB1 group. T2DM risk significantly and positively correlated with HMGB1 and PDMPs. HMGB1-induced PDMP production was simulated in vitro using healthy platelets. Furthermore, The combination of a SGLT2 inhibitor and a DPP-4 inhibitor significantly reduced HMGB1 and PDMP levels. These results suggest that in addition to abnormal glucose metabolism, HMGB1-dependent PDMP production and the resulting development of atherosclerosis are also a concern in patients with T2DM.