Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus

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 (DP...

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Main Authors: Shosaku Nomura MD, Takehito Taniura MD, Jun Ichikawa MD, Ayako Iwama MD, Tomoki Ito MD
Format: Article
Language:English
Published: SAGE Publishing 2024-11-01
Series:Clinical and Applied Thrombosis/Hemostasis
Online Access:https://doi.org/10.1177/10760296241302082
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author Shosaku Nomura MD
Takehito Taniura MD
Jun Ichikawa MD
Ayako Iwama MD
Tomoki Ito MD
author_facet Shosaku Nomura MD
Takehito Taniura MD
Jun Ichikawa MD
Ayako Iwama MD
Tomoki Ito MD
author_sort Shosaku Nomura MD
collection DOAJ
description 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.
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spelling doaj-art-007a4de8bfb549c0a702e79a621eab5f2025-08-20T02:27:32ZengSAGE PublishingClinical and Applied Thrombosis/Hemostasis1938-27232024-11-013010.1177/10760296241302082Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes MellitusShosaku Nomura MD0Takehito Taniura MD1Jun Ichikawa MD2Ayako Iwama MD3Tomoki Ito MD4 Center of Thrombosis and Hemostasis, , Moriguchi, Japan Department of Internal Medicine, Rokujizo Medical Hospital, Kyoto, Japan First Department of Internal Medicine, , Hirakata, Japan First Department of Internal Medicine, , Hirakata, Japan First Department of Internal Medicine, , Hirakata, JapanWe 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.https://doi.org/10.1177/10760296241302082
spellingShingle Shosaku Nomura MD
Takehito Taniura MD
Jun Ichikawa MD
Ayako Iwama MD
Tomoki Ito MD
Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus
Clinical and Applied Thrombosis/Hemostasis
title Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus
title_full Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus
title_fullStr Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus
title_full_unstemmed Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus
title_short Risk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus
title_sort risk of atherosclerosis due to hmgb1 dependent platelet derived microparticles in patients with type 2 diabetes mellitus
url https://doi.org/10.1177/10760296241302082
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