Significance of ketone body metabolic shift in diabetes and long-term prognosis prediction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06797
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Chiba University
• Principal Investigator: Sato Hiromi 千葉大学, 大学院薬学研究院, 准教授 (30506887)
• Co-Investigator(Kenkyū-buntansha): 樋坂 章博 千葉大学, 大学院薬学研究院, 教授 (80420206)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: SGLT2阻害薬 / 脂肪細胞 / マクロファージ / 心血管イベントリスク / 糖尿病 / メタボローム / 炎症

Outline of Final Research Achievements

In this study, we aimed to predict overall cardiovascular event risk (CVR) in patients with type 2 diabetes mellitus (T2DM), utilizing individual subject information from the ACCORD study conducted in T2DM to individually estimate disease time for all disease stages. The increased risk of all-cause mortality based on estimated disease time was expected to be a scientifically valid prediction. The correlation between metabolic shifts and tissue inflammation suggested by the cardioprotective effects of SGLT2 inhibitors was also examined, especially assuming epicardial fat; SGLT2 inhibitors showed anti-inflammatory effects, and some amino acid and sugar metabolic pathways were altered in conjunction with inflammation and treatment. In the future, we aim to add biomarker information explored by metabolic shift to the parameters of the disease mathematical model for precise prediction.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

2型糖尿病の真のリスクは合併症の予防であり、特に生命に関わる心血管イベントリスク(CVR)の増加を避けることが肝要となる。本研究はCVRの精密かつ定量的な予測に向き合い、病態発症からの疾患時間の推定とその予測に将来資する新規バイオマーカーとしてSGLT2阻害薬で着目されている代謝シフトの関与に挑んだ。今後とも継続的な調査によって予測の精度を高め、また代謝シフトの側面から病態の合理的な理解を進めることができれば、糖尿病および心筋梗塞や心不全などの疾患領域に対しても、個々の患者に適した治療選択や予後予測に貢献できると考える。