Investigation of the association between blood glucose variability and left ventricular diastolic dysfunction in high-precision continuous subcutaneous measurements

Research Project

Project/Area Number	18K15436
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 52010:General internal medicine-related
Research Institution	National Cardiovascular Center Research Institute
Principal Investigator	TOCHIYA MAYU 国立研究開発法人国立循環器病研究センター, 病院, 医師 (80778697)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000) Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords	2型糖尿病 / 心不全 / HFpEF / ケトン体 / 拡張不全型心不全 / 血糖変動 / 心筋微小循環
Outline of Final Research Achievements	In type 2 diabetic patients with some cardiac complications, treatment with an SGLT2 inhibitor, which has been shown to prevent HFpEF, resulted in a decrease in left ventricular end-diastolic diameter and an increase in flow-dependent vasodilatory response after 6 months. The study also showed a decrease in left ventricular end-diastolic diameter and an increase in flow-dependent vasodilation response after 6 months. In addition, a correlation was observed between improvement in left ventricular diastolic performance (E/e ratio) and increases in ketone bodies (acetoacetic acid and 3-hydroxybutyric acid), suggesting that the increase in ketone bodies caused by SGLT2 inhibitors is associated with improvement in left ventricular diastolic performance. Further studies will examine the relationship between sustained blood glucose levels and left ventricular end-diastolic diameter in type 2 diabetes mellitus.
Academic Significance and Societal Importance of the Research Achievements	近年増加し続ける糖尿病患者において、心不全合併を予防することは糖尿病患者の生命予後改善のために重要な課題である。ケトン体上昇は心筋微小循環を介した心筋代謝の改善効果も示されていることから、本研究の成果により、未だ有効な治療法が確立していないHFpEF全体に対する治療戦略解明へと発展する可能性が高まると考えられる。