Establishment of a novel predictive index for the progression of cerebro-heart renal involvement in lifestyle-related diseases focusing on monocyte and microglial functions
| Project/Area Number |
19K07905
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Department of Clinical Research, National Hospital Organization Kyoto Medical Center |
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Principal Investigator |
Yamakage Hajime 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (40598900)
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| Co-Investigator(Kenkyū-buntansha) |
浅原 哲子 (佐藤哲子) 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究部長 (80373512)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | TREM2 / 脳心腎連関 / 糖尿病 / 肥満 / 早期予知バイオマーカー / 治療戦略 / 単球・ミクログリア |
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| Outline of Research at the Start |
肥満症・糖尿病/一般住民コホートにて、炎症・単球機能（M1/M2・TREM2）と脳心腎連関進展との関連を検討する。さらに、臨床研究成績を裏付ける基礎検討として、TREM2欠損マウス、肥満・糖尿病及び腎不全モデルマウスにて、脳・心臓・腎臓における炎症状態や単球・Mφ活性化レベル・TREM2発現、血清sTREM2レベルを明らかにし、脳心腎連関における
M1/M2極性・TREM2の病態意義を明らかにする。
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| Outline of Final Research Achievements |
This study showed that high blood sTREM2 levels were associated with cognitive decline in diabetic patients in the National Hospital Organization Multicenter Diabetes and Obesity Cohort. We also reported that in the non-obese diabetic HbA1c exacerbation group, initially high levels of sTREM2 were significantly associated with cognitive decline at 2 years, and that sTREM2 is a novel predictive indicator of cognitive decline. We also observed that a decrease over time in eGFRcys, converted by cystatin C, was associated with the development of CVD. Furthermore, we reported that SGLT2 inhibitors improved renal function. We also reported the characteristics of diabetic dementia focusing on TREM2 in a newly constructed cohort of dementia and mild cognitive impairment.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において、多施設肥満症・糖尿病コホートと認知症コホートを基盤に、肥満・糖尿病における認知症・腎症進展における単球・ミクログリア機能・sTREM2の病態意義について報告した。今後さらに、糖尿病・肥満症の脳心腎連関アウトカム・リスクに対する血中sTREM2との関連解析、糖尿病・肥満の有無別、薬物治療別などのサブ解析を行い、TREM2に着目した脳心腎連関進展予防戦略を提案する。特に未だ詳細が解明されていない肥満の認知症への影響、糖尿病性腎症及び認知症の病態・特徴を明らかにし、糖尿病・肥満症に伴う脳心腎連関進展における革新的な早期診断法・高リスク群抽出法と先制医療の構築を目指す。
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Report
(5 results)
Research Products
(17 results)
