| Project/Area Number |
19K08975
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2024-03-31
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 非アルコ－ル性脂肪性肝疾患 / 非アルコール性脂肪性肝疾患 / 連続肝生検 / SGLT2阻害薬 / SU薬 / 肝病理組織 / 非アルコ-ル性脂肪性肝疾患 |
|---|
| Outline of Research at the Start |
非アルコ-ル性脂肪性肝疾患（NAFLD）患者は多彩な背景を有している。本研究では糖尿病を背景とするNAFLDを対象に絞り、多数例の連続肝生検組織を用いて、その病理の進展と、発現遺伝子の変化を解析するとともに、人工膵臓を用いた詳細な糖尿病病態解析を行い、糖尿病を背景とするNAFLDの病態と、その進展阻止にむけた基盤研究を行う。さらに、糖尿病治療の違いがもたらす効果とNAFLD進展との関連を解析する。
|
| Outline of Final Research Achievements |
Tofogliflozin and, to a lesser degree, glimepiride significantly reduced the score of liver histology for 48 weeks in participants with liver biopsy specimen-confirmed NAFLD and type 2 diabetes, with no significant difference between the agents under a similar reduction in glucose levels. The percentage of participants in the tofogliflozin group who had an improvement in the fibrosis stage after 48 weeks in this trial was 60%. The tofogliflozin-mediated improvement in the fibrosis stage in the current study is greater than that of past reported treatment. The reduction in steatosis scores was significantly associated with the tofogliflozin-mediated reduction in HbA1c and weight. On the other hand, reduction in fibrosis scores was significantly associated with HbA1c at baseline and the tofogliflozin-mediated glycemic control but not the weight reduction. These findings suggest that glycemic control, rather than weight reduction, contributes to liver fibrosis alleviation.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究では、糖尿病治療薬が、糖尿病を改善するだけでなく、線維化を含めたNAFLDの組織像を改善させることを示した。他施設では、消化器領域で肝臓病理の研究を、代謝領域で臓器特異的インスリン感受性の研究を行なうなど、領域が分かれて研究を行なっている。本研究では、領域を統合して解析し、前向き研究で行った介入試験の症例を対象に、肝臓病理・糖代謝の変化との関連性を明らかにし、NAFLDを有する糖尿病患者の肝臓病理を改善する作用点を明らかにすることができた。
|
