Pilot Trial on the Effect of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness

• Material Type: 博士論文
• Title: Pilot Trial on the Effect of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness
• Author/Editor: 中村, 祐太
• Author Heading: 中村, 祐太
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2024-03-19
• Publication Date (W3CDTF): 2024-03-19
• Alternative Title: ミトコンドリア糖尿病患者における5-アミノレブリン酸の耐糖能改善効果に関するパイロット研究
• Periodical title: Diabetes Therapy
• No. or year of volume/issue: 14
• Volume: 14
• Pages: 447-459
• ISSN (Periodical Title): EISSN : 1869-6961
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2024-03-19
• Dissertation Number: 甲共医歯薬第38号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: 5-Aminolevulinic acid; 5-ALA; Maternally inherited diabetes and deafness; Mitochondria; Mitochondrial diabetes mellitus
• Target Audience: 一般
• Note (General): Introduction: The amino acid 5-aminolevulinic acid (5-ALA) is the first heme biosynthetic precursor. The combination of 5-ALA with sodium ferrous citrate (SFC) enhances heme production, leading to increased adenosine triphosphate (ATP) production in mitochondria. We investigated whether administering 5-ALA/SFC improves glucose tolerance with an increase in insulin secretion in patients with maternally inherited diabetes and deafness (MIDD), which is characterized by an insulin secretory disorder due to impaired mitochondrial ATP production. Methods: This was a single-arm, open-label, interventional study. We prospectively administered the oral glucose tolerance test (OGTT) twice in five patients with MIDD who had received intensive insulin therapy: before and 24 weeks after an administration of 5-ALA/SFC (200/232 mg per day). We measured the concentrations of glucose, insulin, C-peptide, and proinsulin at fasting, and 30, 60, and 120 min after glucose load in each OGTT. The primary endpoint was the changes in the area under the curve (AUC) of serum insulin from 0 to 120 min during OGTT from baseline to 24 weeks. Results: The serum insulin AUC (µU/mL) during the 120-min OGTT tended to increase from baseline to 24 weeks but not significantly (17.1 ± 13.7 versus 22.3 ± 13.4, p = 0.077). The plasma glucose AUC (mg/dL) during the 120-min OGTT at 24 weeks was not significantly decreased; the late phase of glucose excursion from 60 to 120 min was significantly decreased compared with baseline (357 ± 42 versus 391 ± 50, p = 0.041). The mean level of glycated hemoglobin (HbA1c) decreased from 8.3 ± 1.2% at baseline to 7.9 ± 0.3% at 24 weeks (p = 0.36) without increasing the daily dose of insulin injections. Conclusion: The 24-week administration of 5-ALA/SFC did not demonstrate a significant improvement in insulin secretion in patients with MIDD. Further investigations with a larger number of patients and a placebo control group are required to clarify the potential efficacy of 5-ALA/SFC for ameliorating mitochondrial dysfunctions in MIDD.; 長崎大学学位論文 学位記番号:共博(医歯薬)甲第38号 学位授与年月日:令和6年3月19日; Author: Yuta Nakamura, Ai Haraguchi, Ichiro Horie, Atsushi Kawakami & Norio Abiru; Citation: Diabetes Therapy, 14, pp.447-459; 2022; Nagasaki University (長崎大学), 博士(医学) (2024-03-19)
• Format (IMT): application/pdf
• Source: https://nagasaki-u.repo.nii.ac.jp/record/2000899/files/KISYK38_Nakamura.pdf （fulltext）; https://nagasaki-u.repo.nii.ac.jp/record/2000899/files/KISYK38_Nakamura.pdf
• Access Restrictions: インターネット公開
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• Related Material (URI): HDL; http://hdl.handle.net/10069/0002000767
• Related Material (DOI): 10.1007/s13300-022-01335-8
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ