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GLP-1 受体激动剂通过下调与脂质代谢相关基因的表达来调节糖尿病合并脂肪肝的进展。

Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism.

机构信息

Jinhua Municipal Central Hospital, Department of Neurology, Jinhua, 321000, China.

Jinhua Municipal Central Hospital, Department of Endocrinology, Jinhua, 321000, China.

出版信息

Appl Biochem Biotechnol. 2023 Aug;195(8):5238-5251. doi: 10.1007/s12010-023-04505-x. Epub 2023 May 4.

DOI:10.1007/s12010-023-04505-x
PMID:37140780
Abstract

Non-alcoholic fatty liver disease is mostly associated with diabetes mellitus. Dulaglutide is approved in type 2 diabetes as a hypoglycemic agent. However, its effects on liver fat and pancreatic fat contents are not evaluated yet. The objectives of the study were to evaluate the effects of dulaglutide on liver fat content, pancreatic fat content, liver stiffness, and liver enzyme levels. Patients have taken 0.75 mg subcutaneous dulaglutide each week for 4 weeks, then 1.5 mg weekly for 20 weeks plus standard treatment (metformin plus sulfonylurea and/or insulin; DS group, n = 25), or patients have taken standard treatment (metformin plus sulfonylurea and/or insulin) alone (ST group, n = 46) for type 2 diabetes management. Both groups reported a decrease in liver fat content, pancreatic fat content, and liver stiffness after interventions (p < 0.001 for all). After interventions, the DS group reported a higher decrease in liver fat content, pancreatic fat content, and liver stiffness than that of the ST group (p < 0.001 for all). After interventions, the DS group reported a higher decrease in body mass index than that of the ST group (p < 0.05). There were significant improvements in liver function tests, kidney function tests, lipid profiles, and blood counts after interventions (p < 0.05 for all). Both groups reported a decrease in body mass index after interventions (p < 0.001 for both). The DS group significantly decrease body mass index after interventions (p < 0.05) than the ST group.

摘要

非酒精性脂肪性肝病主要与糖尿病相关。度拉糖肽在 2 型糖尿病中被批准为一种降糖药物。然而,其对肝脂肪和胰腺脂肪含量的影响尚未得到评估。本研究的目的是评估度拉糖肽对肝脂肪含量、胰腺脂肪含量、肝硬度和肝酶水平的影响。患者每周皮下注射 0.75 毫克度拉糖肽,持续 4 周,然后每周 1.5 毫克,持续 20 周,加用标准治疗(二甲双胍加磺脲类和/或胰岛素;DS 组,n = 25),或患者单独接受标准治疗(二甲双胍加磺脲类和/或胰岛素)(ST 组,n = 46)治疗 2 型糖尿病。两组患者在干预后均报告肝脂肪含量、胰腺脂肪含量和肝硬度降低(所有 p < 0.001)。干预后,DS 组肝脂肪含量、胰腺脂肪含量和肝硬度的降低幅度高于 ST 组(所有 p < 0.001)。干预后,DS 组的体重指数降低幅度高于 ST 组(p < 0.05)。干预后肝功能检查、肾功能检查、血脂谱和血常规均有显著改善(所有 p < 0.05)。两组患者在干预后体重指数均降低(均 p < 0.001)。DS 组干预后体重指数显著低于 ST 组(p < 0.05)。

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本文引用的文献

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A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D).2 型糖尿病伴非酒精性脂肪性肝病的胰高血糖素样肽 1 受体激动剂(GLP1-RA)作用的荟萃分析。
Sci Rep. 2021 Nov 11;11(1):22063. doi: 10.1038/s41598-021-01663-y.
2
Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial).度拉糖肽对 2 型糖尿病合并非酒精性脂肪性肝病患者肝脂肪的影响:随机对照试验(D-LIFT 试验)。
Diabetologia. 2020 Nov;63(11):2434-2445. doi: 10.1007/s00125-020-05265-7. Epub 2020 Aug 31.
3
Liraglutide improves insulin sensitivity in high fat diet induced diabetic mice through multiple pathways.
利拉鲁肽通过多种途径改善高脂肪饮食诱导的糖尿病小鼠的胰岛素敏感性。
Eur J Pharmacol. 2019 Oct 15;861:172594. doi: 10.1016/j.ejphar.2019.172594. Epub 2019 Aug 11.
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Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.度拉糖肽与 2 型糖尿病患者的心血管结局(REWIND):一项双盲、随机、安慰剂对照试验。
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Diabet Med. 2018 Oct;35(10):1434-1439. doi: 10.1111/dme.13697. Epub 2018 Jun 22.
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Endocr J. 2017 Mar 31;64(3):269-281. doi: 10.1507/endocrj.EJ16-0449. Epub 2016 Dec 3.
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