Hypoglycemic drugs, circulating inflammatory proteins, and gallbladder diseases: A mediation mendelian randomization study

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2024-10-02 DOI:10.1016/j.diabres.2024.111882

Zi-Qi Wang , Jin-Yan Zhang , Xingyao Tang , Jian-Bo Zhou

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引用次数: 0

Abstract

Background

The relationship of hypoglycemic drugs, inflammatory proteins and gallbladder diseases remain unknown.

Methods

Four hypoglycemic drugs were selected as exposure: glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and metformin. The outcome were two gallbladder diseases: cholecystitis and cholelithiasis. Mendelian Randomization (MR) was employed to determine the association between hypoglycemic drugs and gallbladder diseases.

Results

DPP-4i and SGLT-2i had no effect on cholecystitis and cholelithiasis. However, a causal relationship was found between inhibition of ETFDH gene, a target of metformin expressed in cultured fibroblasts, and cholelithiasis (OR: 0.84, 95 %CI: (0.72,0.97), p = 0.021), as well as between GLP1R expression in the brain caudate basal ganglia and cholecystitis (OR: 1.29, 95 %CI: (1.11,1.49), p = 0.001). The effect of ETFDH inhibition on cholelithiasis through Interleukin-10 receptor subunit beta (IL-10RB) levels and Neurotrophin-3 (NT-3) levels, with a mediated proportion of 8 % and 8 %, respectively.

Conclusion

Metformin plays a protective role in cholelithiasis, while GLP-1RA have a harmful effect on the risk of cholecystitis. Metformin may reduce the risk of cholelithiasis by modulating the levels of Neurotrophin-3 (NT-3) and Interleukin-10 receptor subunit beta (IL-10RB). Further clinical and mechanistic studies are required to confirm these findings.

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降糖药、循环炎症蛋白与胆囊疾病：调解泯灭随机化研究。

背景：降糖药物、炎症蛋白与胆囊疾病的关系尚不清楚：降糖药物、炎症蛋白与胆囊疾病的关系尚不清楚：方法：选择四种降糖药物作为暴露对象：胰高血糖素样肽-1受体激动剂（GLP-1RA）、二肽基肽酶-4抑制剂（DPP-4i）、钠-葡萄糖共转运体2抑制剂（SGLT-2i）和二甲双胍。结果是两种胆囊疾病：胆囊炎和胆石症。研究采用孟德尔随机法（MR）确定降糖药物与胆囊疾病之间的关联：结果：DPP-4i 和 SGLT-2i 对胆囊炎和胆石症没有影响。然而，研究发现二甲双胍在培养成纤维细胞中表达的靶点 ETFDH 基因受抑制与胆囊炎之间存在因果关系（OR：0.84，95 %CI：(0.72,0.97)，p = 0.021），大脑尾状基底节中 GLP1R 的表达与胆囊炎之间也存在因果关系（OR：1.29，95 %CI：(1.11,1.49)，p = 0.001）。ETFDH抑制通过白细胞介素-10受体亚基β（IL-10RB）水平和神经营养素-3（NT-3）水平对胆囊炎产生影响，介导比例分别为8%和8%：结论：二甲双胍对胆囊炎有保护作用，而GLP-1RA对胆囊炎的风险有害。二甲双胍可通过调节神经营养素-3（NT-3）和白细胞介素-10受体亚基 beta（IL-10RB）的水平来降低胆囊炎的风险。要证实这些发现，还需要进一步的临床和机理研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.