| アブストラクト | INTRODUCTION: Insulin Autoimmune Syndrome (IAS) is a rare yet clinically significant drug-induced adverse reaction, characterized by hypoglycemic episodes caused by insulin autoantibodies. While individual drug associations are documented in case reports, systematic pharmacovigilance analyses supporting drug-induced IAS are lacking in the literature. This study aims to identify drugs associated with IAS through pharmacovigilance analysis and explore potential molecular mechanisms. METHODS: We conducted a comprehensive analysis of IAS reports in the FDA Adverse Event Reporting System (FAERS) database (2004-2024) using multiple disproportionality analysis methods. Drug-gene interaction networks were constructed using DGIdb, GeneCards, and SwissTarget- Prediction databases, with subsequent protein-protein interaction analysis and pathway enrichment performed using STRING and DAVID databases. RESULTS: Analysis of 228 IAS reports revealed significant associations with 17 medications, 16 of which were not documented in the current IAS literature. Captopril showed the strongest association (ROR: 1777, 95% CI: 1051-3005), followed by thiamazole and clopidogrel. Network analysis identified enrichment in the PI3K-Akt signaling pathway, insulin resistance, and AMPK pathways, suggesting these pathways may play a role in the development of IAS. DISCUSSION: This study identified novel drug associations with IAS, highlighting the high risk of captopril in patients with the HLA-DRB1*0406 genotype, and the need for close monitoring of elderly patients on thiamazole or clopidogrel, particularly for hypoglycemia. Additionally, monitoring PI3K-Akt pathway disruption is crucial, as it may impair Treg function and promote the production of autoantibodies against insulin. CONCLUSIONS: The study identified 17 medications associated with IAS and emphasized the potential role of the PI3K-Akt pathway, recommending avoidance of certain drugs and enhanced monitoring in high-risk patients. |
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| ジャーナル名 | Endocrine, metabolic & immune disorders drug targets |
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| Pubmed追加日 | 2025/8/24 |
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| 投稿者 | Xiao, Sa; Lin, Long; Chen, Xiao-Hong; Lei, Lu-Wen; Wang, Min |
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| 組織名 | Department of Pharmacy, The Sixth Affiliated Hospital, School of Medicine, South;China University of Technology, Foshan 528200, Guangdong, China.;Department of Clinical Medicine, Xiamen Medical College, Xiamen 361023, Fujian,;China.;Department of Basic Medicine, Xiamen Medical College, Xiamen 361023, Fujian,;Department of Pharmacy, Xiangya Hospital, Central South University, Changsha;410005, Hunan, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/40849770/ |
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