Shaopeng Ming, Zhouyan Wu, Jingjing Li, Yicheng Su, Jianyou Yu, Hongtao Liu, Yanzhuo Zhang
This study combined FAERS pharmacovigilance analysis, network toxicology, molecular docking and transcriptome sequencing to explore potential mechanisms of dexmedetomidine-induced diabetes insipidus. FAERS data mining uncovered a robust adverse signal, indicating a strong correlation between dexmedetomidine and diabetes insipidus for clinical reference. Six hub genes and PI3K/AKT, MAPK pathways may be associated with this side effect. These findings facilitate high-risk population management and individualized sedation, and supply molecular candidates for future validation studies.
BACKGROUND: Dexmedetomidine is widely used for clinical sedation, while clinical data suggest a potential correlation between its administration and diabetes insipidus. This exploratory study aimed to characterize molecular correlates linking dexmedetomidine and diabetes insipidus via multiomics and pharmacovigilance analysis.
METHODS: FAERS data (2004-2024) were mined for disproportionality analysis to screen suggestive association signals. Network toxicology predicted shared targets of dexmedetomidine and diabetes insipidus, followed by GO/KEGG enrichment, PPI network construction and molecular docking. Transcriptome sequencing of 10 treated patients preliminarily validated bioinformatic correlations.
RESULTS: A strong suggestive association signal was detected (ROR=471.47). A total of 105 overlapping targets were screened, among which IL6, IL10, INS, IL1B, AKT1 and IFNG served as core correlated hub genes. Docking confirmed stable binding between dexmedetomidine and these proteins. Enrichment revealed enriched MAPK cascade, kinase activity and PI3K/AKT pathways, which may correlate with abnormal AQP2 function. Transcriptomics identified differential expression of inflammation-immune genes after infusion, consistent with predicted molecular correlations.
CONCLUSION: This study combined FAERS pharmacovigilance analysis, network toxicology, molecular docking and transcriptome sequencing to explore potential mechanisms of dexmedetomidine-induced diabetes insipidus. FAERS data mining uncovered a robust adverse signal, indicating a strong correlation between dexmedetomidine and diabetes insipidus for clinical reference. Six hub genes and PI3K/AKT, MAPK pathways may be associated with this side effect. These findings facilitate high-risk population management and individualized sedation, and supply molecular candidates for future validation studies.