钙调磷酸酶抑制剂诱导药物性高血糖的机制及临床研究进展OA

Calcineurin inhibitor(CNI)is potent immunosuppressive agents and serve as cornerstone therapies in the treatment of organ transplantation and autoimmune diseases,with cyclosporine A and tacrolimus being the representative drugs.Long-term use of CNI can lead to drug-induced hyperglycemia,severely affecting patients'prognosis.The pathogenesis involves multilevel pathological alterations:at the pancreatic β-cell level,CNI directly damage β-cell by inducing calcium overload,oxidative stress,and mitochondrial dysfunction,suppressing the expression of key insulin synthesis factors and promoting apoptosis;in peripheral tissues,CNI interfere with insulin receptor substrate phosphorylation and inhibit the phosphatidylinositol 3 kinase/protein kinase B signaling pathway,resulting in decreased glucose uptake and insulin resistance;additionally,CNI can also induce β-cell injury by suppressing the secretion and receptor signal transduction of glucagon-like peptide-1,as well as by activating the nuclear factor kappa B pathway to promote inflammatory responses.Clinical studies demonstrate that the incidence of CNI-associated hyperglycemia is closely related to drug type,dosage,and individual patient factors.For high-risk patients,dose adjustment of CNI,switching to agents with lower metabolic toxicity when necessary,and selection of appropriate glucose-lowering regimens based on glycemic levels are recommended.Future research should further elucidate the molecular mechanisms of CNI metabolic toxicity and optimize individualized pharmacotherapy strategies to improve long-term patient outcomes.