PDF(Sci-hub)
Abstract：
Diabetes mellitus (DM) is a risk factor for cancer in many organs and associated with an increased risk of cholangiocarcinoma (CCA). The molecular linkage between these diseases has been demonstrated in preclinical studies, which have highlighted the role of hyperinsulinemia and hyperglycemia in the carcinogenesis and progression of CCA. Recent studies on the emerging role of antidiabetic medication in the development and progression of CCA showed a subclass of antidiabetic drug with a therapeutic effect on CCA. Although associations between CCA, insulin analogues and sulfonylureas are unclear, incretin-based therapy is likely associated with an increased risk for CCA, and may lead to CCA progression, as demonstrated by in vitro and in vivo experiments. In contrast, biguanides, especially metformin, exert an opposite effect, associated with a reduced risk of CCA and inhibited in vitro and in vivo CCA progression. The association between incretin-based therapy and the risk of CCA needs further clarification, as metformin is being studied in an ongoing clinical trial. Understanding the association between DM and CCA is critical for preventing the development of CCA in patients with DM, and for establishing the appropriateness of antidiabetic medication to treat CCA. Determining how metformin affects CCA can lead to repurposing this safe and well-known drug for improving CCA treatment, regardless of the diabetes status of patients.
摘要：
糖尿病（DM）是许多器官中癌症的危险因素，并与胆管癌（CCA）的风险增加有关。这些疾病之间的分子联系已在临床前研究中得到证实。其中强调了高胰岛素血症和高血糖在CCA的发生和进展中的作用。最近关于抗糖尿病药物在CCA的发展和发展中的新兴作用的研究表明，抗糖尿病药物的亚类对CCA具有治疗作用。尽管CCA之间有关联，胰岛素类似物和磺脲类药物尚不清楚，基于肠促胰岛素的治疗可能与CCA的风险增加有关，并可能导致CCA进展，如体外和体内实验所证明的。相比之下,双胍,尤其是二甲双胍,产生相反的效果，与CCA风险降低相关，并抑制体外和体内CCA进展。基于肠促胰岛素的治疗与CCA风险之间的关系需要进一步澄清，二甲双胍正在正在进行的临床试验中进行研究。了解DM和CCA之间的关系对于预防DM患者CCA的发展至关重要。并确定抗糖尿病药物治疗CCA的适当性。确定二甲双胍如何影响CCA可以导致重新利用这种安全和众所周知的药物来改善CCA治疗，无论患者的糖尿病状况如何。
