Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States.
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Can J Diabetes. 2021 Apr;45(3):282-290. doi: 10.1016/j.jcjd.2020.09.008. Epub 2020 Sep 17.
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.
糖尿病（DM）是许多器官癌症的危险因素，与胆管癌（CCA）风险增加相关。这些疾病之间的分子联系在临床前研究中得到了证实，这些研究强调了高胰岛素血症和高血糖在 CCA 的发生和发展中的作用。最近关于新型降糖药物在 CCA 发生和发展中作用的研究表明，一类降糖药物对 CCA 具有治疗作用。尽管 CCA、胰岛素类似物和磺酰脲类药物之间的关联尚不清楚，但基于肠促胰岛素的治疗可能与 CCA 的风险增加相关，并可能导致 CCA 进展，这已通过体外和体内实验得到证实。相比之下，双胍类药物，特别是二甲双胍，发挥相反的作用，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 风险之间的关联需要进一步澄清，因为二甲双胍正在进行一项正在进行的临床试验。了解 DM 和 CCA 之间的关联对于预防糖尿病患者 CCA 的发生以及确定降糖药物治疗 CCA 的适宜性至关重要。确定二甲双胍如何影响 CCA 可以导致重新利用这种安全且众所周知的药物来改善 CCA 的治疗，而不论患者的糖尿病状况如何。
