Kawaguchi Takumi, Kohjima Motoyuki, Ichikawa Tatsuki, Seike Masataka, Ide Yasushi, Mizuta Toshihiko, Honda Koichi, Nakao Kazuhiko, Nakamuta Makoto, Sata Michio
Division of Gastroenterology, Department of Medicine and Department of Digestive Disease Information & Research, Kurume University School of Medicine, Kurume, 830-0011, Japan,
J Gastroenterol. 2015 Mar;50(3):333-41. doi: 10.1007/s00535-014-0968-5. Epub 2014 Jun 10.
Diabetes mellitus is associated with various cancers; however, little is known of the relationship between cancer and diabetes in chronic liver disease (CLD) patients. The aim of this study is to investigate the morbidity and associated factors of cancer, including the use of anti-diabetics, in CLD patients with diabetes.
We performed a multicenter survey in 2012 and 478 CLD patients with diabetes were enrolled (age 64.3 ± 12.1 years, female/male 187/291). A frequency analysis of cancer and antidiabetic use was performed. Independent factors for cancer were analyzed using logistic regression and decision-tree analysis.
The morbidity of cancer was 33.3%. Hepatocellular carcinoma (HCC) and extra-hepatic cancer were diagnosed in 24.7 and 11.3% of enrolled patients, respectively. The frequency of antidiabetic use was 66.5%. Of prescribed antidiabetics, 39% were dipeptidyl-peptidase 4 inhibitors; however, their use was not significantly associated with cancer. In contrast, the use of exogenous insulin (OR 2.21; 95% CI 1.16-4.21, P = 0.0165) and sulfonylurea (OR 2.08; 95% CI 1.05-3.97, P = 0.0353) were independently associated with HCC and extra-hepatic cancer, respectively. In decision-tree analysis, exogenous insulin and sulfonylurea were also identified as a divergence factor for HCC and extra-hepatic cancer, respectively.
We found a high morbidity of not only HCC, but also extra-hepatic cancer in CLD patients with diabetes. We also showed a possible association between the use of antidiabetics and the morbidity of cancer. Thus, a large-scale cohort study is needed to establish a therapeutic strategy for diabetes to suppress carcinogenesis in CLD patients.
糖尿病与多种癌症相关；然而，慢性肝病（CLD）患者中癌症与糖尿病之间的关系鲜为人知。本研究旨在调查CLD合并糖尿病患者的癌症发病率及相关因素，包括抗糖尿病药物的使用情况。
我们在2012年进行了一项多中心调查，纳入了478例CLD合并糖尿病患者（年龄64.3±12.1岁，女性/男性187/291）。对癌症和抗糖尿病药物使用情况进行了频率分析。使用逻辑回归和决策树分析来分析癌症的独立因素。
癌症发病率为33.3%。分别有24.7%和11.3%的入组患者被诊断为肝细胞癌（HCC）和肝外癌症。抗糖尿病药物的使用频率为66.5%。在处方的抗糖尿病药物中，39%为二肽基肽酶4抑制剂；然而，其使用与癌症无显著关联。相比之下，外源性胰岛素的使用（比值比2.21；95%置信区间1.16 - 4.21，P = 0.0165）和磺脲类药物的使用（比值比2.08；95%置信区间1.05 - 3.97，P = 0.0353）分别与HCC和肝外癌症独立相关。在决策树分析中，外源性胰岛素和磺脲类药物也分别被确定为HCC和肝外癌症的分歧因素。
我们发现CLD合并糖尿病患者不仅HCC发病率高，肝外癌症发病率也高。我们还显示了抗糖尿病药物的使用与癌症发病率之间可能存在关联。因此，需要进行大规模队列研究以制定糖尿病治疗策略，从而抑制CLD患者的致癌作用。
