Sun G E C, Wells B J, Yip K, Zimmerman R, Raghavan D, Kattan M W, Kashyap S R
Endocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.
Diabetes Obes Metab. 2014 Mar;16(3):276-83. doi: 10.1111/dom.12231. Epub 2013 Dec 5.
To analyse the association between cancer incidence and oral diabetes therapy (biguanide, sulphonylurea, thiazolidinedione and meglitinide) in men and women with type 2 diabetes mellitus.
A retrospective analysis of the electronic health record-based Cleveland Clinic Diabetes Registry (25 613 patients) was cross-indexed with the histology-based tumour registry (48 051 cancer occurrences) over an 8-year period (1998-2006). Multiple imputations were used to account for missing data. Cox regression with propensity scores was used to model time for the development of incident cancer in each of the imputed datasets and the results were pooled.
During 51 994 person follow-up years, 892 incident cancer cases were identified; prostate (14.5%) and breast (11.7%) malignancies were most frequent. In women, thiazolidinedione use was associated with a 32% decreased cancer risk compared with sulphonylurea use [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.48-0.97, in the adjusted analysis]. Comparison of insulin secretagogues (sulphonylurea and meglitinide) versus insulin sensitizers (biguanide and thiazolidinedione) demonstrated a 21% decreased cancer risk in insulin sensitizers [HR 0.79 (95% CI 0.64-0.98) in the adjusted analysis]. Oral diabetes therapy showed no significant difference in men. Adjustments were made for age, body mass index (BMI), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, coronary heart disease (CHD), diabetes oral monotherapy, race, gender, haemoglobin A1c, statin use, income, insulin use, glomerular filtration rate (GFR), new diabetes status, prior cancer, prior cerebrovascular accident (stroke or transient ischaemic event), systolic/diastolic blood pressure, tobacco use (ever/never) and the propensity score for receiving a biguanide.
Oral insulin sensitizers, particularly thiazolidinedione, are associated with decreased malignancy risk in women with type 2 diabetes mellitus.
分析2型糖尿病男性和女性患者的癌症发病率与口服糖尿病治疗药物（双胍类、磺脲类、噻唑烷二酮类和格列奈类）之间的关联。
对基于电子健康记录的克利夫兰诊所糖尿病登记处（25613例患者）进行回顾性分析，并在8年期间（1998 - 2006年）与基于组织学的肿瘤登记处（48051例癌症病例）进行交叉索引。采用多重填补法处理缺失数据。在每个填补数据集中，使用倾向评分的Cox回归对新发癌症发生时间进行建模，并汇总结果。
在51994人年的随访期间，共识别出892例新发癌症病例；前列腺癌（14.5%）和乳腺癌（11.7%）最为常见。在女性中，与使用磺脲类药物相比，使用噻唑烷二酮类药物与癌症风险降低32%相关[风险比（HR）0.68；95%置信区间（CI）0.48 - 0.97，校正分析]。胰岛素促泌剂（磺脲类和格列奈类）与胰岛素增敏剂（双胍类和噻唑烷二酮类）的比较显示，胰岛素增敏剂使癌症风险降低21%[校正分析中HR为0.79（95%CI 0.64 - 0.98）]。口服糖尿病治疗在男性中无显著差异。对年龄、体重指数（BMI）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、甘油三酯、冠心病（CHD）、糖尿病口服单药治疗、种族、性别、糖化血红蛋白A1c、他汀类药物使用、收入、胰岛素使用、肾小球滤过率（GFR）、新糖尿病状态、既往癌症、既往脑血管意外（中风或短暂性脑缺血事件）、收缩压/舒张压、吸烟情况（曾经/从不）以及接受双胍类药物的倾向评分进行了校正。
口服胰岛素增敏剂，尤其是噻唑烷二酮类药物，与2型糖尿病女性患者的恶性肿瘤风险降低相关。
