Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH, USA.
Diabetes Care. 2011 Sep;34(9):1965-71. doi: 10.2337/dc11-0699. Epub 2011 Jul 20.
In vitro evidence suggests insulin glargine promotes tumors; observational human studies are conflicting. We aimed to expand understanding of this potential treatment risk.
This retrospective cohort study of type 2 diabetic patients >68 years old used Medicare inpatient, outpatient (2003-2008), and prescription data (2006-2008). Adjusting for patient characteristics, dose, and metformin use, Cox models yielded hazard ratios (HRs) for incident cancer (breast, prostate, pancreas, colon, any site) associated with three forms of insulin: nonglargine, glargine, or glargine plus nonglargine (combination).
Overall, 81,681 patients were followed for a mean of 23.1 months. Mean age was 77.4 years. Treatment group distribution was 20.7% glargine, 60.5% nonglargine, 18.7% combination insulin. We observed 5,466 incident cancers; crude rates did not vary by treatment group. In fully adjusted models, nonglargine use was the referent; glargine was not associated with significant increased risk of any cancer measure. In secondary analyses including only the top quartile of daily insulin dose patients, glargine was not associated with any cancer risk difference; combination insulin was associated with higher breast cancer risk (HR 1.75 [95% CI 1.10-2.78]) and lower colon cancer risk (0.33 [0.13-0.80]). In age-stratified analyses of highest-dose users, combination insulin conferred a higher risk of breast cancer in those ≤75 years old (2.87 [1.45-1.59]).
The general lack of association between glargine-only use and cancer is reassuring. Breast cancer risk associated with high-dose combination insulin in secondary analyses could result from multiple comparisons, residual confounding, or true association; further research is warranted.
体外证据表明胰岛素甘精能促进肿瘤；观察性人体研究结果存在矛盾。我们旨在扩大对这种潜在治疗风险的认识。
这项针对年龄＞68 岁 2 型糖尿病患者的回顾性队列研究使用了医疗保险住院、门诊（2003-2008 年）和处方数据（2006-2008 年）。通过调整患者特征、剂量和二甲双胍的使用情况，Cox 模型得出了与三种胰岛素（非甘精胰岛素、甘精胰岛素和甘精胰岛素加非甘精胰岛素[联合]）相关的新发癌症（乳腺癌、前列腺癌、胰腺癌、结肠癌、任何部位）的风险比（HR）。
总体而言，81681 例患者的中位随访时间为 23.1 个月。平均年龄为 77.4 岁。治疗组分布为：20.7%甘精胰岛素、60.5%非甘精胰岛素、18.7%联合胰岛素。我们观察到 5466 例新发癌症；粗发病率不因治疗组而异。在完全调整后的模型中，非甘精胰岛素为参照；甘精胰岛素与任何癌症指标的风险增加均无显著相关性。在仅包括每日胰岛素剂量最高四分位数患者的二次分析中，甘精胰岛素与任何癌症风险差异均无相关性；联合胰岛素与更高的乳腺癌风险相关（HR 1.75 [95%CI 1.10-2.78]），与更低的结肠癌风险相关（0.33 [0.13-0.80]）。在最高剂量使用者的年龄分层分析中，联合胰岛素使≤75 岁患者的乳腺癌风险更高（2.87 [1.45-1.59]）。
甘精胰岛素单独使用与癌症之间普遍缺乏关联令人欣慰。在二次分析中，高剂量联合胰岛素与乳腺癌风险相关可能是由于多次比较、残留混杂因素或真实关联所致；需要进一步研究。
