Bowker Samantha L, Majumdar Sumit R, Veugelers Paul, Johnson Jeffrey A
Institute of Health Economics, Edmonton, Alberta, Canada.
Diabetes Care. 2006 Feb;29(2):254-8. doi: 10.2337/diacare.29.02.06.dc05-1558.
Numerous studies have identified an increased risk of cancer in type 2 diabetes. We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer.
This was a population-based cohort study using administrative databases from Saskatchewan Health. Cancer-related mortality was compared among inception cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox regression was used to estimate the hazard ratio (HR) of cancer-related mortality, after adjusting for age, sex, insulin use, and chronic disease score. All statistical tests were two-sided.
We identified 10,309 new users of metformin or sulfonylureas with an average follow-up of 5.4 +/- 1.9 years (means +/- SD). The mean age for the cohort was 63.4 +/- 13.3 years, and 55% were men. Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of 1,443) for subjects who used insulin. After multivariate adjustment, the sulfonylurea cohort had greater cancer-related mortality compared with the metformin cohort (adjusted HR 1.3 [95% CI 1.1-1.6]; P = 0.012). Insulin use was associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5-2.4; P < 0.0001).
Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk.
大量研究已证实2型糖尿病患者患癌风险增加。我们探讨了2型糖尿病患者抗糖尿病治疗与癌症相关死亡率之间的关联，推测增加胰岛素水平的药物可能会促进癌症发生。
这是一项基于人群的队列研究，使用了萨斯喀彻温省卫生部门的行政数据库。比较了二甲双胍使用者和磺脲类单药治疗使用者起始队列中的癌症相关死亡率。在调整年龄、性别、胰岛素使用情况和慢性病评分后，采用多变量Cox回归来估计癌症相关死亡率的风险比（HR）。所有统计检验均为双侧检验。
我们确定了10309名新使用二甲双胍或磺脲类药物的患者，平均随访时间为5.4±1.9年（均值±标准差）。该队列的平均年龄为63.4±13.3岁，55%为男性。随访期间，磺脲类单药治疗使用者的癌症死亡率为4.9%（3340例中的162例），二甲双胍使用者为3.5%（6969例中的245例），使用胰岛素的受试者为5.8%（1443例中的84例）。多变量调整后，与二甲双胍队列相比，磺脲类队列的癌症相关死亡率更高（调整后HR为1.3[95%CI 1.1 - 1.6]；P = 0.012）。胰岛素使用与调整后的癌症相关死亡率HR为1.9（95%CI 1.5 - 2.4；P < 0.0001）相关。
与使用二甲双胍的患者相比，使用磺脲类药物和外源性胰岛素的2型糖尿病患者癌症相关死亡率显著增加。这种风险增加是否与磺脲类药物和胰岛素的有害作用、二甲双胍的保护作用有关，或者是由于与治疗选择和癌症风险相关的一些未测量的效应，目前尚不确定。
