Onitilo Adedayo A, Berg Richard L, Engel Jessica M, Stankowski Rachel V, Glurich Ingrid, Williams Gail M, Doi Suhail A R
Corresponding Author: Adedayo A. Onitilo, MSCR, FACP; Marshfield Clinic Weston Center; 3501 Cranberry Boulevard; Weston, WI 54476; .
Clin Med Res. 2013 Dec;11(4):201-9. doi: 10.3121/cmr.2013.1160. Epub 2013 May 8.
Diagnosis and duration of type 2 diabetes mellitus (DM) appear to be associated with decreased prostate cancer risk. Limitations of previous studies include methods of subject selection and accurate definition of DM diagnosis. We examined the temporal relationship between DM and prostate cancer risk exploring the period of greatest risk starting from the prediabetic to the post-diabetic period using clinical and administrative data to accurately define the date of DM diagnosis.
We identified 5,813 men who developed DM between January 1, 1995 and December 31, 2009 (reference date, date of DM onset or matched date for non-diabetic cohort) and 28,019 non-diabetic men matched by age, smoking history, residence, and reference date. Prostate cancer incidence before and after the reference date was assessed using Cox regression modeling adjusted for matching variables, body mass index, insurance status, and comorbidities. Primary outcomes included hazard ratio (HR) and number needed to be exposed to DM for one additional person to be harmed (NNEH) or benefit (NNEB) with respect to prostate cancer risk.
After full adjustment, the HR for prostate cancer before DM diagnosis was 0.96 (95% CI 0.85-1.08; P=0.4752), and the NNEB was 974 at DM diagnosis. After the reference date, the fully-adjusted HR for prostate cancer in diabetic men was 0.84 (95% CI 0.72-0.97, P=0.0167), and the NNEB 3 years after DM onset was 425. The NNEB continued to decrease over time, reaching 63 at 15 years after DM onset, suggesting an increasing protective effect of DM on prostate cancer risk over time. No significant difference between the diabetic and non-diabetic cohort was found prior to reference date.
Prostate cancer risk is not reduced in pre-diabetic men but decreases after DM diagnosis and the protective effect of DM onset on prostate cancer risk increases with DM duration.
2型糖尿病（DM）的诊断及病程似乎与前列腺癌风险降低有关。既往研究的局限性包括受试者选择方法及DM诊断的准确定义。我们利用临床和管理数据准确界定DM诊断日期，探讨从糖尿病前期到糖尿病后期前列腺癌风险最高的时间段，研究DM与前列腺癌风险之间的时间关系。
我们确定了1995年1月1日至2009年12月31日期间患DM的5813名男性（参考日期，DM发病日期或非糖尿病队列的匹配日期）以及按年龄、吸烟史、居住地和参考日期匹配的28019名非糖尿病男性。使用经匹配变量、体重指数、保险状况和合并症调整的Cox回归模型评估参考日期前后的前列腺癌发病率。主要结局包括前列腺癌风险方面的风险比（HR）以及每新增1例受伤害（NNEH）或受益（NNEB）的人所需的DM暴露人数。
完全调整后，DM诊断前前列腺癌的HR为0.96（95%CI 0.85 - 1.08；P = 0.4752），DM诊断时的NNEB为974。参考日期后，糖尿病男性中前列腺癌的完全调整后HR为0.84（95%CI 0.72 - 0.97，P = 0.0167），DM发病后3年的NNEB为425。NNEB随时间持续下降，DM发病后15年时降至63，表明DM对前列腺癌风险的保护作用随时间增加。在参考日期之前，糖尿病队列和非糖尿病队列之间未发现显著差异。
糖尿病前期男性的前列腺癌风险并未降低，但DM诊断后风险降低，且DM发病对前列腺癌风险的保护作用随DM病程增加。
