Prostate Cancer Risk in Pre-Diabetic Men: A Matched Cohort Study

Background: 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. Methods: 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. Results: 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. Conclusion: 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