Association of type 2 diabetes mellitus and antidiabetic medication with risk of prostate cancer: a population-based case-control study.

Abstract

Background: Prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood. Methods: To assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.1. Results: Overall, a decreased risk of PCa was observed for men with T2DM (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.78-0.84), as compared to men without T2DM. The decreased risk of PCa was consistently showed across duration of T2DM. With respect to use of antidiabetic drugs, this inverse association with duration was also found for all medications types, as compared to men without T2DM, including insulin, metformin and sulphonylurea (SU) (e.g. 3-<5yr insulin OR:0.69, 95%CI:0.60-0.80; 3-<5yr metformin OR: 0.82, 95%CI: 0.74-0.91; 3-<5yr SU OR: 0.72, 95%CI: 0.62-0.83). When stratifying by PCa risk categories, this decreased risk was most evident for diagnosis of low and intermediate-risk PCa (low-risk OR: 0.65, 95%CI: 0.66-0.70, intermediate-risk OR: 0.80, 95%CI: 0.75-0.85). Conclusions: The study showed an inverse association between pre-existing T2DM and PCa across different durations of T2DM and all types of T2DM medication received. This inverse association was most evident for low- and intermediate-risk PCa, suggesting that whilst T2DM and its medication may protect some men from developing PCa, the relationship warrants further study.

Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study)

“…This is compatible with the reported effect of insulin in the viability of PCa cells 40 . However, studies have been more focused on the effect of its use than on its duration, and they have yielded inconsistent findings with a meta-analysis declaring no association 41 , another indicating increased risk, 42 and recent original articles finding a protective relationship 13,19 . Time of exposure to antidiabetic agents may also be an additional source of heterogeneity 21 .…”

“…Some studies have not found differences by grade of disease [12][13][14] , whereas other authors have reported a higher risk of high-grade disease in patients with T2DM 15 . The most recent studies have found that lower rates in T2DM patients was limited to low/intermediate-grade PCa, with detection bias as a plausible explanation for this relationship [16][17][18][19] . However, none of these studies evaluated whether genetic susceptibility to PCa may play a modifying role in this complex association.…”