Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies

Abstract

Purpose: Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.

Materials and methods: A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.

Results: Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61-0.83, I²=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79-1.13, I²=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77-1.18, I²=98%) at diagnosis. According to GRADE, the evidence certainty was very low.

Conclusions: Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.

Keywords: Diabetes mellitus; Early detection of cancer; Meta-analysis; Prostatic neoplasms; Risk factors; Systematic review.

Fig. 1. Flow diagram of studies exploring the association between diabetes and prostate cancer risk. Presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Moher et al [22].

Fig. 2. Percentage of studies (%) showing a decreased, no association, or increased risk between diabetes diagnosis and prostate cancer development, according to the type of analysis (i.e., crude, univariable, or multivariable) and prostate cancer stage (i.e., all, early, and advanced stages). The number of studies (n) included in the statistical model for each analysis type is also shown.

Fig. 3. Pooled RR and 95% CI of diabetes as a risk factor for all (A), early (B), and advanced (C) PC development. A protective effect was observed for early stages (B), while no association was found for all (A) and advanced (C) stages. Visual examination of funnel plots (A–C) indicates little or no evidence of publication bias, later confirmed by the Egger’s test (p>0.05). PC: prostate cancer, RR: risk ratio, CI: confidence interval.