Insulin therapy and risk of prostate cancer: a systematic review and meta-analysis of observational studies

Abstract

Background: Previous observational studies have shown that insulin therapy may modify the risk of prostate cancer (PCa). However, these studies yielded controversial results. Thus, we performed this meta-analysis to determine whether insulin use was associated with PCa risk in patients with diabetes mellitus (DM).

Method: A literature search was carried out in PubMed, EMBASE, and Cochrane Library Central database between January 1966 and January 2013. Fixed-effect and random-effect models were used to estimate pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were also performed.

Result: A total of 11 (10 cohorts, and one case-control) studies published between 2007 and 2013 were included in the meta-analysis, representing data for 205,523 male subjects and 7,053 PCa cases. There were five studies investigating the influence of insulin and other glucose-lowering agents on the risk of PCa , and six studies investigating the influence of glargine and non-glargine insulin. Insulin use was not associated with PCa risk when compared with other glucose-lowering agents (RR=0.89, 95% CI, 0.72-1.09). Use of insulin glargine did not contribute to susceptibility to PCa as compared with use of non-glargine insulin (RR=1.26, 95% CI, 0.86-1.84). Sensitivity analysis confirmed the stability of present results, since no individual study affected the pooled result significantly.

Conclusions: Our results suggest that, there may be no significant association between insulin use and risk of PCa as compared with other glucose-lowering agents in patients with DM, and there was no substantial evidence for increase risk of PCa among insulin glargine users as compared to non-glargine insulin users. Further studies are warranted to validate these conclusions.

Figure 1. Flow diagram for study selection.

Figure 2. Forest plot: comparison of insulin vs. other glucose-lowering therapies and risk of prostate cancer.

Figure 3. Forest plot: comparison of insulin glargine vs. non-glargine insulins and risk of prostate cancer.

Figure 4. Funnel plots for publication bias.

A: Funnel plot for studies investigating insulin vs. other glucose-lowering agents and risk of prostate cancer. No publication bias was observed ( P_{Begg’s test}= 0.327, P_{Egger’s test} = 0.246) .B: Funnel plot for studies investigating insulin glargine vs. non-glargine and risk of prostate cancer. No publication bias was observed ( P_{Begg’s test}= 0.851, P_{Egger’s test} = 0.718). C: Filled funnel plot of comparison of insulin vs. other glucose-lowering therapies and risk of prostate cancer. The filled diamonds represent one presumed missing study.