Background: Insulin is known to have direct and indirect effects on cell cycle progression,
proliferation and metastatic activities. We performed a dose-response meta-analysis to investigate the
association between hyperinsulinemia and all-cause cancer related mortality.
Methods: A systematic literature search was conducted on MEDLINE and SCOPUS databases to include
all published articles up to January 2019. Combined hazard ratios (HRs) with 95% Confidence Intervals
(CIs) were estimated using DerSimonian and Laird random-effects models. A dose-response
analysis was also conducted to further explore insulin’s relationship with cancer-related mortality.
Results: We identified seven studies, with a total of 23,990 participants, who reported the association
between hyperinsulinemia and cancer-related mortality. Results from the eligible studies indicated that
higher fasting insulin levels were not associated with an increased risk of cancer mortality (pooled HR:
1.14, 95% CI: 0.99-1.32), however, significant heterogeneity was present (I2 = 60.3%, P heterogeneity =
0.001). A subgroup analysis based on gender demonstrated a significant association between fasting insulin
level and cancer mortality in men (pooled HR: 1.92, 95% CI: 1.23-3.01, P heterogeneity = 0.281).
Conclusion: This dose-response meta-analysis showed a direct significant association between fasting
insulin level and cancer mortality in men.