Fasting insulin and risk of cancer related mortality in non-diabetic adults: A dose-response meta-analysis of cohort studies

BACKGROUND: Insulinis 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 in 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.