Association between circulating insulin-like growth factor 1 and risk of all-cause and cause-specific mortality.

Background Insulin-like growth factor 1 (IGF-1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF-1 concentrations influence early death risk in the general population remains largely unknown. Methods We included 380,997 participants who had serum IGF-1 measurement and no history of cancer, cardiovascular disease (CVD) or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. Results Over a median follow-up of 8.8 years, 10,753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF-1 levels and mortality. Compared to the fifth decile of IGF-1, the lowest decile was associated with 39% (95% CI: 29%-50%), 20% (95% CI: 8%-34%), and 39% (95% CI: 14%-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7%-28%) and 38% (95% CI: 11%-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. Conclusions Our findings indicate that both low and high concentrations of serum IGF-1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF-1 in early death occurrence and possible implications for mitigating the risk.