Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis

The association between IGF-1 levels and mortality in humans is complex with low levels being associated with both low and high mortality. The present meta-analysis investigates this complex relationship between IGF-1 and all-cause mortality in prospective cohort studies. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Cochrane Library up to September 2019. Published studies were eligible for the meta-analysis if they had a prospective cohort design, a hazard ratio (HR) and 95% confidence interval (CI) for two or more categories of IGF-1 and were conducted among adults. A random-effects model with a restricted maximum likelihood heterogeneity variance estimator was used to find combined HRs for all-cause mortality. Nineteen studies involving 30,876 participants were included. Meta-analysis of the 19 eligible studies showed that with respect to the low IGF-1 category, higher IGF-1 was not associated with increased risk of all-cause mortality (HR = 0.84, 95% CI = 0.68-1.05). Dose-response analysis revealed a U-shaped relation between IGF-1 and mortality HR. Pooled results comparing low vs. middle IGF-1 showed a significant increase of all-cause mortality (HR = 1.33, 95% CI = 1.14-1.57), as well as comparing high vs. middle IGF-1 categories (HR = 1.23, 95% CI = 1.06-1.44). Finally, we provide data on the association between IGF-1 levels and the intake of proteins, carbohydrates, certain vitamins/minerals, and specific foods. Both high and low levels of IGF-1 increase mortality risk, with a specific 120-160 ng/ml range being associated with the lowest mortality. These findings can explain the apparent controversy related to the association between IGF-1 levels and mortality.