The following is a summary of “Iron Metabolic Biomarkers and the Mortality Risk in the General Population: A Nationwide Population-Based Cohort Study,” published in the June 2024 issue of Endocrinology by Sun, et al.

Iron is vital for human physiology, yet its relationship with mortality risk, especially concerning diabetes mellitus (DM), remained insufficiently explored. For a study, researchers sought to investigate the associations between iron metabolic biomarkers and all-cause and cause-specific mortality risk in the general population. Additionally, they sought to examine variations in these associations between individuals with and without DM.

The study encompassed 29,166 adults from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999 to 2010, with follow-up data linked to the National Death Index until December 31, 2019. Associations between iron metabolic biomarkers and outcomes were estimated using Cox proportional hazard models and Fine-Gray subdistribution hazard models.

Throughout a median follow-up period extending nearly two decades, a total of 9,378 deaths were recorded, with 3,420 attributed to cardiovascular disease (CVD) and 1,969 to cancer. Notably, a significant linear correlation emerged between serum ferritin (SF) levels and all-cause mortality across the entire cohort, including those without diabetes mellitus (DM). Additionally, all studied groups observed distinct J-shaped relationships between transferrin saturation (TSAT) levels and all-cause mortality and CVD mortality. Within the general population, individuals in the second (Q2), third (Q3), and fourth (Q4) quartiles exhibited adjusted hazard ratios (HRs) for all-cause mortality of 1.07 (95% CI: 1.00-1.15), 1.05 (95% CI: 0.98-1.12), and 1.13 (95% CI: 1.05-1.21) for SF, respectively. Conversely, the HRs for TSAT in the Q2, Q3, and Q4 groups were 0.94 (95% CI: 0.88-0.99), 0.92 (95% CI: 0.86-0.97), and 0.93 (95% CI: 0.88-0.99), respectively. Among individuals without DM, elevated SF levels in the Q4 quartile were associated with adjusted HRs of 1.19 (95% CI: 1.03-1.37) for CVD mortality and 1.25 (95% CI: 1.05-1.48) for cancer mortality. Conversely, in those with DM, the adjusted HRs for the Q4 quartile of TSAT were 0.76 (95% CI: 0.62-0.93) for CVD mortality and 1.47 (95% CI: 1.07-2.03) for cancer mortality.

Aberrant iron metabolism is correlated with elevated mortality risk in the general population. Notably, the relationship between iron status and mortality varies significantly between individuals with and without DM, underscoring the necessity for tailored strategies for managing iron homeostasis.

Reference: academic.oup.com/jes/article/8/6/bvae063/7637764