Positive or U-Shaped Association of Elevated Hemoglobin Concentration Levels with Metabolic Syndrome and Metabolic Components: Findings from Taiwan Biobank and UK Biobank

Iron overnutrition has been implicated with a higher risk of developing metabolic and cardiovascular diseases, including metabolic syndrome (MetS), whereas iron deficiency anemia exacerbates many underlying chronic conditions. Hemoglobin (Hb) concentration in the blood, which reflects a major functional iron (i.e., heme iron) in the body, may serve as a surrogate of the nutritional status of iron. We conducted sex-specific observational association studies in which we carefully titrated the association between Hb deciles and MetS and its components among the Taiwanese Han Chinese (HC) from the Taiwan Biobank and Europeans of White ancestry from the UK Biobank, representing two large ethnicities. Our data show that at higher-than-normal levels of Hb, increasing deciles of Hb concentration were significantly associated with MetS across all sex subgroups in both ethnicities, with the highest deciles resulting in up to three times greater risk than the reference group [Taiwanese HC: OR = 3.17 (95% CI, 2.75–3.67) for Hb ≥ 16.5 g/dL in men, OR = 3.11 (2.78–3.47) for Hb ≥ 14.5 g/dL in women; European Whites: OR = 1.89 (1.80–1.98) for Hb ≥ 16.24 g/dL in men, OR = 2.35 (2.24–2.47) for Hb ≥ 14.68 g/dL in women]. The association between stronger risks and increasing Hb deciles was similarly observed with all metabolic components except diabetes. Here we found that both the highest Hb decile groups and contrarily the lowest ones, with respect to the reference, were associated with higher odds of diabetes in both ethnic groups [e.g., Taiwanese HC men: OR = 1.64 (1.33–2.02) for Hb ≥ 16.5 g/dL, OR = 1.71 (1.39–2.10) for Hb ≤ 13.5 g/dL; European Whites women: OR = 1.39 (1.26–1.45) for Hb ≥ 14.68 g/dL, OR = 1.81 (1.63–2.01) for Hb ≤ 12.39 g/dL]. These findings confirm that elevated Hb concentrations, a potential indicator of iron overnutrition, may play a role in the pathophysiology of MetS and metabolic components.