ESPE Yearbook of Paediatric Endocrinology

Biomedical and Environmental Sciences, 2021, 34(8): 623–631 doi: 10.3967/bes2021.086

Brief Summary: This cross-sectional study identified associations between serum ferritin levels with dyslipidemia and the MetS in both adult men and women. In addition, significant associations were found for ferritin levels with the risks of insulin resistance, prediabetes and T2DM in women.

Comment: Ferritin is a protein that is essential for various vital body organs, processes, functions and diseases. It is particularly needed for iron storage and supply. Obesity is a risk factor for iron deficiency anemia. However, BMI has been shown to be negatively associated with serum iron in adolescents with overweight/obesity but positively associated with plasma ferritin. Thus, circulatory ferritin does not reflect iron deficiency in obesity. Serum ferritin is an acute-phase reactant protein, similar to C-reactive protein, which increases in response to inflammatory processes in people with obesity, including the release of adipokines by adipocytes. Therefore, it is possible that inflammation-induced obesity results in iron deficiency, with elevated iron levels. Elevated serum ferritin levels have been associated with an increased risk of myocardial infarction malignancy and are directly involved in sideroblastic anemias, neurodegenerative disorders, inflammation and hemophagocytic syndrome.

For both genders in this study, the probability of having dyslipidemia increased with serum ferritin levels, suggesting that ferritin affects pathways involved in lipid metabolism. Ferritin may block apolipoprotein B secretion, leading to the accumulation of cellular triglyceride (TG). Ferritin functions as a direct mediator of the immune system, increasing the production of some proinflammatory mediators; chronic inflammation is considered one of the primary mechanisms underlying the MetS. Indeed, in both genders, the probability of having the MetS was also shown to increase as serum ferritin increased. In addition, ferritin can actively participate in the generation of reactive oxygen species. Excessive reactive oxygen species can reduce insulin receptors’ affinity, which affects the level of insulin delivery in the muscle and liver. Ferritin was associated with hyperglycemia in women only, independently of age, BMI, and liver and renal factors.

This study adds to previous findings on serum ferritin and the prevalence of the MetS and its components, showing a linear dose–response relationship and different risks between the sexes.