Alterations of Hepcidin and Iron Markers Associated with Obesity and Obesity-related Diabetes in Gambian Women

Wellcome Open Res. 2025 Sep 9:9:666. doi: 10.12688/wellcomeopenres.22997.2. eCollection 2024.

Abstract

Aims: Obesity, type 2 diabetes (T2D), and chronic inflammation are associated with disturbances in iron metabolism. Hepcidin is hypothesized to play a role in these alterations owing to its strong association with inflammation via the JAK-STAT3 pathway. The current study investigated the differences between inflammatory markers and iron indices and their association with hepcidin in lean women, women with obesity, and women with obesity and T2D (obesity-T2D) in The Gambia.

Materials and methods: In a cross-sectional study design, fasted blood samples were collected from three groups of women: lean women (n=42, geometric mean (GM) body mass index (BMI)=20.9 kg/m 2), women with obesity (n=48, GM BMI=33.1 kg/m 2) and women with obesity-T2D (n=30, GM BMI=34.5 kg/m 2). Markers of inflammation (IL-6 and CRP) and iron metabolism [hepcidin, iron, ferritin, soluble transferrin receptor (sTfR), transferrin, transferrin saturation, and unsaturated iron-binding capacity (UIBC)] were compared using linear regression models. Simple regression analyses were performed to assess the association between hepcidin levels and respective markers.

Results: Women with obesity and obesity-T2D showed elevated levels of inflammatory markers. There was no evidence that markers of iron metabolism differed between lean women and obese women, but women with obesity-T2D had higher transferrin saturation, higher serum iron concentration, and lower UIBC. Serum hepcidin concentrations were similar in all the groups. Hepcidin was not associated with markers of inflammation but was strongly associated with all other iron indices (all P<0.002).

Conclusion: Contrary to our original hypothesis, hepcidin was not associated with markers of inflammation in the three groups of Gambian women, despite the presence of chronic inflammation in women with obesity and obesity-T2D.

Keywords: Hepcidin; Inflammation; Iron Metabolism; Obesity; Type 2 Diabetes.

Plain language summary

What is already known on this topic: Obesity, type 2 diabetes (T2D), and chronic inflammation are linked to disturbances in iron metabolism, with hepcidin possibly playing a key role in this relationship. While the role of hepcidin in iron metabolism has been well studied in the context of infectious diseases, its role in metabolic disorders, such as obesity and T2D, remains insufficiently explored.

What this study adds: This study provides new insights into the link between hepcidin, iron indices, and inflammation markers in lean women, women with obesity, and women with obesity-T2D from The Gambia. Surprisingly, no association was found between hepcidin levels and markers of inflammation in women with obesity and obesity-T2D, which contradicts what was initially expected.

How this study might affect research practice or policy: This study generated hypotheses regarding the interconnectedness of iron metabolism, insulin metabolism, and pathogenesis of T2D, which should be investigated further in this specific study population. Understanding these mechanisms and links may lead to better care practices and interventions for women with T2D in The Gambia and beyond.