Relationship Between Hepatic Iron Concentration and Glycemic Metabolism, Prediabetes, and Type 2 Diabetes: A Systematic Review

Abstract

Context: Emerging research has suggested a potential link between high iron levels, indicated by serum ferritin levels, and the development of type 2 diabetes (T2D). However, the role of hepatic iron concentration (HIC) on T2D development and progression is not well understood.

Objectives: This study aims to systematically review the literature on HIC and/or the degree of hepatic iron overload (HIO) in individuals with prediabetes and/or diagnosed T2D, and to analyze associations between HIC and markers of glucose metabolism.

Data sources: The databases Medline, PubMed, Embase, CINAHL, and Web of Knowledge were searched for studies published in English from 1999 to March 2024. This review followed the Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.

Data extraction: Data were extracted following the established eligibility criteria. Study characteristics and biomarkers related to prediabetes, T2D, and HIO were extracted. The risk of bias was analyzed using the Newcastle-Ottawa Scale. Data were stratified by the exposure and analyzed in subgroups according to the outcome. Data regarding the HIC values in controls, individuals with prediabetes, and individuals with T2D and the association estimates between HIC or HIO and markers of glycemic metabolism, prediabetes, or T2D were extracted.

Data analysis: A total of 12 studies were identified, and data from 4110 individuals were analyzed. HIO was not consistently observed in prediabetic/T2D populations; however, elevated HIC was frequently observed in prediabetic and T2D individuals, and was associated with the disruption of certain glycemic markers in some cases.

Conclusion: The extent of iron overload, as indicated by hepatic iron load, varied among the prediabetic and T2D populations studied. Further research is needed to understand the distribution and regulation of iron in T2D pathology.

Keywords: ferritin; glycaemic regulation; hepatic iron; insulin resistance; iron; iron homeostasis; iron metabolism; iron overload; iron stores; liver iron; minerals; prediabetes; type 2 diabetes.