Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes

Area of Science:

• Endocrinology
• Metabolic Diseases
• Molecular Biology

Background:

• Previous studies suggest an association between iron overload (IO) and type 2 diabetes mellitus (T2DM).
• The precise molecular mechanisms underlying this association remain unclear.

Purpose of the Study:

• To investigate the relationship between iron overload markers and diabetes risk using epidemiological data.
• To explore the molecular mechanisms linking iron overload to type 2 diabetes mellitus through bioinformatics analysis of transcriptome data.

Main Methods:

• Utilized National Health and Nutrition Examination Survey (NHANES) data (2017-2018) for epidemiological analysis.
• Analyzed Gene Expression Omnibus (GEO) transcriptome data using bioinformatics to identify molecular pathways.
• Performed correlation and protein-protein interaction network analyses on key genes.

Main Results:

• A "W" shaped relationship was observed between serum iron and diabetes risk, and a "∧" shape correlation between unsaturated iron binding capacity (UIBC) and diabetes risk.
• Serum iron positively correlated with fasting plasma glucose and HOMAB; UIBC positively correlated with fasting insulin.
• Two IO-related genes, TFRC and SLC11A2, were downregulated in T2DM and positively correlated with insulin secretion-related genes, interacting with key genes like VAMP2 and HIF1A.

Conclusions:

• Iron overload is associated with elevated fasting plasma glucose (FPG) and worsened HOMAB.
• The IO-related genes TFRC and SLC11A2 may contribute to T2DM development by affecting insulin secretion.
• These genes represent potential therapeutic targets for type 2 diabetes mellitus patients.