This Chinese epidemiological paper hints to me that a safe iron chelator treatment such as ATH434 could be one additional method in type 2 diabetes prevention. Parkinson's disease and type2 of diabetes are related as we know.

Diabetol Metab Syndr

. 2023 Jun 21;15(1):134.

doi: 10.1186/s13098-023-01110-0.

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

Xuekui Liu ^{# 1 2}, Xiu Hong ^{# 1}, Shiqiang Jiang ^{# 2}, Rui Li ¹, Qian Lv ¹, Jie Wang ¹, Xiuli Wang ¹, Manqing Yang ¹, Houfa Geng ³, Yang Li ⁴

Affiliations expand

• PMID: 37344885

PMCID: PMC10283296 DOI: 10.1186/s13098-023-01110-0Free PMC article

Abstract

Background: Many previous studies have reported the association between iron overload (IO) and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanism is not clear.

Methods: Epidemiological data from the National Health and Nutrition Examination Survey 2017-2018 (NHANES) was used to systematically explore the association between IO and diabetes. Furthermore, transcriptome data from Gene Expression Omnibus (GEO) were analyzed using bioinformatics methods to explore the underlying functional mechanisms at the molecular level.

Results: Data from NHANES showed a "W" shape relationship between serum iron (frozen) and the risk of diabetes (P < 0.001) as well as a "∧" shape correlation between serum unsaturated iron binding capacity (UIBC) and the risk of diabetes (P = 0.007). Furthermore, the serum iron (frozen) was positively associated with fasting plasma glucose and HOMAB (P < 0.05), and UIBC was positively associated with fasting insulin (P < 0.05). Transcriptome data showed that two IO-related genes [Transferrin receptor (TFRC) and Solute carrier family-11 member-2 (SLC11A2)] were down-regulated in T2DM. The correlation analysis showed that expression levels of TFRC and SLC11A2 were significantly and positively correlated with genes involved in insulin secretion (P < 0.05). Protein-protein interaction network analysis showed that TFRC and SLC11A2 interacted with four key genes, including VAMP2, HIF1A, SLC2A1, and RAB11FIP2.

Conclusion: We found that IO status was associated with increased FPG and aggravated HOMAB, and two IO-related genes (TFRC and SLC11A2) might induce the occurrence of T2DM by influencing insulin secretion, which provides potential therapeutic targets for T2DM patients.