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Document Type

Conference Proceedings

Abstract

Objective: To review and synthesize evidence on how iron dysregulation and ferroptosis (E) contribute to brain structural and cognitive changes (O) in type 2 diabetes mellitus (P), identifying potential biomarkers of early neuro-metabolic injury. Methods: A scoping mini-review of eleven English-language studies (2014-2025) was conducted using PubMed and Scopus with the terms diabetes, brain iron, ferroptosis, quantitative susceptibility mapping, and neurocognition. Sources included four human neuroimaging studies, three mechanistic reviews, one experimental chelation trial, one metabolic MRI study, one iron-glucose review, and one integrative neurodegeneration review. Data was synthesized narratively with qualitative bias assessment. Results: Across human neuroimaging cohorts (n = 168), type 2 diabetes was associated with ≈ 20-30% higher magnetic susceptibility in the putamen, caudate, hippocampus, and substantia nigra versus controls. In a 40-patient study, putaminal iron correlated with HbA1c (r = 0.46, p < 0.01), and higher basal-ganglia iron predicted slower gait and poorer cognition (r = –0.37, p < 0.05). Meta-analysis confirmed a moderate pooled effect size (SMD = 0.42, 95% CI 0.19-0.65). Mechanistically, hyperglycemia and insulin resistance activated ferroptotic pathways through hepcidin-ferroportin imbalance, transferrin-receptor upregulation, and lipid oxidation. Experimentally, iron chelation reversed cortical oxidative injury and memory deficits in diabetic rodent models. Conclusion: Evidence from imaging, mechanistic, and experimental studies supports brain iron accumulation and ferroptosis as contributors to diabetes-related neurodegeneration. While most findings are cross-sectional or preclinical, integrating glycemic and iron regulation may offer new neuroprotective avenues. Larger longitudinal studies are needed to confirm causality and clinical benefit.

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