Iron–Manganese Imbalance as a Pattern Based Model of Type 2 Diabetes Risk: A Synthesis of Epidemiological Evidence

A pattern‑based probabilistic model linking iron–manganese imbalance to type 2 diabetes risk, supported by epidemiological, mechanistic, and cross‑species evidence.

Key findings:
• Higher ferritin and heme iron intake are consistently associated with increased T2D risk.
• Higher manganese intake is consistently associated with reduced T2D risk.
• Direct Fe/Mn ratio (hair) more than doubles in individuals with T2D.
• A plant‑based Fe‑Mn dietary pattern is associated with 33% lower T2D progression and 42% higher probability of regression.
• The Fe/Mn ratio shows a dose‑dependent increasing trend with diabetes prevalence in NHANES data.
• Iron and manganese share evolutionarily conserved transport pathways (DMT1/NRAMP) and jointly influence oxidative balance via the Fenton reaction and MnSOD.
• The pattern is conserved across species (plants, nematodes, fruit flies, dairy cattle, humans), suggesting Fe/Mn balance is a fundamental biological principle rather than a human‑specific nutritional concept.

Conclusion: From a probabilistic perspective, higher Fe/Mn ratio is associated with increased T2D risk. The model does not claim causation but provides a robust, evidence‑based framework that complements glucose‑centric approaches and generates testable predictions for future research.

All code and data for the NHANES analysis are publicly available at:
https://github.com/mineral-pentagon/fe-mn-diabetes