Study Links Higher Serum Iron Levels to Lower Insulin Resistance

The study, published in The Journal of Clinical Endocrinology & Metabolism, revealed that higher serum iron (SI) levels might actually protect against insulin resistance.

Among a cohort of 2,900 adults, researchers discovered that elevated serum iron levels were associated with reduced insulin resistance. In contrast, higher iron intake and increased serum transferrin receptor (sTfR) levels were correlated with greater IR. Transferrin saturation was identified as the most reliable predictor of IR, surpassing other iron-related indicators in its predictive accuracy.

Evidence connecting markers of iron status to insulin resistance remains sparse. To fill this knowledge gap, Haiqing Zhang, Shandong University, Jinan, Shandong, China, and colleagues aimed to investigate the relationship between iron status and IR among U.S. adults.

For this purpose, the researchers analyzed data from 2,993 participants of the National Health and Nutrition Examination Survey (NHANES) spanning the periods 2003-2006 and 2017-2020. A HOMA-IR value of ≥2.5 defines insulin resistance.

The team employed weighted linear and multivariable logistic regression analyses to explore the linear relationships between iron status and IR. They utilized restricted cubic splines (RCS) to uncover potential non-linear dose-response associations. Additionally, stratified analyses were conducted based on age, sex, body mass index (BMI), and physical activity (PA). Finally, receiver operating characteristic (ROC) curve analysis assessed the predictive value of iron status for IR.

The following were the key findings of the study:

• In weighted linear analyses, serum iron exhibited a negative correlation with HOMA-IR (β = -0.03).
• In weighted multivariate logistic analyses, iron intake and serum transferrin receptor (sTfR) were positively correlated with IR (OR =1.02; OR =1.07).
• Also, SI and transferrin saturation (TSAT) were negatively correlated with IR (OR =0.96; OR =0.98) after adjusting for confounding factors.
• RCS depicted a nonlinear dose-response relationship between sTfR and TSAT and IR. This correlation remained consistent across various population subgroups.
• ROC curve showed that TSAT performed better than iron intake, SI, sTfR, and TSAT in ROC analyses for IR prediction.

"All biomarkers showed a significantly reduced risk of insulin resistance as iron levels increased. These findings enhance our understanding of the relationship between iron status and IR, offering a robust foundation for further investigation into the mechanisms driving this connection," the researchers concluded.

Reference:

Liu, X., Zhang, Y., Chai, Y., Li, Y., Yuan, J., Zhang, L., & Zhang, H. Iron status correlates strongly to Insulin Resistance among U.S. Adults: A nationwide population-base study. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgae558