Biomarkers of iron metabolism are independently associated with impaired glucose metabolism and type 2 diabetes: the KORA F4 study

Abstract

ObjectiveIron has been suggested to play a role in the etiology of type 2 diabetes mellitus (T2DM). Except for ferritin, evidence is sparse for other markers of iron metabolism that are regulated differently and might act through independent pathways. We therefore investigated the associations of serum ferritin, transferrin, soluble transferrin receptor (sTfR), transferrin saturation (TSAT), sTfR-to-log10ferritin (sTfR-F) index, and iron with impaired glucose metabolism (IGM/‘prediabetes’), T2DM, and four continuous glucose and insulin traits.Design and methodsData from 2893 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (Germany) was investigated through regression analysis. The results were adjusted for socio-demographic, life-style, and obesity measures as well as metabolic, inflammatory, and other iron biomarkers following a step-wise approach. Non-linearity was tested by adding a non-linear spline component to the model.ResultsFerritin and transferrin were positively associated with IGM (fourth vs first sex-specific quartile: ferritin odds ratio (OR)=2.08 (95% CI 1.43–3.04) and transferrin OR=1.89 (95% CI 1.32–2.70)), T2DM (ferritin OR=1.98 (95% CI 1.22–3.22) and transferrin OR=2.42 (95% CI 1.54–3.81)), and fasting as well as 2-h glucose. TSAT (OR=0.55 (95% CI 0.34–0.88)) and iron (OR=0.61 (95% CI 0.38–0.97)) were inversely associated with T2DM, sTfR-F-index was inversely associated with IGM (OR=0.67 (95% CI 0.48–0.95)). There was no strong evidence for non-linear relationships.ConclusionsThe observed associations of several markers of iron metabolism with hyperglycemia and insulin resistance suggest that iron stores as well as iron-related metabolic pathways contribute to the pathogenesis of IGM and T2DM. Moreover, TSAT levels are decreased in T2DM patients.