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

Abstract

Objective: Iron 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-log 10 ferritin (sTfR-F) index, and iron with impaired glucose metabolism (IGM/'prediabetes'), T2DM, and four continuous glucose and insulin traits. Design and methods: Data 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 sociodemographic, 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. Results: Ferritin and transferrin were positively associated with IGM (fourth vs first sex-specific quartile: ferritin odds ratio (OR)Z2.08 (95% CI 1.43-3.04) and transferrin ORZ1.89 (95% CI 1.32-2.70)), T2DM (ferritin ORZ1.98 (95% CI 1.22-3.22) and transferrin ORZ2.42 (95% CI 1.54-3.81)), and fasting as well as 2-h glucose. TSAT (ORZ0.55 (95% CI 0.34-0.88)) and iron (ORZ0.61 (95% CI 0.38-0.97)) were inversely associated with T2DM, sTfR-F-index was inversely associated with IGM (ORZ0.67 (95% CI 0.48-0.95)). There was no strong evidence for non-linear relationships. Conclusions:The 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.

Soluble transferrin receptor and risk of type 2 diabetes in the obese and nonobese

“…This finding is consistent with a previous study conducted by Rajpathak et al [7] in a sample of obese subjects from the USA DPP cohort. Other studies in a general German population from the EPIC-Potsdam [9] and KORA [14] cohorts, and in a Spanish population at high cardiovascular risk from the PREDIMED cohort [13] found no association between sTfR and risk of T2DM. This factor may be obesity, a known risk factor for T2DM [2].…”

“…In a general German population from the EPIC-Potsdam [9] and Cooperative Health Research in the Region of Augsburg (KORA) [14] cohorts, and in Spanish population at high cardiovascular risk from the PREDIMED cohort [13], serum ferritin, but not sTfR, was associated with a higher risk of T2DM. In a general German population from the EPIC-Potsdam [9] and Cooperative Health Research in the Region of Augsburg (KORA) [14] cohorts, and in Spanish population at high cardiovascular risk from the PREDIMED cohort [13], serum ferritin, but not sTfR, was associated with a higher risk of T2DM.…”

Diabetes inHFEHemochromatosis

“…In cohorts unselected for hemochromatosis, TS was inversely related to prediabetes [75] and diabetes [73, 76, 77]. In the HEIRS Study, mean TS was lower in non-Hispanic whites with diabetes [73].…”

“…SF levels were positively associated with fasting glucose [81]; impaired glucose metabolism [77]; insulin levels [81]; prediabetes [75]; and diabetes [73, 76–78, 82–85] in cross-sectional studies of participants unselected for hemochromatosis diagnoses. In a longitudinal study, SF levels were positively associated with glucose intolerance and IR [86].…”

MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study

“…Biomarkers associated with this 'prediabetic' state (impaired fasting glucose and/or impaired glucose tolerance) may help to elucidate the pathophysiological pathways leading to type 2 diabetes [2,3].…”