Cornelia Huth1, Simon Beuerle2, Astrid Zierer2, Margit Heier1, Christian Herder1, Thorsten Kaiser2, Wolfgang Koenig2, Florian Kronenberg2, Konrad Oexle2, Wolfgang Rathmann1, Michael Roden1, Sigrid Schwab2, Jochen Seissler1, Doris Stöckl1, Christa Meisinger1, Annette Peters1, Barbara Thorand1. 1. Institute of Epidemiology IIHelmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstraße 1, D-85764 Neuherberg, GermanyGerman Center for Diabetes Research (DZD)Partner Neuherberg, GermanyMONICA/KORA Myocardial Infarction RegistryCentral Hospital of Augsburg, Augsburg, GermanyInstitute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyGerman Center for Diabetes Research (DZD)Partner Düsseldorf, GermanyInstitute of Laboratory MedicineClinical Chemistry and Molecular Diagnostics, University Leipzig, Leipzig, GermanyDepartment of Internal Medicine II - CardiologyUniversity of Ulm Medical Center, Ulm, GermanyDivision of Genetic EpidemiologyDepartment of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Human GeneticsKlinikum Rechts der Isar, Technische Universität München, Munich, GermanyInstitute of Biometrics and EpidemiologyGerman Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Endocrinology and DiabetologyMedical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyMedizinische Klinik und Poliklinik IVDiabetes Zentrum - Campus Innenstadt, Klinikum der Ludwig-Maximilians-Universität, München, GermanyClinical Cooperation Group DiabetesLudwig-Maximilians-Universität München and Helmholtz Zentrum München, München, Germany Institute of Epidemiology IIHelmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstraße 1, D-85764 Neuherberg, GermanyGerman Center for Diabetes Research (DZD)Partner Neuherberg, GermanyMONICA/KORA Myocardial Infarction RegistryCentral Hospital of Augsburg, Augsburg, GermanyInstitute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University 2. Institute of Epidemiology IIHelmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstraße 1, D-85764 Neuherberg, GermanyGerman Center for Diabetes Research (DZD)Partner Neuherberg, GermanyMONICA/KORA Myocardial Infarction RegistryCentral Hospital of Augsburg, Augsburg, GermanyInstitute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyGerman Center for Diabetes Research (DZD)Partner Düsseldorf, GermanyInstitute of Laboratory MedicineClinical Chemistry and Molecular Diagnostics, University Leipzig, Leipzig, GermanyDepartment of Internal Medicine II - CardiologyUniversity of Ulm Medical Center, Ulm, GermanyDivision of Genetic EpidemiologyDepartment of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Human GeneticsKlinikum Rechts der Isar, Technische Universität München, Munich, GermanyInstitute of Biometrics and EpidemiologyGerman Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Endocrinology and DiabetologyMedical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyMedizinische Klinik und Poliklinik IVDiabetes Zentrum - Campus Innenstadt, Klinikum der Ludwig-Maximilians-Universität, München, GermanyClinical Cooperation Group DiabetesLudwig-Maximilians-Universität München and Helmholtz Zentrum München, München, Germany.
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-log10ferritin (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 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. RESULTS: Ferritin 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. 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.
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-log10ferritin (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 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. RESULTS: Ferritin 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. 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.
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