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Cross-Talk Between Body Iron Stores and Diabetes: Iron Stores are Associated with Activity and Microsatellite Polymorphism of the Heme Oxygenase and Type 2 Diabetes

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Abstract

To assess the relationship between the length of (GT) n repeats in HO-1 gene promoter and heme oxygenase (HO) enzymatic activity in mononuclear cells with iron (Fe) stores in type 2 diabetic mellitus (DM2) patients and metabolic syndrome (MS) subjects, we studied 163 patients with DM2, 185 with MS, and 120 controls subjects. We evaluated iron status (hemoglobin and serum Fe, ferritin, and transferrin receptor), and we determined the length of (GT) n repeats in HO-1 gene promoter by capillary electrophoresis and HO enzymatic activity in mononuclear cells and assessed the relationship between these results and Fe stores. Only 1/163, 6/185, and 7/120 had iron deficiency anemia in DM2 patients, MS subjects, and controls, respectively. No iron overload (ferritin >200 μg/L) was detected in all the subjects studied. DM2 patients had higher iron deposits, total body iron, and heme oxygenase activity (a suggestion of high oxidative stress condition) than MS subjects and controls. In DM2, we found a positive association between serum iron and HO activity. There were no difference in allelic frequency between the three groups; however, among DM2 and MS patients, the frequency of short/medium (SM) genotype of (GT) n repetition was increased and medium/medium (MM) genotype of (GT) n repetition was lower than controls. These results imply that DM2 patients and individuals with MS carrying SM repeats might have higher susceptibility to develop diabetes consequences. This increased susceptibility could be Fe-mediated oxidative stress.

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Acknowledgements

We thank the staff from the Diabetic Program, Nutrition Unit, of Juan de Dios Hospital, for their teamwork and persistent efforts in this project.

This work was supported by Fondo Nacional de Ciencia y Tecnología (FONDECYT) grant # 1051006 and 1085173, Chile.

The authors' responsibilities were as follows—MA: study design, management of laboratory work, data collection, analysis, and interpretation and writing of the manuscripts; DJ, MF, and VC: laboratory analysis, data collection, analysis, and interpretation; EH: study design, management of hematological patients, revision of the manuscripts; EC: management of the field site, sample collection, revision of the manuscripts; and CA: study design, management of diabetics patients, and revision of the manuscripts. None of the authors had a personal or financial conflict of interest.

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Authors and Affiliations

  1. Micronutrient Laboratory, Nutrition Institute and Food Technology (INTA), University of Chile, El Líbano 5524, Macul, Santiago, Chile

    Miguel Arredondo, Marcela Fuentes, Denisse Jorquera, Valeria Candia & Eva Hertrampf

  2. Diabetes Unit, Department of Medicine, Medicine Faculty, University of Chile, Chacabuco 419, Santiago, Chile

    Elena Carrasco

  3. Department of Clinical Biochemistry and Immunohematology, Health Science Faculty, University of Talca, Lircay S/N, Talca, Chile

    Elba Leiva & Verónica Mujica

  4. Department of Nutrition, Medicine Faculty, University of Chile, Av. Independencia 1027, Santiago, Chile

    Francisco Pérez

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  1. Miguel Arredondo
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  2. Marcela Fuentes
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  3. Denisse Jorquera
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  4. Valeria Candia
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  5. Elena Carrasco
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  6. Elba Leiva
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  7. Verónica Mujica
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  8. Eva Hertrampf
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  9. Francisco Pérez
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Correspondence to Miguel Arredondo.

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Arredondo, M., Fuentes, M., Jorquera, D. et al. Cross-Talk Between Body Iron Stores and Diabetes: Iron Stores are Associated with Activity and Microsatellite Polymorphism of the Heme Oxygenase and Type 2 Diabetes. Biol Trace Elem Res 143, 625–636 (2011). https://doi.org/10.1007/s12011-010-8895-7

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  • DOI: https://doi.org/10.1007/s12011-010-8895-7

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