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Original Research

Body Iron Stores and Glucose Intolerance in Premenopausal Women

Role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism

  1. M. Ángeles Martínez-García, PHD1,
  2. Manuel Luque-Ramírez, MD, PHD1,
  3. José L. San-Millán, PHD2 and
  4. Héctor F. Escobar-Morreale, MD, PHD1
  1. 1Department of Endocrinology, Hospital Universitario Ramón y Cajal and Universidad de Alcalá, Madrid, Spain and Centro de Investigaciones Biomédicas en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain;
  2. 2Department of Molecular Genetics, Hospital Universitario Ramón y Cajal and Universidad de Alcalá, Madrid, Spain and Centro de Investigaciones Biomédicas en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain.
  1. Corresponding author: Héctor F. Escobar-Morreale, hescobarm.hrc{at}salud.madrid.org.
Diabetes Care 2009 Aug; 32(8): 1525-1530. https://doi.org/10.2337/dc09-0420
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Role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism

Abstract

OBJECTIVE Increased serum ferritin levels and iron stores may be involved in the development of abnormal glucose tolerance in women presenting with obesity and/or polycystic ovary syndrome (PCOS). We aimed to study the determinants of serum ferritin levels in premenopausal women among indexes of insulin resistance, adiposity, hyperandrogenism, and genotypes pertaining to inflammation, oxidative stress, and iron metabolism.

RESEARCH DESIGN AND METHODS A total of 257 premenopausal women, classified depending on the presence or absence of PCOS, obesity, and/or abnormal glucose tolerance, underwent a complete metabolic evaluation, serum ferritin, haptoglobin, and C-reactive protein (CRP) measurements, and genotyping for proinflammatory and prooxidant variants and mutations in the HFE gene.

RESULTS Serum ferritin concentrations were increased in women presenting with PCOS and/or abnormal glucose tolerance, independent of obesity. A stepwise multivariate linear regression analysis (R2 = 0.18, P < 0.0001) retained menstrual dysfunction (β = 0.14, P = 0.035), free testosterone (β = 0.14, P = 0.052), insulin sensitivity index (β = −0.12, P = 0.012), the His63Asp variant in HFE (β = 0.16, P = 0.008), and abnormal glucose tolerance (β = 0.15, P = 0.015) as significant predictors of the logarithm of ferritin levels, whereas CRP, haptoglobin, waist-to-hip ratio, or variants in the TNFα, TNFRSF1B, IL6, IL6ST, IL6Rα, PON1, and HFE Cys282Tyr mutation exerted no influence.

CONCLUSIONS Androgen excess (partly because of hyperandrogenemia and partly because of menstrual dysfunction), insulin resistance, abnormal glucose tolerance, and the HFE His63Asp variant correlate with ferritin levels in premenopausal women.

Footnotes

  • M.L.-R. is currently affiliated with the Department of Endocrinology, Hospital Universitario de La Princesa, Madrid, Spain.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received March 4, 2009.
    • Accepted April 23, 2009.
  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

  • © 2009 by the American Diabetes Association.
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Diabetes Care: 32 (8)

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Body Iron Stores and Glucose Intolerance in Premenopausal Women
M. Ángeles Martínez-García, Manuel Luque-Ramírez, José L. San-Millán, Héctor F. Escobar-Morreale
Diabetes Care Aug 2009, 32 (8) 1525-1530; DOI: 10.2337/dc09-0420

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Body Iron Stores and Glucose Intolerance in Premenopausal Women
M. Ángeles Martínez-García, Manuel Luque-Ramírez, José L. San-Millán, Héctor F. Escobar-Morreale
Diabetes Care Aug 2009, 32 (8) 1525-1530; DOI: 10.2337/dc09-0420
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