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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. Mª Ángeles Martínez-García, Ph.D.,
  2. Manuel Luque-Ramírez, M.D., Ph.D.,
  3. José L. San-Millán, Ph.D. and
  4. Héctor F. Escobar-Morreale, M.D., Ph.D. (hescobarm.hrc{at}salud.madrid.org)
  1. Departments of Endocrinology and
  2. Molecular Genetics, Hospital Universitario Ramón y Cajal & Universidad de Alcalá, Madrid, and Centro de Investigaciones Biomédicas en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM, Spain

    Abstract

    Objective: Increased serum ferritin levels and iron stores might 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: Two hundred fifty-seven premenopausal women, classified depending on the presence or absence of PCOS, obesity and/or abnormal glucose tolerance, were submitted to 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, independently of obesity. A stepwise multivariate linear regression analysis (R2 = 0.18, P < 0.0001) retained menstrual regularity (β = 0.14, P = 0.035), free testosterone (β = 0.14, P = 0.052), insulin sensitivity index (β = − 0.12, P = 0.012), 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 neither CRP, haptoglobin, waist to hip ratio nor variants in the TNFα, TNFRSF1B, IL6, IL6ST, IL6Rα, PON-1 and HFE Cys282Tyr mutation exerted any influence.

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

    Footnotes

      • Received March 4, 2009.
      • Accepted April 23, 2009.
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