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

• Published in: Diabetes care Vol. 32; no. 8; pp. 1525 - 1530
• Main Authors: Martínez-García, M. Ángeles, Luque-Ramírez, Manuel, San-Millán, José L, Escobar-Morreale, Héctor F
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2009
• Subjects: adiposity; Adult; Anemia; animal ovaries; Aryldialkylphosphatase; Aryldialkylphosphatase - genetics; Biological and medical sciences; blood; blood serum; Body Mass Index; C-reactive protein; Dextrose; Diabetes; Diabetes. Impaired glucose tolerance; Diet; DNA; DNA - blood; DNA - genetics; Drug resistance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exons; Female; Ferritin; Ferritins; Ferritins - blood; genes; Genetic aspects; Genetic Variation; genetics; Genomics; genotype; genotyping; Glucose; Glucose Intolerance; Glucose Intolerance - metabolism; glucose tolerance; Haptoglobin; Humans; Inflammation; Inflammation - genetics; Inflammation - physiopathology; Insulin; Insulin resistance; Insulin Resistance - physiology; interleukin-6; Interleukin-6 - genetics; Iron; Iron - metabolism; linear models; Medical research; Medical sciences; Medicine, Experimental; Menopause; Menstrual Cycle; Menstrual Cycle - physiology; Metabolic diseases; Metabolism; Miscellaneous; mutation; Nutrition; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - physiopathology; Original Research; Oxidative stress; Oxidative Stress - genetics; Physiological aspects; physiology; physiopathology; polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Polycystic Ovary Syndrome - physiopathology; Polymorphism, Genetic; premenopause; Premenopause - physiology; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reference Values; regression analysis; STAT6 Transcription Factor; STAT6 Transcription Factor - genetics; Stein-Leventhal syndrome; Stress; testosterone; waist-to-hip ratio; women; Endocrinopathy; Human; Oxidative stress; Pancreatic hormone; Genetic variability; Premenopause; Genomics; Genotype; Inflammation; Insulin; Variant; Target tissue resistance; Iron storage; Young adult; Female; Hyperandrogenism; Insulin resistance; Woman; Genome; Impaired glucose tolerance; Body
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc09-0420

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.