Soren Harnois-Leblanc1,2, Maria Isabel Hernandez2, Ethel Codner3, Fernando Cassorla3, Sharon E Oberfield4, Natasha I Leibel4, Revi P Mathew5, Svetlana Ten6, Denis A Magoffin7, Christianne J Lane8, Michael I Goran9, Ricardo Azziz10,11, Jean-Patrice Baillargeon1,12, David H Geller9,13. 1. Research Center, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada. 2. Department of Preventive and Social Medicine, School of Public Health, Université de Montréal, Montréal, QC, H3T 1J4, Canada. 3. Instituto de Investigaciones Materno Infantil, School of Medicine, University of Chile, Santiago, Chile. 4. Department of Pediatrics, Columbia University Medical Center, New York, NY, USA. 5. Division of Pediatric Endocrinology, School of Medicine, Vanderbilt University, Nashville, TN, USA. 6. Richmond University Medical Center, Staten Island, NY, USA. 7. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 8. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 9. Center for Endocrinology, Diabetes and Metabolism, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 10. Departments of Obstetrics and Gynecology, and Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, ALUSA. 11. Department of Health Policy, Management and Behavior, School of Public Health, University at Albany, SUNY, Rensselaer, NYUSA. 12. Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. 13. Children's Hospital Los Angeles, Los Angeles, CA, USA.
Abstract
CONTEXT: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. OBJECTIVE: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. DESIGN: Cross-sectional study. SETTING: Seven academic centers in North America, South America, and Europe. PATIENTS: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). MAIN OUTCOME MEASURES: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. RESULTS: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). CONCLUSIONS: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.
CONTEXT: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. OBJECTIVE: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. DESIGN: Cross-sectional study. SETTING: Seven academic centers in North America, South America, and Europe. PATIENTS: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). MAIN OUTCOME MEASURES: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. RESULTS: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). CONCLUSIONS: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.
Authors: Alison N Jeffery; Brad S Metcalf; Joanne Hosking; Adam J Streeter; Linda D Voss; Terence J Wilkin Journal: Diabetes Care Date: 2012-01-25 Impact factor: 19.112