학술논문
Alterations in nonesterified free fatty acid trafficking rather than hyperandrogenism contribute to metabolic health in obese women with polycystic ovary syndrome.
Document Type
Academic Journal
Author
Ezeh U; California IVF Fertility Center, Sacramento, California; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama; Department of Obstetrics and Gynecology, Alta Bates Summit Medical Center (Sutter), Berkeley, California.; Chen YI; Department of Pediatrics and Medicine, Harbor- University of California (UCLA) Medical Center, Torrance, California; Department of Medicine, The David Geffen School of Medicine, UCLA, Los Angeles, California.; Pall M; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.; Buyalos RP; Fertility and Surgical Associates of California, Thousand Oaks, California.; Chan JL; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.; Pisarska MD; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, UCLA, Los Angeles, California.; Azziz R; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama; Department of Medicine, Heersink School of Medicine, UAB, Birmingham, Alabama; Department of Healthcare Organization and Policy, School of Public Health, UAB, Birmingham, Alabama; Department of Health Policy, Management and Behavior, School of Public Health, State University of New York at Albany, Albany, New York. Electronic address: razziz@uabmc.edu.
Source
Publisher: Elsevier for the American Society for Reproductive Medicine Country of Publication: United States NLM ID: 0372772 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1556-5653 (Electronic) Linking ISSN: 00150282 NLM ISO Abbreviation: Fertil Steril Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: To determine whether alterations in nonesterified fatty acid (NEFA) dynamics or degree of hyperandrogenism (HA) contribute to the difference in insulin sensitivity between women with metabolically healthy obese polycystic ovary syndrome (PCOS) (MHO-PCOS) and women with metabolically unhealthy obese PCOS (MUO-PCOS).
Design: Prospective cross-sectional study.
Setting: Tertiary-care academic center.
Patients: One hundred twenty-five obese women with PCOS.
Intervention: Consecutive obese (body mass index [BMI] ≥ 30 kg/m2 ) oligo-ovulatory women (n = 125) with PCOS underwent an oral glucose tolerance test and a subgroup of 16 participants underwent a modified frequently sampled intravenous glucose tolerance test to determine insulin-glucose and -NEFA dynamics.
Main Outcome Measures: Degree of insulin resistance (IR) in adipose tissue (AT) basally (Adipo-IR) and dynamically (the nadir in NEFA levels observed [NEFAnadir ], the time it took for NEFA levels to reach nadir [TIME nadir ], and the percent suppression in plasma NEFA levels from baseline to nadir [%NEFA supp ]); peak lipolysis rate (S NEFA ) and peak rate of NEFA disposal from plasma pool (K NEFA ); whole-body insulin-glucose interaction (acute response of insulin to glucose [AIRg], insulin sensitivity index [Si], glucose effectiveness [Sg], and disposition index [Di]); and HA (hirsutism score, total and free testosterone levels, and dehydroepiandrosterone sulfate levels).
Results: A total of 85 (68%) women were MUO-PCOS and 40 (32%) were MHO-PCOS using the homeostasis model of assessment of IR. Subjects with MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, waist-to-hip ratio, HA, and lipoprotein levels. By a modified frequently sampled intravenous glucose tolerance test, eight women with MUO-PCOS had lesser Si, KNEFA , and the percent suppression in plasma NEFA levels from baseline to nadir (%NEFA supp ) and greater TIME nadir , NEFA nadir , and baseline adipose tissue IR index (Adipo-IR) than eight subjects with MHO-PCOS, but similar fasting NEFA levels and S NEFA . Women with MUO-PCOS had a higher homeostasis model of assessment-β% and fasting insulin levels than women with MHO-PCOS. In bivalent analysis, Si correlated strongly and negatively with Adipo-IR and NEFA nadir , weakly and negatively with TIME nadir , and positively with K NEFA and %NEFA supp , in women with MUO-PCOS only.
Conclusion: Independent of age and BMI, women with MUO-PCOS have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, compared with women with MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese women with PCOS.
Competing Interests: Declaration of Interests U.E. serves as an investor in Concentric Analgesics, Inc. M.D.P. reports consulting fees from Ferring Pharmaceuticals; reports honorarium from Natera; and is on the Board of Directors of American Board of Obstetrics and Gynecology. R.A. reports funding from Foundation for Research and Education Excellence and National Institutes of Health for the submitted work; funding from Ferring Pharmaceuticals; reports royalties from Wolters Kluwer Health, Johns Hopkins University Press, Springer, and McGraw Hill; serves as a consultant for Spruce Bioscience, Core Access Surgical Technology, May Health, Rani Therapeutics, and Fortress Biotech; reports honoraria from Davidson-Mestman course; is an advisor for Arora Forge and investor in Martin Imaging; is on the data safety monitoring board for a multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole and placebo on live birth for infertility in women with polycystic ovary syndrome and Supporting Understanding of PCOS Education and Research (SUPER) Study; is CEO of ASRM (1/20-6/22) outside the submitted work; serves as a consultant for Spruce Bioscience, Core Access Surgical Technology, May Health, Rani Therapeutics, and Fortress Biotech; and is advisor for Arora Forge and investor in Martin Imaging. Y.I.C. has nothing to disclose. M.P. has nothing to disclose. R.P.B. has nothing to disclose. J.L.C. has nothing to disclose.
(Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
Design: Prospective cross-sectional study.
Setting: Tertiary-care academic center.
Patients: One hundred twenty-five obese women with PCOS.
Intervention: Consecutive obese (body mass index [BMI] ≥ 30 kg/m
Main Outcome Measures: Degree of insulin resistance (IR) in adipose tissue (AT) basally (Adipo-IR) and dynamically (the nadir in NEFA levels observed [NEFA
Results: A total of 85 (68%) women were MUO-PCOS and 40 (32%) were MHO-PCOS using the homeostasis model of assessment of IR. Subjects with MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, waist-to-hip ratio, HA, and lipoprotein levels. By a modified frequently sampled intravenous glucose tolerance test, eight women with MUO-PCOS had lesser Si, K
Conclusion: Independent of age and BMI, women with MUO-PCOS have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, compared with women with MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese women with PCOS.
Competing Interests: Declaration of Interests U.E. serves as an investor in Concentric Analgesics, Inc. M.D.P. reports consulting fees from Ferring Pharmaceuticals; reports honorarium from Natera; and is on the Board of Directors of American Board of Obstetrics and Gynecology. R.A. reports funding from Foundation for Research and Education Excellence and National Institutes of Health for the submitted work; funding from Ferring Pharmaceuticals; reports royalties from Wolters Kluwer Health, Johns Hopkins University Press, Springer, and McGraw Hill; serves as a consultant for Spruce Bioscience, Core Access Surgical Technology, May Health, Rani Therapeutics, and Fortress Biotech; reports honoraria from Davidson-Mestman course; is an advisor for Arora Forge and investor in Martin Imaging; is on the data safety monitoring board for a multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole and placebo on live birth for infertility in women with polycystic ovary syndrome and Supporting Understanding of PCOS Education and Research (SUPER) Study; is CEO of ASRM (1/20-6/22) outside the submitted work; serves as a consultant for Spruce Bioscience, Core Access Surgical Technology, May Health, Rani Therapeutics, and Fortress Biotech; and is advisor for Arora Forge and investor in Martin Imaging. Y.I.C. has nothing to disclose. M.P. has nothing to disclose. R.P.B. has nothing to disclose. J.L.C. has nothing to disclose.
(Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)