title: Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome.
abstract: What are the most relevant factors associated with non-alcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS)?
  
  
  
  Insulin resistance (IR) and lipid accumulation product (LAP) are independently associated with NAFLD in PCOS.
  
  
  
  Obesity and IR are frequently present in both women with PCOS and subjects having NAFLD. The coexistence of PCOS and NAFLD might synergistically increase the risk for both type 2 diabetes (T2DM) and cardiovascular disease (CVD). LAP, calculated from waist circumference (WC) and triglycerides (TGs) concentrations [(WC-58) × TGs], has been shown to represent an integrated marker of cardiometabolic risk in women with PCOS.
  
  
  
  This cross-sectional study included 600 Caucasian women diagnosed with PCOS by the Rotterdam criteria between May 2008 and May 2013.
  
  
  
  The study was done at the university hospitals in Belgrade, Serbia and Thessaloniki, Greece. All subjects underwent anthropometric measurements and analyses of fasting blood glucose, insulin, lipids, total testosterone and SHBG, as well as liver tests (transaminases, γ-glutamyltransaminase, total bilirubin and alkaline phosphatase). Calculations for a NAFLD liver fat score (NAFLD-LFS) (with, accordingly, determination of metabolic syndrome and testing for T2DM) as well as homeostasis model assessment of IR (HOMA-IR), LAP as a marker of visceral adiposity, and free androgen index (FAI) were performed. We evaluated the prevance of NAFLD and analyzed associations of the above variables with NAFLD.
  
  
  
  NAFLD was more prevalent in patients with PCOS than in controls (50.6 versus 34.0%, respectively). Women with PCOS had higher readings for WC, LAP, insulin and HOMA-IR, total cholesterol and TGs than controls (P < 0.001). In PCOS women, the NAFLD-LFS significantly (P < 0.001) correlated with WC, BMI, glucose, HOMA-IR, TGs, LAP and FAI. In multivariate logistic regression, HOMA-IR and LAP were independently associated with NAFLD (P ≤ 0.001).
  
  
  
  A possible weakness of the study may be the absence of structural confirmation of liver status. Hovewer, liver biopsy is invasive, difficult to perform in large populations and carries some risk of complications while magnetic resonance spectroscopy does not provide any information regarding the presence of fibrosis and is not routinely available. Another possible limitation could be the measurement of total testosterone by radioimmunoassay, which can be inaccurate when determining low levels of testosterone. Finally, fewer controls than subjects in the study group could have affected the significance of the results.
  
  
  
  There is a debate on the most accurate clinical method for diagnosing liver disease as an early predictor of T2DM and CVD in general population and in PCOS women. There current study provided data on this issue from a cohort of Caucasian women with PCOS.
  
  
  
  The study was supported by a research grant by the Serbian Ministry of Science and Education (grant nos 41009 and 175032). All authors have no competing interests.
authors.affiliation: Clinic of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia djmacut@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Macut
authors.affiliation: First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Tziomalos
authors.affiliation: Clinic of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
authors.forename: I
authors.initials: I
authors.lastname: Božić-Antić
authors.affiliation: CHC Bezanijska Kosa, Faculty of Medicine, University of Belgrade, 11080 Belgrade, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Bjekić-Macut
authors.affiliation: Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Katsikis
authors.affiliation: Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Papadakis
authors.affiliation: CHC Bezanijska Kosa, Faculty of Medicine, University of Belgrade, 11080 Belgrade, Serbia.
authors.forename: Z
authors.initials: Z
authors.lastname: Andrić
authors.affiliation: Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Panidis
mesh_terms: D001786:Blood Glucose; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008111:Liver Function Tests; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000378:metabolism; D015995:Prevalence; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D012738:Sex Hormone-Binding Globulin; D014280:Triglycerides; D013739:Testosterone
keywords: insulin resistance; lipid acumulation product; metabolic syndrome; non-alcoholic fatty liver disease; polycystic ovary syndrome