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Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome.
Hum Reprod. 2016 06; 31(6):1347-53.HR

Abstract

STUDY QUESTION

What are the most relevant factors associated with non-alcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS)?

SUMMARY ANSWER

Insulin resistance (IR) and lipid accumulation product (LAP) are independently associated with NAFLD in PCOS.

WHAT IS KNOWN ALREADY

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.

STUDY DESIGN, SIZE, DURATION

This cross-sectional study included 600 Caucasian women diagnosed with PCOS by the Rotterdam criteria between May 2008 and May 2013.

PARTICIPANTS, SETTINGS, METHODS

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.

MAIN RESULTS AND THE ROLE OF CHANCE

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).

LIMITATIONS, REASONS FOR CAUTION

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.

WIDER IMPLICATIONS OF THE FINDINGS

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.

STUDY FUNDING/COMPETING INTERESTS

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+Show Affiliations

Clinic of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia djmacut@gmail.com.First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece.Clinic of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.CHC Bezanijska Kosa, Faculty of Medicine, University of Belgrade, 11080 Belgrade, Serbia.Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece.Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece.CHC Bezanijska Kosa, Faculty of Medicine, University of Belgrade, 11080 Belgrade, Serbia.Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27076501

Citation

Macut, D, et al. "Non-alcoholic Fatty Liver Disease Is Associated With Insulin Resistance and Lipid Accumulation Product in Women With Polycystic Ovary Syndrome." Human Reproduction (Oxford, England), vol. 31, no. 6, 2016, pp. 1347-53.
Macut D, Tziomalos K, Božić-Antić I, et al. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. Hum Reprod. 2016;31(6):1347-53.
Macut, D., Tziomalos, K., Božić-Antić, I., Bjekić-Macut, J., Katsikis, I., Papadakis, E., Andrić, Z., & Panidis, D. (2016). Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. Human Reproduction (Oxford, England), 31(6), 1347-53. https://doi.org/10.1093/humrep/dew076
Macut D, et al. Non-alcoholic Fatty Liver Disease Is Associated With Insulin Resistance and Lipid Accumulation Product in Women With Polycystic Ovary Syndrome. Hum Reprod. 2016;31(6):1347-53. PubMed PMID: 27076501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. AU - Macut,D, AU - Tziomalos,K, AU - Božić-Antić,I, AU - Bjekić-Macut,J, AU - Katsikis,I, AU - Papadakis,E, AU - Andrić,Z, AU - Panidis,D, Y1 - 2016/04/12/ PY - 2015/11/01/received PY - 2016/03/15/accepted PY - 2016/4/15/entrez PY - 2016/4/15/pubmed PY - 2018/3/6/medline KW - insulin resistance KW - lipid acumulation product KW - metabolic syndrome KW - non-alcoholic fatty liver disease KW - polycystic ovary syndrome SP - 1347 EP - 53 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 31 IS - 6 N2 - STUDY QUESTION: What are the most relevant factors associated with non-alcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Insulin resistance (IR) and lipid accumulation product (LAP) are independently associated with NAFLD in PCOS. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 600 Caucasian women diagnosed with PCOS by the Rotterdam criteria between May 2008 and May 2013. PARTICIPANTS, SETTINGS, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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). LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: 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. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/27076501/Non_alcoholic_fatty_liver_disease_is_associated_with_insulin_resistance_and_lipid_accumulation_product_in_women_with_polycystic_ovary_syndrome_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dew076 DB - PRIME DP - Unbound Medicine ER -