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非酒精性脂肪性肝病与多囊卵巢综合征女性的胰岛素抵抗及脂质堆积产物相关。

Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome.

作者信息

Macut D, Tziomalos K, Božić-Antić I, Bjekić-Macut J, Katsikis I, Papadakis E, Andrić Z, Panidis D

机构信息

Clinic of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia

First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece.

出版信息

Hum Reprod. 2016 Jun;31(6):1347-53. doi: 10.1093/humrep/dew076. Epub 2016 Apr 12.

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.

摘要

研究问题

多囊卵巢综合征(PCOS)女性中,与非酒精性脂肪性肝病(NAFLD)相关的最关键因素有哪些?

总结答案

胰岛素抵抗(IR)和脂质蓄积产物(LAP)与PCOS患者的NAFLD独立相关。

已知信息

肥胖和IR在PCOS女性和NAFLD患者中都很常见。PCOS和NAFLD并存可能会协同增加2型糖尿病(T2DM)和心血管疾病(CVD)的风险。由腰围(WC)和甘油三酯(TGs)浓度计算得出的LAP[(WC - 58)×TGs],已被证明是PCOS女性心脏代谢风险的综合标志物。

研究设计、规模、持续时间:这项横断面研究纳入了2008年5月至2013年5月期间根据鹿特丹标准诊断为PCOS的600名白人女性。

参与者、研究地点、方法:该研究在塞尔维亚贝尔格莱德和希腊塞萨洛尼基的大学医院进行。所有受试者均接受了人体测量,并对空腹血糖、胰岛素、血脂、总睾酮和性激素结合球蛋白(SHBG)进行了分析,同时还进行了肝功能检查(转氨酶、γ-谷氨酰转肽酶、总胆红素和碱性磷酸酶)。计算了NAFLD肝脏脂肪评分(NAFLD-LFS)(相应地,确定代谢综合征并检测T2DM)以及IR的稳态模型评估(HOMA-IR)、作为内脏肥胖标志物的LAP和游离雄激素指数(FAI)。我们评估了NAFLD的患病率,并分析了上述变量与NAFLD的相关性。

主要结果及偶然性的作用

PCOS患者中NAFLD的患病率高于对照组(分别为50.6%和34.0%)。PCOS女性的WC、LAP(脂质蓄积产物)、胰岛素和HOMA-IR、总胆固醇及TGs读数均高于对照组(P < 0.001)。在PCOS女性中,NAFLD-LFS与WC、体重指数(BMI)、血糖、HOMA-IR、TGs、LAP和FAI显著相关(P < 0.001)。在多因素逻辑回归分析中,HOMA-IR和LAP与NAFLD独立相关(P≤0.001)。

局限性、需谨慎的原因:该研究的一个可能弱点是缺乏肝脏状况的结构确认。然而,肝活检具有侵入性,在大样本人群中难以实施且存在一些并发症风险,而磁共振波谱分析无法提供任何关于纤维化存在的信息且并非常规可用。另一个可能的局限性是通过放射免疫分析法测量总睾酮,在测定低水平睾酮时可能不准确。最后,研究组中的对照人数少于受试者人数可能影响了结果的显著性。

研究结果的更广泛意义

对于在普通人群和PCOS女性中作为T2DM和CVD早期预测指标的肝病最准确临床诊断方法存在争议。本研究提供了一组患有PCOS的白人女性在这个问题上的数据。

研究资金/利益冲突:该研究由塞尔维亚科学和教育部的一项研究资助(资助编号41009和175032)。所有作者均无利益冲突。

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