Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies
Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies
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DOI：
10.1093/humrep/dew243
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发表时间：
2016-11-01
影响因子：
6.1
通讯作者：
Stepto, Nigel K.
中科院分区：
文献类型：
--
作者：
Cassar, Samantha;Misso, Marie L.;Stepto, Nigel K.
基于金标准胰岛素钳夹研究的荟萃分析，多囊卵巢综合征（PCOS）女性的内源性胰岛素抵抗（IR）程度以及BMI对总体IR的相对贡献如何？我们报道了PCOS患者胰岛素敏感性（IS）的固有降低（-27%），这与BMI无关。PCOS是普遍的、复杂的，并以IR为基础，但围绕PCOS中内在IR的程度存在争议，BMI的影响和不同诊断标准的影响（NIH对比鹿特丹）。对截至2015年5月30日发表的研究进行了Medline和All EBM数据库的系统综述和荟萃分析。如果将诊断为PCOS的绝经前妇女与对照组进行IS比较，则纳入研究，IS通过金标准正常血-高胰岛素钳夹测量。本系统性综述遵循系统性综述和荟萃分析首选报告项目（PRISMA）指南的原则。使用混合建模和基于量值的推断（表示为平均效应+/- 99% CI）进行荟萃分析。我们推断，相对于通过标准化得出的最小重要变化-3.7%或3.8%，该影响是小的、中等的或大的。当CI与最小重要正值和负值重叠时，认为影响不明确。影响用反映真实值大小的不确定性的概率进行限定（可能，75-95%;非常可能，95-99.5%;最可能，> 99.5%）。其中28篇文章被纳入荟萃分析。总体而言，PCOS女性的IS低于对照组（平均效应-27%，99%CI +/- 6%;大，最有可能更低）。与对照组妇女相比，较高的BMI加剧了PCOS患者IS减少-15%（+/- 8%;中度，最有可能更低）。仅用美国国立卫生研究院（NIH）标准诊断的妇女与用鹿特丹标准诊断的妇女之间IS没有明显差异。低水平的性激素结合球蛋白（SHBG）与IS水平降低有关（-10%，+/- 10%;这项系统性综述和荟萃分析继承了样本量小、数据缺失等混杂问题，（例如某些激素、腰围和臀围）以及缺乏鹿特丹标准表型报告，BMI对PCOS患者IS的影响大于对照组。SHBG似乎是PCOS中IR的潜在有价值的标志物，而调整BMI后的睾酮显示出与IS的意想不到的相互作用，这值得进一步研究。N.K.S.），以及莫纳什大学。H.J.T.他是NHMRC研究员。N.K. S澳大利亚政府的合作研究网络（CRN）计划提供支持。供资机构在设计、方法、数据管理或分析或出版决定方面没有发挥任何作用。所有作者均声明无利益冲突。
What is the degree of intrinsic insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) and the relative contribution of BMI to overall IR based on meta-analysis of gold standard insulin clamp studies?We report an inherent reduction (-27%) of insulin sensitivity (IS) in PCOS patients, which was independent of BMI.PCOS is prevalent, complex and underpinned by IR but controversies surround the degree of intrinsic IR in PCOS, the effect of BMI and the impact of the different diagnostic criteria (NIH versus Rotterdam) in PCOS.A systematic review and meta-analysis of Medline and All EBM databases was undertaken of studies published up to 30 May 2015. Studies were included if premenopausal women diagnosed with PCOS were compared with a control group for IS, measured by the gold standard euglycaemic-hyperinsulinaemic clamp. The systematic review adheres to the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analyses were performed using mixed modelling and magnitude-based inferences expressed as mean effect +/- 99% CI. We inferred the effect was small, moderate or large relative to a smallest important change of -3.7% or 3.8% derived by standardisation. Effects were deemed unclear when the CI overlapped smallest important positive and negative values. Effects were qualified with probabilities reflecting uncertainty in the magnitude of the true value (likely, 75-95%; very likely, 95-99.5%; most likely, > 99.5%).A total of 4881 articles were returned from the search. Of these, 28 articles were included in the meta-analysis.Overall IS was lower in women with PCOS compared with controls (mean effect -27%, 99% CI +/- 6%; large, most likely lower). A higher BMI exacerbated the reduction in IS by -15% (+/- 8%; moderate, most likely lower) in PCOS compared with control women. There was no clear difference in IS between women diagnosed by the original National Institutes of Health (NIH) criteria alone compared with those diagnosed by the Rotterdam criteria. Low levels of sex hormone-binding globulin (SHBG) were associated with reduced levels of IS (-10%, +/- 10%; small, very likely negative), which was not confounded by BMI.This systematic review and meta-analysis inherited the confounding problems of small sample sizes, missing data (e.g. some hormones, waist and hip girths) and the lack of Rotterdam criteria phenotype reporting, limiting the evidence synthesis and meta-analysis.BMI has a greater impact on IS in PCOS than in controls. SHBG appears a potentially valuable marker of IR in PCOS, whereas testosterone after adjustment for BMI demonstrated an unexpected interplay with IS which warrants further investigation.This work was supported by grants from the National Health & Medical Research Council (NHMRC), grant number 606553 (H.J.T., N.K.S.), as well as Monash University. H.J.T. is an NHMRC Research Fellow. N.K.S. is supported through the Australian Government's Collaborative Research Networks (CRN) programme. The funding bodies played no role in the design, methods, data management or analysis or in the decision to publish. All authors declare no conflict of interests.N/A.