多囊卵巢综合征患者胰岛素抵抗的研究进展

多囊卵巢综合征(PCOS)是一种常见的影响生育功能的妇科内分泌疾病,被认为与遗传、代谢、内分泌及环境等多因素相关。PCOS患者的胰岛素抵抗增加了2型糖尿病、高血压、脂质代谢异常等发生的风险,越来越多的研究开始关注PCOS患者的胰岛素抵抗,本文从胰岛素抵抗的发生机制、评估、治疗等方面阐述其在PCOS中的研究进展。     

胰岛素抵抗对多囊卵巢综合征患者妊娠结局的影响

目的:探讨胰岛素抵抗(IR)对多囊卵巢综合征(PCOS)患者妊娠结局的影响.方法:选择2005年1月～2009年1月就诊的40例PCOS患者,将稳态模型胰岛素抵抗指数( HOMA- IR)≥2.69的22例PCOS患者作为胰岛素抵抗组,余20例作为对熙组,比较两组妊娠合并症、并发症和新生儿情况.结果:在妊娠期糖尿病( ...     

多囊卵巢综合征患者胰岛素受体基因外显子17多态性的研究

目的探讨胰岛素受体（INSR）基因外显子17多态性与多囊卵巢综合征（PCOS）发病的关系。方法应用聚合酶链反应限制性内切酶片段长度多态性分析（PCR—RFLP）法对中国汉族96例PCOS患者和56例对照者INRS基因外显子17第1,058位点的多态性进行检测,分析并比较INRS基因外显子17第1,058位点T、C等位基因频率与PCOS胰岛素抵抗、高雄激素血症之间的关系。结果（1）PCOS患者INSR基因外显子17第1,058位点T等位基因出现频率为41．7％,明显高于正常对照组的14．3％（P〈0.05）。（2）PCOS患者出现T等位基因者的体重指数（BMI）明显低于出现C等位基因患者（P〈0.05）。（3）PCOS胰岛素抵抗组与非胰岛素抵抗组T、C等位基因出现频率无统计学差异（P〉0．05）。（4）PCOS高雄激素组与无高雄激素组INSR基因T、C等位基因频率无统计学差异（P〉0．05）。结论INSR基因17外显子C／T单核酸多态性与PCOS患者肥胖密切相关,与PCOS的高雄激素血症、胰岛素抵抗（IR）无明显关系。认为INSR基因第17外显子C／T单核酸多态性仅系PCOS的一个易感基因,对PCOS的发病无决定性作用。     

维生素D与多囊卵巢综合征相关性的研究进展

维生素D缺乏在多囊卵巢综合征(PCOS)妇女中常见,它与PCOS妇女的胰岛素抵抗、高雄激素表现、心血管疾病危险及生育功能下降有关。适当补充维生素D可减轻PCOS的危险因素,改善PCOS妇女的健康。     

罗格列酮对多囊卵巢综合征卵巢颗粒细胞芳香化酶的表达和雌二醇分泌的影响

研究罗格列酮对多囊卵巢综合征(PCOS)患者卵巢颗粒细胞芳香化酶(aromatase)的表达和雌二醇(E2)分泌的影响,以了解罗格列酮对PCOS卵巢颗粒细胞的局部作用。一、材料与方法1.研究对象:选择2004年11月至2005年3月在本院生殖中心接受体外受精-胚胎移植(IVF-ET)治疗并伴有胰岛素抵抗的PCOS患者(PCOS组)及同期非PCOS原因导致不育的患者(非PCOS组)各5例。胰岛素(INS)释放试验:空腹INS>16·15mIU/L,餐后(服75 g葡萄糖)INS 1 h>109·8mIU/L或2 h>89·0 mIU/L,其中一项阳性即为胰岛素抵抗。诊断标准,满足以下三项中的任意两项即可…     

多囊卵巢综合征患者血脂异常与胰岛素抵抗的相关性研究

目的探讨多囊卵巢综合征(PCOS)患者血脂异常与胰岛素抵抗的相关性。方法收集在我院就诊的符合鹿特丹标准、未经药物治疗的PCOS患者200例,记录患者的一般资料,检测基础性激素水平及血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)水平,行口服葡萄糖耐量试验(OGTT)和胰岛素释放实验(IRT),计算体重指数(BMI)、胰岛素抵抗稳态指数模型(HOMA-IR)等参数。并按TG水平将患者分为血脂正常组(TG1.7 mmol/L)和血脂异常组(TG≥1.7mmol/L),比较两组患者的BMI、各时相血糖水平和胰岛素水平、HOMA-IR指数,以及生殖内分泌指标等的差异,探讨TG与HOMA-IR的相关性,并分析TG、HDL、低密度脂蛋白(LDL)作为评估胰岛素抵抗替代指标的可行性。结果 PCOS患者血脂异常的发生率为16.69%。除半小时血糖两组间比较无显著性差异外,血脂异常组患者的年龄、BMI、游离睾酮(FT)、HOMA-IR以及各时相血糖水平和胰岛素水平均显著高于血脂正常组(P均0.05)。用TG作为替代指标预测胰岛素抵抗的ROC曲线下面积为0.798,最佳切点为1.025mmol/L,对应的敏感度和1-特异度分别为0.806和0.317,阳性似然比提高了2.54倍。结论 TG可以作为预测PCOS患者胰岛素抵抗的替代指标。当TG水平≥最佳切点1.025mmol/L时,患者发生胰岛素抵抗的风险显著增加。     

桂枝茯苓胶囊加黄连素临床治疗多囊卵巢综合征疗效观察

目的总结桂枝茯苓胶囊加黄连素治疗多囊卵巢综合征(PCOS)的效果,探讨胰岛素抵抗与PCOS的关系。方法将60例PCOS合并不孕患者随机分为对照组和观察组,各30例。对照组用二甲双胍和克罗米芬治疗,观察组用桂枝茯苓胶囊、黄连素和克罗米芬治疗,均治疗3个月经周期。结果 2组患者均有不同程度的高雄激素班症,LH、LH/FSH和T升高,E2降低。体质量、腰围、臀围、腰臀比(WHR)、体质量指数(BMI)均有不同程度缓解,血脂异常均有不同程度改善,停药3个月后仍能维持疗效,观察组更为理想。2组患者胰岛素抵抗相关指标显著改善,以治疗组为优。对照组和观察组排卵率分别为24.44%、21.11%,治疗3个月后妊娠率分别为53.33%和70.00%。结论 PCOS患者存在者显著的胰岛素抵抗和性激素分泌失调,桂枝茯苓胶囊加黄连素治疗可改善胰岛素抵抗及症状、体征,恢复月经周期和排卵,提高妊娠率。     

PCOS患者胰岛素抵抗与肥胖对IVF结局的影响

目的探讨PCOS患者胰岛素抵抗与肥胖对IVF结局的影响,以期为临床加强对PCOS患者胰岛素抵抗及肥胖的管理提供一定参考。方法选择2015～2017年就诊于烟台毓璜顶医院生殖医学中心接受IVF助孕治疗的第一周期鲜胚移植/冻融胚胎移植(FET)的患者590人,根据是否合并PCOS分为PCOS组(347例)和对照组(243例)。PCOS组患者又根据稳态评估-胰岛素抵抗指数(HOMA-IR)分为两个亚组:合并胰岛素抵抗(IR)的PCOS-IR组(200例),不合并IR的PCOS-NIR组(147例);按照不同的体重指数(BMI)水平分为PCOS体重正常组(115例)、PCOS超重组(132例)和PCOS肥胖组(94例)。比较各组患者的基本情况、IVF治疗相关参数及妊娠结局。结果 (1)PCOS-NIR组的抗苗勒管激素(AMH)、b-LH、b-FSH、高密度脂蛋白(HDL)水平均显著高于PCOS-IR组(P0.05)。对照组Gn总量、HCG日大卵泡数、MⅡ卵数、2PN受精卵数、优胚数均显著低于PCOS-NIR、PCOS-IR组(P0.05),临床妊娠率显著高于PCOS-IR组(P0.05);PCOS-NIR组的着床率、临床妊娠率显著高于PCOS-IR组(P0.05)。(2)按BMI分组后发现,PCOS肥胖、超重组的HOMA-IR、TG均显著高于PCOS体重正常组(P0.05);对照组的Gn天数、HCG日大卵泡数、获卵数、MⅡ卵数、2PN受精卵数、优胚数均显著低于PCOS不同BMI亚组,临床妊娠率则显著高于不同BMI亚组(P0.05);PCOS体重正常组的着床率、临床妊娠率均显著高于PCOS超重、肥胖组(P0.05)。结论 PCOS合并IR与肥胖均会对IVF结局产生不利的影响,且肥胖可加剧PCOS患者的IR程度。     

多囊卵巢综合征与复发性流产的研究进展

复发性流产(RSA)的发生与多种因素相关,包括年龄、遗传、内分泌与代谢障碍、免疫因素、子宫发育异常、血栓形成倾向、感染、精液质量和生活方式等。多囊卵巢综合征(PCOS)是一种以持续性无排卵、多卵泡不成熟、雄激素水平升高和胰岛素抵抗为主要特征的生殖功能障碍与糖代谢异常并存的内分泌紊乱综合征。PCOS患者RSA的发生率明显高于普通人群,30%~40%的PCOS患者存在自然流产史。目前,PCOS患者易发生RSA的具体发病机制尚不明确,可能与高黄体生成素血症、高雄激素血症、胰岛素抵抗、肥胖、高泌乳素血症、黄体功能不全、血栓形成等有关。本文从上述方面对PCOS患者发生RSA的常见原因及其预防进行综述。     

79例多囊卵巢综合征患者血清C肽水平测定分析

多囊卵巢综合征（PCOS）是一种以内分泌紊乱为主伴多种代谢异常的临床综合征,基本的病理生理改变为无排卵性月经异常及高雄激素血症。近年来的研究表明胰岛素抵抗（IR）与PCOS的发病过程相关,IR可能是PCOS发生发展的重要因素之一,IR所产生的代偿性高胰岛素血症,可引起糖代谢、脂代谢紊乱,增加心血管病的危险。     

Assessing and treating insulin resistance in women with polycystic ovarian syndrome

Polycystic ovarian syndrome(PCOS) is a highly prevalent hormonal and metabolic disorder among reproductive aged women worldwide.Women with PCOS have widely varying phenotypes and seek medical care for differing reasons.In addition to concern for menstrual cycle function,ovulation,hirsutism and acne,many PCOS women have abnormal glucose metabolism.While diabetes mellitus and impaired glucose tolerance are easily diagnosed,the diagnosis of and concern for insulin resistance as a precursor disorder is underappreciated.Insulin resistance may be the first important marker of metabolic disease in PCOS women at risk for metabolic syndrome and coronary artery disease.     

Polymorphism of insulin gene variable number tandem repeats correlated with polycystic ovary syndrome

Objective: To investigate the correlation between the insulin gene variable number tandem repeats (INS-VN-TR) with polycystic ovary syndrome(PCOS) and metabolic features related to insulin resistance (IR).Methods: One hundred and thirty patients with PCOS (PCOS group) and 130 normal women (control group) were included. Genotyping of INS-VNTR was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results: The distribution of genotype of INS-VNTR was similar in PCOS group, but the Ⅲ allele frequency of INS-VNTR was higher in PCOS patients than that in controls, and Logistic regression analysis revealed that the Ⅲ allele was associated with increased risk of PCOS[adjusted odd ratio(OR) = 2.31;95% confidence interval(CD =1.07-4.98), compared with the Ⅰ allele. The distribution of genotype and the Ⅲ allele frequency of INS-VNTR in PCOS insulin resistance (PCOS-IR) group were significantly higher than that in PCOS non-insulin resistance group (PCOS-NIR). Moreover, PCOS women with Ⅲ allele had statistically significantly higher fasting insulin level and HOMA-IR than those of PCOS women with Ⅰ allele.Conclusion: INS-VNTR may not be a susceptibility gene, but INS-VNTR polymorphism may play an important role in the occurrence of insulin resistance in patients with PCOS.     

Role of insulin and insulin resistance in androgen excess disorders

Insulin has complex effects on cell growth, metabolism and differentiation, and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events. Among the several metabolic and growth-promoting effects of insulin, insulin resistance is defined as an attenuated effect of insulin on glucose metabolism, primarily the limited export of blood glucose into skeletal muscle and adipose tissue. On the other hand, not all the signaling pathways and insulin-responsive tissues are equally affected, and some effects other than the metabolic actions of insulin are overexpressed. Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion. Polycystic ovary syndrome (PCOS) is the most common form of androgen excess disorder (AED), and its pathogenesis is closely associated with insulin resistance. Patients with idiopathic hirsutism also exhibit insulin resistance, albeit lower than patients with PCOS. Although it is not as evident as in PCOS, patients with congenital adrenal hyperplasia may have insulin resistance, which may be further exacerbated with glucocorticoid overtreatment and obesity. Among patients with severe insulin resistance syndromes, irrespective of the type of disease, hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins. It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs, including PCOS. It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance. Instead, the treatment decision should be based on the constellation of the signs, symptoms and presence of obesity; acanthosis nigricans; and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose.     

AMH在多囊卵巢综合征中的研究进展

多囊卵巢综合征(PCOS)是一种常见的妇科内分泌、代谢紊乱性疾病,同时也是一种生殖障碍性疾病,严重危害女性身心健康,但是其具体发病机制目前仍不明确。越来越多的研究证明,抗苗勒氏管激素(AMH)与卵泡生长发育、卵泡募集与成熟、高雄激素血症、胰岛素抵抗等均具有密切关系,在PCOS的发生发展过程中也具有重要调节作用。因此,本文结合AMH与PCOS的最新研究进行综述,以期探讨二者关系及其潜在发病机制,为PCOS的诊治提供新的思路。     

Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative and nonoxidative glucose disposal in PCOS patients are associated with a consistent downregulation of OXPHOS gene expression using GSEA and GenMAPP analysis. Quantitative real-time PCR analysis validated these findings and showed that reduced levels of peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1alpha) could play a role in the downregulation of OXPHOS genes in PCOS. In these women with PCOS, the decrease in OXPHOS gene expression in skeletal muscle cannot be ascribed to obesity and diabetes. This supports the hypothesis of an early association between insulin resistance and impaired mitochondrial oxidative metabolism, which is, in part, mediated by reduced PGC-1alpha levels. These abnormalities may contribute to the increased risk of type 2 diabetes observed in women with PCOS.     

Enhanced mitogenic signaling in skeletal muscle of women with polycystic ovary syndrome

Insulin resistance in polycystic ovary syndrome (PCOS) results from a postbinding defect in signaling. Insulin receptor and insulin receptor substrate (IRS)-1 serine hyperphosphorylation by an unidentified kinase(s) contributes to this defect. We investigated whether insulin resistance is selective, affecting metabolic but not mitogenic pathways, in skeletal muscle as it is in cultured skin fibroblasts in PCOS. Extracellular signal-regulated kinase (ERK)1/2 activation was increased in skeletal muscle tissue and in cultured myotubes basally and in response to insulin in women with PCOS compared with control women. Mitogen-activated/extracellular signal-regulated kinase kinase (MEK)1/2 was also activated in PCOS, whereas p38 mitogen-activated protein kinase phosphorylation and signaling from the insulin receptor to Grb2 was similar in both groups. The activity of p21Ras was decreased and Raf-1 abundance increased in PCOS, suggesting that altered mitogenic signaling began at this level. MEK1/2 inhibition reduced IRS-1 Ser312 phosphorylation and increased IRS-1 association with the p85 subunit of phosphatidylinositol 3-kinase in both groups. We conclude that in PCOS skeletal muscle, 1) mitogenic signaling is enhanced in vivo and in culture, 2) ERK1/2 activation inhibits association of IRS-1 with p85 via IRS-1 Ser312 phosphorylation, and 3) ERK1/2 activation may play a role in normal feedback of insulin signaling and contribute to resistance to insulin's metabolic actions in PCOS.     

二甲双胍在多囊卵巢综合征的作用

生殖及代谢异常是多囊卵巢综合征(PCOS)的特征性表现。已证实高胰岛素血症及胰岛素抵抗,导致血中雄激素水平过高,是PCOS的重要发病机制。二甲双胍(metformin)称为胰岛素增敏剂,用于治疗PCOS后,可减轻高雄激素血症,使月经周期规律,改善卵巢对诱导排卵的反应,提高妊娠率,降低早孕流产率,且能减低发展为II型糖尿病及心血管疾病的危险性。本文就国外近年有关metformin运用于PCOS的进展作一综述。     

Markers of insulin resistance in Polycystic ovary syndrome women: An update

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.