多囊卵巢综合征伴胰岛素抵抗的研究进展

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是国内外研究者、医患人员非常关心的育龄期妇女常见的内分泌代谢疾病,其主要表现为闭经、月经量减少、肥胖、不孕、体多毛等。多数伴有胰岛素抵抗（insulin resistance,IR）的发生,胰岛素抵抗（insulin resistance,IR）是指正常水平的胰岛素促进葡萄糖摄取及利用能力下降,机体各组织、器官代偿性分泌胰岛素以维持机体血糖稳定的一种代谢状态。近年来的研究不断证实PCOS患者2型糖尿病、血脂代谢紊乱及代谢综合征（metabolicsyndrome,MS）等并发症的发病率明显增高。运动能够改善2型糖尿病患者胰岛素抵抗的说法已经得到了共识,其分子机制也逐渐分明。PCOS患者胰岛素抵抗的研究目前仍处于进一步探讨阶段,但是经过近几年的努力已经有了新的进展,若在PCOS胰岛素抵抗患者的治疗过程中给予一定的运动干预,相信一定能够有新的突破。本文就PCOS患者胰岛素抵抗研究的机制、诊断及治疗方法的新进展简单做一综述。     

Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

Background

Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls.

Research Design and Methods

Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method).

Results

Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons).

Conclusion

Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.     

Osteocalcin Levels on Oral Glucose Load in Women being Investigated for Polycystic Ovary Syndrome

ObjectiveOsteocalcin (OC) might play a hormone-like role in energy metabolism and the regulatory circuit between the pancreas and osteoblasts. Effects of a 75-g oral glucose tolerance test (OGTT) on total OC, undercarboxylated (ucOC), and carboxylated osteocalcin (cOC) in insulin-resistant (IR) and noninsulin-resistant (nIR) premenopausal women was evaluated, and the relationships of changes in OC, ucOC, and cOC with area under the curve (AUC) insulin and the Matsuda index were examined.MethodsIn this cross-sectional study, 105 premenopausal women underwent OGTT; 18 were IR (homeostatic model assessment of insulin resistance [HOMA-IR] > 2.6; (2 with type 2 diabetes, 2 with impaired glucose tolerance), and 87 were nIR (3 with impaired glucose tolerance). Changes in total OC, ucOC, and cOC were evaluated 60 and 120 minutes after glucose loading.ResultsAt baseline, IR subjects had significantly lower levels of total OC, cOC, and ucOC. In nIR women, total OC decreased by 19% from 18.0 ng/mL (14.5-24.7) at baseline to 14.6 ng/mL (10.9-17.8) after 120 minutes, ucOC decreased by 22% from 3.2 ng/mL (2.1-4.5) to 2.5 ng/mL (1.7-3.5), and cOC decreased by 26% from 14.9 ng/mL (12.1-20.4) to 11.1 ng/mL (9.0-14.5) (P < .001, respectively). No significant decreases were noted in IR subjects. The declines in OC and cOC predicted AUCinsulin (ΔOC: β = 0.301, P = .001; ΔcOC: β = 0.315, P < .001) and the Matsuda index (ΔOC: β = − 0.235, P = .003; ΔcOC: β = − 0.245, P = .002).ConclusionsGlucose intake lowers levels of OC, ucOC, and cOC in nIR women, the extent of which predicts IR and insulin sensitivity in premenopausal women. OC parameters seem suppressed in IR women. There might be a differential osteoblast response to oral glucose in IR and nIR women, with OC reflecting this finding. (Endocr Pract. 2014;20:5-14)     

Optimal Waist Circumference for Prediction of Metabolic Syndrome in Young Korean Women With Polycystic Ovary Syndrome

The International Diabetes Federation consensus proposed an ethnically specific criteria of waist circumference (WC) for central obesity, but, the nationwide definition is still debated in Korea. For the detection of the optimal WC cutoff value, the nonadipose components of the metabolic syndrome (MS) were defined by modification of revised 2003 Rotterdam consensus as having two or more risk factors such as hypertension, hyperglycemia, and dyslipidemia without consideration of abdominal obesity. By using receiver‐operating characteristic (ROC) curve analysis, cutoff points of WC and visceral fat area (VFA) for prediction of MS were 80 cm and 53.1 cm². WC cutoff points corresponding to VFA >53.1 and 100 cm² were 73.3 and 77.8 cm. The sensitivity and specificity of currently used value of WC 88 cm were 41.9 and 91.5%, suggesting that it could be too high in Korean population. Central obesity defined as WC >80 cm was significantly associated with nonadipose components of MS after adjustment for age, BMI, cholesterol, triglycerides, fasting insulin, and free testosterone levels. Central obesity with WC of >80 cm predicted the presence of nonadipose MS (odds ratio 16.6; 95% confidence interval (CI) 6.5–42.6). It was also significant (odds ratio 14.7; 95% CI 3.4–64.3) when we applied the WC value of 70 cm instead of 80 cm. In conclusion, WC of 80 and 70 cm could be appropriate cutoff points to identify the MS and visceral adiposity in Korean women with polycystic ovary syndrome (PCOS), respectively. Therefore, PCOS women with a WC over 70 cm should be closely monitored for the development of MS.     

Premicroalbuminuria in Women with Polycystic Ovary Syndrome: A Metabolic Risk Marker

ObjectiveTo determine the relationship between urinary albumin excretion and features of the metabolic syndrome in women with polycystic ovary syndrome (PCOS).MethodsWe retrospectively analyzed the medical records of 189 premenopausal women (mean age ± SD, 28.9 ± 7.7 years) with PCOS and 81 control patients (mean age ± SD, 37.9 ± 8.6 years) from a single endocrinology practice. Exclusion criteria were diabetes, heart disease, kidney disease, use of lipid-lowering agents, and use of antihypertensive agents (except spironolactone). The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. Premicroalbuminuria was defined as an ACR > 7 mg/g.ResultsThe prevalence of ACR > 7 mg/g was 31.2% in the PCOS group (N = 189) and 35.8% in the control group (N = 81). The metabolic syndrome was noted in 16.3% (27 of 166) of patients with PCOS and in 2.9% (2 of 69) of control subjects. Nine percent of patients with PCOS who had an ACR ≤ 7 mg/g but 30.9% of those with an ACR > 7 mg/g had the metabolic syndrome. Patients with PCOS who had an ACR > 7 mg/g had significantly higher blood pressure and alanine aminotransferase levels than did those with an ACR ≤ 7 mg/g. In the patients with PCOS who had an ACR ≤ 7 mg/g versus those who had an ACR > 7 mg/g, no significant difference was found in frequency of use of metformin, spironolactone, or oral contraceptives.ConclusionIn women with PCOS, an ACR > 7 mg/g was strongly associated with the metabolic syndrome, high blood pressure, and elevated alanine aminotransferase levels. It may be useful to consider ACR > 7 mg/g as an associated sign of the presence of metabolic syndrome in women with PCOS. (Endocr Pract. 2008;14: 193-200)     

多囊卵巢综合征患者胰岛素受体基因外显子17的多态性研究

目的：探索胰岛素受体基因外显子17 的基因多态性与多囊卵巢综合症（PCOS）的关系,为多囊卵巢综合症的治疗寻找新的途径。方法：利用PCR-SSCP技术检测45 例多囊卵巢综合症患者（实验组）与40 例健康妇女（对照组）全血中胰岛素受体基因外显子17 位点1058 的基因多态性,同时测定PCOS 患者的一般指标及血清学指标。按照体重指数、胰岛素抵抗、有无高雄激素血症比较胰岛素受体基因外显子17位点1058 C、T等位基因出现的频率。结果：实验组患者T 等位基因出现的频率为71.2%,明显高于对照组的25%（P〉0.05）;实验组非肥胖组患者中T 等位基因出现的频率为69.2%,明显高于肥胖组患者的25%（P〈0.01）,亦高于对照组,差异具有统计学意义（P〈0.05）。根据胰岛素受体基因外显子17 出现T、C 基因的频率,将其分为1、2 两组,1 组出现T基因的频率的BMI（20.34± 2.47）明显低于2 组出现C 基因的频率的BMI（26.68± 5.52）;PCOS 患者胰岛素抵抗组与非胰岛素抵抗组中INSR 基因外显子17 出现T、C等位基因的频率无明显差别（P〉0.05）;PCOS 患者高雄激素组组与无高雄激素组中胰岛素受体基因外显子17 出现T、C等位基因的频率无明显差别（P〉0.05）。结论：胰岛素受体基因外显子17 中T/C 单核酸多态性表现与PCOS 患者的发病密切相关,T 等位基因的高发频率与非肥胖因型PCOS 患者的发病密切相关;瘦型PCOS 患者与肥胖型患者胰岛素抵抗的发病机制或许不同;T 等位基的高发频率与PCOS 的主要临床表现如：胰岛素抵抗、高雄激素血症并无明显相关关系。     

多囊卵巢综合征患者胰岛素受体基因外显子 17 的多态性研究

摘要 目的： 探索胰岛素受体基因 外显子 17 的基因多态性与多囊巢综合症 （PCOS ） 的关系, 为多囊巢综合症的治疗寻找新的 途径。方法： 利用 PCR-SSCP 技术检测 45 例多囊巢综合症患者 （实验组） 与 40 例健康妇女 （对照组）全血中胰岛素受体基因外 显子 17 位点 1058 的基因多态性, 同时测定 PCOS 患者的一般指标及血清学指标。按照体重指数、 胰岛素抵抗、有无高雄激素血 症比较胰岛素受体基因外显子 17 位点 1058C、 T 等位基因出现的频率。 结果： 实验组患者 T 等位基因出现的频率为 71.2%, 明显 高于对照组的 25%(P>0.05); 实验组非肥胖组患者中 T 等位基因出现的频率为 69.2%, 明显高于肥胖组患者的 25%(P<0.01), 亦高 于对照组, 差异具有统计学意义(P<0.05)。根据胰岛素受体基因外显子 17 出现 T、 C 基因的频率, 将其分为 1、 2 两组, 1 组出现 T 基因的频率的 BMI(20.34± 2.47)明显低于 2 组出现 C 基因的频率的 BMI(26.68± 5.52); PCOS 患者胰岛素抵抗组与非胰岛素抵 抗组中 INSR 基因外显子 17 出现 T、 C 等位基因的频率无明显差别(P>0.05); PCOS 患者高雄激素组组与无高雄激素组中胰岛素 受体基因外显子 17 出现 T、 C 等位基因的频率无明显差别(P>0.05)。结论： 胰岛素受体基因外显子 17 中 T/C 单核酸多态性表现 与 PCOS 患者的发病密切相关, T 等位基因的高发频率与非肥胖因型 PCOS 患者的发病密切相关; 瘦型 PCOS 患者与肥胖型患 者胰岛素抵抗的发病机制或许不同; T 等位基的高发频率与 PCOS 的主要临床表现如： 胰岛素抵抗、 高雄激素血症并无明显相关 关系。     

Association Study of Gene LPP in Women with Polycystic Ovary Syndrome

Background

Previous genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese population has found that SNPs in LPP gene were nominally significant in PCOS patients (P around 10E-05). Replication of the GWAS was applied to further confirm the relationship between LPP gene and PCOS.

Methods

Three polymorphisms of LPP gene (rs715790, rs4449306, rs6782041) were selected and replicated in additional 1132 PCOS cases and 1142 controls. Genotyping of LPP gene was carried out by Taqman-MGB method.

Results

In rs715790, the allele frequency is significantly different between the PCOS group and the control group. Meta-analysis showed that the allele frequencies of the three SNPs rs715790 (P_meta = 1.89E-05, OR = 1.23), rs4449306 (P_meta = 3.0E-04, OR = 1.10), rs6782041 (P_meta = 2.0E-04, OR = 1.09), were significantly different between PCOS cases and controls.

Conclusions

Our results suggest that LPP gene might be a novel candidate for PCOS.     

Assessing Impaired Glucose Tolerance and Insulin Resistance in Polycystic Ovarian Syndrome with A Muffin Test: An Alternative to the Glucose Tolerance Test

ObjectiveTo determine the sensitivity of a high-glucose load in a meal as an alternative to the standard oral glucose tolerance test (OGTT) in detecting impaired glucose tolerance and insulin resistance in women with polycystic ovarian syndrome (PCOS) and the relationship of body composition to insulin resistance in the PCOS cohort.MethodsIn this prospective, single-center study, women with PCOS who were being followed up as outpatients were recruited. The study was performed between November 2007 and March 2008. All participants underwent OGTT before study enrollment. Participants were given a meal including carbohydrates, fat, and protein. Glucose and insulin levels were measured every 30 minutes for 2 hours after completing the meal. Body composition was measured by dual-energy x-ray absorptiometry.ResultsThirteen of the 15 participants completed the meal tolerance test and the body composition study. Four of 13 participants (31%) had abnormal glucose tolerance with the meal test compared with 2 of 8 participants (25%) who completed the OGTT. Those who had insulin resistance on OGTT were detected with the meal test. The 2-hour insulin levels following the meal were 38% higher than with the OGTT. Of 10 participants with insulin resistance, 9 had a total body fat mass greater than the 90th percentile, whereas 1 of 3 participants (33%) with normal body composition was insulin resistant.ConclusionAdministration of oral glucose load via a meal is an effective alternative to the OGTT in diagnosing impaired glucose tolerance and insulin resistance and may be more sensitive, without the adverse effects of the oral glucose load in the OGTT. PCOS is an independent risk factor for impaired glucose tolerance and insulin resistance, regardless of body composition. (Endocr Pract. 2010;16:810-817)     

The Relationship Between Insulin Resistance and CpG Island Methylation of LMNA Gene in Polycystic Ovary Syndrome

We sought to investigate the relationship between the changes of CpG island methylation status of LMNA gene and insulin resistance in polycystic ovary syndrome (PCOS) patients. The genome-wide methylation microarray screening was done in three PCOS cases of insulin resistance and one case of a normal woman. The PCOS insulin resistance-related genes were identified as indicated by the results of gene chip screening. Then, 24 cases of insulin-resistant PCOS patients and 24 cases of normal individuals were studied to identify the effects of the candidate genes using genome-wide study of DNA from the peripheral blood analyzed by MassARRAY^®EpiTYPER? DNA methylation analysis technique. We found that the methylation status of CpG island in the promoter area of LMNA gene was changed. The 20 CG sites in CpG island of LMNA gene were examined using case control experiment among which 12 CpG sites differed significantly (P < 0.05) between two groups while the remaining eight CpG sites differed non-significantly. We, therefore, concluded that the changes in the hypermethylation status of CpG island of LMNA gene were related to the insulin resistance in PCOS patients, indicating that this gene may be involved in the regulation of PCOS-associated insulin resistance.     

Risk of Cardiovascular Events in Mothers of Women with Polycystic Ovary Syndrome

ObjectiveTo assess the prevalence of cardiovascular events in an older population of women with polycystic ovary syndrome (PCOS).MethodsWe took advantage of the high heritability of PCOS and determined the probable PCOS status of mothers of women with PCOS. The prevalence of cardiovascular events was then determined in these mothers with and without PCOS. In a single endocrine clinic, 308 women with PCOS were interviewed about their mothers’ medical history, and the mothers themselves were interviewed if available. The interview addressed menstrual history, fertility, clinical signs of hyperandrogenism, age at incident cardiovascular event, and age at death as reported by daughters. Presence of PCOS in the mothers was defined as a history of infertility, irregular menses, or clinical signs of hyperandrogenism. A cardiovascular event was defined as fatal or nonfatal myocardial infarction, any coronary intervention, angina necessitating emergency department visits, or a cerebrovascular event.ResultsThe mothers were predominantly postmenopausal. Among 182 interviewed (n = 157) or deceased (n = 25) mothers, 59 had probable PCOS. Cardiovascular events were more common (P = .011) among mothers with PCOS (11 of 59 or 18.6%) than among non-PCOS mothers (5 of 123 or 4.1%). After adjustments were made for age and race, probable PCOS was an independent predictor of cardiovascular events (odds ratio, 5.41; 95% confidence interval, 1.78 to 16.40). Cardiovascular events occurred at an early age in mothers of women with PCOS, particularly mothers with probable PCOS themselves.ConclusionPCOS-affected mothers of women with PCOS have a higher risk for cardiovascular events in comparison with non-PCOS mothers, and cardiovascular events appear to occur at an earlier than expected age in mothers with PCOS. (Endocr Pract. 2008;14:1084-1094)     

Serum Concentrations of Fibroblast Growth Factors 19 and 21 in Women with Gestational Diabetes Mellitus: Association with Insulin Resistance,Adiponectin, and Polycystic Ovary Syndrome History

Background

Fibroblast growth factor 19 (FGF19) and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM) and explored their relationships with anthropometric and endocrine parameters.

Method

Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in patients with GDM (n = 30) and healthy pregnant controls (n = 60) matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters.

Results

Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR) and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS) history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history.

Conclusions

Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease.     

Interleukin-6 Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Background

The change of serum interleukin-6(IL-6) levels in women with polycystic ovary syndrome (PCOS), as well as the relations between IL-6 levels and body mass index (BMI), insulin resistance(IR) and androgen status of PCOS patients, are not fully understood.

Methods

A literature search was performed in October 2015 using PubMed, Embase and the Cochrane Library databases to identify studies. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs).

Results

Twenty articles with 25 case-control studies included 1618 women (922 PCOS patients and 696 controls) were included in this study. IL-6 levels in controls were significantly lower than that of PCOS patients (SMD = 0.78, 95%CI = 0.41–1.16, P<0.001), with significant heterogeneity across studies (I² = 91% and P<0.001). Meta-regression analysis model indicated IR status was the main source of heterogeneity (P = 0.005). Results from group analysis suggested that high IL-6 levels in PCOS were significantly associated with Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR) ratio and total testosterone ratio (T ratio), and was found in both lean and obese women with PCOS. Cumulative meta-analysis results indicated the total effect size (SMD) had tend to be stable since 2012(0.79 to 0.92).

Conclusions

A high IL-6 level is not an intrinsic characteristic of PCOS, but may be a useful monitoring biomarker for the treatment of PCOS.     

右归丸联合小檗碱对多囊卵巢综合征胰岛素抵抗的研究

目的:观察右归丸联合小檗碱治疗多囊卵巢综合征(PCOS)的临床疗效。方法:将114例PCOS伴胰岛素抵抗患者随机分为2组。对照组57例给予达英-35+二甲双胍,实验组57例给予右归丸联合小檗碱治疗。通过比较治疗前后的胰岛素水平(FINS)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FPG)、肿瘤坏死因子(TNF)及白介素-6(IL-6)水平的变化,观察右归丸联合小檗碱对PCOS胰岛素抵抗的作用疗效。结果:治疗前后实验组与对照组分别各自比较,HOMA-IR、FINS、TC、TG、TNF、IL-6显著下降,差异有统计学意义(P0.05);两组间治疗前各项指标无统计学意义(P0.05),治疗后与对照组比较,实验组TNF、IL-6水平显著下降(P0.05)。结论:右归丸联合小檗碱能显著改善患者的血脂及慢性炎症状态,最终改善胰岛素敏感性。     

Role of Haptoglobin in Polycystic Ovary Syndrome (PCOS), Obesity and Disorders of Glucose Tolerance in Premenopausal Women

Background

Hp² alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance.

Methodology/Principal Findings

Serum haptoglobin and the haptoglobin α–chain polymorphism were determined in 141 patients with polycystic ovary syndrome and 102 non-hyperandrogenic women. Of the whole group of 243 premenopausal women, 117 were obese and 51 showed abnormal glucose tolerance. Although serum haptoglobin concentrations were similar in PCOS patients and controls, the former presented with an increased frequency of Hp² alleles (62% vs. 52%, P = 0.023). Circulating haptoglobin levels increased with obesity (P<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes.

Conclusions/Significance

Serum haptoglobin concentrations in premenopausal women are largely dependent on the haptoglobin polymorphism and on the presence of obesity, with insulin resistance and chronic inflammation possibly modulating this relationship. The association of polycystic ovary syndrome with Hp² alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients.     

Nonobese Young Females with Polycystic Ovary Syndrome Have Nutritive Microvascular Dysfunction: A Pilot Study

ObjectiveTo investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables.MethodsFourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/ m²) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCV_max), and time taken to reach RBCV_max (TRBCV_max).ResultsSubjects with PCOS had lower RBCV and higher TRBCV_max compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, F < .01) and (5 [5-6] vs. 4 [3-5] s, P < .05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCV_max (ρ = -0.49, P < .05) and to TRBCV_max (ρ = 0.41, P < .05). SHBG correlated with RBCV_max (ρ = 0.52, P < .01) while estradiol (E₂) levels correlated with RBCV (ρ = 0.80, P < .001) and RBCV_max (ρ = 0.46, P < .05).ConclusionMicrovascular dysfunction characterized by reduced RBCV_maxand prolonged TRBCV_maxwas present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction. (Endocr Pract. 2014;20:1281-1289)     

Zinc and Homocysteine Levels in Polycystic Ovarian Syndrome Patients with Insulin Resistance

In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.     

Utility of Hemoglobin-A1C in Nondiabetic Women With Polycystic Ovary Syndrome

ObjectiveHemoglobin A1c (A1C) >5.7% is now accepted as a biomarker for identifying individuals at risk for diabetes. Compared to the general population, women with polycystic ovary syndrome (PCOS) have a higher risk for diabetes. Our goal was to determine what glucose homeostasis abnormalities can be identified by A1C >5.7% in women with PCOS.MethodsIn a cross-sectional study, nondiabetic women with PCOS (according to the National Institutes of Health [NIH] criteria) were divided into 2 groups based on A1C (<5.7% [n = 23] and >5.7% [n = 25]). Oral glucose tolerance tests (OGTT) and frequently sampled intravenous glucose tolerance tests (FS-IVGTT) were conducted, and body composition, cardiovascular risk factors, and sex steroid levels were assessed.ResultsCompared to women with A1C <5.7%, those with A1C >5.7% were older (35.1 ± 1.1 years vs. 31.1 ± 1.1 years; P = .04), had higher glucose levels at fasting and during OGTT, and had a lower insulin sensitivity index (SI: 2.0 ± 0.2 vs. 4.2 ± 0.6; P = .0195) and disposition index (DI: 1,014 ± 82 vs. 1,901 ± 217; P = .011) during FS-IVGTT. They also had higher triglycerides, high-sensitivity C-reactive protein (hs-CRP), and fatty acid-binding protein 4 (FABP4) levels. There was no difference in serum androgen levels.ConclusionA1C >5.7% identified the subgroup of PCOS patients with higher insulin resistance, inadequate compensatory insulin response, impaired glucose disposition, and increased cardiovascular risk factors. Thus, A1C represents an inexpensive and informative biomarker to identify PCOS patients at risk for metabolic abnormalities. (Endocr Pract. 2013;19:284-289)     

罗格列酮结合二甲双胍对多囊卵巢综合征患者胰岛素抵抗指数的影响及临床疗效

目的:探讨罗格列酮与二甲双胍联合给药对多囊卵巢综合征(PCOS)患者胰岛素抵抗指数(HOMA-IR)的变化影响与临床效果的评价。方法:回顾性选取我院收治的PCOS患者127例列为研究样本,按照用药方案差异分为两组,对照组62例采用二甲双胍进行治疗;研究组65例采用罗格列酮联合二甲双胍治疗。观察并比较两组患者治疗前后HOMA-IR、血清性激素水平、排卵率及副反应发生情况。结果:治疗后,研究组HOMA-IR低于对照组,排卵率高于对照组(P0.05);研究组患者血清E2及T水平低于对照组,而FSH及SHBG水平高于对照组(P0.05);两组患者副反应发生率比较,差异无统计学意义(P0.05)。结论:罗格列酮辅助二甲双胍治疗PCOS可显著改善患者HOMA-IR,对性激素平衡有良好作用,副作用较小。