Serum activin A and inhibin A elevated in pre–eclampsia: no relation to insulin sensitivity

Objective To assess the possible role of serum levels of activin A, inhibin A and pro-αC inhibin (pro-Design αC) in insulin sensitivity in pre-eclampsia.
Design A prospective study.
Setting Helsinki University Central Hospital.
Participants Twenty-two nulliparous women with proteinuric pre-eclampsia and 16 healthy nulliparous controls in the third trimester of pregnancy.
Methods Serum samples were collected before and after intravenous injection of glucose (0.3 g/kg) and insulin (0.03 IU/kg) (the minimal model for testing insulin sensitivity), and were assayed for activin A, inhibin A and pro–αC.
Main outcome measures Comparison of the levels of activin A, inhibin A and pro-αC between pre-eclamptic and healthy pregnant women, and the association of these proteins with insulin sensitivity.
Results In pre-eclampsia elevated levels of activin A (139%,  P = 0.0001  ), inhibin A (39%,   P = 0.003  ), and pro-αC (92%,   P = 0.0008  ) were observed. The amount of proteinuria (0.3–10.5 g/day) correlated positively with serum concentrations of activin A (   P = 0.01  ) and inhibin A (   P = 0.02  ). These glycol-proteins were not associated with insulin sensitivity either in women with pre-eclampsia or controls. A 2.9-fold rise in blood glucose and a 52.5-fold rise in insulin during testing using the minimal model were not accompanied by any significant changes in activin A, inhibin A, and pro-αC.
Conclusion Activin A, inhibin A, and pro–αC are elevated in pre-eclampsia but do not appear to relate to the insulin sensitivity in pre-eclamptic or normal pregnancies.     

Wedge resection to improve insulin resistance in polycystic ovary syndrome: a study among Chinese women

Objective To investigate the relation between androgen excess and insulin resistance in nonobese Chinese women with polycystic ovary syndrome.
Design A prospective, controlled study.
Setting School of Clinical Medicine, Nanjing University.
Subjects There were three groups: Group 1 (   n = 15  ) comprised nonobese women with polycystic ovary syndrome; Group 2 comprised 12 of these 15 women in whom bilateral wedge resection had been performed six months to one year before enrolling in the study. Group 3 was a control group comprised of 15 normally menstruating women of similar age and body mass index.
Methods An oral glucose (100 g) tolerance test was performed in all women in each group. The areas under the response curve of serum glucose, insulin, C-peptide (C-P), insulin/glucose (I/G) and C-P/insulin (C/I) were calculated by trapezoid rule.
Results When fasting the three groups had similar levels of glucose, insulin, C-P, I/G and C/I. During the oral glucose tolerance test women of Group 1 had a significantly higher mean serum area of the curve of glucose, insulin, C-P and I/G levels and lower C/I values, compared with the other two groups. Women of Group 2 and those in the control group showed similar levels of these indices during the oral glucose tolerance test.
Conclusions Androgen excess in women with polycystic ovary syndrome may be responsible for a defect in peripheral insulin sensitivity and hepatic extraction which could be reversed by removing excessive androgens with wedge resection.     

Insulin response to oral glucose in healthy,lean young women and patients with polycystic ovary syndrome

Background and aim. Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women.

Methods. In a case–control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion.

Results. Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 ± 4.5 years (range 15–32 years) and their mean body mass index (BMI) was 19.7 ± 2.6 kg/m². Mean blood glucose at 0, 1 and 2 h was 88.2 ± 7.2, 115.5 ± 25.5 and 91.8 ± 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 ± 1.1, 32.7 ± 26.5 and 14.6 ± 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 ± 3.1, 7.0 ± 3.1 and 11.4 ± 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 ± 0.2.

The age of the PCOS women ranged from 15 to 40 years (mean 23.4 ± 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m² (mean 27.7 ± 6.3 kg/m²). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM. Glucose/insulin ratio at 0, 1 and 2 h was lower (8.3 ± 4.2, 2.0 ± 1.6 and 3.2 ± 3.5) than that of healthy controls. HOMA-IR was 3.1 ± 3.0.

Conclusion. Women with PCOS had an exaggerated insulin response to glucose. Thirty-eight percent of PCOS women had some form of abnormal glucose tolerance. Greater insulin response was seen with impairment of glucose tolerance. Obesity had no effect on fasting insulin or insulin response to oral glucose in PCOS women with NGT.     

Screening for insulin resistance in women with polycystic ovarian syndrome.

INTRODUCTION: Insulin resistance is implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). Insulin-sensitizing agents are increasingly used in the treatment of infertility and hirsutism in PCOS. However, not all women with PCOS are insulin-resistant. OBJECTIVE: To assess the degree of insulin resistance within a clinic population of women referred for treatment of oligomenorrhoea or infertility. DESIGN: We evaluated 25 consecutive PCOS outpatients referred for treatment of menstrual dysfunction/infertility and a matched control group. All underwent a standard oral glucose tolerance test (OGTT) with serial insulin measurements. Insulin sensitivity was calculated using homeostasis model assessment (HOMA). RESULTS: Five of the 25 clinic patients had abnormal glucose handling (two had previously unknown type 2 diabetes and three had impaired glucose tolerance). Fasting and 2-h insulin levels were significantly higher in the PCOS women. Mean HOMA-S (insulin sensitivity) was even lower for PCOS women with normal GTT status (mean (95% confidence interval): 0.53 (0.34-0.72)) than for controls (0.94 (0.84-1.04)) (F = 4.2, p < 0.001). HOMA-B (pancreatic beta-cell function) was nearly tripled for normal GTT status PCOS women at 273 (205-342) versus 105 (70-139) for controls (F = 6.8, p < 0.001). CONCLUSIONS: The results suggest a role for routine measurement of HOMA-S in identifying women with PCOS with insulin resistance with a view to targeting them with insulin-sensitizing agents.     

Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance

We studied the in vitro response to insulin of granulosalutein cells derived from patients with polycystic ovary syndrome (PCOS) and clinically defined insulin resistance. Insulin sensitivity was assessed by continuous infusion of glucose with model assessment test (CIGMA). Insulin resistant (PCOS-IR; n = 8), non-insulin resistant (PCOS-NIR; n = 9) patients with PCOS, and women with tubal factor infertility (TF; n = 8) underwent controlled ovarian stimulation with long-term gonadotropin-releasing hormone (GnRH) agonist, recombinant follicle stimulating hormone (FSH), and in vitro fertilization. Primary cultures of granulosa-lutein cells were incubated with insulin (10, 100, 500 ng/ml) and/or luteinzing hormone (LH) (10, 100 ng/ml) in the presence of low density lipoprotein (100 μg/ml). The progesterone and lactate accumulation were measured in the culture medium. LH potently stimulated the progesterone secretion in all groups. Insulin alone had no effect on progesterone release in any of the groups, but stimulated lactate formation in the PCOS-NIR and TF groups. Insulin augmented the effect of LH on progesterone secretion selectively in the PCOS-NIR group. The expression of the insulin receptor was determined by Western blotting in separate cultures of granulosa-lutein cells, and showed receptor down-regulation in the PCOS-IR patients. We infer that the in vitro effect of insulin on progesterone and lactate release by granulosa-lutein cells is impaired in insulin resistant PCOS patients.     

Prevalence and predictors of abnormal glucose metabolism in Mediterranean women with polycystic ovary syndrome

Impaired glucose tolerance (IGT) and Type 2 diabetes mellitus (DM) are common in women with polycystic ovary syndrome (PCOS) in American studies. However, whether rates are similar in other countries with a lower frequency of insulin resistance is not clear. Our purpose was to investigate the prevalence of abnormal glucose metabolism (AGM) in women with PCOS and asses the ability of clinical data and biochemical tests to predict these abnormalities within our population. One hundred and three PCOS women undergo a 75-g oral glucose tolerance test. Glucose tolerance was categorised according to World Health Organisation criteria. Glucose tolerance was abnormal in 18.5% of women: 10.7% had IGT and 7.7% had DM. Women with DM were older than those with IGT or normal glucose tolerance. Women with AGM were more obese, had a higher waist/hip ratio and free testosterone levels than normal glucose metabolism patients. QUICKI was the best predictor of AGM. Receiver operating characteristics analysis suggested a threshold value of 0.31 in quantitative insulin-sensitivity check index (QUICKI) (94.1% sensitivity, 86% specificity, 57.1 positive predictive value and 98.6 negative predictive value) for the prediction of AGM. In conclusion, Mediterranean women with PCOS are at lower risk of AGM than that published from other countries; however, the incidence is still high compared with populations of women without PCOS. We recommend that PCOS patients undergo periodic metabolic screening for AGM using QUICKI.     

Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance.

We studied the in vitro response to insulin of granulosa-lutein cells derived from patients with polycystic ovary syndrome (PCOS) and clinically defined insulin resistance. Insulin sensitivity was assessed by continuous infusion of glucose with model assessment test (CIGMA). Insulin resistant (PCOS-IR; n = 8), noninsulin resistant (PCOS-NIR; n = 9) patients with PCOS, and women with tubal factor infertility (TF; n = 8) underwent controlled ovarian stimulation with long-term gonadotropin-releasing hormone (GnRH) agonist, recombinant follicle stimulating hormone (FSH), and in vitro fertilization. Primary cultures of granulosa-lutein cells were incubated with insulin (10, 100, 500 ng/ml) and/or luteinizing hormone (LH) (10, 100 ng/ml) in the presence of low density lipoprotein (100 micrograms/ml). The progesterone and lactate accumulation were measured in the culture medium. LH potently stimulated the progesterone secretion in all groups. Insulin alone had no effect on progesterone release in any of the groups, but stimulated lactate formation in the PCOS-NIR and TF groups. Insulin augmented the effect of LH on progesterone secretion selectively in the PCOS-NIR group. The expression of the insulin receptor was determined by Western blotting in separate cultures of granulosa-lutein cells, and showed receptor down-regulation in the PCOS-IR patients. We infer that the in vitro effect of insulin on progesterone and lactate release by granulosa-lutein cells is impaired in insulin resistant PCOS patients.     

Use of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndrome

OBJECTIVE: To determine the prevalence of insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) using baseline fasting blood measurements of glucose and insulin. DESIGN: Prospective clinical study. SETTING: Academic endocrinology unit in Palermo, Italy. PATIENT(S): Two hundred and sixty-seven women with PCOS, consecutively evaluated, and 50 consecutively selected ovulating controls. INTERVENTION(S): Fasting blood was obtained for glucose and insulin measurements from all women. For 60 women with PCOS and 20 controls an insulin tolerance test (ITT) was also performed. MAIN OUTCOME MEASURE(S): Assessment of normal and abnormal values for fasting insulin, glucose/insulin ratio, and the calculated indices of the homeostasis model assessment (HOMA), quantitative sensitivity check index (QUICKI), as well as Kitt (kinetic disappearance of glucose) values after ITT. Evaluation was performed of the ability to detect IR using these methods in obese and nonobese women with PCOS. RESULT(S): Normal insulin sensitivity was defined by insulin levels <12 mU/mL, glucose/insulin ratios of >6.4, HOMA values of <47, and QUICKI values of >0.333. In the entire PCOS groups, IR was diagnosed in 65.4% of women using glucose/insulin ratios and in 77% and 79.2% using HOMA and QUICKI. In obese women (body mass index >28 in 48% of group), IR was present in 76.7% as measured by glucose/insulin ratios but was significantly higher (95.3%) using values of either HOMA or QUICKI (P<.01). All indices correlated with Kitt values with QUICKI showing the best correlation. CONCLUSION(S): Insulin resistance was detected in approximately 80% of women with PCOS, and in 95% of obese women. The detection of IR is superior using the calculated indices HOMA and QUICKI.     

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in Asian women with polycystic ovary syndrome.

OBJECTIVES: To determine the prevalence of abnormalities of glucose metabolism in Asian women with polycystic ovary syndrome (PCOS) and to assess the different impacts of the 1985 and 1999 WHO consultations and the ADA criteria for the diagnosis of type 2 diabetes mellitus (DM). METHODS: Eighty-five women with PCOS were consecutively included in the study at the Reproductive Endocrinology Unit, Department of Ob-Gyn, Ramathibodi Hospital, Mahidol University. All women underwent a standard oral glucose tolerance test (OGTT). Fasting insulin and testosterone levels were also measured. RESULTS: Seventy-nine women consented to the OGTT. The prevalence of impaired glucose tolerance (IGT) and type 2 DM was 22.8 and 15.2% with the 1985 WHO criteria, and 20.3 and 17.7% according to the 1999 WHO consultation criteria, respectively. The recommendation of the ADA using the fasting glucose levels could only determine a prevalence of 6.3% for type 2 DM. The fasting insulin and testosterone levels were significantly higher in DM than IGT and normal glucose tolerance (NGT) subgroups. The PCOS women with abnormalities of glucose metabolism had a greater body mass index (BMI), higher fasting glucose and 2-h post-load glucose levels than those with NGT. The prevalence of glucose intolerance significantly increased with BMI. CONCLUSIONS: Similar to other ethnic populations, Asian women with PCOS are at risk of developing IGT and type 2 DM especially if obese. The recommendation of the ADA is not appropriate for the diagnosis of type 2 DM in PCOS women.     

多囊卵巢综合征患者不同糖代谢状态的临床分析

目的:探讨多囊卵巢综合征(PCOS)患者不同糖代谢状态的临床表现以及生殖内分泌和糖脂代谢特点。方法:选择连续就诊的1 212 PCOS患者,检测双侧卵巢窦前卵泡数、血清性激素、血脂水平,并行口服葡萄糖糖耐量试验(OGTT)及胰岛素(Ins)检测,计算体质量指数(BMI)、葡萄糖(Glu)和Ins曲线下面积等参数。根据血糖水平将PCOS患者分为糖耐量正常(NGT)组、空腹血糖受损(IFG)组、糖耐量受损(IGT)组、混合型糖耐量受损(CGI)组及糖尿病(T2DM)组,比较各组PCOS患者糖、脂代谢指标及激素水平的差异。结果:PCOS患者糖耐量异常的发生率为35.3%(428/1 212),其中10.3%(125/1 212)为IFG,18.5%(224/1 212)为IGT,6.5%(79/1 212)为CGI,糖尿病发生率为5.9%(71/1 212)。随着糖代谢紊乱的加重,BMI明显上升,多囊卵巢(PCO)表现的比例有所减少,雄激素水平下降,LH/FSH比值逐渐下降。在IGT组、CGI组和T2DM组,随着糖代谢状态的恶化,各时相的血糖及胰岛素水平逐渐升高,糖负荷后2 h的Ins分泌较糖负荷后1 h明显增加,但在IFG组不明显,且其InsAUC和GluAUC较NGT组无统计学差异;各组的血脂水平逐渐增高,高密度脂蛋白(HDL)逐渐下降,但IFG组血脂较NGT组无升高(P0.05)。结论:PCOS患者糖代谢紊乱与脂代谢异常明显相关;雄激素异常水平与糖代谢异常无关。     

Screening for insulin resistance in women with polycystic ovarian syndrome

Introduction Insulin resistance is implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). Insulin-sensitizing agents are increasingly used in the treatment of infertility and hirsutism in PCOS. However, not all women with PCOS are insulin-resistant.

Objective To assess the degree of insulin resistance within a clinic population of women referred for treatment of oligomenorrhoea or infertility.

Design We evaluated 25 consecutive PCOS outpatients referred for treatment of menstrual dysfunction/infertility and a matched control group. All underwent a standard oral glucose tolerance test (OGTT) with serial insulin measurements. Insulin sensitivity was calculated using homeostasis model assessment (HOMA).

Results Five of the 25 clinic patients had abnormal glucose handling (two had previously unknown type 2 diabetes and three had impaired glucose tolerance). Fasting and 2-h insulin levels were significantly higher in the PCOS women. Mean HOMA-S (insulin sensitivity) was even lower for PCOS women with normal GTT status (mean (95% confidence interval): 0.53 (0.34–0.72)) than for controls (0.94 (0.84–1.04)) (F?=?4.2, p?<?0.001). HOMA-B (pancreatic β-cell function) was nearly tripled for normal GTT status PCOS women at 273 (205–342) versus 105 (70–139) for controls (F?=?6.8, p?<?0.001).

Conclusions The results suggest a role for routine measurement of HOMA-S in identifying women with PCOS with insulin resistance with a view to targeting them with insulin-sensitizing agents.     

Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies

We aimed at investigating whether insulin resistance (IR)/sensitivity are impaired in obese/non-obese polycystic ovary syndrome (PCOS) and obese/non-obese healthy controls. A comprehensive literature search was performed for observational, English language studies. Meta-analysis was performed with the random effects model according to the heterogeneity. Eligible studies, involving 3037 women in four groups of: 1-obese, PCOS; 2-non-obese, PCOS, 3-obese, non-PCOS and 4-Non-obese, non-PCOS were included. Based on the insulin resistance index (HOMA-IR) analysis, the pooled mean (95% Conf. Interval) of HOMA IR in groups 1–4 were 4.38 (3.84, 4.92), 2.68 (2.16, 3.20), 2.44 (2.06, 2.82) and 1.34 (1.06, 1.63), respectively. Meta-analysis showed that group 1 (obese, PCOS patients) statistically have the highest IR and group 4 (non-obese, non-PCOS women) have the highest insulin sensitivity. Group 2 (non-obese, PCOS patients) and group 3 (obese, non-PCOS women) were between this range and they had lower IR than group 1 (obese, PCOS) and lower insulin sensitivity than group 4 (non-obese, non-PCOS). So, there were statistical differences between all groups except between groups 2 and 3. Insulin sensitivity indexes (quickie and ISI), also confirm the IR index (HOMA-IR) results. Based on different IR/sensitivity indexes, we found no evidence of any different effects of BMI?≥?30?kg/m² on IR/sensitivity. In conclusion, PCOS status intensifies the adverse effects of obesity on IR, it has to be appropriately addressed in primary and secondary preventive cares and treatments provided for these women.     

罗格列酮用于多囊卵巢综合征促排卵治疗的效果观察

目的　探讨罗格列酮 (rosiglitazone)对存在胰岛素抵抗的多囊卵巢综合征 (polycysticovarysyndrome ,PCOS)患者促排卵治疗的效果。 方法　选择存在胰岛素抵抗的PCOS患者 96例 ,将其随机分为A、B、C组。A组 (2 8例 )口服氯米芬、B组 (3 2例 )口服罗格列酮、C组 (3 6例 )口服罗格列酮联合氯米芬 ,3组用药时间均为 3个月经周期。比较 3组用药前后的胰岛素抵抗指数的变化和排卵情况。结果　B组和C组患者治疗后 ,应用稳态模型评估的胰岛素抵抗指数 (homeostasismodelassessmentinsulinresistance ,HOMAIR)分别由 1 2± 0 6、1 1± 0 5下降为 0 6± 0 2、0 6± 0 4,两组治疗前后比较 ,差异也有显著性 (P <0 0 5)。C组治疗后排卵率为 80 % ,明显高于A组的 59%和B组的 3 5% ,差异有显著性 (P <0 0 5)。结论　罗格列酮能有效地改善胰岛素抵抗 ,提高促排卵治疗的成功率     

Comparison of two insulin sensitizers,metformin and myo-inositol,in women with polycystic ovary syndrome (PCOS)

Insulin resistance (IR) plays a pivotal role in PCOS. Insulin-sensitizer agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS. The purpose of this study is to compare their effects on the clinical and metabolic features of the women with PCOS. Fifty PCOS women with IR and/or hyperinsulinemia were randomized to treatment with metformin (1500?mg/day) or myo-inositol (4?g/day). IR was defined as HOMA-IR >2.5, while hyperinsulinemia was defined as a value of AUC for insulin after a glucose load over the cutoff of our laboratory obtained in normal women. The Matsusa Index has been calculated. The women have been evaluated for insulin secretion, BMI, menstrual cycle length, acne and hirsutism, at baseline and after 6 months of therapy. The results obtained in both groups were similar. The insulin sensitivity improved in both treatment groups. The BMI significantly decreased and the menstrual cycle was normalized in about 50% of the women. No significant changes in acne and hirsutism were observed. The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.     

Impact of insulin resistance on pregnancy complications and outcome in women with polycystic ovary syndrome

The aim of the study was to determine the risk of developing gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH)/pre-eclampsia in a cohort of pregnant women with the polycystic ovary syndrome (PCOS) and known insulin sensitivity status. Pregnancies and neonatal outcome were recorded in a prospective cohort study comprising 29 non-insulin-resistant PCOS women, 23 insulin-resistant PCOS women and a control group of 355 women who had conceived after assisted reproduction. Hypertension, pre-eclampsia and GDM were recorded as well as pregnancy duration, method of delivery and birth weight. The frequency of hypertension was significantly elevated in PCOS women (11.5%) compared to controls (0.3%), p < 0.01. However, the frequency of pre-eclampsia was significantly elevated only in the insulin resistant PCOS women (13.5%) compared to controls (7.0%), p < 0.02. GDM was significantly more frequent in PCOS women (7.7%) than controls (0.6%), p < 0.01. Insulin resistance prior to pregnancy, determined by continuous infusion of glucose with model assessment (CIGMA) test, did not further increase the frequency of GDM. Newborns from PCOS pregnancies were significantly more often delivered by Caesarean section than controls (40.3 vs. 27.3%, p < 0.05) and transferred to neonatal intensive care unit more often than controls (19.2 vs. 9.0%, p < 0.01). Thus we show that the frequencies of pre-eclampsia and GDM are increased in PCOS pregnancies.     

Influence of insulin resistance on total renin level in normotensive women with polycystic ovary syndrome

OBJECTIVE: To evaluate the influence of insulin resistance on the plasma total renin level in normotensive women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, controlled study. SETTING: University hospital. PATIENT(S): Twenty-five normotensive women with PCOS were compared with 11 normotensive control women with regular cycles and no features of PCOS. INTERVENTION(S): Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Insulin resistance was estimated by continuous infusion of glucose with model assessment in the early follicular phase. MAIN OUTCOME MEASURE(S): Plasma levels of total renin and angiotensin II and serum levels of gonadotropins, DHEAS, total T, free T, 17 alpha-hydroxyprogesterone, and PRL were determined. RESULT(S): Plasma concentrations of angiotensin II were similar in the PCOS group and the control group. The concentration of total renin in plasma was higher in women with PCOS than in healthy women independent of insulin resistance. The sensitivity and specificity of the plasma total renin level to diagnose women with PCOS were calculated as 80% and 71.4%, respectively. CONCLUSION(S): The plasma total renin level is higher in normotensive women with PCOS than in healthy women independent of insulin resistance.     

多囊卵巢综合征患者糖耐量异常及相关因素分析

目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者糖耐量受损(IGT)和2型糖尿病(NIDDM)的发生率及其高危因素。方法:回顾分析101例PCOS患者口服葡萄糖耐量(OGTT)实验后的临床资料,多因素logistic回归分析探讨PCOS患者糖耐量异常的危险因素。结果:(1)根据葡萄糖耐量实验结果分成糖耐量正常组(NGT)77例与糖耐量异常组(AGT)24例(IGT22例、NIDDM2例),IGT发生率21.8%,NIDDM发生率1.98%;(2)AGT组的年龄、腰臀比(WHR)、体重指数(BMI)、睾酮(T)、空腹血糖(FPG)、2h血糖增高,与NGT组的差异有统计学意义(P<0.05),空腹胰岛素(FINS)、2h胰岛素、稳态模式胰岛素抵抗指数(HOMA-IR)升高,差异有统计学意义(P<0.01)。初潮年龄、黄体生成素/卵泡刺激素(LH/FSH)两组差异无统计学意义(P>0.05);(3)AGT组糖尿病家族史发生率高于NGT组,差异有统计学意义(P<0.01);(4)多因素logistic回归分析显示,年龄、BMI、2型糖尿病家族史、空腹胰岛素升高为PCOS糖耐量异常的高危因素。结论:多囊卵巢综合征发生糖耐量受损、糖尿病的危险性增加,葡萄糖耐量2h血糖水平是监测PCOS糖耐量异常的较好指标。年龄、BMI、2型糖尿病家族史、空腹胰岛素升高是PCOS糖耐量异常发生的危险因素。     

Insulin resistance in nonobese Japanese women with polycystic ovary syndrome is associated with poorer glucose tolerance,delayed insulin secretion,and enhanced insulin response

PurposeTo determine the prevalence of insulin resistance (IR) and impaired glucose tolerance (IGT) in PCOS patients, the optimal screening method, and to compare our findings between nonobese and obese Japanese women with PCOS.MethodsNinety‐eight PCOS patients were included in this research from 2006 to 2013. Glucose tolerance test (OGTT) was performed. Serum glucose and insulin concentration were assayed before and 30, 60, and 120 min after taking 75 g of glucose.ResultsAll examined metabolic parameters were significantly favorable in the nonobese subjects, below 25 kg/m². HOMA‐IR, fasting insulin, glucose₁₂₀, and insulin₁₂₀ showed strong correlations with BMI. A total of 1.4 % of nonobese women had IR based on fasting insulin or HOMA‐IR. However, 15.5 % (11/71) of nonobese women had IR as determined by a continuous increase of serum insulin level in OGTT. In comparison, the prevalence of IR among the obese women ranged from 41 to 59 %. AUC_glucose, glucose₆₀, glucose₁₂₀, and insulin₁₂₀ in nonobese women with a continuous insulin increase were higher than those without such a continuous increase.ConclusionsAll examined metabolic parameters were significantly correlated with BMI. As the presence of a continuous increase of insulin level reflects to some degree poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response compared with non‐continuous insulin increase, OGTT might not been excluded to determine IR and IGT for nonobese women with PCOS.     

Neuropeptide Y, leptin, galanin and insulin in women with polycystic ovary syndrome.

It has been reported that polycystic ovary syndrome (PCOS) is very frequently associated with obesity, insulin resistance and hyperinsulinemia. However, metabolic disorders may lead to suppression of reproductive hormone secretion during undernutrition and in obesity. Some neuropeptides, such as neuropeptide Y (NPY) and galanin, modulate the control of appetite and play an important role in the mechanism of luteinizing hormone-releasing hormone (LHRH) secretion. NPY and galanin regulate appetite via both central and peripheral mechanisms. The interaction between central and peripheral signals for the control of food intake is due to leptin. Leptin can modulate the activity of NPY and other peptides in the hypothalamus that are known to affect eating behavior. In order to evaluate the relationship between NPY, galanin and leptin, 28 women with PCOS, 32 obese women (non-PCOS) and 19 lean healthy women (control group) were investigated. Obese women with PCOS were divided into two groups: PCOS (A) overweight (body mass index, BMI 26-30 kg/m2), and PCOS (B) obese (BMI 31-40 kg/m2). Plasma NPY, galanin and leptin concentrations were measured by radioimmunoassay. Plasma leptin levels in obese women with PCOS (groups A and B) were significantly higher than those in the control group (p < 0.05, p < 0.05, respectively). A significant positive correlation between plasma leptin and BMI in women with PCOS was found (r = 0.427, p < 0.01). A positive correlation was demonstrated between leptin and testosterone in PCOS (r = 0.461, p < 0.01). Plasma galanin concentrations in PCOS were higher than in the control group but the differences were not significant. Plasma NPY levels were significantly elevated in both non-obese (normal) and obese women with PCOS (group A) (p < 0.01, p < 0.005, respectively). However, in obese non-PCOS women plasma NPY levels gradually increased with increase in BMI. No significant correlations were found between galanin, NPY and percentage change in response of LH to LHRH, as well as between NPY and insulin, and galanin and testosterone. Plasma insulin concentrations in women with PCOS (group B) were significantly higher than in the control group (p < 0.001). Increased plasma NPY levels are found in both obese and non-obese women with PCOS. The increase in NPY is independent of the increase in BMI. In obese women with PCOS, plasma leptin is increased compared with control lean women. Serum insulin concentration is increased in obese women with PCOS. A positive correlation exists between leptin and BMI as well as between leptin and testosterone in women with PCOS. These results may suggest that the feedback system in the interaction between leptin and NPY is disturbed in PCOS.     

Insulin sensitivity in pre-eclampsia

Objective To investigate whether pre-eclampsia is associated with an exaggeration of the insulin resistance seen in normotensive pregnancy.
Design Minimal model analysis of a frequently sampled intravenous glucose tolerance test to assess insulin sensitivity.
Setting Royal Maternity Hospital, Belfast.
Participants Eleven women with pre-eclampsia and 11 matched normotensive pregnant women.
Results Insulin sensitivity (S_I) was increased in the group with pre-eclampsia compared with the normotensive women (mean [±SEM]: 2.6 [0.4] vs 1.6 [0.2] 10⁻⁴ min⁻¹ per mU/L;   P = 0.028  ). This was accompanied by a decrease in glucose effectiveness (S_G) (1*1 ±0.1 vs 1.7 ±0.1 10⁻² mid,   P = 0.006  ) in the pre-eclamptic women. In the normotensive group there was a significant inverse correlation between S, and mean arterial blood pressure ( Y =−0.65;   P = 0.03  ), but no such relation existed in the group with pre-eclampsia.
Conclusions As with other forms of secondary hypertension, and unlike essential hypertension, the pathophysiology of pre-eclampsia is not associated with insulin resistance.