Phenotypic characteristics according to insulin sensitivity in non-obese Korean women with polycystic ovary syndrome

Over 50% of women with polycystic ovary syndrome (PCOS) have been reported to have varying degree of insulin resistance and it may contribute to hyperandrogenism. The aim of the study is to identify whether the insulin resistance is present in non-obese Korean women with PCOS and whether the phenotype is different according to insulin sensitivity. Seventy-three non-obese (BMI<23 kg/m(2)) women with PCOS and 34 age and BMI comparable control women with regular menstrual cycles were examined. Standard 75 g OGTT was performed to determine the status of glucose tolerance. Insulin sensitivity was measured by euglycemic hyperinsulinemic clamp technique. The fasting plasma glucose (p<0.01) and post-glucose load plasma insulin (p<0.01) of women with PCOS were higher than those of controls. Glucose disposal rate (M-value) was lower in women with PCOS compared to controls (p<0.05). Insulin resistant (IR) and insulin sensitive (IS) PCOS were divided by the M-value of 25-percentile (5.5mg/kg min) in controls. Between IR and IS groups, DHEAS (p<0.01), post-glucose load plasma insulin (p<0.05) showed differences after the adjustment for BMI. Our non-obese women with PCOS showed significant insulin resistance compared to their age and BMI comparable control subjects and their insulin resistance may contribute to hyperandrogenism especially via adrenal androgen overproduction.     

多囊卵巢综合征患者胰岛素抵抗与糖脂代谢及性激素的研究

目的通过高胰岛素正葡萄糖钳夹试验评估多囊卵巢综合征(PCOS)患者的胰岛素抵抗,探讨伴胰岛素抵抗PCOS患者糖脂代谢及性激素水平特点。方法将2017年7月至2019年2月就诊于遵义医科大学附属医院内分泌科住院及门诊的73例PCOS患者和体重指数及年龄匹配的27名健康女性行高胰岛素正葡萄糖钳夹试验,根据葡萄糖代谢率、体重指数和稳态模型评估的胰岛素抵抗指数(HOMA-IR)分组,分析PCOS患者糖脂代谢及性激素指标的变化及差异。结果在PCOS组中,糖调节受损者占3.23%(1/31),血脂代谢异常者占9.68%(3/31);而在PCOS合并胰岛素抵抗组中,糖调节受损者占7.14%(3/42),血脂代谢异常者达47.62%(20/42),5例患者被诊断为代谢综合征,占11.90%。相关分析显示,葡萄糖代谢率与体重指数、腰臀比、收缩压、空腹血糖、空腹胰岛素、HOMA-IR、皮质醇、三酰甘油、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、游离雄激素指数(FAI)和谷氨酰转肽酶(GGT)呈负相关(P<0.05),与高密度脂蛋白胆固醇(HDL-C)呈正相关(P=0.028);HOMA-IR与体重指数、腰臀比、收缩压、空腹血糖、空腹胰岛素、HbA1C、LDL-C呈正相关(P<0.05),与葡萄糖代谢率和HDL-C呈负相关(P<0.05);体重指数与腰臀比、收缩压、空腹血糖、空腹胰岛素、HOMA-IR、三酰甘油和LDL-C呈正相关(P<0.05),与葡萄糖代谢率、HDL-C和性激素结合球蛋白(SHBG)呈负相关(P<0.01)。多元线性逐步回归分析表明,体重指数、总胆固醇、三酰甘油和皮质醇是影响葡萄糖代谢率的重要因素,空腹血糖、空腹胰岛素和收缩压是HOMA-IR的重要影响因素,葡萄糖代谢率、HOMA-IR、HDL-C和SHBG仍然是影响体重指数的重要影响因素。结论FAI、SHBG和皮质醇可能参与到PCOS患者的胰岛素抵抗发生中,存在胰岛素抵抗的PCOS患者更容易发生代谢紊乱。     

The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis

While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone‐binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment‐insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total‐cholesterol and low‐density lipoprotein‐cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.     

多囊卵巢综合征患者代谢综合征患病风险研究

目的 研究多囊卵巢综合征(PCOS)患者代谢综合征(MS)患病率,并探讨MS发生的危险因素.方法 比较348例年轻的PCOS患者及113名非PCOS正常女性的MS及其组分的患病率.结果 PCOS组MS的患病率为27.0%,明显高于正常对照组的10.6%(P<0.01),除甘油三酯外,其他MS组分在PCOS组均高于正常对照组(P<0.05或P<0.01),但校正年龄和体重指数(BMI)后,差异就不存在统计学意义(P=0.737).分层分析也显示PCOS非肥胖组和肥胖组的MS患病率与相应的正常对照组均无明显差异(均P>0.05).多元逐步回归分析显示稳态模型评估的胰岛素抵抗指数(HOMA-IR)和BMI是MS的独立预测因素(均P<0.01).结论 肥胖和胰岛素抵抗是MS的独立危险因素,PCOS单独并不增加MS的发生风险.     

The metabolic syndrome in polycystic ovary syndrome

Much overlap is present between the polycystic ovary syndrome (PCOS) and the metabolic syndrome. This article reviews the existing data regarding the prevalence, characteristics, and treatment of the metabolic syndrome in women with PCOS. The prevalence of the metabolic syndrome in PCOS is approximately 43-47%, a rate 2-fold higher than that for women in the general population. High body mass index and low serum HDL cholesterol are the most frequently occurring components of the metabolic syndrome in PCOS. The pathogenic link between the metabolic syndrome and PCOS is most likely insulin resistance. Therefore, the presence of the metabolic syndrome in PCOS suggests a greater degree of insulin resistance compared to PCOS without the metabolic syndrome. Obesity, atherogenic dyslipidemia, hypertension, impaired fasting glucose/impaired glucose tolerance, and vascular abnormalities are all common metabolic abnormalities present in PCOS. Lifestyle modification has proven benefit and pharmacological therapy with insulin-sensitizing agents has potential benefit in the treatment of the metabolic syndrome in women with PCOS.     

Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is characterized by insulin resistance with compensatory hyperinsulinemia. Insulin resistance also plays a role in the metabolic syndrome (MBS). We hypothesized that the MBS is prevalent in PCOS and that women with both conditions would present with more hyperandrogenism and menstrual cycle irregularity than women with PCOS only. We conducted a retrospective chart review of all women with PCOS seen over a 3-yr period at an endocrinology clinic. Of the 161 PCOS cases reviewed, 106 met the inclusion criteria. The women were divided into two groups: 1) women with PCOS and the MBS (n = 46); and 2) women with PCOS lacking the MBS (n = 60). Prevalence of the MBS was 43%, nearly 2-fold higher than that reported for age-matched women in the general population. Women with PCOS had persistently higher prevalence rates of the MBS than women in the general population, regardless of matched age and body mass index ranges. Acanthosis nigricans was more frequent in women with PCOS and the MBS. Women with PCOS and the MBS had significantly higher levels of serum free testosterone (P = 0.002) and lower levels of serum SHBG (P = 0.001) than women with PCOS without the MBS. No differences in total testosterone were observed between the groups. We conclude that the MBS and its components are common in women with PCOS, placing them at increased risk for cardiovascular disease. Women with PCOS and the MBS differ from their counterparts lacking the MBS in terms of increased hyperandrogenemia, lower serum SHBG, and higher prevalence of acanthosis nigricans, all features that may reflect more severe insulin resistance.     

Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS)

OBJECTIVE: To determine the prevalence of adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) using age- and race-specific normative values. DESIGN: Cross-sectional observational study. PATIENTS: One hundred and eight-two (88 Black and 94 White) age-matched healthy eumenorrhoeic nonhirsute women (controls) and 213 (27 Black and 186 White) women with PCOS were recruited. MEASUREMENTS: Total testosterone (T), free T, androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS) and SHBG, as well as fasting insulin and glucose, were measured in plasma. RESULTS: The mean total T, free T, A4, DHEAS and body mass index (BMI) were higher in women with PCOS than in control women. DHEAS levels were significantly lower in Black controls than White controls, whereas fasting insulin and BMI were higher in Black controls. In control and Black PCOS women, DHEAS levels did not correlate with BMI, waist-to-hip ratio (WHR) or fasting insulin. Among White women with PCOS, DHEAS levels correlated negatively with BMI and fasting insulin. DHEAS levels decreased similarly with age in control and PCOS women of either race. For each race and age group the upper 95% normative values for log DHEAS was calculated, and the number of PCOS subjects with log DHEAS values above this level were assessed. The prevalence of supranormal DHEAS levels was 33.3% and 19.9%, respectively, among Black and White women with PCOS. CONCLUSIONS: The prevalence of DHEAS excess is approximately 20% among White and 30% among Black PCOS patients, when using age- and race-adjusted normative values. This study also indicates that the age-associated decline in DHEAS levels is observable and similar in both control and PCOS women, regardless of race. While BMI and fasting insulin had little impact on circulating DHEAS levels in healthy women, among White PCOS patients these parameters were negatively associated with circulating DHEAS levels.     

多囊卵巢综合征患者性激素结合球蛋白和总睾酮与胰岛素抵抗的相关性

目的 了解性激素结合球蛋白(SHBG)和总睾酮在预测多囊卵巢综合征(PCOS)患者胰岛素抵抗和生殖内分泌以及糖脂代谢紊乱中的作用.方法 选择2004年6月至2006年5月在复旦大学附属妇产科医院就诊的344例PCOS患者为病例组,年龄12～35岁,平均年龄(23±5)岁.选择同期月经规律、基础体温双相的100名妇女作为对照组,比较PCOS患者SHBG和总睾酮与对照组的差异,并用Spearman相关分析法分别分析SHBG和总睾酮与其他指标的相关性,Logistic回归分析胰岛素抵抗的风险因子并做SHBG对胰岛素抵抗的受试者操作特征(ROC)曲线,获得预测胰岛素抵抗的风险值,比较不同水平SHBG患者的糖脂代谢紊乱的程度.结果 PCOS患者SHBG为(114±88)mmol/L,与对照组[(201±106)mmol/L]比较差异有统计学意义(t=-5.60,P<0.01),总睾酮为(2.8±1.0)nmol/L,与对照组[(1.7±0.6)nmol/L]比较差异有统计学意义(t=7.73,P<0.01);SHBG与空腹胰岛素、胰岛素释放试验曲线下面积、口服葡萄糖耐量试验(OGTT)的葡萄糖曲线下面积、胰岛素抵抗指数、甘油三酯和腰围/臀围比呈负相关(r值分别为:-0.30、-0.26、-0.29、-0.19、-0.20、-0.29、-0.22,均P<0.01);总睾酮与空腹胰岛素(r=0.14,P<0.01)、胰岛素释放试验(1、2、3 h的r值分别为0.15、0.12、0.11,均P<0.05)以及相应的曲线下面积(r=0.15,P<0.05)、胰岛素抵抗指数(r=0.11,P<0.05)呈正相关.Logistic回归分析发现SHBG是PCOS患者胰岛素抵抗的独立危险因素(OR=3.741).由ROC曲线得到SHBG预测胰岛素抵抗的大致风险值为88 mmol/L(95%CI为0.668～0.774).在低SHBG(<88 mmol/L)患者中,空腹胰岛素、胰岛素释放试验相应的曲线下面积、胰岛素抵抗指数、空腹血糖、OGTT的葡萄糖曲线下面积与高SHBG(≥88 mmoL/L)患者比较差异有统计学意义(t值分别为-6.45、-5.08、-6.19、-3.16、-3.66,均P<0.01),甘油三酯也高于高SHBG患者(t=-2.06,P<0.05).结论 PCOS患者总睾酮水平高于对照组,SHBG低?     

Polycystic ovary syndrome, metabolic syndrome, cardiovascular risk and the role of insulin sensitizing agents

The Polycystic Ovary Syndrome (PCOS) affects 6 to 10% of women of childbearing age. Insulin resistance and hyperinsulinemia are present in nearly all PCOS patients and play a central role in the development of both hyperandrogenism and metabolic syndrome (MS). MS occurs in approximately 43% of PCOS patients, raising the cardiovascular risk to up seven fold in these patients. Several serum, functional and structural markers of endothelial dysfunction and subclinical atherosclerosis were described in PCOS patients, even those young and non-obese. However, despite the fact that PCOS adversely affects the cardiovascular profile, long-term studies did not demonstrate a consistent raise in cardiovascular mortality, which seems to be more observed in the post-menopausal period. Recently, oral contraceptives are being substituted for insulin sensitizing agents (metformin and glitazones) in the PCOS treatment, due to their effects on insulin resistance and cardiovascular risk.     

Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome

OBJECTIVE: Application of the newly introduced Rotterdam criteria for polycystic ovary syndrome (PCOS) generates four phenotypic subgroups, defined by the presence/absence of three diagnostic elements: polycystic ovarian (PCO) morphology (P); hyperandrogenism (H); and oligo-amenorrhoea (O). Whilst PCOS is associated with adverse metabolic features, the strength of the association within individual subgroups is not established. We characterized the metabolic and endocrine profiles of PCOS women who are oligomenorrhoeic but normoandrogenaemic, and compared these to other PCOS women and controls. DESIGN: Retrospective dataset analyses. PATIENTS: A total of 309 Europid PCOS women, all with PCO morphology, of whom 191 were also hyperandrogenaemic and oligomenorrhoeic (PHO), 76 hyperandrogenaemic with normal menses (PH) and 42 oligomenorrhoeic but normoandrogenaemic (PO); plus 76 Europid control women without PCOS. MEASUREMENTS: Metabolic parameters: fasting insulin, lipids, homeostasis model assessment (HOMA) measures of insulin sensitivity; endocrine variables: LH, FSH; prevalence of metabolic syndrome. RESULTS: Insulin sensitivity: PO women were indistinguishable from controls, and markedly less insulin-resistant than PHO women (vs. controls, P = 0.38 after adjustment for BMI and age; vs. PHO, P = 0.003). Metabolic syndrome: the prevalence in PO women (7.1%) was similar to that in controls (3.9%), and lower than in PHO women (29.3%, P < 0.0001). LH levels: PO women were intermediate between controls (vs. controls, P = 0.008) and PHO women (vs. PHO, P = 0.06). CONCLUSIONS: Normoandrogenaemic, oligomenorrhoeic women with PCOS are metabolically similar to control women with significantly fewer metabolic features than PCOS women who are also hyperandrogenaemic. However, higher than normal LH and lower sex hormone-binding globulin (SHBG) concentrations in the PO women support the view that they form part of the spectrum of PCOS.     

Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.     

Early metabolic derangements in daughters of women with polycystic ovary syndrome

CONTEXT: Polycystic ovary syndrome (PCOS) is a familial endocrine-metabolic dysfunction, increasingly recognized in adolescent girls with hyperandrogenism. However, it is difficult to establish whether the metabolic abnormalities described in PCOS are present before the onset of hyperandrogenism. In children, a strong association of adiponectin levels with metabolic parameters of insulin resistance has been described. OBJECTIVE: The objective of the study was to evaluate adiponectin serum concentrations and metabolic parameters in prepubertal and pubertal daughters of women with PCOS to identify girls with increased metabolic risk. DESIGN: Fifty-three prepubertal and 22 pubertal (Tanner stages II-V) daughters of PCOS women (PCOSd) and 32 prepubertal and 17 pubertal daughters of control women (Cd) were studied. In both groups, an oral glucose tolerance test was performed with measurement of glucose and insulin. Adiponectin, leptin, C-reactive protein, SHBG, sex steroids, and lipids were determined in the fasting sample. RESULTS: Both groups had similar chronological ages, body mass index sd score, and Tanner stage distribution. In the prepubertal girls, 2-h insulin was higher (P = 0.023) and adiponectin levels were lower (P = 0.004) in the PCOSd group, compared with the Cd group. In the pubertal girls, triglycerides (P = 0.03), 2-h insulin (P = 0.01), and serum testosterone concentrations were higher (P = 0.012) and SHBG lower (P = 0.009) in PCOSd, compared with Cd, but adiponectin levels were similar in both groups. CONCLUSIONS: Some of the metabolic features of PCOS are present in daughters of PCOS women before the onset of hyperandrogenism. Adiponectin appears to be one of the early markers of metabolic derangement in these girls.     

Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents

Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population. The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course. We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 +/- 1.9 yr; body mass index (BMI), 22.5 +/- 1.5 kg/m(2)], 22 obese with PCOS (age, 15.5 +/- 1.4 yr; BMI, 35.9 +/- 6.2 kg/m(2)), and 15 obese controls (age, 14.4 +/- 1.5 yr; BMI, 35.8 +/- 7.1 kg/m(2)). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, Delta4-androstenedione (Delta4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I(AUC120)). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, Delta4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I(AUC120), and log I(AUC120) were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, Delta4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls. Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.     

Prediction of insulin sensitivity in nonobese women with polycystic ovary syndrome

Insulin resistance is a frequent (although not constant) abnormality in both obese and nonobese women with polycystic ovary syndrome (PCOS). It plays a key role in the predisposition to type 2 diabetes, which is the most important health consequence of the syndrome. Identification of patients with insulin resistance is significant both for follow-up and for therapeutic reasons. The aim of the study was to evaluate the relationships between insulin sensitivity, measured by euglycemic clamp, and both endocrine and metabolic indices and to identify the best model for predicting insulin sensitivity. A total of 41 nonobese women fulfilling the diagnostic criteria for PCOS were enrolled in the study. None of the androgens correlated with the insulin sensitivity index. All clamp parameters correlated with SHBG, triglycerides, and body mass index, although no correlation was found with waist to hip ratio or waist circumference. The close relationship between insulin sensitivity and SHBG was documented by factor analysis and by its presence in all prediction models as the most significant (or even the single) predictor of the insulin sensitivity index. In conclusion: 1) a decreased level of SHBG can be used as a single reliable parameter in the prediction of insulin sensitivity in nonobese women with PCOS; and 2) waist to hip ratio, waist circumference, and androgen concentrations have no predictive value.     

Circulating ghrelin levels in patients with polycystic ovary syndrome

The syndrome of polycystic ovaries (PCOS) is associated with adiposity and metabolic changes predisposing to insulin resistance and diabetes mellitus. Because the recently discovered GH secretagogue, ghrelin, is intimately involved in the control of appetite and weight regulation, we studied ghrelin levels in a group of 26 otherwise healthy women with PCOS. They were compared with 61 healthy female control subjects and 5 gastrectomized women. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and continuous infusion of glucose with model assessment (CIGMA) in all patients. In PCOS women, serum ghrelin levels were significantly lower than in healthy lean or obese controls (P < 0.001). In insulin-sensitive PCOS women, ghrelin concentrations compared well with the healthy controls, whereas in insulin-resistant PCOS ghrelin levels were significantly lower and indistinguishable from the low levels found in the gastrectomized women. There was a close correlation of ghrelin to insulin sensitivity (HOMA, r(2) = 0.330, P < 0.002; CIGMA, r(2) = 0.568, P < 0.0001). Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations (P < 0.02). Ghrelin levels did not correlate to any of the parameters of hyperandrogenemia, to the LH/FSH ratio, to body mass index, or to fasting insulin and glucose concentrations. In summary, ghrelin levels are decreased in PCOS women and are highly correlated to the degree of insulin resistance. This suggests that ghrelin could be linked to insulin resistance in PCOS women. However, whether low ghrelin in PCOS is a cause or the consequence of insulin resistance awaits further investigations.     

Risk of atherosclerosis in women with polycystic ovary syndrome: a study from South India

Women with polycystic ovary syndrome (PCOS) often present for cosmetic and or reproductive symptoms; attention is generally not paid to the future risk of atherosclerosis for these women. Given that Asian Indians are insulin resistant and prone to metabolic syndrome at an earlier age, we assessed glucose/insulin ratio and intimal medial thickness (IMT) in young women with PCOS from south India. In this cross-sectional case control study, we assessed insulin resistance and carotid IMT in 40 women presenting with hyperandrogenic features of PCOS. Insulin resistance was assessed by fasting glucose/insulin ratio and IMT by the Doppler system with electrical linear transducer midfrequency of 12 MHz. Women with PCOS had higher fasting insulin levels (36.58 +/- 17.81 muU/mL, vs. 16.60 +/- 3.22 muU/mL in controls; p < 0.001), higher insulin resistance (glucose/insulin ratio 2.81 +/- 1.47 vs. 5.47 +/- 1.46 in controls; p < 0.001), and greater IMT (0.53 +/- 0.14 mm vs. 0.39 +/- 0.06 mm in controls; p < 0.001). Women with PCOS had a higher body mass index (BMI) (26.46 +/- 5.24 vs. 23.24 +/- 3.05 in controls; p < 0.001), and the differences between PCOS and controls persisted, even among those who had a BMI of less than 25. We concluded that South Indian women with the reproductive abnormalities of PCOS have greater insulin resistance and IMT, and therefore they must be advised about lowering the risk of future vascular disease.     

Retinol-binding protein in nonobese women with polycystic ovary syndrome

Objective Although polycystic ovary syndrome (PCOS) is frequently associated with insulin resistance, cardiovascular disease and various metabolic diseases, the mechanisms linking PCOS to metabolic changes are not fully understood. Retinol‐binding protein (RBP) was recently reported as an adipocytokine that may link insulin resistance and lipid metabolism. The aim of this study was to investigate the potential role of RBP in women with PCOS. Research design and methods Fifty women with PCOS and 40 healthy women, all of whom were age‐ and weight‐matched, were studied. Blood was obtained to determine RBP levels as well as metabolic and hormonal parameters, and the homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated for each subject. Results The RBP levels were higher (P < 0·01) in women with PCOS after adjusting for age, body mass index (BMI), mean blood pressure, triglyceride (TG), high density lipoprotein (HDL)‐cholesterol, low density lipoprotein (LDL)‐cholesterol, fasting glucose, fasting insulin, estimated glomerular filtration rate (GFR), LH/FSH, total testosterone and SHBG levels. PCOS status was the strongest predictor of elevated RBP levels. In both the PCOS and control groups, RBP levels were significantly correlated with HOMA‐IR (P = 0·03 in the PCOS group; P = 0·01 in controls). In addition, RBP levels were significantly correlated with total cholesterol, LDL‐cholesterol and TG levels in PCOS (P < 0·01, P < 0·01 and P = 0·01, respectively). Conclusions Higher RBP levels in the PCOS group, when compared to the non‐PCOS group, were observed, and this difference may play a role in the pathophysiology found in women with PCOS. Further studies are needed to clarify the role of RBP in these women.     

Genetic determinants of insulin action in polycystic ovary syndrome.

INTRODUCTION: Insulin resistance is associated with both type 2 diabetes (T2 D) and polycystic ovary syndrome (PCOS). There is an association of T2 D with several polymorphisms in candidate genes related to insulin resistance. However, there is limited information about the association of these polymorphisms with PCOS. METHODS: 57 non-diabetic women with PCOS and a control group of 567 healthy non-diabetic women underwent an oral glucose tolerance test (OGTT). They were genotyped for the polymorphisms Gly972Arg in IRS-1, Gly1057Asp in IRS-2, SNP 43, 44, and 45 in CAPN10, Pro12Ala in PPAR(gamma)2, C-512 T in FOXC2, and T45 G in adiponectin. RESULTS: Women with PCOS had higher 2-h blood glucose levels (6.5 +/- 0.2 vs. 6.0 +/- 0.06 mmol/l, p = 0.03) compared to control women, higher fasting insulin (79 +/- 7 vs. 53 +/- 2 pmol/l, p = 0.02), and a lower insulin sensitivity estimated from the OGTT (12.4 +/- 1.1 vs. 19.1 +/- 0.5 U, p = 0.0001). More homozygous G allele carriers of the T45 G polymorphism in the adiponectin gene were found in women with PCOS compared to controls (13.2 % vs. 2.6 %, p = 0.008). In women with PCOS, G-allele carriers had lower fasting insulin levels than TT carriers (61 +/- 9 vs. 88 +/- 10, p = 0.02) in contrast to controls (p = 0.03 for interaction genotype x PCOS). The other polymorphisms were distributed equally among women with PCOS and controls (all p > 0.5). SUMMARY: We found a higher prevalence of the T45 G polymorphism in the adiponectin gene in women with PCOS compared to controls. This was not associated with a more insulin resistant phenotype in PCOS, however. Other frequent polymorphisms in genes related to insulin resistance and type 2 diabetes showed no association with PCOS.     

Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity

This study was performed to determine whether the sisters of women with polycystic ovary syndrome (PCOS) have evidence for insulin resistance. Three hundred and thirty-six women with PCOS, 307 sisters of these probands, and 47 control women were studied. The sisters were grouped by phenotypes: PCOS [hyperandrogenemia (HA) with chronic oligo- or amenorrhea, n = 39], HA with regular menses (n = 36), unaffected (UA; n = 122), and unknown (n = 110). The analyses were adjusted for age and body mass index. PCOS and HA sisters of women with PCOS had similar and significantly elevated fasting insulin levels (P = 0.001) as well as similar and significantly decreased fasting glucose/insulin ratios (P < 0.001) suggestive of insulin resistance compared with UA sisters and control women. Markers of insulin resistance were associated with hyperandrogenemia and not with menstrual irregularity. PCOS sisters also had decreased levels of SHBG (P = 0.02) suggestive of higher ambient insulin levels. PCOS sisters had increased levels of proinsulin (P = 0.04) compared with control women, which suggested pancreatic beta-cell dysfunction in this group of sisters. The magnitude of obesity also differed significantly among the groups of sisters. The PCOS sisters were significantly more obese than all the other groups, and the HA sisters were more obese than the UA sisters. We conclude that markers of insulin resistance are associated with hyperandrogenemia rather than menstrual irregularity in the sisters of women with PCOS. Menstrual irregularity may be related to the magnitude of insulin sensitivity or insulin secretion or to other factors associated with obesity.