Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters

Several studies have demonstrated that low levels of serum adiponectin are present in obesity, insulin resistance, hypertension and hyperlipidemias. The aim of our study was to determine whether serum adiponectin level is different between patients with polycystic ovarian syndrome (PCOS) and control subjects. We also investigated relationships between various cardiovascular risk factors, levels of serum adiponectin and other hormones, such as androstendione, testosterone, estradiol, DHEAS, sex hormone binding globulin (SHBG), and leptin. We also analysed the correlation between serum adiponectin and free androgen index. Ninety-one women with clinical diagnosed PCOS and 53 healthy control subjects, carefully matched by body mass index (BMI) and age, were enrolled in the study. The fasting blood samples were obtained and all participants underwent an oral 75 g glucose tolerance test. The prevalences of impaired glucose tolerance (IGT), hypertension and hypertriglyceridemia were higher in the PCOS group. PCOS women had increased androgen concentrations and higher free androgen index and decreased level of serum SHBG. Lower serum adiponectin concentrations were observed among cases than in controls (median 13.7 microg/ml vs 17.8 microg/ml, p<0.001) despite being matched by BMI. In the PCOS group adiponectin levels correlated significantly with: BMI (r=-0.32, p=0.002), waist circumference (r=-0.32, p=0.003), waist-to-hip ratio (WHR, r=-0.38, p=0.001), triglycerides (r=-0.31, p=0.007), SHBG (r=0.30, p=0.003) and free androgen index (r=-0.29, p=0.02). In contrast, the adiponectin level does not appear to be related to total testosterone, DHEAS and leptin levels. The adiponectin and SHBG levels were found to be decreased in PCOS women with IGT compared to PCOS women with normal glucose tolerance, but after adjustment by BMI or WHR, the differences were no longer statistically significant. To exclude a possible confounding effect due to a higher prevalence of IGT in the PCOS group, this comparison was repeated for the subgroup of 58 PCOS women and 48 control women after excluding those with IGT. Neither adiponectin nor SHBG were significantly different between those subgroups. Multiple regression analysis revealed that serum adiponectin concentrations were best predicted by WHR, free androgen index and presence of IGT when all patients were considered. In PCOS subjects, the only independent predictor of adiponectin concentrations was glucose tolerance status. CONCLUSIONS: Lower adiponectin levels were observed in PCOS group than in control women, and these differences were probably due to higher prevalence of IGT in these cases.     

Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome

OBJECTIVE: The polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance predisposing to diabetes mellitus type 2 and atherosclerosis. Adiponectin is a recently discovered adipocytokine with insulin-sensitizing and putative antiatherosclerotic properties. The aim of the study was to elucidate determinants of circulating adiponectin levels and to investigate the potential role of adiponectin in insulin resistance in PCOS women. PATIENTS AND MEASUREMENTS: Plasma adiponectin and parameters of obesity, insulin resistance and hyperandrogenism were measured In 62 women with PCOS and in 35 healthy female controls. RESULTS: Both in PCOS and controls, adiponectin levels were lower in overweight or obese women than in normal-weight women, without any difference between PCOS and controls after adjustment for body mass index (BMI). In PCOS and in controls there was a significant correlation of adiponectin with BMI (r = -0.516, P < 0.001), fasting insulin (r = -0.404, P < 0.001), homeostasis model sensitivity (HOMA %S) (r = -0.424, P < 0.001) and testosterone (r = -0.279, P < 0.01), but no correlation with androstenedione (r = -0.112, P = 0.325), 17-OH-progesterone (r =-0.031, P = 0.784) or the LH/FSH ratio (r =-0.033, P = 0.753). Multiple linear regression analysis revealed that BMI and HOMA %S but not testosterone were independently associated with adiponectin plasma levels, explaining 16% (BMI) and 13% (HOMA %S) of the variability of adiponectin, respectively. In PCOS patients insulin sensitivity, as indicated by continuous infusion of glucose with model assessment (CIGMA %S) was significantly correlated with adiponectin (r = 0.55; P < 0.001), BMI (r =-0.575; P < 0.001), waist-to-hip ratio (WHR) (r =-0.48; P = 0.001), body fat mass assessed by dual-energy X-ray-absorptiometry (DEXA) [Dexa-fat (total) (r = -0.61; P < 0.001) and Dexa-fat (trunk) (r = -0.59; P < 0.001)] and with testosterone (r = -0.42; P = 0.001). Multiple linear regression analysis demonstrated that markers of obesity such as BMI, total or truncal fat mass, age and adiponectin were independently associated with CIGMA %S, and that circulating adiponectin accounted for about 18% of the degree of insulin resistance in PCOS. By contrast, testosterone was not a significant factor, suggesting that PCOS per se did not affect insulin sensitivity independent from obesity, age and adiponectin. Metformin treatment for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma adiponectin (P = 0.59) despite significant loss of weight and fat mass and improvement in hyperandrogenaemia. CONCLUSIONS: PCOS per se is not associated with decreased levels of plasma adiponectin. However, circulating adiponectin is independently associated with the degree of insulin resistance in PCOS women and may contribute to the development and/or maintenance of insulin resistance independent from adiposity.     

非酒精性脂肪性肝病患者血清瘦素和脂联素与胰岛素抵抗的关系

目的 探讨非酒精性脂肪性肝病(NAFLD)患者血清瘦素、脂联素的变化及其与胰岛素抵抗的关系. 方法 选取NAFLD患者60例,同期门诊体检健康者60名为对照组,ELJSA法测定血清瘦素、脂联素水平,并检测体质量指数、腰臀比、甘油三酯、总胆固醇、高密度脂蛋白胆固醇(HDL-C)、空腹血糖、ALT、AST、γ-谷氨酰转肽酶(GGT),稳态模型评估的胰岛素抵抗指数(HOMA-IR).采用SPSS10.0软件包进行统计学分析,计量资料差异性比较用方差分析和t检验,多因素相关性用Spearman分析和Logistic回归分析. 结果 血清瘦素、脂联素水平NAFLD组分别为(12.37±1.99)μg/L和(12.69±2.83)mg/L,对照组分别为(5.20±1.03)μg/L和(22.83±4.61)mg/L,t值分别为24.661和14.516,P值均<0.01;HOMA-IR,NAFLD组为4.86±0.63,对照组为1.91±0.41,t值为30.451,P<0.01.Logistic多因素回归分析显示瘦素与腰臀围之比、HOMA-IR、空腹血糖呈独立正相关,β值分别为8.175、0.974和0.564,P值均<0.01;脂联素与HOMA-IR、体质量指数呈独立负相关,β值分别为-0.495和-0.314,P值均<0.01.结论 NAFLD患者血清瘦素、脂联素的变化与胰岛素抵抗有关.     

Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome

BACKGROUND Women with polycystic ovary syndrome (PCOS) exhibit elevated serum advanced glycation end-products (AGE) compared with healthy subjects. Short-term administration of orlistat has been shown to reduce the postmeal increase in serum AGE levels in women with PCOS and in controls. OBJECTIVE: To evaluate the long-term effect of orlistat and a low-calorie diet on serum AGE levels, and on the hormonal and metabolic profile of obese PCOS and normal women. DESIGN: A clinical trial of 6 months of orlistat administration with an energy-restricted diet [basic metabolic rate (BMR) 600 kcal/day] in all subjects. SUBJECTS: Twenty-nine women with PCOS [aged 27.52 +/- 5.77 years; body mass index (BMI) 35.43 +/- 5.31 kg/m(2)] and 18 controls (aged 32.06 +/- 5.64 years; BMI 36.39 +/- 6.47 kg/m(2)). MEASUREMENTS: Serum AGE levels (U/ml), hormonal and metabolic profile. RESULTS: PCOS and controls did not differ in BMI (P = 0.58), waist-to-hip ratio (WHR) (P = 0.44), fasting insulin concentration (P = 0.45) and glucose-to-insulin ratio (GIR) (P = 0.34). PCOS women exhibited statistically higher AGE (P < 0.001) and testosterone levels (P < 0.001) compared with controls. After 6 months of orlistat treatment, AGE levels showed a statistically significant decrease in both groups (PCOS: baseline 9.08 +/- 1.84, post-orlistat 8.56 +/- 1.95, P = 0.001; controls: baseline 5.02 +/- 0.62, post-orlistat 4.91 +/- 0.69, P = 0.03), independently of the BMI reduction in the PCOS group. A significant reduction was observed in BMI (PCOS: P < 0.001; controls: P < 0.001), WHR (PCOS: P = 0.002; controls: P = 0.04), fasting insulin (PCOS: P < 0.001; controls: P = 0.008), and testosterone concentrations in PCOS (P < 0.001). SHBG concentration (PCOS: P = 0.004; controls: P = 0.008) and GIR (PCOS: P < 0.001; controls: P = 0.03) were significantly increased. A significant improvement was also observed in insulin resistance indices post-treatment in both groups. CONCLUSIONS: Our data suggest that orlistat has a beneficial effect in reducing elevated AGE levels and improving the hormonal and metabolic profile in women with PCOS after 6 months of treatment, independently of BMI changes.     

Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children

OBJECTIVE: To evaluate the relationship between serum leptin levels and metabolic syndrome, fasting insulin level and anthropometric index in obese pre-pubertal children. DESIGN: A cross-sectional study was carried out on obese children. SUBJECTS: A study was made of 41 obese children (aged 6-9 y) and the same number of non-obese children (control group), matched by age and sex. METHODS: Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined in each child. Serum leptin, glucose, insulin, lipid profile, sex hormone binding globulin (SHBG), plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA) and fibrinogen were all measured. RESULTS: The serum leptin level was significantly higher in obese children (15.47 vs 4.73 ng/ml). In the obese group, leptin showed a positive correlation with BMI (P<0.001), insulin (P<0.001), triglycerides (P<0.05), PAI-1 (P<0.05) and t-PA (P<0.05), and correlated negatively with SHBG (P<0.01), apolipoprotein A-I (P<0.05) and high-density lipoproteins cholesterol (HDL-C) (P<0.05). Corrected for BMI and WHR, leptin (P partial=0.002) is only an independent predictive factor for basal insulin. Using multivariant regression analysis, only insulin (P partial=0.003) and BMI (P partial=0.018) were independent predictive factors for leptin. CONCLUSION: For this age group, high leptin resistance may be another component of metabolic syndrome, and may be involved in its etiopathogenesis. The involvement of leptin in this syndrome may be indirect, modulating the insulin's action.     

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.     

肿瘤坏死因子α和瘦素在肥胖及胰岛素抵抗中的作用

目的探讨血清TNFα及瘦素在肥胖和胰岛素抵抗中的作用。方法2型糖尿病病人84例,健康对照84例,分别测定血清TNFα、瘦素、血脂、空腹及餐后血糖、血清免疫反应性胰岛素(IRI)水平。并准确测量血压、身高、体重、腰臀围比(WHR)。结果肥胖者的TNFα及瘦素显著高于体重正常者,女性的瘦素血清水平高于男性2倍以上。相关分析结果显示,TNFα与HOMA胰岛素抵抗指数(HOMAIR)、WHR、空腹IRI呈正相关(r值分别为0.43、0.53、0.59,P<0.01),与高密度脂蛋白胆固醇呈负相关(r=-0.35,P<0.01)。瘦素与HOMAIR、空腹IRI呈正相关(r=0.31、0.29,P<0.05),男性的瘦素与WHR显著相关。TNFα与瘦素之间存在显著的正相关(r=0.29,P<0.05)。多元逐步回归分析表明,HOMAIR与TNFα的相关性最强,瘦素次之。血清TNFα水平与空腹血糖呈正相关。结论肥胖者的血清TNFα及瘦素水平与胰岛素抵抗密切相关,高水平的TNFα可能直接作用于脂肪组织调节瘦素的释放,而TNFα和瘦素协同作用诱导胰岛素的分泌,从而导致胰岛素抵抗。     

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?     

The associations between plasma adiponectin, ghrelin levels and cardiovascular risk factors

OBJECTIVE: Ghrelin is a recently discovered peptide, which is produced primarily in the stomach. This orexigenic peptide participates not only in the induction of mealtime hunger but also in long-term body weight regulation and energy homeostasis. Adiponectin is a protein secreted by adipocytes, and has been proposed to mediate obesity-related insulin resistance. Moreover, concentrations of adiponectin are reduced in individuals with obesity, insulin resistance and cardiovascular disease. However, human data are sparse about the direct relationship between adiponectin, ghrelin and cardiovascular risk factors including insulin resistance. DESIGN: Three hundred and thirty-eight elderly Korean women (mean age+/-s.d., 72.3+/-5.5 years) were included in the present study. METHODS: Plasma ghrelin and adiponectin levels were measured by RIA. Anthropometric measurements were taken and a 75 g oral glucose tolerance test performed. Fasting insulin and lipid profile were measured and insulin resistance was determined using the homeostasis model assessment insulin resistance index (HOMA-R) and the quantitative insulin sensitivity check index. RESULTS: Plasma adiponectin levels were negatively correlated with central obesity indices such as waist circumference (r=-0.27, P<0.001) and waist-to-hip ratio (WHR) (r=-0.32, P<0.001), and with insulin resistance indices such as fasting insulin (r=-0.17, P=0.004) and HOMA-R (r=-0.13, P=0.035). Plasma ghrelin levels were negatively correlated with WHR (r=-0.12, P=0.03), but plasma adiponectin and ghrelin levels were not correlated (r=0.03, P=0.66). Multiple regression analysis showed that adiponectin was associated with WHR, fasting insulin and fasting glucose levels. When ghrelin was used as a dependent variable, only WHR remained in the final fitted model. CONCLUSION: Fasting plasma adiponectin and ghrelin levels were found to be associated with central obesity or insulin resistance. However, plasma adiponectin and ghrelin concentrations were not associated with each other in elderly Korean women.     

Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups.

Hepatic sex-hormone binding globulin (SHBG) production is down-regulated by insulin and low levels reflect insulin resistance. Because insulin resistance is closely related to the development of cardiovascular disease in different ethnic groups we examined ethnic variation in SHBG across populations with different baseline cardiovascular risk and metabolic syndrome prevalence. Participants were population-based, of European (n = 142), Pakistani (n = 130), and African-Caribbean (AfC) origin (n = 193). SHBG, fasting lipids, and glucose concentrations plus insulin sensitivity (HOMA-S) were determined. Age adjusted SHBG was significantly lower in both Pakistani men and women. Circulating SHBG levels were lower in those with impaired vs. normal glucose homeostasis. SHBG correlated positively with HOMA-S (rho = 0.28, p < 0.001), and negatively with WHR (rho = - 0.38, p < 0.001), BMI (r = - 0.30, p < 0.001), and diastolic blood pressure (rho = - 0.14, p < 0.01) across all ethnic groups. In multivariate logistic regression analysis a low SHBG increased the likelihood of the metabolic syndrome (odds ratio [OR] = 0.42 [0.21 - 0.82], p = 0.01) as did higher fasting NEFA (OR 1.47 [1.04 - 2.08], p = 0.03), low IGFBP-1 concentrations (OR 0.6 [0.44 - 0.81], p = 0.001), age (OR 1.05 [1.02 - 1.09], p = 0.003), and Pakistani ethnicity (p = 0.001) in a model which also contained gender, lnCRP, IGF-I, and IGF-II. As ethnic differences in SHBG level closely parallel differences in insulin resistance. Its measurement may be useful in identifying individuals at particular risk of the metabolic syndrome, for early intervention.     

Metabolic profile in sons of women with polycystic ovary syndrome

CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder with strong familial aggregation. It has been demonstrated that parents and brothers of PCOS women exhibit insulin resistance and related metabolic defects. However, metabolic phenotypes in sons of PCOS women have not been described. OBJECTIVE: Our objective was to assess the metabolic profiles in sons of women with PCOS during different stages of life: early infancy, childhood, and adulthood. DESIGN: Eighty sons of women with PCOS (PCOS(S)) and 56 sons of control women without hyperandrogenism (C(S)), matched for age, were studied. In early infancy, glucose and insulin were determined in the basal sample. In children and adults, a 2-h oral glucose tolerance test was performed with measurements of glucose and insulin. Adiponectin, leptin, C-reactive protein, SHBG, and serum lipids were determined in the basal sample during the three periods. RESULTS: During early infancy, PCOS(S) showed higher weight (P = 0.038) and weight sd score (P = 0.031) than C(S). During childhood, weight (P = 0.003), body mass index (BMI) (P < 0.001), BMI sd score (P < 0.001), waist circumference (P = 0.001), total cholesterol (P = 0.007), and low-density lipoprotein cholesterol (P = 0.022) were higher in PCOS(S) compared with C(S), but after adjusting for BMI, these differences were nonsignificant. During adulthood, PCOS(S) exhibited higher weight (P = 0.022), BMI (P = 0.046), and waist circumference (P = 0.028) than C(S). Fasting insulin (P = 0.030), homeostasis model assessment for insulin resistance (P = 0.034), total cholesterol (P = 0.043), low-density lipoprotein cholesterol (P = 0.034), and 2-h insulin (P = 0.006) were also significantly higher and insulin sensitivity index composite significantly lower in PCOS(S) than in C(S) (P = 0.003). After adjusting for BMI, only 2-h insulin and insulin sensitivity index composite remained significantly different. CONCLUSIONS: This study indicates that sons of PCOS women exhibit higher body weight from early infancy. In addition, insulin resistance became evident as the subjects got older, which may place them at risk for the development of type 2 diabetes and cardiovascular disease.     

Elevated serum levels of interleukin-18 are associated with insulin resistance in women with polycystic ovary syndrome

Overproduction of proinflammatory factors is associated with obesity and diabetes. Interleukin (IL)-18 as a member of IL-1 cytokine family is increased in obese, in diabetic, and even in polycystic ovary syndrome (PCOS) patients. In the present study we evaluated the association of serum IL-18 levels with insulin resistance in PCOS women. Forty-two PCOS women and 38 control subjects were enrolled in this study and matched with respect to age and body mass index (BMI). Serum IL-18 levels and hormones were measured for all subjects. Furthermore, euglycemic hyperinsulinemic clamp test was performed in selected 30 PCOS women and 11 control subjects. Serum IL-18 levels were elevated in PCOS women compared with the control (p=0.003). IL-18 levels were positively correlated with homeostasis model assessment index (HOMA) β index, which assesses β cell function (p=0.035), but were inversely correlated with clamp indices, which best-represent insulin resistance status: M, Clamp ISIS100, and MCRg values (p=0.006, 0.010, and 0.009 respectively). No correlation was found between IL-18 and age, BMI, waist-to-hip ratio (WHR), lipid profile, dehydroepiandrosterone-sulfate (DHEAS), sex hormone-binding globulin (SHBG), or fasting insulin levels. In conclusion, in the present study, serum IL-18 levels were significantly increased in PCOS women and firmly associated with insulin resistance displayed by euglycemic hyperinsulinemic clamp test. It indicates that IL-18 may be a contributing factor linking inflammation and insulin resistance in PCOS women.     

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.     

Evidence for altered adipocyte function in polycystic ovary syndrome

BACKGROUND: Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes. METHODS: Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin, adiponectin, and resistin) as well as hormonal parameters and markers of insulin resistance as assessed by the quantitative insulin-sensitivity check index. Body mass index (BMI) was stratified into obese, overweight, and normal subgroups for comparisons between PCOS and controls. RESULTS: Adiponectin was lower (P < 0.05) and resistin was higher (P < 0.05) while leptin was similar to matched controls. Breakdown of the groups into subgroups showed a strong body mass relationship for leptin with no changes in resistin although adiponectin was lower in PCOS, even controlling for BMI. In controls, leptin and adiponectin and leptin and resistin correlated (P < 0.05) but not in PCOS. In controls, all adipocytokines correlated with markers of insulin resistance but not in PCOS. CONCLUSIONS: When matched for BMI status, decreased adiponectin in PCOS represent the most marked change. This alteration may be the result of altered adipose tissue distribution and function in PCOS but no correlation with insulin resistance was found.     

Association of insulin resistance with anti-Mullerian hormone levels in women without polycystic ovary syndrome (PCOS)

Objective  To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti-Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS).
Design/patients/measurements  We recruited 120 healthy, reproductive age women without PCOS. An overnight fasting blood draw, anthropometric measurements, analyses of serum levels of AMH, adipokines (leptin, adiponectin and RBP4) and total testosterone, a homeostasis model assessment for insulin resistance (HOMA-IR) and a transvaginal ultrasound scan were performed between the third and fifth day of their spontaneous menstrual cycles.
Results  Higher HOMA-IR levels were associated with lower levels of AMH. After adjustment for age, serum AMH levels negatively correlated with insulin, fasting glucose, HOMA-IR and RBP4. However, a positive correlation was identified between serum AMH and adiponectin. A final multiple stepwise linear regression demonstrated that HOMA-IR was independently associated with AMH.
Conclusion  An independent relationship exists between HOMA-IR and AMH in women without PCOS, possibly due to the effect of abnormal insulin action on AMH secretion by granulosa cells.     

Circulating leptin concentrations in polycystic ovary syndrome: relation to anthropometric and metabolic parameters

OBJECTIVE To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17–36 years, body mass index (BMI) 29.9 ± 0.9 kg/m², mean ± SD) and 18 control women (25–47 years, BMI 25 ± 1.7 kg/m²). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations. MEASUREMENTS Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. RESULTS Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 ± 1.3 vs 12.1 ± 2.3 μg/l, mean ± SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. CONCLUSIONS Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.     

Elevated serum RBP4 is associated with insulin resistance in women with polycystic ovary syndrome

Retinol binding protein 4 (RBP4) is a novel adipocyte-secreted protein that contributes to systemic insulin resistance. Experiments in mice suggest that elevated RBP4 causes insulin resistance. In the present study, we determined serum RBP4 concentration and evaluated its association with insulin resistance in women with polycystic ovarian syndrome (PCOS); 39 PCOS women and 45 healthy control subjects were enrolled in this study. Serum RBP4, fasting plasma glucose (FPG) and fasting serum insulin (FINS) were measured in all subjects. Furthermore, oral glucose tolerance test (OGTT), Botnia clamp (an intravenous glucose tolerance test followed by an euglycemic hyperinsulinemic clamp), and measurements of sex hormones were performed in 13 control subjects and all the PCOS women. The levels of serum RBP4 were elevated in PCOS women compared with the control (11.69 +/- 6.72 versus 7.75 +/- 5.96 microg/mL, p = 0.006). RBP4 levels were positively correlated with WHR (r = 0.216, p = 0.048), and intravenous glucose tolerance test beta cell index (IVGTT-beta index) which reflected beta cell function (r = 0.309, p = 0.028), but were inversely correlated with M value during Botnia clamp, which represented insulin sensitivity (r = -0.362, p = 0.008). No correlation was found between RBP4 and age, BMI, blood pressure, FPG, FINS, 2-h postprandial glucose, 2-h postprandial insulin, free testosterone, total testosterone, follicle-stimulating hormone (FSH), or luteinizing hormone (LH). In a linear stepwise regression analysis with a model including age, BMI, WHR, free testosterone, IVGTT-beta index, and M value as independent variables, only M value showed significant correlation with serum RBP4 levels (r2 = 0.105, f = 6.640, p = 0.012). In conclusion, serum RBP4 levels are significantly increased in PCOS women and associated with insulin resistance, which indicates that RBP4 may be a contributing factor linking adipose tissue with insulin resistance in PCOS.     

Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women

Increased total and intraabdominal fat (IAF) obesity as well as other metabolic conditions associated with the insulin resistance syndrome (IRS) are related to low levels of sex hormone-binding globulin (SHBG) in young and older Caucasian (CAU) and young African-American (AA) women. We examined whether postmenopausal AA women, a population with a high incidence of obesity and IRS despite low IAF, would have higher levels of circulating SHBG compared with CAU women, and whether there would be negative relationships between indexes of obesity and risk factors associated with IRS and SHBG levels. We measured body composition, SHBG, free testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55 CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of comparable obesity (48% body fat, by dual energy x-ray absorptiometry). Compared with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9 +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109 cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but similar waist to hip ratio (0.83). Both groups had similar SHBG (117 vs. 124 nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35% higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women SHBG correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = -0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r = 0.30; P = 0.03). The relationship between insulin area and SHBG in CAU women disappeared after adjusting for IAF, whereas the relationship between high density lipoprotein cholesterol and SHBG persisted after adjusting for IAF, but not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both groups, but it was related to insulin only in the Caucasian women (P< 0.01). There was a racial difference in the slopes (P< 0.05) of the relationships of leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after adjustment for fasting insulin. These results suggest that the metabolic relationships between total and regional obesity, glucose, and lipid metabolism with SHBG in CAU women are different from those in postmenopausal obese AA women.     

Hormonal influences on the relationships between body fatness, body fat distribution, lipids, lipoproteins, glucose and blood pressure in French working women

The independent associations between overall obesity, body fat distribution, lipids, lipoproteins, glucose, blood pressure and some hormonal factors (sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG) and fasting insulin) were cross-sectionally examined in 205 French working women. After adjustment for age, overall adiposity assessed by body mass index (BMI) was significantly associated with most metabolic parameters, whereas regional adiposity assessed by the waist-hip ratio (WHR) was significantly associated only with triglyceride, systolic and diastolic blood pressure. Blood pressure, glucose but not triglyceride, were also negatively and significantly correlated with SHBG and positively with fasting insulin. Negative independent associations were found between SHBG and both BMI and WHR, whereas CBG was positively associated only with WHR. Fasting insulin was no longer related to WHR after adjustment for BMI. After controlling for the effect of SHBG or insulin, the associations between triglyceride, blood pressure and both BMI and WHR were not substantially modified. After adjustment for BMI and WHR, fasting insulin was independently associated with both HDL cholesterol and diastolic blood pressure. In conclusion, in these French women, hormonal factors under study appeared to have little influence on the relationships between body fatness, body fat distribution, metabolic variables and blood pressure.     

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.