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.     

Association between Circulating Tumor Necrosis Factor-Alpha, Interleukin-6, and Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome

Background: Insulin resistance is a common finding in both obese and lean women with polycystic ovary syndrome (PCOS). Factors contributing to insulin resistance are still controversial. The purpose of the study was to compare the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations in normal weight women with PCOS and a weightmatched healthy control group, and also to evaluate the role of these cytokines in the pathogenesis of insulin resistance. Methods: Thirty-two women with PCOS and 25 age- and weight-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound. Fasting insulin, glucose, lipid profile, follicle-stimulating hormone (FSH), leutinizing hormone (LH), prolactin, testosterone, sex hormone binding globulin (SHBG), 17-hydroxyprogesterone, IL-6, TNF-alpha concentrations, and insulin sensitiviy indices homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were measured. Results: TNF-alpha and IL-6 concentrations were significantly higher in women with PCOS than in the control group. Significant correlations were found between TNF-alpha serum concentrations and Body Mass Index (BMI), waist circumference, triglyceride concentrations, fasting insulin, and insulin resisitance indices (p < 0.001). IL-6 concentrations were correlated with fasting glucose and insulin resistance (p < 0.05). Conclusions: The study demonstrated that TNF-alpha and IL-6 concentrations were elevated in normal weight women with PCOS. The findings may contribute to evidence of insulin resistance in lean women with PCOS.     

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.     

多囊卵巢综合征α2-HS-糖蛋白水平测定及其意义

目的通过比较多囊卵巢综合征(PCOS)患者与正常对照人群血清中α2-HS-糖蛋白(AHSG)的水平,探讨AHSG在PCOS患者中的临床作用。方法随机选取2007年1～12月在广西医科大学第一附属医院妇科门诊就诊的PCOS患者34例为PCOS组,以月经正常的非PCOS患者27例为对照组。测量其身高、体质量、腰围、臀围、性激素水平、空腹血糖、空腹胰岛素和血脂,计算出体质量指数(BMI)、腰臀比(WHR)、稳态模型的胰岛素抵抗指数(IRI)。ELISA法检测所有研究对象血清中的AHSG水平,并将AHSG与所测临床指标进行多因素分析。结果 P-COS组患者血清AHSG水平高于对照组(P<0.05);IRI值高于对照组(P<0.05)。血清AHSG浓度与IRI、BMI、WHR呈正相关性(P<0.05)。结论 PCOS患者与AHSG、IRI有密切关系,AHSG参与了PCOS患者代谢综合症的发生发展,肥胖的PCOS患者更容易发生胰岛素抵抗。     

多囊卵巢综合征妇女的β-3-肾上腺素能受体基因与胰岛素抵抗的关系

目的探讨β     

Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study

Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35 microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin during a 75-g oral glucose tolerance test; early phase insulin and C-peptide secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment. Metformin did not have any effect on glucose tolerance or insulin sensitivity, but fasting insulin concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P = 0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P = 0.01), and hepatic insulin clearance increased during the treatment. Furthermore, metformin decreased serum testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2 nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any significant effect on glucose tolerance, serum insulin levels, or insulin sensitivity, but it increased slightly the body mass index (P = 0.09) and significantly serum leptin concentrations (P < 0.001) and decreased serum testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on insulin and glucose metabolism also have to be taken into consideration in nonobese subjects. Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with anovulation may also benefit from metformin treatment.     

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.     

Obesity, insulin, sex steroids and ovulation

Obesity is a major feature in women with polycystic ovary syndrome (PCOS), and evidence suggests that obesity contributes to the pathogenesis of PCOS by aggravating the intrinsic insulin resistance of these women. Hyperinsulinemia appears to increase circulating androgens in PCOS by stimulating ovarian androgen production and suppressing serum SHBG, and also appears to play a pathogenic role in the anovulation of the disorder. The use of insulin sensitizing drugs has been shown to decrease serum insulin in both obese and nonobese women with PCOS, and to simultaneously reduce circulating ovarian androgens and to improve ovulation.     

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.     

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。     

多囊卵巢综合征糖代谢异常与性激素结合球蛋白基因启动子(TAAAA)n多态性的关系

目的探讨性激素结合球蛋白（SHBG）基因启动子（TAAAA）n重复多态与多囊卵巢综合征（PCOS）及其糖代谢异常的关系。方法353名正常育龄妇女为对照组，241例PCOS患者中180例接受口服糖耐量试验、胰岛素释放试验并被分为非胰岛素抵抗（NIR）组、高胰岛素血症（HI）组、异常糖代谢（AGM）组；基因片段分析法检测荧光标记多态片段长度，并测序鉴定其重复次数；比较组间临床及代谢参数、（TAAAA）n多态等位基因及基因型分布。结果（1）PCOS组体重指数、腰臀比、腰围、血压、空腹胰岛素、胰岛素抵抗指数（Homa—IR）、甘油三酯水平高于对照组，AGM组高于HI组、NIR组；胰岛素敏感指数变化相反；组间各参数比较差异均有统计学意义（均P〈0．05）。（2）检测到（TAAAA）6～10次重复5种等位基因、14种基因型，但5种等位基因频率和总基因型分布及各基因型分布PCOS组与对照组比较差异无统计学意义。（3）PCOS糖代谢3组间5种等位基因频率和总基因型分布无统计学差异，但3组间7／9基因型分布不同（χ^2=9．671，P〈0．01），AGM组7／9基因型分布频率明显高于NIR、HI组（χ^2=6，792，P〈0．01；χ^2=6．538，P〈0．05）。结论SHBG基因启动子（TAAAA）n重复多态及其分布与PCOS无明显相关，但（TAAAA）n多态7／9重复基因型与PCOS糖代谢异常发生、进展可能有关。PCOS糖代谢异常可能与肥胖等其他因素相关。故该SHBG基因多态性并不能预测PCOS的高危个体。     

Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome

Racial origin and family history of type 2 diabetes impact upon the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes, both of which are common in women with polycystic ovary syndrome (PCOS). We examined the effects of race and family history of type 2 diabetes on the risk of IGT and type 2 diabetes in a large cohort of women with PCOS. Data obtained at baseline were analyzed from 408 premenopausal women with PCOS. Multivariate linear regression models were used to assess the impact of race (white, black, and other) and family history of type 2 diabetes on body mass index, waist circumference, and waist to hip ratio; glycemic measures (glucose and insulin levels obtained during a standard 75-g oral glucose tolerance test, fasting glucose to insulin ratio, and homeostasis model assessment model of insulin resistance derived from fasting levels of glucose and insulin), hemoglobin A(1c), and SHBG, and dehydroepiandrosterone sulfate levels. Sixteen (4%) of the 408 patients had type 2 diabetes, 94 (23%) had IGT, and the remaining 298 (73%) had normal glucose tolerance. A history of type 2 diabetes in either parent (FHxPOS) was present in seven (44%) of the 16 diabetic women with PCOS, 37 (39%) of the 94 women with IGT, and 62 (21%) of those with normal glucose tolerance (P < 0.01, by chi(2) test). The prevalences of IGT and type 2 diabetes were significantly higher in FHxPOS PCOS women compared with FHxNEG PCOS women, IGT evident in 37 (35%) FHxPOS compared with 57 (19%) FHxNEG women, and type 2 diabetes evident in seven (7%) FHxPOS compared with nine (3%) FHxNEG women. Among the 392 nondiabetic subjects, after adjustment for the effects of race, FHxPOS differed significantly from FHxNEG patients in having a higher mean waist to hip ratio, hemoglobin A(1c) level, 2-h glucose level, fasting glucose and insulin levels, glucose to insulin ratio, homeostasis model assessment model of insulin resistance, and areas under the glucose and insulin curves during the oral glucose tolerance test. A family history of type 2 diabetes was present with a significantly greater frequency among women with PCOS who had IGT or type 2 diabetes compared with those with normal glucose tolerance. Conversely, a family history of type 2 diabetes in a first-degree relative was associated with a significantly higher risk for IGT or type 2 diabetes in women with PCOS. Even among nondiabetic women with PCOS, a positive family history of type 2 diabetes was strongly associated with metabolic characteristics associated with an increased risk for type 2 diabetes. Finally, the fasting glucose concentration was poorly associated with 2-h glucose concentrations among PCOS women with IGT, suggesting that the fasting glucose concentration is inadequate to predict the presence of IGT in PCOS.     

Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial function in non-obese young women with polycystic ovary syndrome

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit elevated levels of serum C-reactive protein (CRP) and impaired endothelium dysfunction which are directly correlated with insulin resistance. Because rosiglitazone improves insulin sensitivity, we tested whether rosiglitazone treatment ameliorates high-sensitivity (hs)CRP levels and endothelial dysfunction in these patients. DESIGN: Thirty-one women with PCOS were recruited (mean age, 24.7+/-3.9 (s.e.) years; mean body mass index (BMI), 25.6+/-3.2 kg/m2). All women were treated with 4 mg rosiglitazone daily for 12 months. METHODS: Serum levels of testosterone, LH, FSH, sex hormone-binding globulin (SHBG), insulin and hsCRP were measured. The BMI, hirsutism scores and insulin sensitivity indices were calculated before and after treatment. Arterial endothelium and smooth muscle function was measured by examining brachial artery responses to endothelium-dependent and endothelium-independent stimuli before and after treatment. RESULTS: After treatment with rosigitazone there were significant decreases in serum testosterone (91.2+/-37.5 vs 56.1+/-21.8 ng/dl; P < 0.01) and fasting insulin concentrations (12.5+/-7.6 vs 8.75+/-4.03 microU/ml; P = 0.015). Insulin resistance indices were significantly improved after rosiglitazone treatment (P < 0.05). There were no significant changes in BMI, waist circumference, serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, FSH and LH levels. Hirsutism score was decreased significantly after treatment (10.8+/-1.8 vs 7.6+/-1.7; P < 0.05). Twenty-four of the women reverted to regular menstrual cycles. Levels of SHBG increased significantly after treatment (28.7+/-8.7 vs 48.4+/-11.2 nmol/l; P < 0.01). Serum hsCRP levels were decreased significantly after rosiglitazone treatment (0.25+/-0.1 vs 0.09+/-0.02 mg/dl; P = 0.006). There was also significant improvement in endothelium-dependent vascular responses after rosiglitazone treatment (9.9+/-3.9 vs 16.4+/-5.1%; P < 0.01). CONCLUSIONS: We conclude that rosiglitazone treatment improves insulin sensitivity in women with PCOS. It also decreases androgen production without significant weight gain. More importantly, it has beneficial effects on endothelial dysfunction and low-grade chronic inflammation in normal weight young women with PCOS.     

Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P 相似文献   

The metabolic syndrome in young Korean women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and consequent hyperinsulinemia. Insulin resistance also plays an important role in the metabolic syndrome (MS). We conducted a cross-sectional study to determine the prevalence of the MS in young Korean women with PCOS and whether it is associated insulin resistance. One hundred and seventeen young women with PCOS (age: 26+/-5, 16-39 years) were evaluated for the frequency of MS according to the modified Adult Treatment Panel III. Total testosterone (T), free T, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured, and insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp technique. The prevalence of MS in women with PCOS was 14.5%, nearly 3.5-fold higher than in age-matched women in Korean urban population (4.3%) [J.-Y. Oh, Y.-A. Sung, Y.S. Hong, E. Barrett-Conner, Prevalence and factor analysis of metabolic syndrome in an urban Korean population, Diabetes Care 27 (2004) 2027-2032]. The most frequently occurring component of MS was low HDL cholesterol (45%), and the least frequent was high fasting serum glucose level (0.9%). PCOS women with MS had significantly higher free T, and lower SHBG compared with those without MS. And women with MS showed significantly lower M-value and higher fasting/post-glucose load insulin levels. M-value was still significantly lower in women with MS even after the adjustment for BMI. MS is frequent in young Korean women with PCOS and it reflects more severe insulin resistance. These results suggest the importance of early and regular screening of metabolic disturbance in even young women with PCOS.     

Insulin sensitivity and hyperprolactinemia

It has been shown that prolactin (PRL) induces glucose intolerance, hyperinsulinemia and insulin resistance in several animal species. In women with microprolactinomas, the sensitivity to insulin is lower in hyperprolactinemia than in normoprolactinemia. Thirty non-obese women with hyperprolactinemia and 30 healthy non-obese women were included into the study. Age, body weight (bw), height, body mass index (BMI), waist circumference, hip circumference and waist to hip ratio of both patients with hyperprolactinemia and control subjects were not different. Mean serum prolactin level was higher in hyperprolactinemic patients than in control group (84.5 +/- 51.1 ng/ml and 13.8 +/- 5.3 ng/ml respectively, p<0.002). Mean HOMA-(%B) index of hyperprolactinemic patients was higher than in control subjects (121 +/- 49 and 84 +/- 38, respectively, p<0.02). Mean HOMA-(%S) index was lower in hyperprolactinemic patients (56 +/- 39 and 105 +/- 55, respectively, p<0.006). Serum total testosterone, free testosterone, androstenedione, estradiol, cortisol, sex hormone binding globulin and DHEA-S levels in both hyperprolactinemic women and healthy subjects, statistically did not show any difference between the two groups. The present data indicate that hyperprolactinemia is associated with an insulin-resistant state. This resistant state may not be a result of obesity, androgenic hormones, and SHBG or pregnancy. It may be the result of serum free fatty acids (FFA) levels, decrement in the number of insulin receptors (by a down-regulation of insulin receptors) or post-binding defect in insulin action or more.     

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?     

Association of sex hormone-binding globulin and insulin resistance among Japanese-American subjects

An association between sex hormone-binding globulin (SHBG) and insulin resistance expressed by the homeostasis model (HOMA-R), and the significance of both variables as risk factors for the development of type 2 diabetes were investigated in 483 Japanese-American subjects. The serum SHBG level was significantly higher in women (68.7 nmol/l) than in men (45.1 nmol/l). This difference was also significant independently of age, body mass index (BMI), waist to hip ratio (WHR), and HOMA-R. When multiple regression analysis was performed after adjustment for age and BMI, SHBG was not correlated with HOMA-R in men. In women, SHBG was not significantly correlated with HOMA-R after adjustment for age, BMI, and WHR. In a 3-year prospective analysis, HOMA-R was significantly higher in converters to type 2 diabetes than non-converters in both men and women which was independent of age, BMI and WHR. However, after adjusting these variables, SHBG was not a significant risk factor either in men or women. These results indicate that SHBG might be related to insulin resistance secondarily via BMI and/or WHR in both men and women among Japanese-Americans. HOMA-R is a useful index for both men and women as a risk factor of type 2 diabetes when only fasting blood samples can be obtained.     

Mitochondrial DNA copy number in peripheral blood in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and various metabolic diseases; and recently, elevated oxidative stress has been detected in PCOS. Mitochondria are highly susceptible to oxidative damage; and disordered mitochondrial function at the cellular level can impact whole-body metabolic homeostasis, leading to the hypothesis that abnormalities in markers of mitochondrial metabolism are related to PCOS. We compared mitochondrial DNA (mtDNA) copy number in women with and without PCOS and investigated the independent relationship between mtDNA copy number and PCOS after adjustment for metabolic parameters. Fifty women with PCOS and 60 age- and body mass index–matched healthy women were studied. Mitochondrial DNA copy numbers as well as metabolic parameters and indices of insulin resistance were assessed. Mitochondrial DNA copy numbers were significantly lower in women with PCOS (P < .01). In the PCOS group, mtDNA copy number was negatively correlated with indices of insulin resistance, waist circumference, and triglyceride levels and positively correlated with sex hormone–binding globulin levels. In multiple logistic regression, the corresponding odds ratios (95% confidence interval) for PCOS by log-transformed mtDNA copy number and homeostasis model assessment of insulin resistance were 0.15 (0.04-0.56) and 4.26 (1.43-12.68), respectively, after adjustment for age, body mass index, and other metabolic factors. We report decreased mtDNA copy numbers in PCOS patients in relation to controls independently of insulin resistance or other metabolic factors. The pathophysiological and clinical significance of this finding requires further investigation.     

Interrelationship between insulin resistance and menopause on the metabolic syndrome and its individual component among nondiabetic women in the kinmen study

BACKGROUND: The literature to date is not clear as to whether any interactive effect exists between insulin resistance and menopause on the metabolic syndrome and its individual components. We explored this issue in 4107 homogeneous, nondiabetic Chinese women in the Kinmen Study. METHODS: Overnight fasting blood samples were drawn for glucose, insulin, lipid, and other biochemical measurements. Demographic and clinical variables including body mass index, waist circumference, and blood pressure were measured and documented during face-to-face interviews with structured questionnaires. Menstrual history was used to define menopause as the absence of menses for 12 consecutive months. RESULTS: Approximately 16% of premenopausal women (390/2423) were insulin-resistant. After adjustment for age, body mass index, lifestyle, and diet, both menopause and insulin resistance were independently and significantly correlated with metabolic syndrome. For each component of the metabolic syndrome, besides the main effect, the interaction (insulin resistance x menopause) had significant correlation with systolic blood pressure, diastolic blood pressure, and waist circumference. CONCLUSIONS: Both insulin resistance and menopause have significant effects on metabolic syndrome independent of age and obesity. In premenopausal and nondiabetic women, various degrees of insulin resistance exist. The synergistic contribution of insulin resistance and menopause to components of the metabolic syndrome were observed with systolic blood pressure, diastolic blood pressure, and waist circumference. This requires further study.