Adipocyte resistin mRNA levels are down-regulated by laparoscopic ovarian electrocautery in both obese and lean women with polycystic ovary syndrome

BACKGROUND: The aim of this study was to investigate serum and adipocyte mRNA expression of resistin in lean and obese women with polycystic ovary syndrome (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE). METHODS: Adipose tissue obtained from 12 women with PCOS (six obese and six lean, body mass index > 27 kg m(-1) as threshold point) before and after LOE was analysed. Gene expression of resistin was measured by semi-quantitative RT-PCR. Ten lean, age-matched healthy women served as controls. RESULTS: Both lean and obese women with PCOS had significantly higher fasting and 2 h insulin and homeostasis model insulin resistance index (HOMA(IR)) values and lower fasting glucose-to-insulin ratios (G(0)/I(0)) than did the controls. The serum levels of glucose and insulin and HOMA(IR) were significantly decreased, and the G(0)/I(0) ratio was significantly increased 3 months after LOE. No difference was found in serum resistin levels between controls and either obese or lean women with PCOS before LOE, nor between PCOS patients before and after LOE. However, resistin mRNA expression levels in both lean and obese women with PCOS before LOE were significantly higher than that in controls and were decreased significantly after LOE back to control levels. CONCLUSION: Local resistin activity may be actively involved in the pathogenesis of PCOS. LOE reduces insulin resistance and down-regulates resistin mRNA expression in lean and obese women with PCOS.     

Serum and adipocyte resistin in polycystic ovary syndrome with insulin resistance

BACKGROUND: The aim of this study was to investigate the relationship between resistin and insulin resistance in patients with polycystic ovary syndrome (PCOS). METHODS: We compared serum resistin levels in 17 PCOS women and 10 lean, healthy, age-matched non-PCOS women and also compared levels of insulin receptor (IR), phosphatidylinositol-3 kinase (PI3-kinase), glucose transporter 4 (GLUT4) protein and resistin mRNA in adipocytes isolated from the omental adipose tissue of five of the PCOS patients and five age- and weight-matched, non-PCOS controls, to look for local defects in insulin action in PCOS. RESULTS: The PCOS group was hyperinsulinaemic and displayed an impaired insulin response in a 75 g oral glucose tolerance test and an abnormal homeostasis model insulin resistance index. Serum resistin levels were similar in PCOS patients and controls; however, resistin mRNA levels were 2-fold higher in adipocytes from PCOS patients. No correlation was found between serum resistin levels and either the BMI or testosterone levels. Western blot analysis showed that adipocyte levels of insulin receptor, PI3-kinase, and GLUT4 were respectively decreased by 56, 39.4 and 54% in PCOS patients compared with controls. CONCLUSIONS: These results suggest that overexpression of the resistin gene in adipocytes may be a local determinant factor in the pathogenesis of PCOS.     

Serum and follicular resistin levels in women with polycystic ovarian syndrome during IVF-stimulated cycles

BACKGROUND: Resistin is a hormone linking obesity and insulin resistance. The aim of this study was to compare resistin levels in serum or follicular fluid from women with polycystic ovarian syndrome (PCOS) and controls, both of whom were undergoing IVF. METHODS: We compared serum and follicular resistin levels in 21 PCOS women and in 18 healthy, normal ovulation, age- and body mass index (BMI)-matched non-PCOS women undergoing IVF. Correlations between serum or follicular fluid resistin levels and reproductive outcome were evaluated. RESULTS: There was no significant difference in either serum or follicular resistin levels between the control group and the PCOS group as a whole or those with insulin resistance [homeostasis model assessment of insulin resistance index applied to oral glucose tolerance test (HOMA(OGTT)) <4.7]. However, resistin levels in follicular fluid were unexpectedly significantly lower than serum levels (P<0.0001) in both the PCOS and control groups. No significant correlation was found between resistin levels and BMI, estradiol, LH, or fasting or 2 h glucose or insulin levels or between follicular resistin levels and fertilization rate, implantation rate, clinical pregnancy rate, or early miscarriage rate in PCOS. CONCLUSION: Resistin is unlikely to be a major determining factor in the growth and maturation of oocytes during IVF-stimulated cycles in PCOS.     

The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome

BACKGROUND: Oxidative stress and hyperhomocysteinaemia are risk factors for cardiovascular diseases. The aim of this study was to assess the effects of rosiglitazone and metformin on cardiovascular disease risk factors such as insulin resistance, oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome (PCOS). METHODS: Fifty lean patients (BMI <25 kg/m2) with PCOS and 35 healthy subjects were included this study. Serum homocysteine, sex steroids, fasting insulin, fasting glucose and lipid levels were measured. Total antioxidant status (TAS; combines concentrations of individual antioxidants) and malonyldialdehyde concentration (MDA) were determined. Insulin resistance was evaluated by using the homeostasis model insulin resistance index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Area under the curve insulin (AUCI) and the insulin sensitivity index (ISI). Patients were divided into two groups. One group was treated with metformin (n = 25) and the other received rosiglitazone (n = 25) for 12 weeks. All measurements were repeated at the end of 12 weeks. RESULTS: Compared with healthy women, those with PCOS had significantly elevated serum MDA, homocysteine, HOMA-IR, AUCI and lipoprotein a levels, and significantly decreased serum TAS, QUICKI and ISI. Serum free testosterone levels showed a significant positive correlation with MDA, AUCI and HOMA-IR, and a negative correlation with TAS, ISI and QUICKI in PCOS patients. HOMA-IR and AUCI significantly decreased, while QUICKI and ISI significantly increased after treatment in both groups. Serum TAS level increased and serum MDA level decreased after the rosiglitazone treatment, but these parameters did not change after the metformin treatment. Serum homocysteine and lipid levels did not change in either group, while serum androgen levels and LH/FSH ratio significantly decreased after the treatment period in only the rosiglitazone-treated group. CONCLUSION: Elevated insulin resistance, oxidative stress and plasma homocysteine levels and changes in serum lipid profile (risk factors for cardiovascular disease) were observed in lean PCOS patients. Rosiglitazone seemed to decrease elevated oxidative stress when compared with metformin treatment in lean PCOS patients.     

Abnormal glucose tolerance in Chinese women with polycystic ovary syndrome

BACKGROUND: The aims of this study were to analyse the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (NIDDM) in Chinese polycystic ovary syndrome (PCOS) patients and to assess the ability of screening tests to predict these abnormalities within this population. METHODS: A total of 102 PCOS patients were evaluated. All patients underwent oral glucose tolerance tests (OGTTs) with blood samples taken at 0, 1 and 2 h. The 2-h plasma glucose level was used to categorize subjects as having IGT or NIDDM. RESULTS: The prevalence of IGT was 20.5% and that of NIDDM was 1.9%. There was no significant relationship between BMI and 2-h plasma glucose levels. The areas under the receiver operating characteristic (ROC) curve for glucose to insulin ratio (G:I), homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were 0.702, 0.734 and 0.733 respectively. ROC analysis suggested a threshold value of 10.7 in G:I ratio (73.9% sensitivity and 59.5% specificity), a value of 2.14 in HOMA (73.9% sensitivity and 73.4% specificity) and a value of 0.34 in QUICKI (73.9% sensitivity and 73.4% specificity) for the prediction of abnormal glucose tolerance (IGT and NIDDM). CONCLUSIONS: Chinese women with PCOS are at increased risk of IGT and NIDDM. Even though G:I, HOMA and QUICKI are easier than OGTT, they could not replace the role of 2-h post-challenge plasma glucose level in the screening of IGT and NIDDM in PCOS women.     

Adiponectin and resistin serum levels in women with polycystic ovary syndrome during oral glucose tolerance test: a significant reciprocal correlation between adiponectin and resistin independent of insulin resistance indices

Polycystic ovary syndrome (PCOS) is associated with an increased incidence of insulin resistance (IR), obesity, and type 2 diabetes. Resistin, an adipocytokine, may represent a link between obesity, and these metabolic disorders. There is also evidence that inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states. In contrast, adiponectin, increases insulin sensitivity, improves glucose tolerance, inhibits inflammatory pathways, while adenovirus-expressed adiponectin reduces atherosclerotic lesions in a mouse model of atherosclerosis. We aimed to assess, in women with PCOS, whether there is a relationship between adiponectin and resistin and the indices of IR, and whether serum levels of these adipocytokines are altered by glucose-induced hyperinsulinaemia. Serum levels of resistin and adiponectin were measured at 0, 60, and 120 min during 75 g oral glucose tolerance test (OGTT), in 19 women with PCOS, age 36.3+/-11.4 years (mean+/-SD), body mass index (BMI) 29.3+/-7.7 kg/m2, and correlated with the indices of IR, such as HOMA-IR, QUICKI, and the insulin resistance index calculated from glucose and insulin levels obtained during OGTT. There was no change in resistin concentrations (7.31+/-4.58, 7.47+/-5.40, 7.22+/-5.12 pg/ml, at 0, 60, and 120 min of OGTT, respectively, P = 0.77), but there was an increase in adiponectin from 11.32+/-4.64 microg/ml at baseline to 14.78+/-7.41 microg/ml, at 120 min of OGTT (P < 0.01). The magnitude of the overall rise in adiponectin was greater from 60 to 120 min (from 12.31+/-5.72 to 14.78+/-7.41 microg/ml, P < 0.006). Neither resistin, nor adiponectin correlated with the indices of IR, lipids, or other hormonal parameters of the PCOS. There was, however, a significant negative correlation between serum resistin and adiponectin (P = 0.001). In conclusion, we observed a strong negative correlation between serum adiponectin and resistin, despite the lack of direct correlation with the indices of IR. Given the opposite effects of resistin and adiponectin on the inflammatory process, we speculate that relative proportion of adiponectin-to-resistin might potentially influence cardiometabolic risk in women with the PCOS independently of IR parameters. The observed increase in adiponectin during OGTT requires further study.     

Adiponectin and resistin in PCOS: a clinical, biochemical and molecular genetic study

BACKGROUND: We conducted a cross-sectional case-control study to evaluate the possible involvement of adiponectin and resistin in the pathogenesis of polycystic ovary syndrome (PCOS). METHODS: Seventy-six PCOS patients and 40 non-hyperandrogenic women matched for BMI and degree of obesity were included. Serum adiponectin and resistin levels, anthropometrical and hormonal variables, the 45 T-->G and 276 G-->T polymorphisms in the adiponectin gene, and the -420 C-->G variant in the resistin gene, were analysed. RESULTS: Serum adiponectin concentrations were reduced in PCOS patients compared with controls (P = 0.038) irrespective of the degree of obesity, whereas serum resistin levels were increased in overweight and obese women compared with lean subjects (P = 0.016), irrespective of their PCOS or controls status. The adiponectin and resistin polymorphisms were not associated with PCOS and did not influence serum levels of adiponectin, resistin and other clinical and hormonal variables. In a multiple regression model, the waist-to-hip ratio, free testosterone levels and age, but not insulin resistance, were the major determinants of hypoadiponectinaemia. CONCLUSIONS: PCOS patients present with hypoadiponectinaemia, in relation with abdominal adiposity and hyperandrogenism. Our present results suggest that hyperandrogenism and abdominal obesity, by reducing the serum levels of the insulin sensitizer adipokine adiponectin, might contribute to the insulin resistance of PCOS.     

Evidence of subpopulations with different levels of insulin resistance in women with polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) is non-uniformly associated with insulin resistance (IR). We examined IR in women with PCOS. METHODS: Sixty-nine PCOS women were subjected to the insulin suppression test (IST) to determine their steady-state plasma glucose (SSPG) as a direct measure of insulin sensitivity. RESULTS: SSPG exhibited a multimodal distribution suggesting the existence of subpopulations. The heterogeneous distribution of plasma glucose at 180 min (P = 0.011), with three modes, suggested differences in the plasma glucose level trajectories during the IST. Hence, the population was separated into three groups: (i) (n = 33), subjects with SSPG < or = 152.5 mg/dl, corresponding to the first to fifth deciles; (ii) (n = 29), subjects in the interval 152.5 mg/dl < SSPG < or = 300 mg/dl; (iii) (n = 7), subjects with SSPG > 300 mg/dl, corresponding to the tenth decile. Plasma glucose distributions at 180 min showed differences in their mean values and ranges among groups (P < 0.0001). The trajectories of the groups differed significantly during the IST (P < 0.0001). CONCLUSIONS: insulin sensitivity in our patients exhibited a discontinuous distribution, implying that PCOS is a heterogeneous disorder possessing subpopulations regarding IR.     

多囊卵巢综合征女性一级亲属胰岛素抵抗及高雄激素血症的临床分析

目的检测多囊卵巢综合征（PCOS）一级亲属的胰岛素及雄激素水平,进一步分析其胰岛素抵抗或高雄激素血症的发病情况。方法选择50例PCOS一级亲属为实验组,50例无PCOS家族史的正常健康者作为对照组,检测两组胰岛素、血脂、血糖、瘦素以及生殖激素睾酮、雄烯二酮水平情况。结果与正常对照组相比,PCOS一级亲属血脂、血糖明显高于对照组,胰岛素敏感性指数降低,胰岛素抵抗指数显著升高（P〈0．05）;游离睾酮、雄烯二酮与对照组差异明显,明显高于正常水平（P〈0．05）,血清瘦素水平与正常组间无明显差异。结论PCOS女性一级亲属较正常健康者更易诱发胰岛素抵抗及高雄激素血症,更容易并发PCOS。     

Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls

BACKGROUND: We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index. RESULTS: No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 +/- 60 versus 95 +/- 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 +/- 2.1 versus 3.1 +/- 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 +/- 2.1 versus 7.1 +/- 2.1 mmol/l, P = 0.042 and 7.0 +/- 2.1 versus 6.0 +/- 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels. CONCLUSIONS: The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.     

Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. METHODS: Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. RESULTS: Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). CONCLUSIONS: Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.     

Leptin, soluble leptin receptor, adiponectin and resistin in relation to OGTT in overweight/obese postmenopausal women

OBJECTIVE: In obese postmenopausal women with normal glucose metabolism (NGT) and impaired glucose tolerance (IGT) we assessed serum leptin, adiponectin, resistin, soluble leptin receptor (sOB-R) during oral glucose tolerance test (OGTT) in order to investigate their response to acute changes in glucose and insulin in the abnormal glucose metabolism, as it is early detected by IGT. METHODS: Thirty in total, overweight/obese postmenopausal women, were included in the study: 15 with NGT and 15 with IGT as it was diagnosed by OGTT. Serum glucose and insulin levels were measured at 30 min intervals, leptin, sOB-R, adiponectin and resistin at 60 min intervals during the 120 min OGTT. RESULTS: In fasting state, leptin, adiponectin, resistin and sOB-R levels did not differ between the two groups. In women with NGT, leptin was positively correlated with BMI, insulin and HOMA, and negatively correlated with QUICKI and with sOB-R; adiponectin was negatively correlated with insulin and HOMA and positively correlated with QUICKI. In women with IGT, resistin was positively correlated with BMI and waist circumference. In both groups, sOB-R was negatively correlated with insulin. During OGTT, in both groups, leptin concentration increased significantly and fasting glucose predicts significantly serum leptin change; there was no change in adiponectin, resistin and sOB-R concentrations. CONCLUSION: In overweight/obese postmenopausal women fat distribution does not affect leptin and adiponectin production. Abnormal glucose metabolism is not accompanied by disturbance in adipokines production. Leptin secretion is acutely regulated by glucose levels in insulin presence.     

Prevalence of islet cell antibodies and its correlation with glucose and insulin response to oral glucose tolerance test in 1st degree relatives of insulin dependent diabetes mellitus probands

93 first degree relatives (1st DR) of insulin dependent diabetes mellitus (IDDM) patients were investigated for detection of islet cell antibodies (ICA) and beta cell functional status. ICA were detected in 26.9% Ist DR subjects (25/93), equally in parents, siblings and offspring. Normal (n = 16), impaired (n = 5) and diabetic (n = 4), glucose curves were seen in 1st DR. Low insulin levels were observed in parents and siblings with normal glucose tolerance test (N-GTT) at 90 min (p < 0.05), and (p < 0.0005) relatives with impaired glucose tolerance and diabetes. Insulin release to glucose (IRG-insulinogenic index) in control group was 352 +/- 42 mu U/mg. From the group of 25 ICA positive cases, 4 had mean IRG of 394 +/- 70 mu U/mg (group A) comparable to control, and had N-GTT; 12 had mean IRG of 107 +/- 15.9 mu U/mg (group B) significantly low (P < 0.005) compared to controls and group A and 9 showed IRG of 75 +/- 29.3 mu U/mg, lower than group B (NS) with abnormal response to glucose load. Loss of insulin secretory ability thus can precede hyperglycemia by years. The ICA positive relatives were grouped based on the immunological status with their probands. ICA status in probands does not give an idea about ICA status in their relatives. This indepth study leads to understand the correlation of genetic, metabolic and immunological parameters for early detection of IDDM in first degree relatives.     

肥胖对不同糖耐量者第一时相胰岛素分泌功能的影响

 目的： 探讨肥胖对不同糖耐量人群第一时相胰岛素分泌功能的影响。方法： 无糖尿病家族史的正常糖耐量者(正常对照,NC)38例、2型糖尿病一级亲属正常糖耐量(NGT)者32例、糖调节受损(IGR)者67例及新诊断的2型糖尿病(T2DM)患者35例参与本试验。这4个组再分为超重/肥胖及正常体重2个亚组。各组均行静脉葡萄糖耐量试验（IVGTT）和口服葡萄糖-胰岛素释放试验（OG-IRT）,计算第一时相胰岛素分泌功能指数(AlR3-5)及胰岛素敏感性指数（ISI）,分析肥胖对不同糖耐量人群胰岛β细胞功能及胰岛素抵抗的影响。结果： NC超重/肥胖亚组较正常体重亚组AIR3-5显著升高（P<0.05）,其余3对亚组间比较差异均无统计学意义（均P>0.05）。超重/肥胖亚组ISI较正常体重亚组有降低趋势,其中IGR两亚组间比较差异无统计学意义（P>0.05）,其余3对亚组间比较差异均有统计学意义（均P<0.05）。ISI与体重指数和腰围在各组均呈负相关（P<0.05）,与AIR3-5在NC组呈负相关（P<0.05）,而在其余各组均呈正相关（均P<0.05）。结论： 肥胖对不同糖耐量人群胰岛β细胞分泌功能影响各不相同。无糖尿病家族史的正常糖耐量者随着胰岛素抵抗的加重,第一时相胰岛素分泌功能代偿性增加,而2型糖尿病一级亲属正常糖耐量者、糖调节受损者和2型糖尿病患者则不能代偿性增加。     

Rosiglitazone and ethinyl estradiol/cyproterone acetate as single and combined treatment of overweight women with polycystic ovary syndrome and insulin resistance

BACKGROUND: Few studies have evaluated insulin sensitizers in comparison/association with oral contraceptives (OC) in women with polycystic ovary syndrome (PCOS) with insulin resistance (IR). This study assessed the effects of a thiazolidinedione versus an anti-androgenic estrogen-progestin followed by their sequential combinations in overweight PCOS women. METHODS AND RESULTS: Twenty-eight candidates in whom elevated insulin was not normalized after 4 months of diet were randomly assigned to 6 months of rosiglitazone 4 mg/day or to ethinyl estradiol 35 mg/cyproterone acetate 2 mg (EE/CPA: 21/28 days cycle). Each group then received both medications for another 6 months. Rosiglitazone reduced insulin, IR indices [homeostasis model assessment (HOMA) and quantitative sensitivity check index (QUICKI)] and the insulin area under the curve in response to an oral glucose tolerance test (OGTT), but had limited effect on lipids, androgens and hirsutism. EE/CPA did not modify insulin and OGTT response but increased high-density lipoprotein cholesterol and triglycerides and decreased androgens and hirsutism. Similar changes occurred during combined treatments. End results were highly significant in combined groups without noticeable side-effects or changes in safety parameters. CONCLUSIONS: In obese PCOS women with high insulin not corrected by diet, the combination of rosiglitazone and EE/CPA may be used to achieve complementary beneficial effects on endocrine-metabolic anomalies and clinical symptoms.     

内脂素、抵抗素在妊娠期糖尿病发病中的作用

目的探讨新近发现的两种脂肪细胞因子——内脂素和抵抗素,与胰岛素抵抗的关系及其在妊娠期糖尿病(GDM)发病中的作用。方法采用病例对照的研究方法,通过检测40例GDM孕妇和40例正常孕妇的血清内脂素(Visfa-tin)、抵抗素(Resistin)空腹血糖(FPG)和空腹胰岛素(FINS)水平,计算HOMA稳态模型胰岛素抵抗指数(IRI),比较两组胰岛素抵抗程度的差异,并进一步分析内脂素、抵抗素与胰岛素抵抗之间的关系及其在GDM发生过程中所起的作用。结果 (1)GDM组的血清内脂素、抵抗素、空腹血糖(FPG)、空腹胰岛素(FINS)和胰岛素抵抗指数(IRI)均明显高于对照组(P<0.01)。(2)相关分析表明:GDM孕妇的血清内脂素、抵抗素均与胰岛素抵抗指数(IRI)呈显著正相关(r=0.568,0.618,P=0.000),而内脂素与抵抗素之间亦呈密切正相关(r=0.919,P=0.000)。结论 (1)GDM孕妇的血清内脂素、抵抗素水平较正常孕妇明显增高。(2)内脂素、抵抗素均与胰岛素抵抗呈正相关。(3)血清内脂素、抵抗素水平增高以及二者对胰岛素敏感性调节所产生的综合效应是诱导妊娠期糖尿病发生或促进其发展的重要因素。     

Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome

To study the contributions of body mass, body fat distribution and family history of type 2 diabetes mellitus to hyperinsulinaemia, insulin secretion and resistance in polycystic ovarian syndrome (PCOS), 17 lean (LC) and 17 obese (OC) healthy control subjects, and 15 lean (LPCOS) and 28 obese (OPCOS) women with PCOS were investigated. Waist:hip ratio (WHR), serum concentrations of sex steroids, glucose and insulin during a 75 g oral glucose tolerance test (OGTT), and insulin and C-peptide early phase secretion, and insulin sensitivity index using a euglycaemic hyperinsulinaemic clamp were assessed. The PCOS subjects had a higher mean WHR than the controls. A trend towards hyperinsulinaemia and impairment of insulin sensitivity (including the rates of both glucose oxidation and non-oxidation) was observed in LPCOS subjects, but only in OPCOS subjects were these changes significant. Early phase insulin secretion but not the early phase C-peptide secretion was increased in PCOS subjects compared to controls, suggesting that peripheral hyperinsulinaemia in PCOS women was mainly due to the observed lowered hepatic insulin extraction and insulin resistance in skeletal muscle. Moreover, the presence of a family history of type 2 diabetes did not affect early phase insulin or C-peptide secretion in the PCOS group. These results confirm and strengthen earlier contentions, that insulin resistance is a characteristic defect in PCOS and is worsened particularly by abdominal obesity.     

Adipocytokine Levels in Obese and Non-obese Subjects: an Observational Study

We evaluated the levels of some inflammatory adipocytokines in 363 obese and 365 non-obese subjects. We measured: body mass index (BMI), waist circumference (WC), fasting plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, blood pressure, lipid profile, retinol binding protein-4 (RBP-4), vaspin, omentin-1, leptin, interleukin-6 (IL-6), visfatin, resistin, adiponectin (ADN), adipsin, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (Hs-CRP). We observed higher BMI, WC, FPI, HOMA index, TC, LDL-C, RBP-4, leptin, IL-6, adipsin, Hs-CRP, vaspin, resistin and TNF-α levels, and lower visfatin, and ADN levels in obese compared to non-obese subjects. Higher WC correlated with lower ADN and visfatin levels, and higher vaspin levels. Higher HOMA index correlated with higher resistin, adipsin, RBP-4, and leptin concentrations, while higher leptin levels correlated with higher TNF-α, Hs-CRP, and IL-6 concentration, and lower ADN values. We confirmed obese subjects’ predisposition to develop dysmetabolic disease and hormonal dysfunctions.     

Dyslipidaemia in poly cystic ovarian syndrome: different groups, different aetiologies?

The objective was to study the pathophysiology of the dyslipidaemiain polycystic ovarian syndrome (PCOS) patients, and to determinehow it is related to hyperinsulin-aemia, hyperandrogenism anddehydroepiandrosterone sulphate (DHEA-S) concentrations. Thelipoprotein lipid profile, anthropometric measurements, endocrineprofile and the presence of insulin resistance were evaluatedin 31 PCOS patients and 20 age-matched healthy women, who servedas controls. PCOS patients had higher fasting insulin concentrations,higher body mass indexes (BMI) and were hyperlipidaemic, withhigher total cholesterol, low density lipoprotein (LDL) andtriglyceride (TG) concentrations. There were no relationshipsbetween plasma lipids and anthropometric variables in the patientgroup as a whole. Insulin-resistant (IR) and non-ER (NIR) PCOSpatients were then evaluated separately. Obesity with markedhyperandrogenism were the predominant features in patients withIR. NIR patients were not obese and had significantly less hyperandrogenism.The adrenal androgen DHEA-S was at the upper limit of its normalrange in both groups. However, both PCOS subgroups exhibitedsimilar significant abnormalities in terms of their lipid parameters.Insulin and DHEA-S concentrations were positively correlatedwith total cholesterol, LDL and TG, and negatively correlatedwith high density lipoprotein, in IR patients. In NIR subjects,insulin was not correlated with any of the lipids and DHEA-Swas negatively related to cholesterol and LDL. Anthropometricvariables were related to lipids in only the NIR patients. ThusPCOS subjects as a group exhibit dyslipidaemia, characterizedby increased total cholesterol, LDL and TG concentrations. Whendivided into IR and NIR subjects, there were no differencesin the degree of lipid abnormalities, despite significant variationsin the BMI and androgen status. Thus, in PCOS subjects, dyslipidaemiamay occur irrespective of insulin resistance. Insulin and DHEA-Sconcentrations were positively correlated with an atherogeniclipid profile in the IR group only. As distinct from syndromeX when IR was present, dyslipidaemia was not related to bodyweight or the waist:hip ratio. In the NTR group there was norelationship between lipids and insulin; DHEA-S, on the otherhand, was negatively related to cholesterol and LDL concentrations.Thus, dyslipidaemla in PCOS patients may occur irrespectiveof insulin resistance, and may have different metabolic aetiologiesdepending on DHEA-S metabolism. It remains to be seen whetherthe two types of PCOS are associated with different risks forischaemic heart disease.     

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

BACKGROUND: The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS). METHODS: A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment. RESULTS: Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04). CONCLUSION: Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.