A pilot study of the long-term effects of acipimox in polycystic ovarian syndrome

BACKGROUND: To evaluate the effects of long-term acipimox administration on glucose-induced insulin secretion and peripheral insulin sensitivity in polycystic ovarian syndrome (PCOS), 20 PCOS subjects (eight lean and 12 obese) and 14 body mass index-matched controls (seven lean and seven obese) were investigated. METHODS: Fasting blood samples were collected for basal hormone and lipoprotein assays, after which patients underwent an oral glucose tolerance test (OGTT). The following day a euglycaemic-hyperinsulinaemic clamp was performed. After 4-6 weeks of treatment with acipimox at a dose of 250 mg given orally three times a day, the patients repeated the study protocol. RESULTS: No significant differences were found in the glucose, insulin or C-peptide responses to OGTT before and after anti-lipolytic drug administration in any group, nor was there any effect on insulin sensitivity. Concerning the lipid profile, acipimox administration led to a significant decrease of cholesterol and low-density lipoprotein levels in obese PCOS patients as well as in obese and lean controls. Lower triglycerides were found after the drug administration in both obese groups. Post-treatment free fatty acid levels were not significantly different when compared with basal values. CONCLUSIONS: Acipimox does not appear to be an effective insulin-lowering drug in PCOS, even if it can be used in obese women with PCOS as an additional therapeutic agent to ameliorate the atherogenic lipid profile of the syndrome.     

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: metabolic aspects

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine-metabolic disorder in women, a high percentage of whom exhibit peripheral insulin resistance. After delivery, in normal women, lactation imposes a metabolic adaptation, the impact of which on the insulin resistance of PCOS patients is not known. The aim of this study was to evaluate the effect of lactation on insulin resistance, glucose and insulin metabolism, and sex hormone-binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP)-1 concentrations in fully breast-feeding normal and PCOS women during the postpartum period (lactational amenorrhoea) and also after weaning. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age and body mass index (BMI) were selected for the study. At the 4th and the 8th week postpartum (pp), and 8 weeks after weaning, a 2 h, 75 g oral glucose tolerance test (oGGT) was performed, followed by an insulin tolerance test 2 days later. For the oGGT, glucose and insulin were measured in each sample and SHBG and IGFBP-1 were determined in the fasting sample. RESULTS: During lactation, fasting insulin levels were similar in both groups. In LPCOS women 2 h insulin concentrations were significantly higher, and SHBG and IGFBP-1 concentrations were significantly lower, than those observed in NL women. In both groups, insulin sensitivity evaluated by the insulin tolerance test was not modified. After weaning, in LPCOS women, SHBG and IGFBP-1 concentrations remained lower and insulin concentrations remained higher than those observed in NL women ( P < 0.05 ). CONCLUSIONS: In PCOS women, insulin resistance is not modified during lactation. Lactation has a transitory beneficial effect on insulin levels and biological markers of insulin resistance.     

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome

BACKGROUND: Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. METHODS: The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. RESULTS: The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. CONCLUSIONS: Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.     

Endocrinology: Insulin hypersecretion together with high luteinizing hormone concentration augments androgen secretion in oral glucose tolerance test in women with polycystic ovarian disease

Female hyperandrogenism is often associated with hyper-insulinaemiaand insulin resistance. We evaluated the hormone responses inan oral glucose tolerance test to investigate the interactionsof gonadotrophins, insulin, C-peptide and androgens in womenwith polycystic ovarian disease (PCOD). In 28 patients withultrasonographically diagnosed PCOD, hyperinsulinaemia and insulinresistance were mainly associated with obesity. Both basal andcumulative sum of insulin to C-peptide ratios were high in obesesubjects, suggesting decreasing hepatic removal of insulin causedby obesity. Nevertheless, in some lean PCOD women, despite normalfasting insulin concentrations, insulin hyper-secretion existed.The mean concentration of testosterone decreased significantlyduring the oral glucose tolerance test both in PCOD and controlwomen, and of androstenedione in the PCOD patients only. However,an increase in androgen responses was found in a subgroup ofPCOD patients, who had both elevated luteinizing hormone (LH)concentrations and hyperinsulinaemic response to oral glucose.In the remaining PCOD patients an inverse correlation betweenLH and insulin was found. The patients with hyperinsulinaemiatogether with LH hypersecretion may represent a subgroup ofPCOD with deranged regulation of androgen secretion.     

Influence of hypo- and hyperglycaemia on plasma leptin concentrations in healthy women and in women with polycystic ovary syndrome

BACKGROUND: Insulin resistance and obesity play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). It is known that experimentally induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion. It is not yet known whether the long-term insulin resistance as found in PCOS patients alters the leptin response to hypo- and hyperglycaemia. METHODS: We induced hyper- and hypoglycaemia by glucose clamp technique in 7 patients with PCOS and 20 healthy controls. After a plasma glucose level of 8.8 mmol/l was reached, the plasma glucose level was reduced stepwise to 6.8, 4.8 and 2.8 mmol/l. RESULTS: The PCOS patients required lower glucose infusion rates to reach the glycaemic targets (P < 0.05). Serum insulin and C-peptide concentrations increased significantly during the clamp compared with the baseline in both groups (P < 0.001 for insulin, and P < 0.001, P < 0.005 for C-peptide control and PCOS, respectively) and increased significantly more in PCOS patients compared with the control group (both P < 0.05). Basal leptin levels were significantly higher in the PCOS group than in the control group (P = 0.005). In the controls, the leptin concentration increased significantly during the clamp (P < 0.001 for each glycaemic target), whereas in the PCOS group, leptin secretion increased only during hypoglycaemia (P = 0.04). CONCLUSIONS: Compared with the healthy controls, the response of leptin secretion to hyper- and hypoglycaemia was diminished in PCOS patients. Changes in leptin secretion seem not to be caused by hyper- and hypoglycaemia, but rather by hyperinsulinaemia. Reduced insulin sensitivity seems to be responsible for the diminished leptin response, which might contribute to the obesity found in PCOS patients.     

Early impaired ��-cell function in chinese women with polycystic ovary syndrome

Background: The pathogenic factors that account for the development of diabetes condition in Chinese women with polycystic ovary syndrome (PCOS) remain elusive. Aim: To clarify the pathogenic features by evaluating the levels of insulin sensitivity and β cell function in these women with PCOS, either separately or by using of a disposition indexes (DIs). Methods: Cross-sectional study involving 137 Chinese women with PCOS and 123 normal women were examined by anthropometry, lipid profile, sex hormone, high-sensitivity C reactive protein, oral glucose tolerance tests and insulin tolerance tests. Results: After controlling for BMI status, the Matsuda Index was significantly lower in women with PCOS in comparison to those of normal women (p<0.000). The early phase of insulin secretion (insulinogenic index) remained significantly lower in lean women with PCOS(LP) than those of both lean and obese women of control group (p=0.007, and p = 0.01, respectively). The mean HOMA-F values were significantly lower (p =0.045) in obese women with PCOS (OP) than those of BMI-matched women. Further, all DIs derived from non-fasting state indexes in women with PCOS were significantly lower than those of BMI-matched control women (p<0.001 for all). Lastly, DIs derived from fasting states indexes in OP were significantly lower than those of LP. Conclusion: Early impaired β cell function was detected in both LP and OP. However, more serious primary defect in insulin action was detected in LP compared to OP. These findings imply that early screening and intervention for PCOS would be therapeutic for Chinese women.     

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.     

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.     

Leptin concentrations in hirsute women with polycystic ovary syndrome or idiopathic hirsutism: influence on LH and relationship with hormonal, metabolic, and anthropometric measurements.

BACKGROUND: The known association between leptin, obesity and insulin action suggests that leptin may have a role in polycystic ovarian syndrome (PCOS) but this has only been addressed peripherally. METHODS: We assessed the influence of leptin on LH and investigated the relationship between leptin and body mass index (BMI), waist:hip ratio (WHR), androgen concentrations, fasting insulin and insulin:glucose ratio (IGR) in 27 women with PCOS and in 20 age- and weight-matched women with regular, ovulatory menstrual cycles and idiopathic hirsutism (IH). RESULTS: Leptin concentrations were significantly higher in obese PCOS women than in normal weight women with either PCOS or IH (P = 0.0028), but did not differ between obese women with PCOS and IH. WHR, insulin concentrations and IGR were significantly higher in obese PCOS patients in comparison with the three other groups. In IH patients, the association between leptin concentrations and WHR was lost after adjustment for BMI. In PCOS patients, a significant correlation was observed between leptin and fasting insulin concentrations, IGR, WHR and LH. After adjustment for BMI, only the correlation with LH remained significant. A stepwise regression model was set up with LH as the dependent variable to test the hypothesis that the concentrations of leptin might be modulating the concentrations of LH in PCOS patients. The relationship of LH concentrations with IGR was found to be BMI dependent. In contrast, leptin concentrations contributed negatively and significantly to LH concentrations, independently of either BMI or IGR. CONCLUSIONS: We speculate that the known attenuation in basal or stimulated response of LH in obese PCOS patients might be related to leptin resistance, which could influence LH hypersecretion. In IH ovulatory patients, normal LH concentrations suggest the presence of preserved regulatory mechanisms of GnRH pulsatility. Further studies are needed to specifically investigate the proposed correlation between leptin and GnRH modulation in PCOS.     

Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries

BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study is that insulin resistance in the ovary is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism), whereas the steroidogenic action of insulin remains intact. METHODS: Granulosa-lutein cells were obtained during IVF cycles from seven women with normal ovaries, six ovulatory women with PCO (ovPCO) and seven anovulatory women with PCO (anovPCO). Mean body mass index was in the normal range in all three groups. Granulosa-lutein cells were cultured with insulin (1, 10, 100 and 1000 ng/ml) and LH (1, 2.5 and 5 ng/ml). Media were sampled at 24 and 48 h and analysed for glucose uptake, lactate production and (48 h only) progesterone production. RESULTS: Insulin-stimulated glucose uptake by cells from anovPCO was attenuated at higher doses of insulin (100 and 1000 ng/ml) compared with that by cells from either ovPCO (P=0.02) or controls (P=0.02). Insulin and LH stimulated lactate production in a dose-dependent manner, but insulin-dependent lactate production was markedly impaired in granulosa-lutein cells from anovPCO compared with either normal (P=0.002) or ovPCO (P<0.0001). By contrast, there was no difference in insulin-stimulated progesterone production between granulosa-lutein cells from the three ovarian types. CONCLUSIONS: Granulosa-lutein cells from women with anovPCOS are relatively resistant to the effects of insulin-stimulated glucose uptake and utilization compared with those from normal and ovPCO, whilst maintaining normal steroidogenic output in response to physiological doses of insulin. These studies support the probability of a post-receptor, signalling pathway-specific impairment of insulin action in PCOS.     

Effect of ovarian suppression on glucose metabolism of young lean women with and without ovarian hyperandrogenism

Gonadal steroids are believed to influence glucose metabolism, oestrogens inducing an improvement and androgens or progestins a deterioration. At baseline and after 3 months of ovarian suppression with a gonadotrophin-releasing hormone analogue (GnRHa: goserelin depot 3.75 mg/28 days), glucose metabolism was evaluated in eight lean women affected by ovarian hyperandrogenism (PCOS) and six age-weight-matched non-hyperandrogenic women (controls) by using both an oral glucose tolerance test (75 g; OGTT) and the minimal model method. The latter method allows calculation of peripheral insulin sensitivity (Si) and glucose dependent glucose utilization (Sg). In PCOS, higher fasting concentrations (P < 0.05) of insulin and C-peptide, and lower Sg (P < 0.05) and Si (P < 0.01) were found. GnRHa did not significantly modify glucose metabolism of controls, while in women with PCOS it decreased fasting glucose (P < 0.05) and significantly increased Si (P < 0.03) up to control values. The present data indicate that strong suppression of ovarian activity improves Si in lean women with PCOS, while it is without relevant effects on glucose metabolism of non-hyperandrogenic women.     

The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance.     

Insulin secretion and sensitivity during oral glucose tolerance test in Korean lean elderly women

Impaired glucose tolerance (IGT) and type 2 diabetes including undiagnosed isolated postchallenge hyperglycemia (IPH) are common in the elderly. The aim of this study was to investigate the insulin secretion and sensitivity in Korean elderly lean diabetic women. Forty-one lean women aged 65-88 years took 2 hr oral glucose tolerance test (OGTT) and were stratified according to the WHO criteria (normal glucose tolerance [NGT], n=20; IGT, n=6; and type 2 diabetics, n=15 including seven IPH). HbA1c and fructosamine progressively increased from the NGT to the diabetic subjects (p=0.006 and p=0.001, respectively). Compared with subjects with NGT, the insulinogenic index, a marker of early insulin secretion and the AUC(ins), a marker of total insulin secretion, decreased significantly in diabetic group [0.53 (-0.44 -1.45) vs. 0.18 (0.00 -1.11), p=0.03 and 306+/-165 vs. 199+/-78 pmol/L, p=0.02 respectively]. A significant difference was found in the AUC(c-peptide) among each group (221+/-59 vs. 206+/-34 vs. 149+/-51 pmol/L, p=0.001 for each). The homeostasis model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, was not different among the groups. We conclude that compared with NGT subjects, elderly lean women with diabetes have impaired oral glucose-induced insulin secretion but have relatively preserved insulin sensitivity. This suggests that insulin resistance is not necessarily an essential component of Korean elderly lean diabetic women.     

Effect of feeding on growth hormone response to growth hormone-releasing hormone in polycystic ovarian syndrome: relation with body weight and hyperinsulinism

The plasma growth hormone (GH) response to direct stimulation with growth hormone-releasing hormone (GHRH) before and after a standard meal was investigated in 14 polycystic ovarian syndrome (PCOS) subjects. Data were compared with those obtained from 14 healthy normovulatory matched patients. All women underwent an oral glucose tolerance test (OGTT) (75 g) and basal plasma hormone concentrations were evaluated. On a different day all subjects had a GHRH test (50 microg GHRH) both before and after lunch randomly. In obese PCOS subjects the GH response to GHRH was blunted after a meal, while in obese control patients there was an enhanced response of GH to GHRH after a meal. Normal control subjects showed an inhibition of the GH response after feeding and lean PCOS subjects showed a trend toward an augmented GHRH related secretion after a meal significantly higher than normal controls (P < 0.05) but not significantly higher than the pre-prandial response. In conclusion, the data indicate in PCOS a derangement of GH secretion related to food ingestion; in particular obese PCOS patients did not exhibit any change of GH response after a meal compared with the paradoxical response observed in obese controls. Several other factors beyond body mass index and hyperinsulinism could be involved in these pathophysiological events.     

Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome

BACKGROUND: The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). METHODS: A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. RESULTS: The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). CONCLUSION: The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.     

Infertility: Effects of weight loss on the hormonal profile in obese, infertile women

This study was designed to investigate the effects of weightloss in obese, infertile women with special interest in changesof blood hormones, menstrual function and pregnancy rate. Bloodglucose, insulin, C-peptide and different steroid and pituitaryhormones during oral glucose loading were determined in a groupof 58 obese women with menstrual irregularities. Of the 58 women,35 took part in a weight-reducing programme lasting 32 ±14 weeks (mean ± SD) with a weight loss of 10.2 ±7.9 kg (therapy group). At the time of first oral glucose tolerancetesting, insulin resistance was a feature in 85% of the womenin the therapy group, and 22% were hyperandrogenaemic Weightloss resulted in a significant reduction in blood glucose, insulin,androstenedione, dihydrotestosterone and oestradiol concentrations.The pregnancy rate was 29% in this group and of them, 80% showedan improvement of their menstrual function. Thus, weight reductionis the appropriate treatment for women with obesity-relatedendocrine derangement, menstrual irregularity and infertility.     

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.     

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.     

Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin.

BACKGROUND: Combined oral contraceptives (COC) effectively suppress hyperandrogenism in women with polycystic ovary syndrome (PCOS), though deterioration of insulin sensitivity during treatment is assumed. The study aim was to investigate insulin action and androgen production during treatment with COC containing low-androgenic progestin. METHODS: A total of 13 PCOS women and nine controls was enrolled into the study. Only non-obese women with a body mass index (BMI) 相似文献   

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.