c-peptide and Polycystic-Ovary-Syndrome

To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of polycystic ovary syndrome (PCOS) patients.. Controlled clinical study.. PCOS patients in a clinical research environment.. 50 overweight PCOS patients were enrolled after informed consent.. All patients underwent hormonal evaluations and an oral glucose tolerance test (OGTT) before and after 12 weeks of therapy (Group A (n¼10): MYO 2 g plus folic acid 200 mg every day; Group B (n¼10): folic acid 200 mg every day). Ultrasound examinations and Ferriman-Gallwey score were also performed.. Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio.. After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid.. MYO administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Drug Therapy, Combination; Estradiol; Female; Folic Acid; Follicle Stimulating Hormone; Glucose Tolerance Test; Humans; Inositol; Insulin; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Prolactin; Testosterone; Treatment Outcome

Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances, in particular from insulin resistance. Accumulating evidence suggests that vitamin D deficiency may contribute to the development of insulin resistance. Hence, we aimed to examine the effect of vitamin D supplementation on metabolic and endocrine parameters in PCOS women.. Fifty-seven PCOS women were included in the study. PCOS women received 20,000 IU cholecalciferol weekly for 24 weeks. Anthropometric measures, oral glucose tolerance test, and blood analyses of endocrine parameters were performed at baseline and after 12 weeks (V2) and 24 weeks (V3).. Forty-six PCOS women finished the study. 25-hydroxyvitamin D [25(OH)D] levels significantly increased from 28.0±11.0 ng/ml at baseline to 51.3±17.3 and 52.4±21.5 at V2 and V3, respectively (p<0.001). We observed a significant decrease of fasting and stimulated glucose (V3, p<0.05) and C-peptide levels (V2 and 3, p<0.001) after vitamin D treatment. Moreover, triglyceride and estradiol levels significantly decreased at V3 (p=0.001) and V2 (p=0.022), respectively, whereas total cholesterol (V2, p=0.008) and LDL cholesterol levels (V2, p=0.005; V3, p=0.026) significantly increased after vitamin D treatment. There were no changes in androgens. At V2, 14 out of 46 PCOS women previously affected by menstrual disturbances (30.4%) reported improvement of menstrual frequency; at V3, 23 out of 46 women (50.0%), who were oligo- or amenorrheic at baseline reported improvement.. Our results suggest that vitamin D treatment might improve glucose metabolism and menstrual frequency in PCOS women. Further randomized controlled trails are warranted to confirm our findings.

Topics: Administration, Oral; Adolescent; Adult; Blood Glucose; C-Peptide; Cholecalciferol; Cholesterol; Cholesterol, LDL; Female; Humans; Menstruation; Menstruation Disturbances; Pilot Projects; Polycystic Ovary Syndrome; Prospective Studies; Vitamin D Deficiency

Low-grade chronic inflammation, evaluated by serum C-reactive protein (CRP) levels, has been connected with the polycystic ovary syndrome (PCOS). Effects of metformin on CRP before and during IVF treatment in women with PCOS are unknown.. A prospective double-blind placebo-controlled study.. Single-center IVF clinic.. Sixty-three PCOS women.. Treatment with 2000 mg/day metformin or identical placebo tablets for at least 14 weeks before and then during IVF treatment, ending on the day of hCG injection.. The CRP levels at five time points ending on the day of ovum collection.. At inclusion of infertile untreated PCOS women, body mass index associated with CRP in multivariable regression analysis (r = 0.18). Androgen levels did not associate with CRP levels. Metformin did not influence CRP levels during pretreatment or IVF cycle. After hCG injection, CRP increased in both the metformin and the placebo groups with no significant difference between the groups.. In infertile PCOS women, CRP levels are unaffected by metformin treatment. The CRP level increases during IVF treatment, and this increase is unaffected by concomitant metformin. We observed an association between CRP levels and body mass index.

Topics: Adult; Androgens; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Double-Blind Method; Female; Fertilization in Vitro; Humans; Hypoglycemic Agents; Infertility, Female; Metformin; Oocyte Retrieval; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Prospective Studies; Time Factors

To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients.. Controlled clinical study.. PCOS patients in a clinical research environment.. Twenty nonobese PCOS patients were enrolled after informed consent.. All patients underwent hormonal evaluations and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations and Ferriman-Gallwey scoring were also performed.. Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy-progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide concentrations.. After 6 months of metformin administration, the plasma LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin sensitivity, expressed as the glucose-to-insulin ratio, was significantly improved under glucose load after 6 months of treatment. Spontaneous LH episodic release showed a significant reduction in pulse amplitude with no changes in pulse frequency. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were significantly reduced.. Metformin administration improves reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By acting on the ovary and restoring normal ovarian activity, metformin positively modulates the reproductive axis (namely GnRH-LH episodic release).

Topics: 17-alpha-Hydroxyprogesterone; Adult; Androstenedione; Area Under Curve; Blood Glucose; C-Peptide; Estradiol; Female; Follicle Stimulating Hormone; Humans; Insulin; Luteinizing Hormone; Menstrual Cycle; Metformin; Obesity; Ovary; Polycystic Ovary Syndrome; Testosterone

Oral contraceptives slightly deteriorate insulin sensitivity. The present study investigated whether they may further unbalance the glucose metabolism of lean women with polycystic ovary syndrome (PCOS). Women with PCOS were assigned to receive for 6 months the biphasic association of 40/30 micro g ethinyl estradiol (EE) and 25/125 micro g desogestrel (DSG; n = 10) or the monophasic association of 35 micro g EE and 2 mg cyproterone acetate (CPA; n = 10). Glucose tolerance was investigated by an oral glucose tolerance test (OGTT). Glucose utilization dependent [insulin sensitivity (SI)] or independent (Sg) of insulin was investigated by the minimal model method applied to a frequently sampled iv glucose tolerance test. EE/DSG increased the response of C peptide to OGTT (1413 +/- 113 vs. 2053 +/- 213 area under the curve; P < 0.009) and the C peptide/insulin ratio (0.085 +/- 0.01 vs. 0.134 +/- 0.01 area under the curve; P < 0.003). It also increased the Sg (0.026 +/- 0.002 vs. 0.034 +/- 0.003; P < 0.04) and decreased the SI (2.40 +/- 0.26 vs. 1.68 +/- 0.27; P < 0.01). EE/CPA did not modify responses to OGTT of glucose, insulin, C peptide, or C peptide/insulin ratio. It did not modify Sg and significantly increased SI (1.47 +/- 0.38 vs. 3.27 +/- 0.48; P < 0.04). The present study indicates that EE/CPA improves SI, whereas EE/DSG impairs SI, but improves insulin clearance. The long-term metabolic effects of these two compounds on women with PCOS require further investigations.

Topics: Adult; Anthropometry; Blood Glucose; Body Weight; C-Peptide; Contraceptives, Oral, Hormonal; Cyproterone Acetate; Desogestrel; Ethinyl Estradiol; Female; Glucose; Glucose Tolerance Test; Hormones; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome

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.. 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.. 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.. 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.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Hypolipidemic Agents; Insulin; Obesity; Pilot Projects; Polycystic Ovary Syndrome; Pyrazines; Thinness; Time Factors; Triglycerides

To evaluate the effects of acute lowering of FFAs on glucose-induced insulin secretion and GH response to GHRH in polycystic ovary syndrome (PCOS), 27 PCOS subjects (11 lean and 16 obese) and 17 body mass index-matched controls (8 lean and 9 obese) were investigated. Patients underwent an oral glucose tolerance test and a GHRH test before and after administration of the antilipolytic drug acipimox (250 mg orally 3 h and 1 h before the starting of the tests). Blood samples were collected for 2 h after GHRH bolus and for 4 h after the oral glucose tolerance test. Serum concentrations of GH, insulin, glucose, and c-peptide were assayed in each sample, and the results were expressed as area under the curve (AUC). No significant differences were found as to glucose, insulin, and c-peptide AUC before and after acute FFA plasma reduction in any of the investigated groups. Basally, lower GH-AUC was found in lean PCOS compared with body mass index-matched controls and in obese vs. lean controls; no significant differences were found as to the same variable between the two obese groups. The acipimox induced FFA suppression elicited in the four groups a sustained increase in the GH response to its trophic hormone; indeed, the GH-AUC nearly doubled with respect to basal evaluation in all the studied groups. However, the antilipolytic drug was not able to abolish the differences found between lean groups in basal conditions. In conclusion, the presented data confirm that FFAs have a main role in regulating GH secretion at the pituitary level; however, it does not seem that they could explain the GH as well as insulin dysfunction of PCOS.

Topics: Adult; Area Under Curve; Body Mass Index; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Growth Hormone-Releasing Hormone; Hormones; Human Growth Hormone; Humans; Hypolipidemic Agents; Insulin; Insulin Resistance; Lipids; Obesity; Polycystic Ovary Syndrome; Pyrazines

To investigate insulin metabolism and its modifications induced by the administration of flutamide, a specific antiandrogen compound, in women with idiopathic hirsutism (IH) and in nonobese women with polycystic ovary syndrome (PCOS).. Prospective, randomized trial.. Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Caligari, Caligari, Italy.. Thirty-two women with normal body mass index participated in the study: 11 with clinical and hormonal features of PCOS and 21 age- and weight-matched normally cycling women with IH (n = 11) and without IH (n = 10, controls).. Each subject with PCOS or IH was assigned randomly to receive either flutamide tablets (250 mg twice a day) or placebo for > or =5 months. Twelve subjects (6 with PCOS, 6 with IH) received flutamide and 10 (5 with PCOS, 5 with IH) received placebo. All subjects ingested 75 g of glucose and then underwent an oral glucose tolerance test (OGTT), 3-7 days after spontaneous or medroxyprogesterone acetate (5 mg daily for 5 days)-induced menses. In women with PCOS or IH, the OGTT was repeated at the fourth month of treatment.. Fasting and OGTT-stimulated levels of glucose, insulin, and C peptide.. Both fasting and OGTT-stimulated levels of insulin and C peptide were significantly higher in women with PCOS and in those with IH than in controls. Placebo did not modify parameters of glucose metabolism. Flutamide was capable of significantly blunting fasting and OGTT-stimulated secretion of insulin only in women with IH.. Hyperinsulinemia exists in women with IH as well as in nonobese women with PCOS. Treatment with flutamide can completely reverse hyperinsulinemia only in women with IH, which suggests that the efficacy of the drug is dependent on peripheral androgen hyperactivity.

Topics: Adult; Androgen Antagonists; Blood Glucose; C-Peptide; Female; Flutamide; Follicle Stimulating Hormone; Glucose Tolerance Test; Hirsutism; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Luteinizing Hormone; Polycystic Ovary Syndrome; Prospective Studies

To investigate the relation between androgen excess and insulin resistance in nonobese Chinese women with polycystic ovary syndrome.. A prospective, controlled study.. School of Clinical Medicine, Nanjing University.. There were three groups: Group 1 (n = 15) comprised nonobese women with polycystic ovary syndrome; Group 2 comprised 12 of these 15 women in whom bilateral wedge resection had been performed six months to one year before enrolling in the study. Group 3 was a control group comprised of 15 normally menstruating women of similar age and body mass index.. An oral glucose (100 g) tolerance test was performed in all women in each group. The areas under the response curve of serum glucose, insulin, C-peptide (C-P), insulin/glucose (I/G) and C-P/insulin (C/I) were calculated by trapezoid rule.. When fasting the three groups had similar levels of glucose, insulin, C-P, I/G and C/I. During the oral glucose tolerance test women of Group 1 had a significantly higher mean serum area of the curve of glucose, insulin, C-P and I/G levels and lower C/I values, compared with the other two groups. Women of Group 2 and those in the control group showed similar levels of these indices during the oral glucose tolerance test.. Androgen excess in women with polycystic ovary syndrome may be responsible for a defect in peripheral insulin sensitivity and hepatic extraction which could be reversed by removing excessive androgens with wedge resection.

Topics: Adult; Analysis of Variance; Androgens; C-Peptide; Female; Follicle Stimulating Hormone; Glucose; Glucose Tolerance Test; Humans; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Prospective Studies

This study was performed in two randomly defined groups of obese patients with polycystic ovaries to investigate the overall effects of hypocaloric diet combined (group 2) or not combined (group 1) with an antiandrogenic therapy (cyproterone acetate, 50 mg/day, plus ethinyl estradiol, 0.05 mg/day) on sex hormone plasma levels, insulin secretion and resistance, and body weight loss and on their reciprocal interrelationships. All obese patients with polycystic ovaries showed elevated luteinizing hormone and androgen levels, hyperinsulinemia, and marked insulin resistance. After an average period of 3 months both groups showed a similar weight loss and a similar reduction in the insulin-resistant state. During treatment in group 1 three patients had a greater frequency of menstrual bleeding, and in one of them an ovulatory cycle was documented. Whereas, no changes in gonadotropin and sex steroid levels were found in group 1, a significant fall was observed in group 2. No relationships were observed between these changes and those which occurred on insulin levels. We conclude that hyperandrogenism in obese patients with polycystic ovaries does not appear to be a primary factor leading to the insulin-resistant state.

Topics: Adolescent; Adult; Androgen Antagonists; Body Weight; C-Peptide; Energy Intake; Female; Glucose Tolerance Test; Gonadal Steroid Hormones; Humans; Insulin; Insulin Resistance; Male; Obesity; Polycystic Ovary Syndrome

Different polycystic ovary syndrome (PCOS) phenotypes are correlated with different clinical severity levels. Insulin resistance correlates with higher severity. In a retrospective study, 130 patients with polycystic ovary syndrome were examined for insulin resistance. The aim of the study was to investigate relationships between glucose metabolism and different PCOS phenotypes and to identify biomarkers or combinations thereof to obtain information on the type of metabolic disorder or the severity of PCOS.. A total of 130 patients with PCOS were included in the study. Biometric data such as weight, height, cycle day and cycle length were compared with glucose metabolism parameters such as fasting glucose, insulin before and 60 and 120 minutes after 75 g glucose intake, intact proinsulin, C-peptide and ovarian function parameters including Anti-Müllerian hormone (AMH) and the soluble AMH receptor (sAMHR2). The parameters were correlated, and their diagnostic performance with respect to different expressions of PCOS was evaluated.. The biomarkers of impaired glucose metabolism showed strong significant difference in HOMA Index, adiponectin, proinsulin and body mass index (BMI) and Insulin levels in 0-60-120 minutes of glucose tolerance test but also with parameters of ovarian function as AMH, AMH z-score sAMHR2, and sAMHR2/AMH ratio. A strong correlation between sAMHR2 and adiponectin (r = .818, P < .0001) was found indicating a relationship between the degree of glucose metabolic impairment and ovarian function.. The parameters glucose, insulin, insulin 60 minutes after intake of 75 g glucose and adiponectin or sAMHR2 enable a biochemical classification of PCOS patients that correlates with morphological PCOS phenotypes. By determining biomarkers, it is possible to classify PCOS patients into subgroups that correlate with different PCOS phenotypes and the clinical severity.

Topics: Anti-Mullerian Hormone; C-Peptide; Female; Glucose; Humans; Insulin Resistance; Phenotype; Polycystic Ovary Syndrome; Retrospective Studies

Our study aims to assay the irisin level and investigate the relationships of irisin level with body mass index (BMI), body composition and bone metabolism in the polycystic ovary syndrome (PCOS) and control women.. Fifty two PCOS and 39 control women were recruited. Serum sex hormone, fasting insulin and C-peptide were tested. Fasting serum irisin and adiponectin were measured with enzyme-linked immunosorbent assay. Body composition and bone mineral density were assayed by dual energy X-ray absorptiometry.. Polycystic ovary syndrome women showed different body compositions compared with controls. Serum irisin level of PCOS did not show significant difference compared with controls although it was decreased. The level of adiponectin in PCOS patients was significantly reduced. BMI had no correlation with irisin level. It indicated a positive correlation between serum irisin levels and bone mineral density in the control group and a negative correlation in the PCOS group after BMI and age adjusted. Furthermore, total lean mass has a significant effect on irisin concentration in the PCOS group. There are no correlations between adiponection and body compositions and bone mineral density in both groups.. The abnormal body composition in PCOS may contribute to the circulation irisin. The crosstalk of irisin in different organs was found and may be related to disease development in PCOS.

Topics: Adiponectin; Adult; Biomarkers; Body Composition; Bone Density; C-Peptide; Case-Control Studies; Female; Fibronectins; Humans; Polycystic Ovary Syndrome; Prognosis; Young Adult

What is the prevalence of reactive hypoglycemia (RH) in polycystic ovary syndrome (PCOS) versus age- and body mass index (BMI)-matched healthy controls.. The prevalence of RH was increased in PCOS versus controls.. Previous studies suggested an increased prevalence of RH in PCOS.. Cross-sectional study of 88 women with PCOS and 34 healthy age- and BMI-matched controls.. Eighty-eight women with PCOS and 34 age- and BMI-matched controls were included. The study was conducted at Odense University Hospital, Denmark. Participants underwent 5 h oral glucose tolerance test (5 h OGTT). Indices of insulin resistance, β-cell function, and area under the curve (AUC) for glucose, insulin and C-peptide were calculated. Insulin clearance was estimated as 5 h AUC C-peptide/insulin. RH was defined as blood glucose ≤3.3 mmol/l during 5 h OGTT.. RH occurred in 15/88 (17%) women with PCOS versus 0/34 controls ( ITALIC! P = 0.01). Nine out of 15 women with RH were obese and 6 were lean ( ITALIC! P = 0.42). Obese patients with RH had significantly higher 5 h AUCs insulin and C-peptide compared with lean patients with RH ( ITALIC! P = 0.02 and 0.04, respectively). Obese patients with RH had significantly lower 5 h AUC C-peptide/insulin versus obese patients without RH ( ITALIC! P = 0.02). In lean patients with RH, 5 h AUCs insulin and C-peptide were similar to lean controls.. The 5 h OGTT was used to diagnose RH and may be a limitation of the study. Although the 5 h OGTT is the most widely accepted method, no gold standard exists in terms of diagnosing RH. The 5 h OGTT was suggested to over-estimate the incidence of RH compared with meal test.. The study supports previous suggestions of increased prevalence of RH in women with PCOS compared with controls.. This study was funded by Jacob Madsen's and Olga Madsen's Foundation, Institute of Clinical Research, Odense University Hospital, Kolding Hospital, AP Møller's Foundation, Bernhard and Marie Kleins Foundation, The Novo Nordisk Foundation, and The Danish Medical Association. The authors declare no conflict of interest.. The trial was registered at www.clinicaltrials.gov (registration numbers NCT00451568 (patients) and NCT01995773 (controls)).

Topics: Adolescent; Adult; Area Under Curve; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Denmark; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Prevalence

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic complications. Metabolic biomarkers with roles in obesity, glycaemic control and lipid metabolism are potentially relevant in PCOS. The aim was to investigate metabolic biomarkers in lean and overweight women with and without PCOS and to determine whether any biomarker was able to predict insulin resistance in PCOS.. Cross-sectional study.. Eighty-four women (22 overweight and 22 lean women with PCOS, 18 overweight and 22 lean women without PCOS) were recruited from the community and categorized based on PCOS and BMI status.. Primary outcomes were metabolic biomarkers [ghrelin, resistin, visfatin, glucagon-like peptide-1 (GLP-1), leptin, plasminogen activator inhibitor -1 (PAI-1), glucose-dependent insulinotropic polypeptide (GIP) and C-Peptide] measured using the Bio-Plex Pro Diabetes assay and insulin sensitivity as assessed by glucose infusion rate on euglycaemic-hyperinsulinaemic clamp.. The biomarkers C-peptide, leptin, ghrelin and visfatin were different between overweight and lean women, irrespective of PCOS status. The concentration of circulating biomarkers did not differ between women with PCOS diagnosed by the Rotterdam criteria or National Institute of Health criteria. PAI-1 was the only biomarker that significantly predicted insulin resistance in both control women (P = 0.04) and women with PCOS (P = 0.01).. Biomarkers associated with metabolic diseases appear more strongly associated with obesity rather than PCOS status. PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and without PCOS.

Topics: Adult; Biomarkers; C-Peptide; Case-Control Studies; Cross-Sectional Studies; Cytokines; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Insulin Resistance; Leptin; Nicotinamide Phosphoribosyltransferase; Overweight; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Predictive Value of Tests; Resistin; Young Adult

Insulin-sensitizer treatment with metformin is common in polycystic ovary syndrome (PCOS). OCT alleles were investigated in PCOS patients to identify genetic 'bad responders' and 'nonresponders' to metformin including their possible effects on glucose metabolism without treatment. We genotyped eight SNPs in OCT1, OCT2 and ATM genes in 676 women with PCOS and 90 control women, we also measured oral glucose tolerance tests prior to treatment. Nonfunctional alleles were present in 29.8% and low-functional alleles in 57.9% of our PCOS cohort. OCT variants were significantly associated with elevated baseline and glucose-induced C-peptide levels in PCOS. Metformin bad responders or nonresponders based on OCT genotypes might be relevant in clinical practice - their modulation of metformin pharmacokinetics and pharmacodynamics and metformin-independent glucose effects remain to be elucidated.

Topics: Adult; Ataxia Telangiectasia Mutated Proteins; C-Peptide; Drug Resistance; Female; Genetic Association Studies; Glucose; Glucose Tolerance Test; Humans; Insulin Resistance; Metformin; Organic Cation Transport Proteins; Organic Cation Transporter 1; Organic Cation Transporter 2; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide

The aim of the presented study is to evaluate metabolic features in adolescents with polycystic ovary syndrome (PCOS) in comparison with age- and BMI-matched subjects. Forty-three adolescents with PCOS according to ESHRE criteria were prospectively evaluated and compared with 48 control subjects. Blood sampling was done in the early follicular phase of menstrual cycle, between 1st and 5th day, for plasma glucose, total and high-density lipoprotein (HDL)-cholesterol, triglycerides, insulin and C peptide. The diagnosis of metabolic syndrome was done according to IDF adolescent criteria. Adolescents with PCOS have increased low-density lipoprotein (LDL)-cholesterol (p < 0.002), decreased HDL-cholesterol (p <0.0007) and increased C peptide levels (p < 0.02) in comparison with healthy adolescents. Total cholesterol, triglycerides, fasting blood glucose, fasting insulin, HOMA-IR, waist-to-hip ratio, systolic and diastolic blood pressure did not differ between the groups. There was no difference when we compared the prevalence of adolescents with at least one feature of metabolic syndrome between PCOS (17 from 43) and healthy controls (27 from 48). In conclusion, adolescents with PCOS have less favourable blood lipid profiles with higher LDL-cholesterol and lower levels of HDL-cholesterol and are more insulin resistant than their healthy counterparts having higher fasting C peptide levels.

Topics: Adolescent; Adult; Body Mass Index; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Czech Republic; Female; Follicular Phase; Humans; Hypercholesterolemia; Insulin Resistance; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Prevalence; Prospective Studies; Young Adult

C-peptide is cleaved from the proinsulin chains A and B during insulin synthesis. The views on its role in human physiology has changed in recent years. Soon after discovery of C-peptide it was believed that this protein is inactive by-product of insulin synthesis, and its role is limited to role in conformational changes of insulin and indicator of exocrine function of the pancreas. At present, it is known that C-peptide is bioactive compound, with multiple functions, and it acts probably through membrane receptor. The known physiological actions of C-peptide are related mainly to kidneys, circulatory and nervous systems function. In kidney, it changes the glomerular filtration and proteinuria. In blood vessels, C-peptide is able to act as a vasodilator. It is also able to improve the neurotransmission rate. The newest data indicates possible involvement of C-peptide in etiopathology of diabetes and polycystic ovary syndrome. The possible role of C-peptide in these disorders is very interesting and requires further studies.

Topics: C-Peptide; Diabetes Mellitus; Endocrine System Diseases; Female; Glomerular Filtration Rate; Humans; Insulin; Pancreas; Polycystic Ovary Syndrome; Proinsulin; Vasodilation

To determine basic anthropometric characteristics and their relationship with the metabolism of saccharides in women with PCOS in the Olomouc region.. Retrospective study of the results of 72 women with PCOS examined in the endocrinology clinic.. The study entailed the processing of data gained on the basis of examination of women sent to endocrinology clinic for examination in the years 2008-2010, who corresponded to the diagnostic criteria for PCOS according to the Rotterdam consensus. The obtained results of anthropometric measurement and characteristic saccharide metabolism were compared with a group of healthy women.. In groups of women of comparable age (PCOS average age 31.6, control group average age 31.4) the average BMI in women with PCOS was 26.76 kg m(-2), the average waist measurement was 84.43 cm, the waist/hips ratio was 0.79, in the control group the average BMI was 24.73 kg m(-2), the waist/hips ratio was 0.76, the differences between the two groups were not statistically significant. There was a statistically significant difference between women with PCOS and the healthy control group in C peptide values, even in comparable anthropometric parameters. Levels of fasting glycaemia and glycated haemoglobin were comparable. Waist measurement, as a parameter for evaluating the level of visceral accumulation of fat in women with PCOS, was related to all monitored characteristics of saccharide metabolism (statistically significant correlation with fasting glycaemia, glycated haemoglobin and C peptide). Unlike the waist measurement, the waist/hips ratio indicated a smaller percentage of women with abnormal obesity in both groups, in women with PCOS it correlated with fasting glycaemia and C peptide.. On the basis of our results it can be stated that women with PCOS do not necessarily differ from the healthy control group in anthropometric parameters. However, with comparable age, BMI and level of visceral obesity, women with PCOS require a greater amount of insulin to maintain normoglycaemia than healthy women.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Female; Glycated Hemoglobin; Humans; Intra-Abdominal Fat; Polycystic Ovary Syndrome; Waist Circumference

The high incidence of insulin resistance, type 2 diabetes, and metabolic syndrome in Western societies and their impact on quality of life emphasize the importance of identifying underlying susceptibility loci for metabolic diseases. The polycystic ovary syndrome (PCOS) susceptibility locus D19S884 allele 8 (A8) is associated with measures of insulin resistance, beta-cell dysfunction, and other metabolic phenotypes in PCOS families. We now investigate the role of D19S884 A8 in pregnancy.. Using the multiethnic Hyperglycemia and Adverse Pregnancy Outcome cohort, we assessed the associations of D19S884 A8 with measures of maternal glycemia and fetal size.. We tested for association of maternal D19S884 A8 with maternal outcomes (fasting, 1-h, and 2-h plasma glucose, and fasting and 1-h C-peptide from an oral glucose tolerance test) and fetal and maternal D19S884 A8 with fetal outcomes (birth weight, length, head circumference, sum of skin folds, fat mass, cord C-peptide, and 2-h neonatal plasma glucose).. We analyzed 4424 Caucasian mothers and 3347 offspring of northern European ancestry, 1957 Thai mothers and 2089 offspring from Bangkok, 1208 Afro-Caribbean mothers and 1209 offspring from Barbados, and 774 Hispanic mothers and 762 offspring from Bellflower, California.. After adjusting for confounding variables and multiple testing, neither maternal nor fetal D19S884 A8 showed significant evidence for association with any of the outcomes tested.. The PCOS susceptibility locus, D19S884 A8, is not a major factor contributing to glycemia during pregnancy or fetal size in a general obstetric population.

Topics: Alleles; Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Development; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Insulin Resistance; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

It is believed that important pathogenic mechanism in polycystic ovary syndrome (PCOS) is hyperinsulinemia. Insulin synthesis is linked to C-peptide release, but the role of C-peptide in PCOS is not well described. THE AIM OF THE STUDY was to evaluate C-peptide serum levels in overweight or obese women with PCOS and assessment of correlation between serum concentrations of C-peptide and androgens and metabolic disturbances in PCOS.. 65 women diagnosed with PCOS were included to the study. I group consisted of 5 overweight PCOS women (27.2 +/- 3.6 years old; BMI 27.3 +/-1.5 kg/m2), and II group included 60 obese PCOS women (26.2 +/- 6.3 years old; BMI 35.0 +/- 4.45 kg/m2). The control group consisted of 10 healthy, ovulatory women with normal weight (aged 28.8 +/- 4.8 years; BMI 21.2 +/- 2.1 kg/m2). Folliculotrophin (FSH), lutrophin (LH), 17beta-estradiol (E2), testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and insulin concentrations were measured in serum. Serum fasting glucose levels and lipid profile was assessed: total cholersterol (Ch), triglycerides (TG), low (LDL) and high density lipoproteins (HDL). C-peptide levels were measured using commercially available test (Human C-Peptide ELISA Kit, Dako).. C-peptide concentrations in PCOS overweight group were 1.39 +/- 0.9, and in PCOS obese group were 1.31 +/- 1.05 nmol/I, whereas among healthy women 1.62 +/- 1.56 nmol/I. Those differences were not statistically significant. C-peptide serum levels did not correlated significantly with FSH, LH, E2, T, DHEAS serum levels within studied groups. Negative correlation between C-peptide and glucose serum levels was found in control group (R = -0.71; p < 0.05). Positive correlation between these values in PCOS overweight group was found (R = 0.90; p < 0.05). In PCOS obese group there was no correlation between these values.. Young obese or overweight women with PCOS are characterized by comparable serum C-peptide levels to serum C-peptide concentration in healthy young women. There is no correlation between serum C-peptide and androgens in obese or overweight patients with PCOS. The link between C-peptide and hyperinsulinemia and other metabolic disturbances in PCOS is very complex and requires further studies.

Topics: Adult; C-Peptide; Female; Humans; Obesity; Overweight; Polycystic Ovary Syndrome; Reference Values

Clinical manifestations and metabolic risk factors may differ in ethnic subgroups of patients with polycystic ovary syndrome (PCOS).. Retrospective trans-sectional study.. One thousand and two premenopausal women with the diagnoses hirsutism or PCOS were divided according to ethnicity: Caucasian (CA, n = 784), Middle East (ME, n = 190), Asian (n = 14) and others (n = 14).. Clinical evaluation (hirsutism, BMI, waist, blood pressure), hormone analyses (testosterone, sex hormone-binding globulin, prolactin, lipids, insulin, glucose) and transvaginal ultrasound were performed. Oral glucose tolerance tests (OGTT) (n = 499) and ACTH tests (n = 434) were performed in a subgroup of patients.. (CA vs ME women) CA women were older [32(25-37) vs 25(18-32) years, median (quartiles)] and had increased BMI compared to ME women. After correcting for age and BMI, CA women were less hirsute, but had increased testosterone levels compared to ME women. The Rotterdam criteria were fulfilled in 56% of both populations, but PCO was diagnosed in 47% CA vs 29% ME women, P < 0·01. CA women had increased blood pressure and smoked at a higher frequency (40 vs 23%), whereas area under the curve for insulin during OGTT was decreased, all P < 0·001. Prolactin levels were significantly lower in CA women compared to ME women [7(5-10) vs 9(6-12) μg/l] and were inversely associated with smoking status.. CA women had a more adverse cardiovascular profile than ME women, whereas insulin sensitivity was higher. The prevalence of the individual Rotterdam criteria differed significantly in the two study populations.

Topics: Adolescent; Adult; Asian People; Body Mass Index; C-Peptide; Female; Follicle Stimulating Hormone; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Luteinizing Hormone; Polycystic Ovary Syndrome; Premenopause; Prolactin; Retrospective Studies; Risk Factors; Sex Hormone-Binding Globulin; Testosterone; White People; Young Adult

To assess the influence of alterations in glucose concentrations on androgen levels in patients with polycystic ovary syndrome (PCOS) and in healthy controls.. Prospective, controlled study.. Tertiary care center.. Seven patients with PCOS and 20 healthy controls.. Hyperinsulinemic glucose clamp study with stepwise reduction of the plasma glucose level from hyperglycemia to hypoglycemia.. Concentrations of insulin, C-peptide, cortisol, T, androstenedione, 17-hydroxyprogesterone, DHEA, and DHEAS during hyperglycemia, euglycemia, and hypoglycemia.. Total T levels and the free androgen index were significantly higher in the PCOS group at baseline and throughout the clamp. The levels of T, androstenedione, DHEAS, and 17-hydroxyprogesterone were not influenced by short-term changes of plasma glucose concentrations in both groups. However, hypoglycemia led to a significant increase in DHEA levels in PCOS patients as well as in controls. Cortisol levels were not increased during hypoglycemia in either group.. In contrast to men, androgen levels are not influenced by short-term changes of plasma glucose levels in PCOS patients and in healthy women. However, DHEA concentrations increase with decreasing glucose levels independently from an activation of the hypothalamic-pituitary-adrenal axis. This supports a gender difference regarding the counterregulatory hormone response to hypoglycemia.

Topics: 17-alpha-Hydroxyprogesterone; Adult; Androgens; Androstenedione; Blood Glucose; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose Clamp Technique; Humans; Hydrocortisone; Insulin; Obesity; Polycystic Ovary Syndrome; Prospective Studies; Reference Values; Testosterone; Waist-Hip Ratio; Young Adult

Polycystic ovary syndrome (PCOS) has been linked to a high risk of type 2 diabetes mellitus. Disturbances in the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been observed in states with impaired glucose regulation. This paper considers the secretion of GIP and GLP-1 after oral glucose load in a group of lean, glucose-tolerant PCOS women in comparison with age- and body mass index (BMI)-matched healthy women.. Case control.. PCOS (n=21, 25.8+/-4.1 years, BMI 21.6+/-1.7 kg/m(2)) and control healthy women (CT, n=13, 28.5+/-7.2 years, BMI 20.3+/-2.5 kg/m(2)) underwent oral glucose tolerance test (OGTT) with blood sampling for glucose, insulin, C-peptide, total GIP, and active GLP-1. Insulin sensitivity was determined both at fasting and during the test.. Repeated measures ANOVA.. Glucose levels and insulin sensitivity did not differ between PCOS and CT. PCOS had significantly higher levels of C-peptide (P<0.05) and tended to have higher insulin levels. The levels of total GIP were significantly higher in PCOS than in CT (P<0.001). Active GLP-1 levels exhibited a significantly different time-dependent pattern in PCOS (P<0.002 for PCOS versus time interaction). GLP-1 concentrations were similar in PCOS and CT in the early phase of OGTT and then reached significantly lower levels in PCOS than in CT at 180 min (P<0.05).. Increased total GIP and lower late phase active GLP-1 concentrations during OGTT characterize PCOS women with higher C-peptide secretion in comparison with healthy controls, and may be the early markers of a pre-diabetic state.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Time Factors

To assess the previously unstudied potential role of C/T (A1330V) polymorphism of the low-density lipoprotein receptor-related protein-5 gene in insulin sensitivity and secretion in polycystic ovary syndrome. The low-density lipoprotein receptor-related protein-5 gene has been found to play a role in determining insulin secretion in animal models.. Case-control study.. Tertiary outpatient clinic.. Women with polycystic ovary syndrome (n = 299; age, 27.5 +/- 7.1 y [mean +/- SD]), according to the European Society of Human Reproduction and Embryology criteria, as well as healthy control women (n = 187, age, 28.9 +/- 9.8 y).. Oral glucose tolerance test, blood sampling.. Glucose, insulin, C peptide, proinsulin during oral glucose tolerance tests, and lipids. Genotyping of C/T (A1330V) polymorphism by polymerase chain reaction-restriction fragment length polymorphism.. There was no difference in the frequency of genotypes between women with polycystic ovary syndrome (CC/CT/TT: 80.3%, 18.4%, 1.3%) and the control women (79.1%, 19.8%, and 1.1%). Carriers of the T allele had statistically significantly higher basal and stimulated C peptide and proinsulin levels than CC homozygotes, both basally and at the 180th minute. Regarding insulin sensitivity, there was no difference between T carriers and CC homozygotes.. Polymorphism of C/T in the low-density lipoprotein receptor-related protein-5 gene is associated with C-peptide and proinsulin secretion but does not influence insulin sensitivity in either healthy women or women with polycystic ovary syndrome.

Topics: Adult; C-Peptide; Czech Republic; Exons; Female; Genetic Predisposition to Disease; Humans; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Prevalence; Proinsulin; Receptors, LDL; Risk Assessment; Risk Factors

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.. 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.. 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).. 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.

Topics: Adult; Blood Glucose; C-Peptide; Female; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Resistance; Leptin; Polycystic Ovary Syndrome

The exaggerated 17-hydroxyprogesterone response to GnRH agonists, which reflects functional ovarian hyperandrogenism (FOH), is believed to be the prominent abnormality in women with polycystic ovary syndrome (PCOS).. Our objectives were to quantify the prevalence of PCOS with FOH and to evaluate whether the presence of FOH may distinguish different clinical and biochemical phenotypes.. We conducted an observational study at an academic hospital that included 148 PCOS women and 22 healthy age-matched normal-weight control women.. A hormone profile was taken at baseline and in response to (1-24)ACTH and to a GnRH agonist, buserelin, administered during dexamethasone suppression.. Based on the data obtained in the control subjects, the PCOS patients were divided into two groups, one with a normal (NR-PCOS, n = 78) and one with a high 17-hydroxyprogesterone response (HR-PCOS, n = 70) to buserelin. The two groups of PCOS subjects had similar anthropometric parameters and clinical signs of hyperandrogenism. Age and body weight at menarche were significantly lower and higher, respectively, in the HR-PCOS group than the NR-PCOS group. Moreover, the HR-PCOS group had higher basal testosterone (P < 0.001), free androgen index (P < 0.01), 17-hydroxyprogesterone (P < 0.05), estrogens (P < 0.05), area under the curve for insulin (insulin(AUC)) (P < 0.05), and C-peptide(AUC) (P < 0.01) and lower insulin sensitivity (as composite insulin sensitivity index) (P < 0.05) than the NR-PCOS group. The response of 17-hydroxyprogesterone to (1-24)ACTH (as percent variation) was lower in the HR-PCOS group with respect to the NR-PCOS group (P < 0.05), whereas the response of cortisol, androstenedione, and dehydroepiandrosterone was similar. Finally, the HR-PCOS group had lower percent suppression of androstenedione (P < 0.001) and 17-hydoxyprogesterone (P < 0.05) to dexamethasone. In a multiple regression model applied in all PCOS women, insulin(AUC) but not androgens or markers of insulin resistance predicted the 17-hydroxyprogesterone response to buserelin to a highly significant extent (t = 3.269; P < 0.01).. This study indicates that the paradigm that FOH is a specific feature of the PCOS status can no longer be sustained. We have shown that women with an exaggerated 17-hydroxyprogesterone response to a GnRH agonist, buserelin, are characterized by more severe hyperandrogenemia, glucose-stimulated beta-cell insulin secretion, and worse insulin resistance than those without evidence of FOH. Our data may be consistent with the hypothesis that excess insulin may represent a candidate factor responsible for FOH in these women, through the overactivation of the cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) enzyme pathway.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adult; Anthropometry; Blood Glucose; Buserelin; C-Peptide; Cosyntropin; Dexamethasone; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Hormones; Humans; Hyperandrogenism; Insulin; Middle Aged; Ovarian Diseases; Phenotype; Polycystic Ovary Syndrome; Prospective Studies

The present study was designed to examine the relationship between Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma gene (PPAR-gamma) and clinical and hormonal characteristics in women with polycystic ovary syndrome (PCOS).. One hundred patients with PCOS and 100 healthy subjects were included in the study. Serum levels of sex steroids were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA). The responses of glucose and insulin to an oral glucose tolerance test were analyzed by calculating the respective area under the curve (AUC) by the trapezoidal method. We used the restriction fragment length polymorphism technique and polymerase chain reaction to examine Pro12Ala polymorphism in exon 2 of PPAR-gamma.. Pro12Ala polymorphism of PPAR-gamma was significantly elevated in control subjects (22%) compared with PCOS subjects (15%). All of the Pro12Ala polymorphisms of PPAR-gamma were heterozygous. When PCOS subjects with the Pro allele and the Ala allele of PPAR-gamma were compared, the latter had lower free testosterone, androstenedione, dehydroepiandrosterone sulfate, insulin and C-peptide levels, as well as lower luteinizing hormone/follicle-stimulating hormone ratio, HOMA insulin resistance index, AUCinsulin, Ferriman-Gallwey score, acne, body mass index and waist-to-hip ratio.. We suggest that Pro12Ala polymorphism of the PPAR-gamma gene may be a modifier of insulin resistance in women with PCOS.

Topics: Adult; Alanine; Androstenedione; Blood Glucose; C-Peptide; Dehydroepiandrosterone Sulfate; Female; Follicle Stimulating Hormone; Glucose Tolerance Test; Heterozygote; Homeostasis; Humans; Insulin; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; PPAR gamma; Proline; Testosterone

Insulin resistance and hyperinsulinemia are often considered intrinsic features of the polycystic ovary syndrome (PCOS). Nevertheless, conflicting results of insulin sensitivity and secretion have been obtained in the subgroup of normal-weight women with PCOS. Differences in body composition, ethnicity, and diet composition and a family history of metabolic diseases may act as confounding variables in women with PCOS. In the present study, insulin sensitivity and secretion were estimated by an iv glucose tolerance test (IVGTT), analyzed by minimal models, in 20 normal-weight healthy women with PCOS and no family history of type 2 diabetes mellitus and in 20 normally ovulating women, matched for age and body mass index. Insulin sensitivity [mean (95% confidence intervals); PCOS 4.0 (2.8-5.1) vs. controls 4.5 (3.5-5.4) 10(-4) min(-1)/microU.ml], and insulin secretion, expressed as the acute insulin response to glucose [PCOS 3.7 (3.3-4.2) vs. controls 3.7 (3.4-4.0) microU/ml] were similar in the two groups. The women with PCOS showed an increased proportion of total body fat (PCOS 29% vs. controls 27.2%; P < 0.01). They also showed decreased glucose effectiveness, i.e. the proportion of glucose uptake independent from insulin activity [PCOS 2.6 (2.1-3.0) vs. controls 3.8 (3.0-4.6) mg x 100 min(-1); P = 0.01]. The levels of insulin sensitivity and of glucose effectiveness did not correlate in either group. Whether the isolated finding of decreased glucose effectiveness could reflect an early stage in the development of the metabolic aberrations often associated with the syndrome remains to be clarified.

Topics: Adult; Blood Glucose; Body Size; Body Weight; C-Peptide; Diet; Energy Intake; Female; Glucose Tolerance Test; Hormones; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Polycystic Ovary Syndrome; Reference Values; Surveys and Questionnaires

The aim was to investigate the clinical, biochemical and ultrasonographic characteristics of Scandinavian women with polycystic ovarian syndrome (PCOS), and to see whether there were any differences between eumenorrhoic and oligoamenorrhoic women.. Eighty women aged between 18 and 40 years with PCOS were investigated in a prospective study. The inclusion criteria were polycystic ovaries (PCO), body mass index (BMI) >25 kg/m(2) and at least one of the following: testosterone >2.5 nmol/L, sex hormone binding globulin (SHBG) <30 nmol/L, fasting C-peptide >1.0 nmol/L, oligoamenorrhea or hirsutism.. Eumenorrhoic and oligoamenorrhoic women with PCOS did not differ in age, age at menarche, blood pressure, BMI, free testosterone index (FTI), insulin C-peptide or fasting glucose. A thicker endometrium and a smaller ovarian volume were found in eumenorrhoic compared to oligoamenorrhoic patients. There was linear association between BMI and the number of diagnostic criteria met.. BMI was associated with the severity of the PCOS. There were no differences in basic clinical and biochemical parameters between eumenorrhoic and oligoamenorrhoic patients with PCOS.

Topics: Adult; Body Mass Index; C-Peptide; Endometrium; Female; Humans; Medical Records; Menstruation; Norway; Ovary; Polycystic Ovary Syndrome; Retrospective Studies; Risk Factors; Sex Hormone-Binding Globulin; Testosterone; Ultrasonography

Increased amount of abdominal fat and obesity are common in polycystic ovary syndrome (PCOS). A higher prevalence of bulimia nervosa and greater cravings for sweets have also been reported in these patients. The present study aimed to compare meal-related appetite and secretion of the 'satiety peptide' cholecystokinin (CCK) and glucose regulatory hormones in PCOS women and controls. Sixteen pairs of women with PCOS and controls matched for age and body mass index participated in the study. After an overnight fast, blood samples were collected during ingestion of a standardized meal. We determined basal and postprandial blood levels of CCK, insulin, C-peptide, glucagon, cortisol, growth hormone and glucose. Self-ratings of appetite were assessed by a visual analog scale. PCOS women had a significantly lower meal-related CCK response (p < 0.05) with no association with satiety, as in the controls (r = 0.64). There was a tendency to higher ratings of craving for sweets in PCOS women (p = 0.07) but no correlation with insulin, as in the controls (r = 0.50). Within the PCOS group, ratings of craving for sweets were inversely related to testosterone (r = - 0.60) and the CCK response was positively correlated with levels of free testosterone (r = 0.50). We conclude that women with PCOS have reduced postprandial CCK secretion and deranged appetite regulation associated with increased levels of testosterone. Impaired CCK secretion may play a role in the greater frequency of binge eating and overweight in women with PCOS.

Topics: Adult; Appetite Regulation; Blood Glucose; Body Mass Index; Bulimia; C-Peptide; Cholecystokinin; Female; Food; Food Preferences; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Polycystic Ovary Syndrome; Satiation; Sex Hormone-Binding Globulin; Testosterone

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.

Topics: Adipose Tissue; Adult; Androgen Antagonists; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Body Composition; Body Constitution; Body Mass Index; Body Weight; C-Peptide; Cyproterone Acetate; Dehydroepiandrosterone Sulfate; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin; Insulin Resistance; Leptin; Lipoprotein(a); Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

The aim of this study was to establish the effect of polycystic ovary syndrome (PCOS) adjusted for adiposity on proinsulin concentrations.. Ninety-one women with PCOS and 72 normal cycling (NC) women were recruited. A 2 h, 75 g oral glucose tolerance test was performed. Glucose and insulin were measured in each sample. Proinsulin and C-peptide were determined at 0 and 30 min and the fasting proinsulin/insulin ratio (PI/I) was calculated. Insulin sensitivity was estimated by insulin sensitivity index (ISI) composite, and beta-cell function was estimated by insulinogenic index.. Insulin, proinsulin and C-peptide concentrations were higher in women with PCOS than in NC women (P < 0.05). PI/I and insulinogenic index were similar in both groups. Proinsulin concentrations increased with body mass index (P < 0.05) only in women with PCOS; therefore, proinsulin concentrations were higher in obese PCOS patients compared with obese control women (P < 0.05). Moreover, a positive association between proinsulin concentrations and waist diameter adjusted for C-peptide (P < 0.05) and a negative association between proinsulin concentrations and ISI composite values were observed in PCOS patients (P < 0.05).. Data suggest that in PCOS patients an elevated proinsulin concentration could reflect insulin resistance more than beta-cell dysfunction. However, the elevated concentration of proinsulin in these patients could also result from impaired beta-cell function resulting from intra-abdominal obesity independently of insulin resistance.

Topics: Adolescent; Adult; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Obesity; Polycystic Ovary Syndrome; Proinsulin

To determine whether hyperinsulinemia has a negative effect on uterine blood supply in patients with polycystic ovary syndrome (PCOS).. Sixty-three patients with normal body mass index were included prospectively in the study: 48 had clinical and hormonal features of PCOS and 15 were normo-ovulatory. All patients underwent Doppler flow measurement of the uterine artery, and determination of serum concentrations of luteinizing hormone, follicle stimulating hormone, prolactin, estradiol, androgens, insulin and C-peptide during the early follicular phase of the menstrual cycle. The 48 PCOS-patients were divided into two groups according to the pulsatility index (PI) value of the uterine artery: Group 1, PI < 3; Group 2, PI >or= 3 and the groups were compared.. The mean PI of the uterine artery (3.01 +/- 1.0 vs. 1.93 +/- 0.3, respectively) and fasting levels of insulin (50.9 +/- 9.3 vs. 40.3 +/- 10.9) and C-peptide (366.9 +/- 118.4 vs. 243.6 +/- 120.3) of PCOS-patients were significantly higher than those of the control group. No correlation was found between insulinemia and C-peptide and PI of the uterine artery and no significant difference was found in insulin and C-peptide levels among the two groups of PCOS-affected patients. Only the serum level of dehydroepiandrosterone sulfate was significantly higher in Group 2, and a direct correlation was found between PI values of the uterine artery and DHEAS plasma levels.. Insulin and C-peptide do not seem to interfere with uterine perfusion in PCOS-affected patients.

Topics: C-Peptide; Case-Control Studies; Female; Humans; Hyperinsulinism; Perfusion; Polycystic Ovary Syndrome; Uterus

Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin resistance and glucose tolerance by means of the continuous infusion of glucose with model assessment (CIGMA) test. The mean concentrations of glucose and insulin at 50, 55 and 60 min of glucose infusion were interpreted using a mathematical model of glucose and insulin homeostasis, and an insulin resistance index (IR1) was obtained. Using insulin and glucose values at 60 min only, a new insulin resistance index (IR2) was obtained using the same mathematical method. In addition, fasting insulin, fasting C-peptide, fasting glucose, fasting insulin:glucose ratio and fasting C-peptide:glucose ratio were also used to assess insulin resistance. There were significant correlations between IR1 and IR2, fasting glucose, fasting insulin, fasting insulin:glucose ratio, fasting C-peptide:glucose ratio. IR2 had the highest correlation with IR1 (r = 0.97, p < 0.001) and provided the best combination of sensitivity (82.9%), specificity (93.9%), positive predictive value (91.9%) and negative predictive value (86.8%). In conclusion, the simplified CIGMA test, using insulin and glucose concentration at 60 min of glucose infusion only, is a highly sensitive and specific measure of insulin sensitivity in women with PCOS.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Kinetics; Mathematics; Models, Biological; Polycystic Ovary Syndrome; ROC Curve; Sensitivity and Specificity

Polycystic ovary syndrome (PCOS) is connected with insulin resistance (IR), and often with the hypersecretion of adrenal androgens. Mutual relationships between IR and adrenal and ovarian steroidogenesis were investigated in the group of 19 oligo/amenorhoeic women with PCOS. The age and body mass index (BMI) of the patients were 21+/-4.7 years and 26.4+/-5 kg/m2 (average+/-SD), respectively. All underwent a 60-minute adrenocorticotrophic hormone (ACTH) stimulation test, a gonadoliberin analogue (GnRHa) test with buserelin and an oral glucose tolerance test (oGTT) in the early follicular phase of the menstrual cycle. When absolute stimulated steroid levels after GnRHa were studied, a significant positive correlation between DHEA and area under curve during oGTT for C peptide (AUC-CP) (r=0.477, p= 0.039) and a borderline negative correlation (r=-0.404, p= 0.087) between AUC-CP and 17-OH progesterone, were found. Considering steroid values after ACTH, a significant positive correlation of IR index was found only with 17-OH-progesterone (r=0.499, p= 0.03). When stimulated enzymatic activities (expressed as product/ precursor ratios) were analyzed using factor analysis, a positive relationship between IR and ovarian C17,20-lyase in both delta4 and delta5 pathway was revealed. On the other hand, no relationship was confirmed between IR and enzymatic activities in the adrenals. The authors conclude that insulin resistance and/or hyperinsulinemia is probably not the primary factor responsible for the exaggerated adrenal androgen secretion found in a great number of patients with PCOS.

Topics: 17-alpha-Hydroxyprogesterone; 3-Hydroxysteroid Dehydrogenases; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Androgens; Blood Glucose; C-Peptide; Dehydroepiandrosterone; Factor Analysis, Statistical; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin Resistance; Ovary; Polycystic Ovary Syndrome; Reference Values; Steroid 17-alpha-Hydroxylase

Little is known about the natural history of polycystic ovary syndrome (PCOS), although preliminary data indicate that affected women are more susceptible than the general population to diabetes and cardiovascular diseases at post-menopausal ages. The aim of this study was to follow-up all main features of the metabolic syndrome in a group of young women with PCOS and to investigate the long-term effects on metabolism and body composition of oestrogen-progestagen (OP) compounds, which are frequently used in these women to treat hyperandrogenism and related clinical features.. Long-term follow-up study.. Thirty-seven women with PCOS were re-evaluated 10.3 +/- 0.8 years (range 6-18 years) after their first assessments (age: before 19.8 +/- 4.9 years; after 29.9 +/- 4.4 years). When first examined, women were instructed to follow a hypocaloric diet if they were obese plus OP, if they agreed to such treatment. Main anthropometric parameters, basal sex hormones and lipids, fasting and glucose-stimulated glucose and insulin levels and several clinical data were recorded before and after follow-up.. In the whole group of women with PCOS we found no changes in body weight and fat mass, whereas both the waist-to-hip ratio and the waist-to-thigh ratio were significantly reduced. No significant changes occurred in mean fasting and glucose-stimulated glucose and insulin concentrations, whereas a significant increase in high-density lipoprotein-cholesterol was found. No significant changes occurred in testosterone levels. During the follow-up period 16 women took OP for an average of 97 +/- 18 months (range 12-180 months) (OP-users) whereas 21 women never took OP (non-OP-users). All OP-users were still taking OP when re-evaluated at the follow-up examination. With respect to baseline values, body mass index was higher in non-OP-users than in their counterparts. Waist circumference (P < 0.025), the waist-to-hip (P < 0.05) and the waist-to-thigh (P < 0.01) ratios decreased significantly only in the OP-users. In addition, percentage changes in waist circumference (P < 0.05) and waist-to-hip ratio (P < 0.05) during the follow-up period were significantly different between the groups. Glucose tolerance (as area under the curve (AUC)) improved (P < 0.05) in OP-users but not in non-OP-users. Moreover, compared to baseline values, basal insulin levels were significantly (P < 0.01) reduced in OP-users but not in non-OP-users. On the contrary, no significant change was found in insulinAUC in the former, whereas it significantly increased (P < 0.05) in the latter. Accordingly, fasting C-peptide decreased (P < 0.05) in OP-users, whereas both fasting (P < 0.01) and stimulated (P < 0.01) C-peptide significantly increased in non-OP-users. Changes in fasting or stimulated insulin and C-peptide in non-OP-users were not associated with parallel changes in testosterone levels. Total cholesterol and triglycerides did not change in either group, but HDL-cholesterol increased (P < 0.05) only in OP-users. Sex hormone-binding globulin concentrations increased significantly (P < 0.01) in OP-users, without any significant change in non-OP-users. Testosterone concentrations did not change significantly in either group, but the testosterone: SHBG ratio significantly decreased in OP-users (P < 0.05) but not in the non-OP-users. Among the clinical features, acanthosis nigricans significantly (P < 0.01) worsened in non-OP-users but not in the OP-users, without any significant change in the hirsutism and acne scores. Pregnancy rates during the follow-up were similar in both groups.. These data indicate that hyperinsulinaemia and insulin resistance tended to worsen spontaneously in women with PCOS, without any worsening of the hyperandrogenism. Long-term oestrogen-progestagen treatment countered this tendency, probably because it improved the pattern of body fat distribution, by reducing abdominal fat depots.

Topics: Adolescent; Adult; Blood Glucose; Body Composition; Body Mass Index; C-Peptide; Cholesterol, HDL; Estrogen Replacement Therapy; Female; Follow-Up Studies; Humans; Insulin; Polycystic Ovary Syndrome; Progestins; Testosterone

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of polycystic ovarian disease (PCOD). On the other hand, being generally admitted that opioids may play a role in glycoregulation and that opioid tone is altered in PCOD, an involvement of the opioids in determining the hyperinsulinemia of PCOD patients could be suggested. The aim of this study was to evaluate the effect of a chronic opioid blockade on insulin metabolism and peripheral insulin sensitivity in PCOD hyperinsulinemic patients. Twenty-three women with PCOD were studied. An oral glucose tolerance test (OGTT) and a clamp study were performed at baseline (during the follicular phase) and after 6 weeks of naltrexone administration (50 mg/d orally). Based on the insulinemic response to the OGTT, 16 women were classified as hyperinsulinemic and seven as normoinsulinemic. Naltrexone treatment significantly reduced fasting (P < .05) and area under the curve (AUC) (P < .02) plasma insulin levels only in the hyperinsulinemic group. Moreover, hyperinsulinemic patients showed similar C-peptide incremental areas after naltrexone treatment, whereas in the same patients the fractional hepatic insulin extraction calculated from the incremental areas of insulin and C-peptide was found to be increased after chronic opioid blockade by naltrexone. For peripheral insulin sensitivity, the hyperinsulinemic group showed significantly lower (P < .01) total-body glucose utilization (M) compared with the normoinsulinemic group. No change in the M value was found after treatment in both groups. These data suggest that the insulin sensitivity and hyperinsulinemia after an OGTT are two distinct deranged features of the insulin disorder of PCOD patients.

Topics: Adolescent; Adult; C-Peptide; Female; Glucose; Humans; Hyperinsulinism; Insulin Resistance; Naltrexone; Opioid Peptides; Polycystic Ovary Syndrome

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.

Topics: Adolescent; Adult; Androgens; Body Composition; Body Constitution; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Proteins; Skinfold Thickness

The pathogenetic mechanisms behind insulin resistance in polycystic ovary syndrome (PCOS) are far from fully elucidated. Aberrant counterregulatory responses to hypoglycaemia have been reported in patients with insulin resistance, and recent reports suggest that plasma glucose may be regulated at lower levels in women with PCOS. In this study we investigated the complete hormonal counterregulatory response to hypoglycaemia in women with PCOS.. Prospective cross-sectional study.. Eight obese (BMI > or = 25) and 10 non-obese (BMI < 25) women with PCOS, diagnosed by means of ultrasonography and clinical signs of chronic anovulation. Eight obese and 9 non-obese controls.. Hypoglycaemia was induced by an intravenous bolus of soluble insulin (0.15 IU/kg body weight). The counterregulatory responses of cortisol, GH, catecholamines, glucagon, chromogranin A (CGA), and neuropeptide Y (NPY) were studied together with symptoms of hypoglycaemia.. The obese women with PCOS had a more pronounced truncal-abdominal body fat distribution (waist hip ratio, WHR) and were hyperinsulinaemic, compared with the obese controls. All the women exhibited blood glucose levels (< 2 mmol/l) well below the threshold for the hormonal counterregulatory response and for the appearance of clinical symptoms. The non-obese women with PCOS showed a greater increase in serum concentrations of GH than the lean controls. The obese women with PCOS exhibited blunted responses of noradrenaline and NPY, but similar increases of adrenaline and CGA, compared with the obese controls. They also showed a lower symptom score during hypoglycaemia. The response of noradrenaline to hypoglycaemia correlated inversely with fasting insulin levels in the women with PCOS. Among all the obese women (PCOS and controls pooled) basal levels of noradrenaline correlated inversely with the WHR.. All the women with PCOS, independent of BMI, body fat distribution and insulin levels, showed preserved counterregulatory responses to hypoglycaemia. The reduced plasma levels of noradrenaline and the lower perception of hypoglycaemic symptoms in the obese women with PCOS could both reflect a lower activation of the sympathetic nervous system. This aberration seems related to truncal-abdominal obesity and hyperinsulinaemia. The finding of an increased response of GH in the lean women with PCOS could support previous suggestions of an altered activity of the GH/IGF-I system in these women.

Topics: Adult; Body Mass Index; C-Peptide; Chromogranin A; Chromogranins; Cross-Sectional Studies; Female; Growth Hormone; Humans; Hypoglycemia; Insulin; Neuropeptide Y; Norepinephrine; Obesity; Polycystic Ovary Syndrome; Prospective Studies

To determine whether hyperinsulinism affects cytochrome P450c17 alpha activity by investigating the correlation between 17-hydroxyprogesterone (17-OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS).. Ultrasound, clinical and hormonal parameters were used to define PCOS in this prospective clinical study. We investigated the correlation between the 17-OHP response to buserelin testing and the insulin response to oral glucose in PCOS.. Twenty-eight women with PCOS and eighteen normal women were included in the study. 17-OHP response to buserelin, and insulin and C-peptide responses to oral glucose were measured.. Twenty-five women with PCOS had an increased 17-OHP response. The PCOS patients showed significantly higher mean post-glucose load insulin and C-peptide levels than controls (P < 0.05). No significant correlations were found between basal 17-OHP and fasting insulin or fasting C-peptide, between peak 17-OHP and fasting insulin, peak insulin or peak C-peptide, between 17-OHP area under the curve (AUC) and insulin AUC or C-peptide AUC, and between percent increment in 17-OHP and insulin AUC or C-peptide AUC (P > 0.05).. Lack of a relationship between the 17-OHP response to the GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not play a role in the dysregulation of the cytochrome P450c17 alpha enzyme seen in PCOS.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adult; Buserelin; C-Peptide; Female; Follicle Stimulating Hormone; Glucose; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Hyperinsulinism; Insulin; Luteinizing Hormone; Polycystic Ovary Syndrome; Prolactin; Steroid 17-alpha-Hydroxylase; Testosterone; Time Factors

The aim of this study was to evaluate the impact of reduced peripheral insulin sensitivity, beta cell hypersecretion and reduced hepatic insulin clearance in the hyper-insulinaemia of lean and obese PCOS patients. A total of 35 women with polycystic ovary syndrome (PCOS) and 10 lean normo-ovulatory controls underwent an oral glucose tolerance test and an euglycaemic-hyper-insulinaemic clamp study. PCOS patients were classified into four groups according to their BMI and insulin secretion (normo-lean; normo-obese; hyper-lean; hyper-obese), and results were compared between groups and with the controls. All the PCOS groups showed significantly higher insulin secretion than controls; there were no differences in insulin response to glucose load between lean and obese normo- and hyper-insulinaemic patients. Secretion of c-peptide was greater in PCOS groups than controls. All the hyper-insulinaemic PCOS patients had lower values of hepatic insulin clearance, independent of BMI, when compared either with controls (P < 0.001) or with PCOS normo-insulinaemic women (P < 0.01). Normo- and hyper-insulinaemic obese patients had similar total body glucose utilization (M value), which was lower than in lean PCOS subjects and controls. Our results suggest that evaluation of insulin resistance alone does not fully characterize the PCOS population; differences in liver metabolism of insulin are present in obese insulin resistant subjects and in lean patients with normal insulin sensitivity when divided into normo- and hyper-insulinaemic subgroups. Insulin resistance and hyper-insulinaemia may represent two distinct features of the insulin disorder in PCOS: the former appear to reflect the presence of obesity, while the latter may be a primary feature of PCOS.

Topics: Adolescent; Adult; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Liver; Obesity; Polycystic Ovary Syndrome

To further investigate the relationship between inappropriate gonadotropin, hyperinsulinemia and androgen excess.. We divided women with polycystic ovarian syndrome (PCOS) into two groups on the basis of LH/FSH (LH/FSH > or = 3, Group 1, n=30; LH/FSH<3, Group 2, n=25) and measured the responses of insulin, C-peptide (C-P), C-P/insulin (C-I) and testosterone concentrations to an oral glucose tolerance test (OGTT) in these patients and 15 control subjects.. Significant positive correlations were found between basal LH and T (r=O.58, p<0.05) in Group 1, and between fasting serum insulin and T (r=0.48, p<0.05) in Group 2. Although these patients had higher, delayed insulin and C-P responses to OGTT than the control group, much greater insulin and C-P levels and lower C/I values were found in Group 2. T concentrations decreased mildly during OGTT in Group 1 and the control, while they increased slightly in Group 2.. Our data suggest that hyperinsulinemia in PCOS is due to a enhanced beta-cell secretion and an impaired hepatic clearance of this hormone, hyperandrogenism may be LH-dependent in Group 1 and insulin-dependent in Group 2.

Topics: Adult; Analysis of Variance; C-Peptide; Female; Follicle Stimulating Hormone; Glucose; Glucose Tolerance Test; Humans; Hyperandrogenism; Insulin; Luteinizing Hormone; Polycystic Ovary Syndrome; Testosterone

The purpose of this work was to investigate the relationship of gonadotropin levels to body weight and insulin levels in woman with polycystic ovary syndrome (PCOS). Specifically, we wished to test the hypothesis that circulating luteinizing hormone (LH) and insulin levels are different in obese and normal weight patients with PCOS. The basal plasma levels of gonadotropins, estrogens, androgens and sex hormone-binding globulin, the gonadotropin responses to gonadotropin releasing hormone (GnRH) and the insulin and C-peptide responses to a 3-hour oral glucose tolerance test (OGTT) were measured in 19 obese and 19 normal weight patients with PCOS and 7 obese and 8 normal weight ovulatory controls. Data of the patients were evaluated according to body weight (obese vs normal weight) and basal LH (high vs normal). There was no significant difference in basal LH and androgen levels and in the insulin response to oral glucose between obese and normal weight patients with PCOS. Compared to the weight matched controls, both obese and non obese patients showed significantly higher LH responses to GnRH and C-peptide responses to OGTT. When the high LH patients (no = 18) were compared those with normal LH (no = 20), the high LH subjects exhibited significantly higher androstenedione levels. Both obese (no = 10) and normal weight (no = 8) patients with high LH showed significantly greater C-peptide responses to OGTT than obese (no = 9) and non obese (no = 11) patients with normal LH. However, as compared with the weight matched controls, both the high LH and normal LH patients had significantly greater C-peptide responses to OGTT. We conclude that obese and non obese patients with PCOS do not seem to differ in the prevalence of elevated LH levels or in the LH secretory pattern. Insulin resistance, expressed by an enhanced pancreatic sensitivity to oral glucose, is present in both the high LH and the normal LH subjects, even though the PCOS patients with elevated LH tend to be more insulin resistant and hyperandrogenic than the normal LH patients.

Topics: Adult; Androgens; Body Mass Index; Body Weight; C-Peptide; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Insulin; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin

We investigated the contributions made by the entero-insular axis, proinsulin and the fractional hepatic extraction of insulin to the hyperinsulinaemia characteristic of polycystic ovarian syndrome (PCOS). We measured plasma glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (7-36 amide) (GLP-1(7-36) amide), immunoreactive insulin (IRI), intact proinsulin (IPI), and C-peptide concentrations during a 75 g oral glucose tolerance test in seven normal weight women with PCOS and eight healthy women. Women with PCOS had higher fasting (P = 0.05) and integrated (P < 0.01) IRI concentrations than controls. Fasting C-peptide levels were similar in both groups but integrated C-peptide (P < 0.05) concentrations were greater in PCOS subjects than controls. Fasting and integrated concentrations of glucose, GIP and GLP-1(7-36) amide were similar in subjects with PCOS and controls. Although fasting IPI concentrations were similar in both groups, integrated IPI concentrations were higher (P = 0.05) in patients with PCOS. Women with PCOS had similar fasting but higher (P < 0.05) integrated IRI:C-peptide molar ratios than controls. Fasting and integrated IPI:IRI molar ratios were similar in both groups. These results confirm that lean women with PCOS have peripheral hyperinsulinaemia. The mild fasting hyperinsulinaemia is due to increased pancreatic secretion, whereas the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and reduced fractional hepatic extraction of insulin. Hyperproinsulinaemia is modest and appropriate in PCOS, GIP and GLP-1(7-36) amide do not contribute to the stimulated hyperinsulinaemia in PCOS.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Neurotransmitter Agents; Peptide Fragments; Polycystic Ovary Syndrome; Proinsulin

In overweight women with polycystic ovary syndrome (PCOS), increased insulin resistance has been observed. Since abdominal obesity is associated with impaired fibrinolytic capacity and elevated levels of plasminogen activator inhibitor (PAI-1) and since PAI-1 seems to be related to insulin resistance, we investigated the possible effects of dietary intervention on lipids, fibrinolysis, coagulation, and insulin sensitivity in obese PCOS women. Nine women aged 22 to 39 years (median weight, 97 kg) ate a protein-rich very-low-calorie diet (VLCD) (Nutrilett, Nycomed Pharma, Oslo, Norway; 421 kcal/d) for 4 weeks (part 1). After significant reductions of body fat (13%, P < .01), two of nine women achieved regular menstruation and became pregnant. Six of the remaining women continued on a conventional low-calorie diet (1,000 to 1,500 kcal/d) for the next 20 weeks (part 2), during which time they were generally able to preserve the body fat loss obtained in part 1 of the study. During part 1, significant reductions of total serum cholesterol (29%, P = .001) and fasting triglyceride ([TG] 31%, P < .05) levels were observed, as well as significant reductions of fasting glucose (6%, P < .05) and insulin (20%, P < .05). Insulin sensitivity (glucose disposal rate [GDR]) was increased by 93% (P < .05). After finishing part 2, insulin sensitivity was still significantly increased (86%, P < .05) and PAI-1 activity was significantly reduced (54%, P < .05). Moreover, overall fibrinolytic activity was significantly improved (serum D-dimer concentration increased by 75%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diet, Reducing; Factor VII; Female; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Insulin; Insulin Resistance; Lipids; Obesity; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Tissue Plasminogen Activator

A total of 17 women affected by polycystic ovarian disease (PCOD) were studied to evaluate the involvement of endogenous opioids in the pathophysiology of the hyperinsulinism in PCOD by administering naltrexone, an oral opioid antagonist. An oral glucose tolerance test (OGTT) was performed at baseline (on day 5 of the cycle) and repeated after 6 weeks of naltrexone administration. Plasma glucose, insulin and connecting peptide (c-peptide) concentrations were evaluated in all samples. Based on their insulinaemic response to OGTT, patients were classified as hyperinsulinaemic or normoinsulinaemic. Naltrexone treatment significantly (P < 0.007) reduced the insulin response to OGTT in the hyperinsulinaemic group without affecting the c-peptide incremental area; in the normoinsulinaemic group there was a slight, but not significant, increase in both c-peptide and insulin incremental areas. The two groups showed similar c-peptide incremental areas after naltrexone treatment. There was no significant difference in the c-peptide:insulin incremental areas molar ratio between the two groups; after treatment, a significant increase in this ratio was observed in both groups. When we considered the data as an expression of the fractional hepatic extraction of insulin, we found a lower value for hyperinsulinaemic in comparison with normoinsulinaemic patients (not significant), and a significant (P < 0.01) improvement of this parameter in the hyperinsulinaemic group after naltrexone administration. In conclusion, we suggest that the contribution to hyperinsulinaemia in PCOD patients may be at least in part due to both increased pancreatic secretion and reduced hepatic removal of insulin. Chronic pharmacological inhibition of opioid tone could improve the insulin plasma concentration by acting chiefly on the liver metabolism of insulin in hyperinsulinaemic patients.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Naltrexone; Narcotic Antagonists; Polycystic Ovary Syndrome

It has been well established that the hypertestosteronemia of patients with polycystic ovarian syndrome (PCO) is associated with hyperinsulinemia and insulin resistance. We have recently noted a disparity between serum levels of insulin and C-peptide in certain hypertestosteronemic women with PCO and hypothesized a possible association between testosterone and insulin metabolism. Therefore, we have studied insulin clearance (baseline steady-state ratios of C-peptide to insulin) in 15 obese PCO women, 12 weight-matched controls (OC), and nine lean controls (LC), and examined the interactions of testosterone and insulin metabolism by examining the correlations between testosterone and insulin clearance and by studying the direct in vitro actions of testosterone on T-lymphocyte insulin binding and degradation. We found that the C-peptide to insulin ratio at baseline and T-lymphocyte insulin degradation of the PCO group were twofold below the LC and OC values. Basal C-peptide to insulin ratios and insulin-degradative activities were significantly and negatively interrelated (r = .56, P < .01), and both of these parameters were highly correlated (P < .01) with basal testosterone levels (r = .49 for basal C-peptide to insulin and r = -.61 for insulin degradation). In experiments where testosterone was added to cell cultures, insulin degradation was impaired in a biphasic fashion. We conclude that (1) elevated testosterone levels may contribute to impairments in insulin metabolism, and (2) the hyperinsulinemia of hyperandrogenic women may occur in part from defects in insulin clearance and peripheral tissue insulin degradation.

Topics: Adult; Blood Glucose; C-Peptide; Cells, Cultured; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Metabolic Clearance Rate; Polycystic Ovary Syndrome; T-Lymphocytes; Testosterone

To assess the oral glucose tolerance test (OGTT)-stimulated insulin secretion and its relation to pulsatile GnRH ovulation induction outcome in patients with multifollicular or polycystic ovaries (PCOs).. Prospective study.. Reproductive Endocrinology Center, University of Bologna, Bologna, Italy.. Eight normal and 29 anovulatory women (8 with multifollicular ovaries and 21 with PCOs).. A standard OGTT was performed in all subjects. In all anovulatory patients, ovulation was induced with pulsatile GnRH (5 micrograms i.v. every 60 minutes). In multifollicular ovary patients, pulsatile GnRH was administered alone, whereas in PCOs it was preceded by GnRH agonist (GnRH-a) suppression.. Glucose, insulin, and C-peptide response to the OGTT, expressed as area under the curve (AUC). Ovulatory rates in response to pulsatile GnRH.. Insulin and C-peptide AUC were greater than controls in both multifollicular ovary and PCO patients. Insulin AUC was positively correlated to ovarian volume. Ovulation was achieved in 88% and 57% of multifollicular ovary and PCO patients, respectively. Body mass index and glucose AUC but not insulin and C-peptide AUC were significantly greater in the anovulatory PCO.. [1] Insulin AUC was increased in both multifollicular ovary and PCO patients; [2] derangements of insulin secretion may be present in a greater variety of anovulatory patients than previously thought; [3] insulin levels during the OGTT did not predict a response to pulsatile GnRH in PCOs, suggesting complex insulin interactions at the ovarian level; [4] given the in vitro stimulatory properties of insulin on granulosa cells synergistic with FSH, we propose that excessive insulin levels may contribute to the ovarian enlargement often found in multifollicular ovary and PCO patients.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Insulin; Insulin Secretion; Ovarian Diseases; Ovarian Follicle; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Ultrasonography

We examined the effects of an oral glucose load on plasma insulin, androgens, and beta-endorphin (beta EP) concentrations in patients carefully selected as having polycystic ovary syndrome (PCOS) and normal glucose tolerance. Our aim was to verify whether insulin resistance is a common feature of PCOS and to differentiate the metabolic abnormalities related to PCOS from those associated with obesity. Plasma immunoreactive insulin (IRI), C-peptide (C-PR), testosterone, androstenedione, dehydroepiandrosterone sulfate, ACTH, and beta EP responses to a 3-h oral glucose tolerance test (OGTT) were evaluated in 10 obese (OB-PCOS) and 10 nonobese (NO-PCOS) patients with PCOS and in 7 obese and 7 nonobese ovulatory controls. OB-PCOS and NO-PCOS did not differ significantly from weight-matched controls in the IRI response, but had a significantly higher C-PR response in terms of mean postglucose load levels and mean incremental areas. During OGTT, mean plasma levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate declined in both PCOS groups as well as in controls, and no significant correlation between the plasma androgen and IRI or C-PR responses was found. The ACTH response in OB-PCOS and NO-PCOS was similar to that in controls, with a progressive decrease until 180 min. A similar decline in plasma beta EP was found in controls, whereas no change in plasma beta EP was observed in OB-PCOS and NO-PCOS. These findings indicate that independently of the presence of obesity, PCOS patients have enhanced insulin secretion in response to OGTT and show a peculiar pattern of changes in plasma beta EP.

Topics: Administration, Oral; Adult; Androgens; Androstenedione; beta-Endorphin; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Radioimmunoassay; Testosterone

This study was performed to investigate whether different patterns of body fat distribution may have distinct effects on the clinical, hormonal, and metabolic features of women with clinical hyperandrogenism such as polycystic ovary syndrome (PCOS). Ninety-seven consecutive women with PCOS were included in the study after assessment of gynecological and obesity history and careful clinical examination. Women were divided into three tertile groups based on the waist to hip ratio (WHR). Those with peripheral body fat distribution (P-BFD) had a WHR of less than 0.80, those with intermediate body fat distribution (I-BFD) had a WHR of 0.81 to 0.90, and those with abdominal body fat distribution (A-BFD) had a WHR exceeding 0.90. Baseline blood and urine samples were obtained for several hormone and lipid determinations, and the response of glucose, insulin, and C-peptide to a glucose oral challenge (75 g) was investigated. In the PCOS group, WHR values were higher than those used to define P-BFD and A-BFD in the normal female population. As WHR values increased, a significantly greater prevalence of obesity and acanthosis nigricans and a lower prevalence of acne was present. No significant differences were present in any of the other clinical features between the three groups. Ovarian morphology and volumes were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adolescent; Adult; Anthropometry; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Feeding Behavior; Female; Humans; Insulin; Lipids; Ovary; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Ultrasonography

Female hyperandrogenism is often associated with hyperinsulinaemia and insulin resistance. We evaluated the hormone responses in an oral glucose tolerance test to investigate the interactions of gonadotrophins, insulin, C-peptide and androgens in women with polycystic ovarian disease (PCOD). In 28 patients with ultrasonographically diagnosed PCOD, hyperinsulinaemia and insulin resistance were mainly associated with obesity. Both basal and cumulative sum of insulin to C-peptide ratios were high in obese subjects, suggesting decreasing hepatic removal of insulin caused by obesity. Nevertheless, in some lean PCOD women, despite normal fasting insulin concentrations, insulin hypersecretion existed. The mean concentration of testosterone decreased significantly during the oral glucose tolerance test both in PCOD and control women, and of androstenedione in the PCOD patients only. However, an increase in androgen responses was found in a subgroup of PCOD patients, who had both elevated luteinizing hormone (LH) concentrations and hyperinsulinaemic response to oral glucose. In the remaining PCOD patients an inverse correlation between LH and insulin was found. The patients with hyperinsulinaemia together with LH hypersecretion may represent a subgroup of PCOD with deranged regulation of androgen secretion.

Topics: Adolescent; Adult; Androgens; Androstenedione; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Testosterone; Ultrasonography

Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome.. Nine obese (BMI > 25 kg/m2) and nine non-obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria.. Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG.. There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients.. The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.

Topics: Adult; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucagon; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Islets of Langerhans; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone

Raised insulin levels are now recognized as a characteristic feature of women with polycystic ovaries (PCO), and hyperinsulinism has been shown to stimulate androgen production in such women. We have, however, recently shown that hyperinsulinaemia is present only in the obese subjects with PCO in whom insulin concentrations correlate with those of luteinizing hormone. We therefore studied 24-hour blood profiles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in obese and non-obese women with PCO, for comparison with their levels of insulin, C-peptide and other hormones, such as androgens which are known to be disturbed in PCO. Mean 24-hour GH levels were higher overall in PCO than in control subjects, although the difference was not significant. When, however, a separate analysis was made in obese as compared with non-obese PCO patients, GH concentrations were significantly higher in the non-obese group than in the obese (p = 0.0005). There was a significant negative correlation between body mass index and mean 24-hour GH concentrations (r = -0.641; p = 0.0006). IGF-I concentrations were however similar in the PCO group overall and in controls, as well as in the obese and non-obese PCO patients. The 24-hour blood glucose profile pattern was significantly different in PCO women from controls (p = 0.009), with absence of post-prandial peaks in blood glucose concentrations. These changes were most marked in the non-obese PCO group, who also had significantly lower blood glucose levels than either controls or obese PCO subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; Body Mass Index; C-Peptide; Circadian Rhythm; Female; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Obesity; Polycystic Ovary Syndrome

To investigate the relative contribution of insulin and sex hormones in determining the abdominal pattern of fat distribution in premenopausal women, five groups of age-matched subjects were examined: Group 1 consisted of 14 normal weight eumenorrheic women (NO); Group 2 of 9 obese eumenorrheic women (OB); Group 3 of 14 normal weight hyperandrogenic women with polycystic ovary syndrome (NO-HA); Group 4 of 10 obese hyperandrogenic women with polycystic ovary syndrome (OB-HA) and, finally, Group 5 of 10 obese hyperandrogenic women with polycystic ovary syndrome and acanthosis nigricans (OB-HA-AN). Both the two normal weight groups and the three obese groups were matched for body mass index values. Sex hormone pattern showed significantly higher LH and testosterone levels in hyperandrogenic women with respect to NO and OB women but obese hyperandrogenic groups (OB-HA and OB-HA-AN) presented significantly lower LH concentrations than NO-HA. Fasting and glucose-stimulated insulin levels were significantly higher in OB than NO, in OB-HA and OB-HA-AN than in OB and NO-HA, and in OB-HA-AN than in OB-HA, without any significant difference between OB and NO-HA. Body fat distribution, expressed by the waist to hip ratio (WHR), showed progressively higher values (p less than 0.01) from NO to OB, NO-HA, OB-HA and, particularly, OB-HA-AN women. Determination coefficients r2 obtained from simple regression analysis showed that the sum of insulin values during the glucose tolerance test and testosterone levels had a more significant power in determining WHR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Acanthosis Nigricans; Adipose Tissue; Adult; Androgens; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Glucose; Gonadal Steroid Hormones; Gonadotropins; Humans; Insulin; Male; Obesity; Polycystic Ovary Syndrome; Regression Analysis

It has been hypothesized that the androgens testosterone and dehydroepiandrosterone (DHEA) may have opposing actions on insulin sensitivity. To test this hypothesis, we selected patients with polycystic ovary syndrome (PCO) and hypertestosteronemia and a group of individuals with adrenal hyperplasia (AH) and elevated DHEA and studied their 1) insulin and glucose responses to a 75-g oral glucose tolerance test, 2) insulin resistance by hypoglycemic responses to a standard dose of intravenous (IV) insulin, and 3) insulin binding and pyruvate dehydrogenase (PDH) responsiveness to insulin in phytohemagglutinin (PHA)-activated T lymphocytes. PCO patients exhibited elevated basal and glucose-challenged insulin levels and had blunted hypoglycemic responses to IV insulin. Conversely, AH patients had hypoglycemic responses to IV insulin significantly greater than and basal and glucose-challenged insulin levels lower than the PCO patients and weight-matched control subjects. In vitro, T-lymphocyte insulin binding of the PCO patients was 40-60% below control values; in AH patients, insulin binding and PDH insulin sensitivity were above those of the control subjects. Testosterone levels in all study subjects were negatively correlated to T-lymphocyte insulin binding and positively correlated to basal insulin, insulin area under the curve (AUC), and insulin-glucose indices. DHEA levels were positively correlated to insulin binding and inversely related to basal insulin, insulin AUC, and insulin-glucose indices. In all instances, the parameters of insulin sensitivity were more strongly correlated to individuals' ratios of DHEA to testosterone than to either of these androgens alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocortical Hyperfunction; Blood Glucose; C-Peptide; Dehydroepiandrosterone; Female; Glucose Tolerance Test; Humans; In Vitro Techniques; Insulin; Insulin Resistance; Lymphocyte Activation; Polycystic Ovary Syndrome; Pyruvate Dehydrogenase Complex; Receptor, Insulin; Reference Values; T-Lymphocytes; Testosterone

The present study was undertaken in order to determine whether patients with polycystic ovary syndrome (PCOS) have LH pulse frequency and/or amplitude higher than those in normal cycling women during the follicular phase, and, if so, to establish possible factors which might influence LH secretion in PCOS. The study was conducted on 14 PCO patients (aged 19-30 years), who were subdivided according to the data on their cycle abnormality into 2 groups: amenorrheic (Am-PCOS, n = 9) and oligomenorrheic (O-PCOS, n = 5). LH pulsatility was assessed in the early follicular phase in controls (n = 5) and O-PCOS and at any time in Am-PCOS. Blood samples were taken every 10 minutes for 4 hours. Pulse analyses of LH data were performed using the Munro program. The buserelin test was performed on the same day by injection of 40 micrograms of buserelin (blood samples were taken every 60 minutes for the following 10 hours). Eleven PCO patients and 12 control subjects had an oral glucose tolerance test (oGTT) (blood samples were taken every 60 minutes for glucose, insulin and C-peptide measurements). Both mean LH pulse frequency and mean pulse intervals were not distinguishably different in PCO women (Am and O) and controls. In contrast, the mean pulse amplitude was significantly higher in the Am-PCOS group than in O-PCOS women and controls (p less than 0.02 and p less than 0.001, respectively). A significant positive correlation was established between nadir LH concentrations and LH pulse amplitude (r = +0.966, p less than 0.001). The LH response to buserelin stimulation was significantly higher in Am-PCOS than in O-PCOS (p less than 0.004). A highly significant positive correlation was observed between LH pulse amplitude and insulin response during oGTT (p less than 0.001) in PCO subjects. Basal (prebuserelin) LH concentrations correlated significantly with fasting insulin levels (p less than 0.008) and insulin and C-peptide responses to oGTT. These results allow us to conclude the following: 1. An increased LH pulse amplitude and an exaggerated LH response to buserelin observed in amenorrheic PCO subjects compared to those in oligomenorrheic PCO subjects fail to support the hypothesis of an intrinsic hypothalamo-pituitary abnormality. 2. The relationship between fasting and glucose-stimulated insulin levels with LH nadir concentrations, pulse amplitude and response to buserelin suggests an etiological role of insulin in the pathogenesis of PCOS.

Topics: Adult; Amenorrhea; Blood Glucose; Buserelin; C-Peptide; Female; Gonadal Steroid Hormones; Humans; Insulin; Luteinizing Hormone; Oligomenorrhea; Polycystic Ovary Syndrome; Pulsatile Flow

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during oral glucose tolerance testing (OGTT) were evaluated in 10 non obese women with polycystic ovarian disease (NOB-PCOD) and 10 obese women with polycystic ovarian disease (OB-PCOD). Mean plasma glucose response at 120 minutes in OB-PCOD showed impaired glucose tolerance. Also in this group, 1 patient had frank diabetes mellitus, whilst 3 other patients had impaired glucose tolerance 1 NOB-PCOD patient had impaired glucose tolerance. Mean plasma glucose levels and mean incremental glucose areas were higher in the OB-PCOD at all time intervals and reached statistical significance at 60 and 90 minutes. Mean plasma IRI levels were also higher in OB-PCOD at all time intervals, and reached statistically significant higher levels at 0, 60 and 90 minutes. Mean serum C-peptide valves were also higher at all time intervals in OB-PCOD. The relationship between acanthosis nigricans, obesity and PCOD was also analysed. It is evident from this study that obesity has a significant negative impact on the overall carbohydrate status in women with PCOD.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Kinetics; Obesity; Polycystic Ovary Syndrome

This study was undertaken in order to evaluate the effect of an oral contraceptive containing 35 micrograms of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Twenty three patients with PCOS were treated with Diane-35 for between 9 and 18 cycles without interruption (a total of 318 treated cycles). Metabolic evaluations, which included measurements of fasting blood glucose, insulin, C-peptide, total cholesterol, triglyceride, total lipids, HDL-cholesterol, LDL-cholesterol and apolipoproteins (Apo A1, Apo A2 and Apo B), were performed before treatment and every 3rd cycle during the treatment period. In the case of 5 women an oral glucose tolerance test (oGTT) was performed before and after the 12th cycle of Diane-35 treatment, with blood samples taken for glucose, insulin and C-peptide measurements. Total cholesterol showed a significant increase after the 6th cycle (p less than 0.001) and reached the mean maximal value after the 9th cycle. A similar increasing trend was observed with LDL-cholesterol, which also reached the maximal mean level after the 9th cycle of treatment (p less than 0.05). There were no significant changes in HDL-cholesterol levels. Significant increases in serum triglyceride (p less than 0.01) and total lipids (p less than 0.001) were observed after the 3rd cycle. Apo A2 concentrations increased significantly after the 6th cycle (p less than 0.001) and showed an increasing trend thereafter. A significant increase was also observed in Apo B concentrations after the 6th cycle but these decreased after the 12th cycle. In spite of these observed increases in serum lipids and lipoproteins, the mean levels remained within the normal range throughout the treatment period. Fasting serum glucose, insulin and C-peptide concentrations did not show any significant changes during the study. Higher insulin and C-peptide responses during the oGTT were observed after the 12th cycle but the differences in the areas under the curve before and after treatment were not significant. A deterioration of blood glucose was observed after treatment with Diane-35, a significant difference in mean values being noted 150 minutes after the glucose overload (p less than 0.005). However, the areas under the curve in blood glucose response before (34.92 +/- 4.12) and after (43.45 +/- 3.61) treatment were not significantly different.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Androgen Antagonists; Apolipoproteins; C-Peptide; Carbohydrate Metabolism; Cholesterol; Cyproterone; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Humans; Insulin; Lipid Metabolism; Male; Polycystic Ovary Syndrome; Triglycerides

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.

Topics: Administration, Oral; Adult; Blood Glucose; C-Peptide; Female; Glucose; Humans; Hyperinsulinism; Injections, Intravenous; Insulin; Polycystic Ovary Syndrome

It is postulated that insulin may play a role in the regulation of ovarian androgen production. In order to test the possible interrelation between serum insulin levels and androgen production, sequential euglycemic insulin clamp (Mode 9:1 on Biostator, insulin infusion rate: 0.1; 0.2 and 0.4 U/kg b. wt/h, each rate for 90 min, BC = 80 mg/dl) was done in 6 patients with polycystic ovary disease and normal glucose tolerance. Insulin, C-Peptide, testosterone and dehydroepiandrosterone-sulphate were measured in 0, 70, 80, 90, 160, 170, 180, 250, 260 and 270 min. Significant suppression of C-Peptide levels were achieved (0 min vs 270 min = 0.81 + 0.25 vs 0.15 + 0.20 nmol/l; P less than 0.05). Basal insulin as well as the mean plateau for each insulin infusion rate were as follows: 28 + 9; 248 + 119; 427 + 69 and 524 + 77 microU/l. There was significant testosterone increase at the end of insulin infusion (0 vs 270 min = 4.8 + 1.2 vs 8.1 + 1.7 nmol/l; P less than 0.05). There were no significant changes in dehydroepiandrosterone-sulphate levels during clamp studies (0 vs 270 min = 1055 + 133 vs 913 + 114 ng/ml; P greater than 0.05). It is concluded that acute insulin infusion under the condition of sequential euglycemic clamp could increase androgen production in the ovaries of patients with PCO.

Topics: Adult; Blood Glucose; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Testosterone; Time Factors

Circulating levels of insulin and C-peptide in response to oral glucose administration (75 g) were measured in 25 PCOS patients (13 were obese and 12 non-obese) without acanthosis nigricans and in 12 non-obese normal cycling women of similar age. Fasting levels of insulin and C-peptide as well as the sums of their levels in response to glucose were significantly greater in PCO patients than in controls despite similar glucose responses. Obese PCO patients had greater basal levels, maximum increments and sums of insulin and C-peptide levels than non-obese PCO patients and controls. PCO patients with increased basal total testosterone levels had significantly greater mean fasting insulin levels (p less than 0.005) than those with normal testosterone levels but their responses to glucose were not significantly different. Hyperprolactinaemic PCO patients had neither basal level nor sums of insulin and C-peptide levels in response to glucose greater than normoprolactinaemic PCO patients. In all PCO patients BMI correlated significantly with insulin (p less than 0.05) and C-peptide levels (p less than 0.001). Total serum testosterone levels correlated significantly with fasting levels and the sum of C-peptide levels in response to glucose. The correlations of total serum testosterone levels with fasting and the sum of insulin levels in response to glucose were also positive but not significant. These results clearly indicate that in PCOS there is a significant degree of hyperinsulinaemia which is mainly related to obesity.

Topics: Body Weight; C-Peptide; Female; Humans; Insulin; Islets of Langerhans; Polycystic Ovary Syndrome; Prolactin; Testosterone

Detailed studies of a family with hyperinsulinemia are reported. The index patient, a 30-yr-old woman with polycystic ovary syndrome, presented with gestational diabetes which was completely resistant to insulin in the presence of severe endogenous hyperinsulinemia. Sensitivity to insulin was regained after delivery. Therapy with cyproterone acetate and ethinyl estradiol for hirsutism exacerbated the hyperinsulinemia toward the levels occurring in pregnancy, with a concomitant deterioration of glucose tolerance. Five other members of her family also were found to have hyperinsulinemia together with high concentrations of circulating C-peptide. Antibodies to insulin and to insulin receptors were not detected, insulin antagonists were not increased, and insulin degradation in the circulation was normal. Insulin extracted from the patient's serum was identical to normal insulin by the criteria of Sephadex chromatography, placental membrane insulin receptor binding, and stimulation of 2-deoxyglucose uptake in isolated rat adipocytes. Although [125I]insulin binding to erythrocytes of all family members and to the patient's placental membranes was markedly reduced, binding to fibroblast cultures from the patient was normal. Insulin-stimulated glucose transport in these fibroblasts also was normal, but there was a mild (20%) reduction in the concentration of cytochalasin B-binding sites in erythrocyte ghosts. Insulin resistance in this family may be due to a partial defect distal to the insulin receptor. This is asymptomatic unless metabolic stresses (pregnancy or steroid administration) are superimposed.

Topics: Adult; C-Peptide; Cytochalasin B; Erythrocytes; Female; Fibroblasts; Hirsutism; Humans; Insulin; Insulin Antibodies; Insulin Resistance; Peptides; Placenta; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Receptor, Insulin; Somatomedins

Using a combined infusion of somatostatin, insulin and glucose, insulin resistance was assessed in vivo in two groups of females with polycystic ovaries (PCO), obese (PB-PCO) and normal weight (NO-PCO) and in two groups of matched (for age, sex and body mass index) controls (OB and NO). A steady state plasma glucose (SSPG) and insulin (SSPI) was attained after 90 min. OB-PCO and NO-PCO showed higher SSPG with respect to matched controls. The SSPG levels were related to body mass index (r = 0.69; P less than 0.001). The SSPG values were significantly correlated with the fasting insulin levels (r = 0.47; P less than 0.003). Gonadotrophin and steroid peripheral blood concentrations were also evaluated in the PCO females. A significant correlation was found between the SSPG values and the dehydroepiandrosterone sulphate levels (r = 0.46; P less than 0.05) and between the fasting insulin levels and the androstenedione concentrations (r = 0.64; P less than 0.01). Moreover, significant correlation coefficients were found between the glucose to insulin ratio and the A (r = -0.59; P less than 0.01) and the DHEA-S (r = -0.50; P less than 0.05) plasma levels. Finally, no relationship between body mass index and A or DHEA-S levels was found in PCO females considered as a group. We conclude that insulin resistance is present in females with PCO and it is mainly due to the presence of obesity, but other factors such as androgen levels, probably of adrenal sources, must be considered as a cause.

Topics: Adult; Androstenedione; Blood Glucose; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose Tolerance Test; Humans; Insulin; Obesity; Polycystic Ovary Syndrome; Somatostatin

Topics: Adult; C-Peptide; Female; Humans; Insulin; Obesity; Peptides; Polycystic Ovary Syndrome