glucagon-like-peptide-1 and Polycystic-Ovary-Syndrome

Despite Polycystic Ovary Syndrome (PCOS) is a very prevalent disorder among women of reproductive age, there is widespread agreement that until now, no pharmacological options are available to tackle the entire spectrum of clinical manifestations encountered in the clinical practice. Obesity and insulin resistance, which commonly characterized this syndrome, prompted the design of studies investigating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) in PCOS. Indeed, a very impressive number of randomized controlled clinical trials (RCTs) and systematic reviews provided robust evidence on the effectiveness of GLP-1RA in PCOS as a new, appealing approach, producing both satisfactory and permanent weight loss, and improvement of insulin resistance at the same time. However, most of the subjects included in the RCTs are PCOS patients with obesity/overweight, whereas a portion of PCOS women, which can even reach 50%, might present a lean phenotype. Moreover, some benefits on clinical and metabolic features of PCOS may not have fully emerged due to the low or medium doses employed in the vast majority of the current studies. Thus, pitfalls in the methodology of these studies have led sometimes to misleading results. In addition, some aspects of GLP-1 beyond weight loss, such as preclinical evidence on GLP-1 effects in directly modulating the hypothalamus-pituitary-gonadal axis, or the effects of GLP-1RA on clinical and biochemical expression of hyperandrogenism, still deserve a greater insight, especially in light of a possible therapeutic use in PCOS women independently of obesity. Aim of this review is to further unravel the possible role of GLP-1 in PCOS pathogenesis, tempting to provide additional supports to the rationale of treatment with GLP-1RA in the management of PCOS also independent of weight loss. For this purpose, the outcomes of RCTs investigating in PCOS the anthropometric and metabolic changes have been treated separately to better underpin the effects of GLP-1 RA, in particular liraglutide, beyond weight loss.

Topics: Body Weight; Female; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Liraglutide; Obesity; Polycystic Ovary Syndrome; Weight Loss

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder among women of reproductive age. The incidence ranges from approx. 6% to 20%. PCOS is characterized by a spectrum of symptoms and clinical features that includes ovarian dysfunction, clinical and/or biochemical hyperandrogenism, and ultrasound evidence of morphologically polycystic ovaries. Obesity is present in 40-70% of patients with the syndrome. Adiposity is involved in exacerbating the negative effects of insulin resistance, hyperinsulinaemia, and hyperandrogenaemia in the course of PCOS. Therefore, it is essential to maintain normal weight or effectively treat overweight/obesity in patients suffering from this endocrinopathy. Apart from diet and lifestyle interventions, an appropriate pharmacological or surgical treatment should be selected for the individual patient. Evidence-based data have unequivocally proven the validity of the use of glucagon-like peptide 1 (GLP-1) analogues in the treatment of overweight/obese patients with PCOS. The result of the GLP-1 therapy is not only a reduction of body weight but also an improvement in insulin resistance and a decrease in hyperandrogenaemia. It also seems that this treatment method increases spontaneous and in-vitro pregnancy rates. Therefore, the GLP-1 treatment of obese PCOS women is a new therapeutic opportunity not only for weight loss but also for a wide range of benefits. This review summarizes and discusses findings regarding obesity and its relation to hyperandrogenism and insulin resistance in PCOS, with special attention paid to the pharmacological treatment of adiposity with GLP-1 analogues.

Topics: Female; Glucagon-Like Peptide 1; Humans; Hyperandrogenism; Insulin Resistance; Obesity; Overweight; Polycystic Ovary Syndrome

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) have become firmly established in the treatment of type 2 diabetes and obesity, disorders frequently associated with diminished reproductive health. Understanding of the role of GLP-1 and GLP-1 RAs in reproduction is currently limited and largely unaddressed in clinical studies.. The purpose of this narrative review is to provide a comprehensive overview of the role of GLP-1 in reproduction and to address a therapeutic perspective that can be derived from these findings.. We performed a series of PubMed database systemic searches, last updated on 1 February 2019, supplemented by the authors' knowledge and research experience in the field. A search algorithm was developed incorporating the terms glucagon-like peptide-1, GLP-1, glucagon-like peptide-1 receptor, GLP-1R, or incretins, and this was combined with terms related to reproductive health. The PICO (Population, Intervention, Comparison, Outcome) framework was used to identify interventional studies including GLP-1 RAs and dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent the degradation of endogenously released GLP-1. We identified 983 potentially relevant references. At the end of the screening process, we included 6 observational (3 preclinical and 3 human) studies, 24 interventional (9 preclinical and 15 human) studies, 4 case reports, and 1 systematic and 2 narrative reviews.. The anatomical distribution of GLP-1 receptor throughout the reproductive system and observed effects of GLP-1 in preclinical models and in a few clinical studies indicate that GLP-1 might be one of the important modulating signals connecting the reproductive and metabolic system. The outcomes show that there is mostly stimulating role of GLP-1 and its mimetics in mammalian reproduction that goes beyond mere weight reduction. In addition, GLP-1 seems to have anti-inflammatory and anti-fibrotic effects in the gonads and the endometrium affected by obesity, diabetes, and polycystic ovary syndrome (PCOS). It also seems that GLP-1 RAs and DPP-4 inhibitors can reverse polycystic ovary morphology in preclinical models and decrease serum concentrations of androgens and their bioavailability in women with PCOS. Preliminary data from interventional clinical studies suggest improved menstrual regularity as well as increased fertility rates in overweight and/or obese women with PCOS treated with GLP-1 RAs in the preconception period.. GLP-1 RAs and DPP-4 inhibitors show promise in the treatment of diabetes and obesity-related subfertility. Larger interventional studies are needed to establish the role of preconception intervention with GLP-1 based therapies, assessing fertility outcomes in obesity, PCOS, and diabetes-related fertility problems. The potential impact of the dose- and exposure time-response of different GLP-1 RAs need further exploration. Future research should also investigate sex-specific variability of GLP-1 on reproductive outcomes, in particular on the gonads where the observations in males are most conflicting.

Topics: Animals; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Gonadal Disorders; Humans; Hypoglycemic Agents; Incretins; Infertility; Male; Obesity; Polycystic Ovary Syndrome; Reproduction; Weight Loss

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females and is often associated with a number of cardiometabolic disorders such as central obesity, dyslipidaemia, hypertension, insulin resistance, hyperinsulinaemia, glucose intolerance and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1), a gut hormone secreted after a meal, enhances glucosestimulated insulin secretion and additionally suppresses appetite and gastric motility. Most studies found impaired GLP-1 kinetics in obese individuals, whereas small studies in PCOS reported reduced, normal or even elevated GLP-1 levels. Apart from their efficacy in patients with T2DM, some GLP-1 receptor agonists (GLP-1 RAs) have been successfully tested in terms of both efficiency and safety in obese individuals without diabetes and liraglutide 3 mg once daily has been approved as an antiobesity drug in the USA and the European Union. Recently, some small trials of short duration using GLP-1 RAs as monotherapy or combined with metformin in obese PCOS women showed positive results regarding weight reduction and a decrease in testosterone levels but without significant effects on insulin levels, insulin sensitivity and menstrual patterns. Longer term studies with more patients and higher doses of liraglutide (as this drug is already approved for obese individuals) are required to determine the precise indications of GLP-1 RAs in PCOS and to evaluate safety issues.

Topics: Animals; Anti-Obesity Agents; Biomarkers; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Kinetics; Liraglutide; Obesity; Polycystic Ovary Syndrome; Signal Transduction; Treatment Outcome

The polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. It is diagnosed by the presence of hyperandrogenemia, insulin resistance (IR), obesity and other endocrine or metabolic disorders. Exenatide (EX) is a kind of glucagon-like peptide, which is a new option for patients with diabetes mellitus. We present a patient with infertility for PCOS. She was overweight and her medical history included IR, right-sided ovarian mucinous cystadenomas, and left-sided teratoma. Although she had been treated with ovarian surgery, clomiphene citrate and gonadotropins, weight loss and metformin, which have been effective for dominant follicle development, she still failed to conceive. Then EX was initiated to intervene for 2 months. EX treatment was successful to improve IR; after that the infertile woman with PCOS became pregnant. EX improves IR and reproduction capacity in PCOS patients, reducing insulin level and ameliorating endocrine disorders, thereby improving ovarian function, promoting follicle development, and providing new avenues for the treatment of infertility with PCOS.

Topics: Adult; Exenatide; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Infertility, Female; Insulin Resistance; Peptides; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Reproductive Techniques, Assisted; Venoms

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

Topics: Adipokines; Bariatric Surgery; Combined Modality Therapy; Comorbidity; Diet, Reducing; Exercise Therapy; Female; Glucagon-Like Peptide 1; Gonadal Steroid Hormones; Humans; Hyperandrogenism; Inflammation; Insulin Resistance; Lactones; Life Style; Metformin; Models, Biological; Motivation; Obesity; Obesity, Abdominal; Orlistat; Polycystic Ovary Syndrome; Prevalence; Sympathetic Nervous System; Weight Loss

Patients with type 1 diabetes mellitus (T1DM) traditionally had a low body mass index and microangiopathic complications were common. The Diabetes Control and Complications Trial, published in 1993, demonstrated that therapy aimed at maintaining HbA1c levels as close to normal as feasible reduced the incidence of microangiopathy. Since then, the use of intensive insulin therapy to optimise metabolic control became generalised, with two main side effects: a higher rate of severe hypoglycaemia and increased weight gain. Approximately 50% of patients with T1DM are currently obese or overweight, which reduces or nullifies the benefits of good metabolic control, and which has other negative consequences; therefore, strategies to achieve weight control in patients with T1DM are necessary. At present, treatment with GLP-1 and SGLT-2 inhibitors has yielded promising short-term results that need to be confirmed in studies with larger numbers of patients and long-term follow-up. It is possible that, in coming years, the applicability of bariatric surgery in obese patients with T1DM will be similar to that of the general population or T2DM.

Topics: Adolescent; Adult; Bariatric Surgery; Body Mass Index; Depression; Diabetes Complications; Diabetes Mellitus, Type 1; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Hirsutism; Humans; Hypoglycemic Agents; Hypogonadism; Insulin; Life Style; Male; Metabolic Syndrome; Obesity; Osteoporosis; Overweight; Polycystic Ovary Syndrome; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Weight Gain

Polycystic ovary syndrome (PCOS) is an endocrine disease of women in reproductive age. It is characterized by anovulation and hyperandrogenism. Most often patients with PCOS have metabolic abnormalities such as dyslipidemia, insulin resistance, and glucose intolerance. It is not surprising that obesity is high prevalent in PCOS. Over 60 % of PCOS women are obese or overweight. Modulation of appetite and energy intake is essential to maintain energy balance and body weight. The gastrointestinal tract, where nutrients are digested and absorbed, plays a central role in energy homeostasis. The signals from the gastrointestinal tract arise from the stomach (ghrelin release), proximal small intestine (CCK release), and distal small intestine (GLP-1 and PYY) in response to food. These hormones are recognized as "appetite regulatory hormones." Weight loss is the key in the treatments of obese/overweight patients with PCOS. However, current non-pharmacologic management of body weight is hard to achieve. This review highlighted the gastrointestinal hormones, and discussed the potential strategies aimed at modifying hormones for treatment in PCOS.

Topics: Cholecystokinin; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Peptide YY; Polycystic Ovary Syndrome

The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

Topics: Adipokines; Adrenal Glands; Adult; Androgens; Cushing Syndrome; Diabetes Mellitus, Type 2; Endocrine System; Estrogens; Fatty Liver; Female; Glucagon-Like Peptide 1; Gonadal Steroid Hormones; Humans; Hyperlipidemias; Hypothalamus; Hypothyroidism; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Obesity; Pancreas; Pituitary Gland; Polycystic Ovary Syndrome; Postmenopause; Thyroid Gland

Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular (CV) risk markers. In this study our aim was to assess the effects of six months treatment with liraglutide 1.8 mg od on obesity, and CV risk markers, particularly platelet function, in young obese women with PCOS compared to controls of similar age and weight.. Carotid intima-media wall thickness (cIMT) was measured by B-mode ultrasonography, platelet function by flow cytometry, clot structure/lysis by turbidimetric assays and endothelial function by ELISA and post-ischaemic reactive hyperemia (RHI). Data presented as mean change (6-month - baseline) ± standard deviation.. Nineteen obese women with PCOS and 17 controls, of similar age and weight, were recruited; baseline atherothrombotic risk markers did not differ between the two groups. Twenty five (69.4%) participants completed the study (13 PCOS, 12 controls). At six months, weight was significantly reduced by 3.0 ± 4.2 and 3.8 ± 3.4 kg in the PCOS and control groups, respectively; with no significant difference between the two groups, P = 0.56. Similarly, HOMA-IR, triglyceride, hsCRP, urinary isoprostanes, serum endothelial adhesion markers (sP-selectin, sICAM and sVCAM), and clot lysis area were equally significantly reduced in both groups compared to baseline. Basal platelet P-selectin expression was significantly reduced at six months in controls -0.17 ± 0.26 but not PCOS -0.12 ± 0.28; between groups difference, 95% confidence interval = -0.14 - 0.26, P = 0.41. No significant changes were noted in cIMT or RHI.. Six months treatment with liraglutide (1.8 mg od) equally affected young obese women with PCOS and controls. In both groups, liraglutide treatment was associated with 3-4% weight loss and significant reduction in atherothrombosis markers including inflammation, endothelial function and clotting. Our data support the use of liraglutide as weight loss medication in simple obesity and suggest a potential beneficial effect on platelet function and atherothrombotic risk at 6 months of treatment.. Clinical trial reg. no. ISRCTN48560305. Date of registration 22/05/2012.

Topics: Adolescent; Adult; Blood Platelets; Cardiovascular Diseases; Carotid Intima-Media Thickness; Female; Fibrinolysis; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin Resistance; Liraglutide; Middle Aged; Polycystic Ovary Syndrome; Risk Factors; Young Adult

Zinc-α2-glycoprotein (ZAG) has been proposed to play a role in the pathogenesis of insulin resistance. Previous studies in humans and in rodents have produced conflicting results regarding the link between ZAG and insulin resistance. The objective of this study was to examine the relationships between ZAG and insulin resistance in cross-sectional and interventional studies.. Serum ZAG (determined with ELISA) was compared with various parameters related to insulin resistance in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM), and in women with or without polycystic ovary syndrome (PCOS). Euglycemic-hyperinsulinemic clamps were performed in healthy and PCOS women. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of ZAG. The effect of a glucagon-like peptide-1 agonist on ZAG was studied in a 12-week liraglutide treatment trial.. Circulating ZAG was lower in patients with IGT and newly diagnosed T2DM than in controls. Circulating ZAG correlated positively with HDL cholesterol and adiponectin, and correlated inversely with BMI, waist-to-hip ratio, body fat percentage, triglycerides, fasting blood glucose, fasting insulin, HbA1c, and homeostasis model assessment of insulin resistance (HOMA-IR). On multivariate analysis, ZAG was independently associated with BMI, HOMA-IR, and adiponectin. ZAG mRNA and protein were decreased in adipose tissue of T2DM patients. Moreover, circulating ZAG levels were lower in women with PCOS than in women with high insulin sensitivity. Liraglutide treatment for 12 weeks significantly increased circulating ZAG levels.. We conclude that ZAG may be an adipokine associated with insulin resistance.

Topics: Adipokines; Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hyperinsulinism; Insulin Resistance; Liraglutide; Male; Middle Aged; Polycystic Ovary Syndrome; Seminal Plasma Proteins; Zn-Alpha-2-Glycoprotein

Topics: Drug Therapy, Combination; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Metformin; Obesity; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant

Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women, it is the principal cause of infertility and amenorrhea. Due to its high recurrence rate, poor prognosis and serious complications, more works on the research of PCOS are needed. Therefore, we performed a protocol for systematic review and meta-analysis to investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists on ovarian dysfunction in PCOS.. This study protocol has been registered in the PROSPERO and the registration number is CRD42020188247. The procedure of this protocol will be conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocols guidance. A comprehensive search of several databases from 1966 to November 2022 will be conducted. The databases includes Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and PubMed. The risk of bias of the included studies will be assessed using the Cochrane tool of risk of bias. All statistical analyses will be conducted using the software program Review Manager version 5.3.. The results of this systematic review will be published in a peer-reviewed journal.. This systematic review will provide evidence to judge whether glucagon-like peptide-1 receptor agonist is superior to metformin in patients with PCOS.

Topics: Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Meta-Analysis as Topic; Polycystic Ovary Syndrome; Systematic Reviews as Topic

Polycystic ovary syndrome (PCOS) increases risk for development of type 2 diabetes. Whey protein ingestion before a carbohydrate load attenuates blood glucose. For our exploratory, case-control study design, we hypothesized that 35 g whey protein isolate (WPI) preloading would increase postprandial incretins and reduce hyperglycemia in women with PCOS. Twenty-nine age-matched women (PCO = 14 and CON = 15) completed oral glycemic tolerance tests (OGTT) following baseline (Day 0) as well as 35 g WPI acute (Day 1) and short-term supplementation (Day 7). Eight venous samples were collected during each test for quantification of glucose, and enteropancreatic hormones and to calculate area under the curve (AUC). Data was analyzed via repeated measures ANCOVA with significance set at P< .05. "Day x time x group" significantly influenced glucose (P = .01) and insulin changes (P = .03). In both groups, AUC

Topics: Adolescent; Adult; Analysis of Variance; Area Under Curve; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Dietary Proteins; Dietary Supplements; Female; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hyperglycemia; Incretins; Insulin; Polycystic Ovary Syndrome; Postprandial Period; Whey Proteins; Young Adult

Topics: Adult; Female; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Obesity; Polycystic Ovary Syndrome; Prediabetic State

As a new hormone, betatrophin has gained attention as a potential new target to combat insulin resistance (IR) and diabetes. Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of the reproductive age with long term sequelae which include IR and metabolic syndrome. The aim of this study is to evaluate the circulating plasma betatrophin levels in overweight/obese or lean women with or without PCOS and also to elucidate possible correlations with anthropometric and metabolic parameters. Thirty-two patients with PCOS as well as fifty-three control subjects were enrolled after obtaining informed written consent. Clinical and biochemical parameters of all subjects were determined. Plasma adiponectin, GLP-1 and betatrophin levels were measured by ELISA. Plasma betatrophin levels were significantly increased in lean patients with PCOS compared with lean and obese controls. Moreover, in PCOS group, betatrophin levels were significantly negatively correlated with waist hip ratio (WHR), fasting insulin level (FINS) and HOMA-IR, whereas, significantly positively correlated with adiponectin level. Multiple regression analysis showed that HOMA-IR was an independent factor influencing serum betatrophin levels. Further follow-up studies are needed to highlight whether and how increased betatrophin secretion play an important role in IR and carbohydrates metabolism in patients with PCOS.

Topics: Adiponectin; Adolescent; Adult; Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Biomarkers; Body Mass Index; China; Cross-Sectional Studies; Female; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Middle Aged; Obesity; Overweight; Peptide Hormones; Polycystic Ovary Syndrome; Premenopause; Thinness; Waist-Hip Ratio; Young Adult

To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls.. Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed.. Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT.. This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Brain; Female; Ghrelin; Glucagon-Like Peptide 1; Gray Matter; Humans; Leptin; Magnetic Resonance Imaging; Obesity; Organ Size; Polycystic Ovary Syndrome; Young Adult

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

Is the secretion of gastrointestinal hormones impaired in patients with polycystic ovary syndrome (PCOS)?. Gastrointestinal hormone levels were abnormal in patients with PCOS.. The hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) are both involved in signaling satiety. Secretion of GLP-1 and PYY in response to nutrients in the small intestine plays an important role in energy metabolism. Most PCOS patients are overweight or obese, which suggests dysregulation of appetite.. In order to evaluate levels of gastrointestinal hormones in PCOS, a cohort study was undertaken, involving 30 PCOS patients and 29 BMI-matched healthy women recruited from Shanghai Renji Hospital between 1 March 2013 and 30 May 2014.. After an overnight fast, all participants underwent an oral glucose tolerance test. Blood was sampled frequently for measurement of blood glucose and plasma insulin, total GLP-1 and PYY concentrations.. Fasting and postprandial insulin levels were significantly higher in patients with PCOS compared with the healthy controls (P < 0.05). Fasting and postprandial GLP-1 (t = 0 and 30 min; mean ± SEM) were also higher in PCOS group (17.5 ± 1.07 pM versus 14.1 ± 1.16 pM, P < 0.05; 29.7 ± 2.39 pM versus 22.8 ± 2.09 pM, P < 0.05). However, there were no differences in plasma PYY between patients with PCOS and healthy controls either fasting or postprandially. PYY levels were lower in obese PCOS patients than in lean PCOS patients (P < 0.05).. The study involved a small number of subjects with PCOS, and examined hormone responses to oral glucose rather than a physiological meal.. Deficient secretion of GLP-1 and PYY does not contribute to excessive food intake in the pathophysiology of PCOS.

Topics: Adult; Dipeptides; Female; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin; Polycystic Ovary Syndrome

Nonalcoholic fatty liver disease (NAFLD) has been linked to polycystic ovary syndrome (PCOS) and carries an increased risk of liver cirrhosis. Procollagen type 3 amino-terminal peptide (PIIINP) is an independent predictor of liver cirrhosis.. To assess whether 6-month treatment with GLP-1 analogue, liraglutide, improves markers of liver fibrosis.. A case-control study comparing women with PCOS to age- and weight-matched controls. PCOS was diagnosed according to the Rotterdam criteria. All participants underwent liver function tests and liver ultrasound scan to assess for fatty infiltration. Serum marker for liver fibrosis, PIIINP, was measured at baseline and after 6-month treatment with liraglutide 1·8 mg od.. Nineteen women with PCOS and 17 controls were recruited, age 32·8 ± 7·2 vs 33·5 ± 6·7 years and weight 100·9 ± 16·7 vs 99·3 ± 14·7 kg, respectively. At baseline, the PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nm (P = 0·01), HOMA-IR 5·1 ± 2·6 vs 3·5 ± 1·3 (P = 0·03), AST 22·4 ± 5·2 vs 18·8 ± 3·4 u/l (P = 0·04), PIIINP 4·4 ± 0·8 vs 3·5 ± 0·8 ug/ml (P = 0·01) and NAFLD seven (35%) vs none (P = 0·005), respectively. Twenty-five (69%) participants completed the study (13 PCOS, 12 controls). Following treatment, weight was reduced by 3·0 ± 4·2 kg (P = 0·01) and 3·8 ± 3·4 kg (P = 0·001), respectively. Similarly, HOMA-IR, hsCRP, triglycerides and urinary isoprostane significantly reduced in both groups. PIIINP significantly reduced the in PCOS group 4·4 ± 0·8 vs 3·7 ± 0·9 ug/ml (P < 0·01), but not in controls 3·5 ± 0·8 vs 3·2 ± 0·7 ug/ml (P = 0·08).. Treatment with liraglutide, and/or associated weight loss, significantly reduced PIIINP levels in obese women with PCOS. This may be an additional beneficial factor when considering the use of liraglutide in women with PCOS, obesity and NAFLD.

Topics: Adult; Case-Control Studies; Female; Glucagon-Like Peptide 1; Humans; Liraglutide; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Obesity; Polycystic Ovary Syndrome; Triglycerides

Topics: Adult; Diabetes Mellitus, Type 2; Drug Synergism; Female; Glucagon-Like Peptide 1; Hirsutism; Humans; Hypoglycemic Agents; Liraglutide; Menstrual Cycle; Metformin; Obesity, Morbid; Polycystic Ovary Syndrome; Testosterone; Weight Loss

We aimed to investigate whether fasting and meal regulated glucagon like peptide 1 (GLP-1) secretion are altered in patients with polycystic ovary syndrome (PCOS) compared to healty women and whether oral contraceptive use influence GLP-1 secretion dynamics in the syndrome.. Prospective observational study.. Fourteen lean normal glucose tolerant patients with PCOS and 11 age- and body mass index (BMI)-matched healthy women.. Glucagon like peptide 1, glucose and insulin levels were measured during a standardized meal tolerance test and area under the curves (AUCs) were calculated. Whereas healthy controls were assessed at baseline, all tests were repeated in women with PCOS after treatment with ethinyl estradiol 30 μg/drospirenone 3 mg (EE/DRSP) for 3 months.. Both fasting and post-meal levels of GLP-1 were significantly reduced in women with PCOS compared to controls (P = 0·022 and P = 0·028, respectively). AUC for GLP-1 was also lower in PCOS (P = 0·012). Glucose and insulin measurements did not show a significant change between the groups. In the PCOS group, GLP-1, glucose and insulin levels did not show any change after 3 months of EE/DRSP use.. GLP-1 levels both at fasting and in response to a meal are blunted in lean women with PCOS compared to healthy women. Short term oral contraception do not alter GLP-1 secretion in PCOS. Disturbance in incretin secretion dynamics might contribute to the risk of impaired glucose tolerance and type 2 diabetes in PCOS.

Topics: Adult; Androstenes; Area Under Curve; Blood Glucose; Estradiol; Fasting; Female; Glucagon-Like Peptide 1; Humans; Insulin; Polycystic Ovary Syndrome; Postprandial Period; Prospective Studies; Young Adult

Insulin resistance is considered to play an important role in the pathogenesis of polycystic ovary syndrome (PCOS) and in the progression to type 2 diabetes. Recent reports concentrate on a possible relationship between incretin secretion and beta-cell function in PCOS. The aim of the present study is to investigate the incretin effect in obese and lean women with PCOS.. Twenty women with PCOS and ten age-matched healthy women were recruited in the study. The oral glucose tolerance test (OGTT) and isoglycemic test were carried out on each participant after an overnight fast at 2-weeks interval. Plasma levels of insulin, glucose, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) were assayed.. Obese women with PCOS demonstrated lower GIP concentrations (area under the curve [AUC]) in response to OGTT compared to the control group. The incretin effect was found significantly augmented in the obese women with PCOS compared to controls. This finding remained robust in the subgroup analysis including only body mass index (BMI)-matched healthy women.. Increased insulinotropic effect could counteract the blunted GIP response to OGTT in obese women with PCOS. It is suggested that the pathology of PCOS may also include impaired activity of the enteroinsular axis.

Topics: Adult; Analysis of Variance; Area Under Curve; Body Mass Index; Case-Control Studies; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Tolerance Test; Greece; Humans; Incretins; Insulin; Obesity; Pilot Projects; Polycystic Ovary Syndrome; Thinness; Young Adult

In normal subjects, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for 70% of the insulin response during a meal; but in diabetic subjects and other insulin-resistant conditions, the incretin effect is impaired. Polycystic ovary syndrome (PCOS) is associated with insulin resistance, and the pathophysiologic mechanisms behind PCOS resemble those of type 2 diabetes mellitus; therefore, women with PCOS may have alterations in the incretin hormone response. Metformin is widely used in the treatment of both type 2 diabetes mellitus and PCOS. Metformin may exert some of its effect on glucose metabolism by increasing GLP-1 biosynthesis and secretion and thereby increasing the incretin effect. The objective of the study was to measure incretin hormone secretion in women with PCOS and to evaluate the effect of metformin treatment. Cross-sectional comparison of 40 women with PCOS (19 lean and 21 obese) and 26 healthy control women (9 lean and 17 obese) and longitudinal evaluation of the effects of 8 months of metformin 1000 mg twice daily in women with PCOS were performed. Plasma concentrations of GIP and GLP-1 were determined frequently during a 75-g glucose tolerance test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp. The incretin hormone response did not differ between subjects with and without PCOS. Subgroup analysis showed lower GIP (area under the curve [AUC]) levels in obese women with PCOS compared with obese control women (P < .05) and compared with lean women with PCOS (P < .05). Metformin increased GIP (AUC) and GLP-1 (AUC) in lean women with PCOS (P < .05), and a similar trend was seen in the obese women (P = .07). The GIP secretion is attenuated in obese women with PCOS, whereas treatment with metformin increases the levels of both GIP and GLP-1 in women with PCOS.

Topics: Adult; Blood Glucose; Cross-Sectional Studies; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Longitudinal Studies; Metformin; Obesity; Polycystic Ovary Syndrome

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

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