Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus (original) (raw)
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Clinical Impact of Insulin Resistance in Women with Polycystic Ovary Syndrome
Polycystic Ovarian Syndrome [Working Title]
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by multiple hormonal imbalances, reflecting on the clinical presentation. Among them, the insulin resistance (IR), defined as a metabolic state characterized by a decrease in cellular ability to respond to insulin signaling, is a key feature of PCOS independently of obesity. Thus, IR occurs in more than 70% of obese PCOS women and in 30-50% of lean ones. Compensatory high insulin levels are both a symptom and an underlying physiopathological driver of PCOS. Insulin appears to disrupt all components of the hypothalamic-pituitary-ovarian axis, and ovarian tissue IR results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia. The latter is the main culprit of the clinical picture in PCOS. Testing for IR can be helpful to rule out other conditions that are commonly misdiagnosed as PCOS and to recommend an appropriate treatment for the different PCOS phenotypes.
Changing patterns of Insulin Resistance in Polycystic Ovary Syndrome
Bangladesh Journal of Obstetrics & Gynaecology, 2016
Objective (s):Aim of the study was to explore the changing patterns of insulin resistance in PCOS women. Methods: The study was conducted at CARE, department of Obstetrics and Gynecology and Biomedical Research Group, BIRDEM hospital. A total number of 103 PCOS women of 15-36 years were included in the present study. They were grouped into NGT (n=68), IGT (n=30), type 2 DM (n=5) according to nature of glucose tolerance. Fasting and glucose stimulated insulin was measured. Results: In IGT group, fasting and glucose-stimulated insulin level were higher when compared with NGT, but no difference between type 2 DM and NGT group was found. Insulin-glucose ratio (after glucose load) was significantly lower in type 2 DM when compared with NGT group (p=0.049), but there was no difference of insulin-glucose ratio (fasting) between type 2 DM and NGT group. PCOS with IGT or Type 2 DM women were more insulin resistant than NGT group. (p=0.015, p=0.042 respectively). Conclusion: Insulin resistance is a major pathophysiologic feature of PCOS with IGT; however â cell secretory defect is associated with type 2 DM in these subjects.
Divergences in Insulin Resistance Between the Different Phenotypes of the Polycystic Ovary Syndrome
The Journal of Clinical Endocrinology & Metabolism, 2013
Context/Objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women.
Women's Health, 2012
Polycystic ovary syndrome (PCOS) and Type 2 diabetes mellitus (T2D) are both obesity-related conditions that share epidemiological and pathophysiological factors. Insulin resistance is a key factor whereby obesity influences the expression of each condition. However, the mechanisms by which insulin resistance contributes towards the manifestation of PCOS and T2D differ in important ways: in PCOS, compensatory hyperinsulinemia results in pleiotropic effects including co-gonadotrophic stimulation of ovarian and adrenal steroidogenesis; in T2D, insulin resistance contributes towards β-cell exhaustion and ultimately to hyposecretion of insulin with resultant dysglycemia. The link between PCOS and Type 1 diabetes mellitus is believed to implicate supraphysiological concentrations of insulin within the systemic circulation. Further progression of the obesity epidemic will ensure even greater prominence of important obesity-related conditions such as PCOS and T2D. Research to gain a cleare...
Insulin Resistance in Polycystic Ovary Syndrome
Paripex Indian Journal Of Research, 2016
Polycystic ovary syndrome (PCOS) is a common endocrine disease with metabolic, reproductive and psychological consequences effecting reproductive age women. In addition to the clinical features of oligo-anovulation, infertility and hyperandrogenism, PCOS is closely interrelated with insulin resistance (IR) and hyperinsulinemia, with a high prevalence. IR is also suggested to have a role in the pathogenesis of PCOS. Post-receptor defects, as well as genetic susceptibility has been held responsible for underlying mechanisms of IR. Assessment of IR includes tests of fasting insulin and blood glucose levels. In especially obese women with PCOS, oral glucose tolerance tests are recommended for screening. To overcome IR, reducing body fat and weight with a healthy diet is the initial step. Therapeutic approach includes insulin-sensitizing agents. The prevention of long-term consequences of IR in PCOS, like cardiovascular disease, type 2 diabetes and endometrium cancer, through appropriate...
Prediction a woman having Polycystic Ovary Syndrome (PCOS) those having Insulin Resistance (IR)
Pakistan Journal of Medical and Health Sciences, 2022
Background: "Polycystic Ovary Syndrome" (PCOS) has been identified as a hazard for growing diabetes. Although it indicates and symptoms of "Polycystic Ovary Syndrome" (PCOS) appear before the signs and symptoms of "Insulin resistance" (IR) first, According to an assumption "Insulin resistance" (IR) may have a part in developing PCOS instead of another factor. Insulin resistance caused by obesity modifies the function of the pituitary gland and hypothalamus in the brain, leading to an increase in the synthesis of androgenic hormones, which correlate to PCOS1. Aim: To analyze outcomes of insulin resistance in women having polycystic ovaries Methodology: A literature search was performed with the use of search engines. The following search engines provided the articles for this systematic review, PubMed, Medscape, NCBI, and Google Scholar. For article searching following keywords were used; Polycystic ovaries, insulin resistance. Results: As a li...
Insulin Resistance and Polycystic ovary Syndrome: A Review
Journal of Drug Delivery and Therapeutics, 2019
Polycystic Ovary Syndrome (PCOS) is the most common, yet complex, endocrine disorder affecting women in their reproductive years and is a leading cause of infertility. This disease appears to be multifactorial and polygenic in nature involving multisystem dysfunction, namely reproduction, endocrine and metabolic. Hyperandrogenism and insulin resistance appear to be central cause to the pathophysiology of the disease. The glucose and insulin metabolism pathways have been studied and debated to understand whether Insulin Resistance is due to a defect in insulin action or a primary defect in β-cell function or decreased hepatic clearance of insulin, or a combination of all these factors. Numerous studies have demonstrated that obese, normal weight and thin women with PCOS have a form of insulin resistance that is unique and intrinsic to the disorder. Moreover obese women with PCOS possess an additional burden of insulin resistance resulting from their excess adiposity. Hyperinsulinemia leads to increase in androgen production directly by acting as a co-gonadotropin, augmenting Luteinizing Hormone activity within the ovary, and indirectly by increasing serum LH pulse amplitude. Whereas Androgens may in turn contribute at least partially to the insulin resistance state linked with PCOS. In this review, we will briefly study the role of insulin resistance in polycystic ovary syndrome.
Is insulin resistance an essential component of PCOS?: The influence of confounding factors
Human Reproduction, 2004
Insulin resistance is often considered a regular component of polycystic ovary syndrome (PCOS). Many interventional studies assume a state of insulin resistance in all patients. However, the evidence is based on small samples that are often insuf®cient to adjust for signi®cant confounding factors. Moreover, several studies have not con®rmed differences in insulin sensitivity between women with PCOS and healthy controls, especially in non-obese patients. This debate article provides an overview of the data published regarding the presence of abnormal or normal insulin sensitivity in PCOS. In conclusion, available data offer evidence that a substantial subgroup of women with PCOS have insulin sensitivity comparable with healthy controls if matched carefully for potential confounding factors.
Is Insulin Resistance an Intrinsic Defect in Asian Polycystic Ovary Syndrome?
Yonsei Medical Journal, 2013
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The purpose of this paper is to present a review of the current research on polycystic ovary syndrome (PCOS). PCOS is one of the most common endocrine disorders in women of reproductive age, affecting 5-10% of the population. Despite its prevalence, PCOS remains largely under unknown. This review has been broken down into two separate chapters. The first is the pathogenesis and related health consequences of PCOS. This chapter focuses on the diagnosis of PCOS as well as the prevalence and incidence of the disease. It then delves into the pathogenesis with a focus on genetics, obesity, insulin resistance and birth weight. Lastly, the health consequences related to PCOS are discussed, with a focus on insulin resistance. The health outcomes reviewed include the metabolic syndrome, cardiovascular disease, and type II diabetes mellitus. The second chapter is a comparison of drug therapies and lifestyle modifications used to treat polycystic ovary syndrome. A short discussion on combination therapy is also included. By focusing on insulin resistance in treatment, it is possible to manage many of the symptoms of PCOS solely through lifestyle modifications. Although many questions remain surrounding polycystic ovary syndrome, this article provides a summary of the current research.
American Journal of Obstetrics and Gynecology, 2004
Objective: This study was undertaken to compare clinical and biochemical characteristics of the insulin resistant (IR) and non-IR subphenotypes of polycystic ovary syndrome (PCOS). Study design: Infertile PCOS women were classified as IR (n = 32) or non-IR (n = 46) on the basis of fasting glucose and insulin levels. The incidence of acanthosis nigricans (AN), hirsutism, and ovulation in response to clomiphene citrate (CC) was compared between the 2 groups, along with serum levels of gonadotropins, and sex steroids. Blood samples from 28 PCOS patients and 8 controls were analyzed by enzymatic immunoassay for autophosphorylated insulin receptor (APIR) and total insulin receptor (TIR) content. Results: Insulin resistance was associated with obesity (odds ratio [OR] = 3.5, P!.05), AN (OR = 6.0, P!.05), hirsutism (OR = 3.1, P!.05), and resistance to CC (OR = 5.0, P!.05). Mean levels of LH, LH/FSH ratios, and testosterone were lower in women with IR (11.5 G 6.8 mIU/mL, 2.0 G 1.0, and 56.6 G 29.0 ng/dL, respectively) compared with women without IR (15.0 G 13.4 mIU/mL, 2.4 G 1.5, and 72.5 G 29.8 ng/dL, respectively) (P!.05). Mean APIR/ TIR ratios in IR women were lower than in non-IR women (P!.05 at 100 nmol/L of insulin) and controls (P!.01 at 1, 10 and 100 nmol/L insulin). Conclusion: Patients with IR are more likely to be obese and have AN, hirsutism, resistance to CC, and lower LH, LH/FSH ratios, and testosterone levels. Furthermore, IR patients appear to have defective autophosphorylation of the insulin receptor, a key element in insulin action, and a possible mechanism for IR in PCOS.
Human Reproduction, 2012
background: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by oligo-or anovulation (ANOV), biochemical or clinical manifestations of hyperandrogenemia (HA) and PCOs. Four phenotypes of PCOS exist [phenotype 1 (ANOV + HA + PCO), phenotype 2 (ANOV + HA), phenotype 3 (HA + PCO) and phenotype 4 (ANOV + PCO)] but the differences between them are not well studied. We compared markers of insulin resistance (IR) and endocrine characteristics between the different PCOS phenotypes. methods: We prospectively studied 1212 consecutive women with PCOS and 254 BMI-matched healthy women. results: Phenotypes 1-4 were present in 48.2, 30.7, 9.7 and 11.4% of patients, respectively. BMI did not differ between the four phenotypes and controls. Both normal weight and overweight/obese women with phenotypes 1 and 2 were more insulin resistant than controls. Overweight/obese, but not normal weight, women with phenotype 4 were more insulin resistant than controls, while IR in women with phenotype 3 did not differ from controls regardless of obesity. In normal weight subjects, women with phenotypes 1 and 2 were more insulin resistant than women with phenotype 4. In overweight/obese subjects, women with phenotype 1 were more insulin resistant than women with phenotypes 2 and 3 and women with phenotype 4 were more insulin resistant than those with phenotype 3. Circulating androgens were higher in normal weight and overweight/obese PCOS patients with phenotypes 1-3 compared with those with phenotype 4, and higher in normal weight PCOS patients with phenotype 1 than in those with phenotype 2.
An insight of association of insulin resistance with polycystic ovary syndrome
Indian Journal of Clinical Anatomy and Physiology, 2022
Polycystic ovary syndrome (PCOS), a multifaceted condition, often has salient features like insulin resistance (IR). Abnormal alternation in insulin synthesis and function usually alters PCOS expressivity by deviating molecular and biochemical activity underlying this pathophysiology.This review intends to unveil the molecular basis of the genetic polymorphism of IR and its correlation with PCOS. It also highlights the existing methods of IR estimation. Searching of different articles using keywords including PCOS, IR, and polymorphism in various databases was performed to illustrate the review article.POCS, and IR are complex and multifactorial conditions in terms of the contributing factors, their interactions, and expressivity. Further studies on diversified genotype responses to environmental and ethnic variances are required for precise understanding.Insulin resistance (IR) and polycystic ovary syndrome (PCOS) are intricately interacted conditions that abnormally alter function...
Clinical medicine (London, England), 2015
Polycystic ovary syndrome (PCOS) is a common condition that typically develops in reproductive-age women. The cardinal clinical and biochemical characteristics of PCOS include reproductive dysfunction and hyperandrogenic features. PCOS is also strongly associated with obesity based on data from epidemiological and genetic studies. Accordingly, PCOS often becomes manifest in those women who carry a genetic predisposition to its development, and who also gain weight. The role of weight gain and obesity in the development of PCOS is mediated at least in part, through worsening of insulin resistance. Compensatory hyperinsulinaemia that develops in this context disrupts ovarian function, with enhanced androgen production and arrest of ovarian follicular development. Insulin resistance also contributes to the strong association of PCOS with adverse metabolic risk, including dysglycaemia, dyslipidaemia and fatty liver. Conversely, modest weight loss of just 5% body weight with improvement ...
Polycystic Ovary Syndrome as Metabolic Disease: New Insights on Insulin Resistance
European Endocrinology
Polycystic ovary syndrome (PCOS) is a very frequent disease that affects reproductive ability and menstrual regularity. Other than the criteria established at the Rotterdam consensus, in these last few years a new issue, insulin resistance, has been found frequently, and at a very high grade, in patients with PCOS. Insulin resistance occurs for several factors, such as overweight and obesity, but it is now clear that it occurs in patients with PCOS with normal weight, thus supporting the hypothesis that insulin resistance is independent of body weight. Evidence shows that a complex pathophysiological situation occurs that impairs post-receptor insulin signalling, especially in patients with PCOS and familial diabetes. In addition, patients with PCOS have a high incidence of non-alcoholic fatty liver disease related to the hyperinsulinaemia. This narrative review focuses on the recent new insights about insulin resistance in patients with PCOS, to better understand the metabolic impa...
Journal of Ovarian Research
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overabundance of androgens; it affects 6–20% of women of reproductive age. PCOS involves various pathophysiological factors, and affected women usually have significant insulin resistance (IR), which is a major cause of PCOS. IR and compensatory hyperinsulinaemia have differing pathogeneses in various tissues, and IR varies among different PCOS phenotypes. Genetic and epigenetic changes, hyperandrogenaemia, and obesity aggravate IR. Insulin sensitization drugs are a new treatment modality for PCOS. We searched PubMed, Google Scholar, Elsevier, and UpToDate databases in this review, and focused on the pathogenesis of IR in women with PCOS and the pathophysiology of IR in various tissues. In addition, the review provides a comprehensive overview of the current progress in the efficacy of insulin sensitization therapy in the management of PCOS, providing the latest evidenc...
The Journal of Clinical Endocrinology & Metabolism, 2014
Women with type 1 diabetes mellitus (DM1) have a higher prevalence of polycystic ovary syndrome (PCOS) than the general population. Objective: The aim of this study was to clarify, in DM1 women with PCOS (PCOS-DM1), the influence of insulin therapy and glycemic control and evaluate the hormonal and phenotypic differences with age-matched and body mass index (BMI)-matched women with PCOS without diabetes. Design, Setting, and Patients: We evaluated 103 DM1 women with and without PCOS treated with intensive insulin therapy; 38 age-matched and BMI-matched women with PCOS without diabetes were compared in a cross-sectional study. Outcome Measurements: Clinical, anthropometric, and metabolic parameters were evaluated. Hormonal evaluation and ovary ultrasound were performed during the follicular phase of the menstrual cycle. Results: Applying the diagnostic criteria of the Androgen Excess Society, 38 (36.89%) women with DM1 showed PCOS. The 38 PCOS-DM1 women showed no differences in treatment and glycemic control compared with DM1 women without PCOS. The only difference was a higher visceral adiposity index in PCOS-DM1 (1.21 Ϯ 0.70 vs 0.90 Ϯ 0.32; P ϭ .002). PCOS-DM1 showed no phenotypic differences with age-matched and BMI-matched PCOS without diabetes. The hormonal pattern was similar except that higher levels of ⌬4androstenedione were found in PCOS-DM1 (12.89 Ϯ 3.49 vs 2.79 Ϯ 1.75 nmol/L; P ϭ .010). Conclusions: The women with PCOS-DM1 do not exhibit particular phenotypic characteristics compared with nondiabetic women with PCOS. However, this pathological disorder must not be underestimated because it could be an additional cardiovascular risk factor in women with DM1.
The insulin-resistant phenotype of polycystic ovary syndrome
Fertility and Sterility, 2010
Objective: To investigate the individual parameters included in the diagnosis of polycystic ovary syndrome (PCOS), and their impact on insulin sensitivity. Design: Cross-sectional study. Setting: Patient(s): Sixty-one women; 36 women with PCOS and 25 age-and weight-matched control women were investigated. Intervention(s): Peripheral insulin sensitivity was evaluated by the hyperinsulinemic euglycemic clamp, glucose tolerance by an oral glucose tolerance test (OGTT), and ovarian morphology by transvaginal ultrasonography (TVS). Main Outcome Measure(s): The Rotterdam criteria were used for diagnosing PCOS, and hirsutism was evaluated by the Ferriman Gallwey score. Insulin sensitivity was calculated as the insulin sensitivity index, and whole body insulin sensitivity was assessed by the homeostatic model assessment insulin resistance (IR) index. Result(s): Multiple regression analysis showed that body mass index (BMI) and hirsutism were independent predictors of IR evaluated by insulin sensitivity index, whereas BMI, total T, and hirsutism were independent predictors of IR evaluated by the homeostatic model assessment IR index. We found no significant association between ovarian morphology and insulin sensitivity or between menstrual frequency and insulin sensitivity.
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Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome
Human Reproduction Update, 2005
Treatment with insulin-sensitizing agents is a relatively recent therapeutic strategy in women with polycystic ovary syndrome (PCOS) and insulin resistance. The key areas addressed in this review include PCOS and the development of type 2 diabetes mellitus and gestational diabetes, as well as the use of insulin-sensitizing agents, particularly metformin, in the management of infertility in obese and non-obese PCOS women. Treatment with metformin in PCOS women undergoing IVF and the use of metformin during gestation will be discussed. The challenge for the health care professional should be the appropriate utilization of pharmacotherapies to improve insulin sensitivity and lower circulating insulin levels resulting in beneficial changes in PCOS phenotype. Further research into the potential role of other insulin-sensitizing agents, such as pioglitazone and rosiglitazone, in the treatment of infertile women with PCOS is needed.
Do ACE I/D gene polymorphism serve as a predictive marker for age at onset in PCOS?
Journal of Assisted Reproduction and Genetics, 2013
Background Polycystic ovary syndrome (PCOS) is an endocrine disorder exhibiting variable age at onset of clinical features allied with complex diseases in the later life. ACE is a pleiotropic molecule associated with various pathophysiological functions. The present study was aimed to establish the frequency of ACE I/D gene polymorphism in patients and controls and to assess the influence of this polymorphism on anthropometric and various clinical features of the condition. Methods ACE I/D genotyping was carried out in 259 PCOS patients and 315 healthy ultrasound scanned women of South Indian origin.
Calpains and Their Multiple Roles in Diabetes Mellitus
Annals of the New York Academy of Sciences, 2006
Type 2 diabetes mellitus (T2DM) can lead to death without treatment and it has been predicted that the condition will affect 215 million people worldwide by 2010. T2DM is a multifactorial disorder whose precise genetic causes and biochemical defects have not been fully elucidated, but at both levels, calpains appear to play a role. Positional cloning studies mapped T2DM susceptibility to CAPN10, the gene encoding the intracellular cysteine protease, calpain 10. Further studies have shown a number of noncoding polymorphisms in CAPN10 to be functionally associated with T2DM while the identification of coding polymorphisms, suggested that mutant calpain 10 proteins may also contribute to the disease. Here we review recent studies, which in addition to the latter enzyme, have linked calpain 5, calpain 3, and its splice variants, calpain 2 and calpain 1 to T2DM-related metabolic pathways along with T2DM-associated phenotypes, such as obesity and impaired insulin secretion, and T2DM-related complications, such as epithelial dysfunction and diabetic cataract.
Clinical Endocrinology, 2007
Objective To evaluate Ped/pea-15 (phosphoprotein enriched in diabetes) expression in polycystic ovary syndrome (PCOS) women. Design and patients Thirty PCOS women were studied and compared with other 30 age-and body mass index (BMI)-matched women, considered as the control group. Both patients and controls were divided according to BMI. All subjects underwent endocrine and metabolic investigation and Ped/pea-15 expression was evaluated by western blot analysis. Insulin resistance was assessed by HOMA model and insulin sensitivity index (ISI) composite. Results Insulin resistance, evaluated by HOMA-R and ISI composite, was significantly higher in PCOS women and in obese controls than in normal weight controls. Ped/pea-15 expression (%) was higher in PCOS women than in controls (440·4 ± 220·7 vs. 163·0 ± 45·5; P < 0·001; range 145·5-987% and 97-281%, respectively), and was positively correlated with insulin, BMI, total testosterone, HOMA index, and family history ( P < 0·001). In patients with PCOS univariate analysis of variance showed no effect of BMI variation ( P = 0·13) on Ped/pea-15 expression levels. On multiple linear regression analysis, the major determinants of Ped/pea-15 overexpression were family history, insulin, and PCOS status independent of BMI. Conclusion These preliminary data (1) highlight the overexpression of Ped/pea-15 in PCOS compared to normal controls, independent of obesity; (2) suggest that Ped/pea-15 overexpression might be an early component of the metabolic syndrome in PCOS; and (3) support the hypothesis that Ped/pea-15 represents a possible useful tool to assess the presence of a genetic condition associated with insulin resistance in PCOS.
Journal of the European Academy of Dermatology and Venereology, 2006
Aim We aimed to identify insulin resistance and its possible association with types, duration and severity of psoriasis, and to evaluate various simple insulinsensitivity indices and beta-cell function in psoriasis. Methods A cross-sectional study was performed in 110 non-obese adults (18-50 years old): 70 with psoriasis (53 type I, 17 type II psoriasis) and 40 healthy individuals. Blood glucose, insulin and C-peptide levels were measured. Oral glucose tolerance test (OGTT); insulin sensitivity and beta-cell function indices derived from a single sample and OGTT were determined and compared in three groups. Results Total, type I and type II psoriatics had IGT rates of 18.6%, 13.2% and 40%, respectively. In the control group IGT was only 2.5%. Homeostasis Model Assessment (HOMA) beta cell index, fasting insulin, Raynaud index, HOMA-IR and FIRI results were higher in total, type I and type II psoriatics than in controls ( P < 0.05, for all). Fasting Belfiore index, QUICKY index, ISI HOMA and FIRI − 1 results were lower in total, type I and type II psoriatics than in controls ( P < 0.05, for all), and type I psoriatics had higher levels of these indices than type II psoriatics ( P < 0.05, for all). Conclusion Our study showed that psoriatic patients were more insulin resistant than healthy subjects and type II psoriatics were more susceptible than type I psoriatics to develop IGT. We suggest that beta-cell function and insulin sensitivity indices are useful methods for measuring insulin resistance in psoriatics. We propose that OGTT should be applied especially in type II psoriatics because of increased rate of IGT in this group.
TNF-α haplotype association with polycystic ovary syndrome – a South Indian study
Journal of Assisted Reproduction and Genetics, 2013
Background Tumor Necrosis Factor Alpha (TNF-α), is a proinflammatory cytokine in the pathogenesis of Polycystic Ovary Syndrome (PCOS). In order to investigate the role of rs1800629 and rs1799964 polymorphisms in relation to anthropometric measures, family history of complex diseases, diet and clinical features, we performed a case control study in PCOS women from South India. Methods A total of 589 samples comprising of 283 patients and 306 controls were enrolled in the present study. Patients were selected based on Rotterdam criteria and ultrasound scanned normal women were selected as controls. Following extraction of DNA, genotyping for rs1800629 and rs1799964 was performed by polymerase chain reaction using tetra primers and PCR-RFLP respectively. Results The distribution of genotypes for rs1799964 was significantly different between the groups (p =0.001), however it was not for rs1800629. Haplotype analysis revealed a significant difference between patients and controls. The predisposing and protective role of haplotype with mutant allele at both loci (combination 3) and haplotype with mutant allele at either loci was reflected by the over representation of combination 3 in patients and combination 2 in controls respectively. In addition, rs1799964 showed an association with dietary habit, clinical hyperandrogenism and AAO. The modifying role of TT genotype on age at onset was noted in quartile analysis. Replicative studies on the influence of TNF-α polymorphism in different ethnic groups may identify the potentiality of these polymorphisms as markers of inflammation and in turn may help the clinicians for the better management of the condition.
Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro
Frontiers in Endocrinology, 2014
Insulin (INS) resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome, and obesity. The mechanism by which INS and estrogen interact is unknown. We hypothesize that estrogen binds directly to INS and the insulin receptor (IR) producing INS resistance. Objectives: To determine the binding constants of steroid hormones to INS, the IR, and INS-like peptides derived from the IR; and to investigate the effect of estrogens on the binding of INS to its receptor. Methods: Ultraviolet spectroscopy, capillary electrophoresis, and NMR demonstrated estrogen binding to INS and its receptor. Horseradish peroxidase-linked INS was used in an ELISA-like procedure to measure the effect of estradiol on binding of INS to its receptor. Measurements: Binding constants for estrogens to INS and the IR were determined by concentration-dependent spectral shifts. The effect of estradiol on INS binding to its receptor was determined by shifts in the INS binding curve. Main Results: Estradiol bound to INS with a K d of 12 × 10 −9 M and to the IR with a K d of 24 × 10 −9 M, while other hormones had significantly less affinity. Twenty-two nanomolars of estradiol shifted the binding curve of INS to its receptor 0.8 log units to the right. Conclusion: Estradiol concentrations in hyperestrogenemic syndromes may interfere with INS binding to its receptor producing significant INS resistance.
Biology of reproduction, 2018
Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in adult females. We tested whether androgens dysregulate pancreatic beta cell function to induce hyperinsulinemia through transcriptional regulation of insulin gene (Ins) in the islets. Adult female Wistar rats implanted with dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia with increased HOMA-IR index in fasting state and glucose intolerance and exaggerated insulin responses following glucose tolerance test. DHT females had no change in islet number, size and beta cell proliferation/apoptosis but exhibited significant mitochondrial dysfunction (higher ADP/ATP ratio, decreased mtDNA copy number, increased reactive oxygen production and downregulation of mitochondrial biogenesis) and enhanced glucose-stimulated insulin ...
Evaluation of early atherosclerotic findings in women with polycystic ovary syndrome
Journal of Ovarian Research, 2011
Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of childbearing age, and it seems better to consider it as an ovarian manifestation of metabolic syndrome. The aim of the current study was to evaluate early atherosclerotic findings in patients with PCOS. Methods: We enrolled 46 women with PCOS and 45 normal control subjects who were referred to our hospital's endocrinology outpatient clinic. Carotid intima media thickness (CIMT) and flow-mediated dilatation (FMD) were performed in both cases and matched controls. Results: Patients with PCOS showed an increased mean CIMT (0.63 ± 0.16 mm) when compared with the control subjects (0.33 ± 0.06 mm). This difference was statistically significant (p = 0.001). The mean FMD in young patients with PCOS was 10.07 ± 1.2%, while it was 6.5 ± 2.06% in normal subjects. This difference was also statistically significant (p = 0.001). Conclusion: Our findings suggest that PCOS is related with early atherosclerotic findings.
BMC Research Notes, 2019
Objective: Study analyzes mutation in mtDNA (Mitochondrial DNA) among diabetic women with PCOS in nondiabetic diabetic women and compared with the healthy control. Women with known case of hyperandrogenism, ovulatory dysfunction and/or polycystic ovaries were selected and anthropometric and demographic variables were collected during their clinical visit. Biochemical estimation of glucose, FSH, LH, estradiol (E2), and insulin levels were analyzed. Mutational analysis of mt-tRNA genes of each individual was compared with the updated consensus Cambridge sequence. The mtDNA content was determined in triplicate using SYBR green PCR mastermix. Results: The clinical and biochemical characteristics of participants showed no statistical difference in age and/or FSH, PRL, E2, PRGE or fasting glucose value between patients of different groups. Women with PCOS-D had significantly higher LH, LH/FSH, TT and fasting insulin levels and HOMA-IR with respect to the control group. Ten different type of mutation were seen in POCS group. Most of these mutations were confined to evolutionarily conserved region. The mtDNA copy numbers were considerably lower PCOS group irrespective of diabetic status. To conclude, the current study inferred that the mutations occur in the mitochondrial genome, mt-tRNA in specific, are the important causal factor in PCOS.
International Journal of Environmental Research and Public Health, 2020
Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, infertility, obesity, and insulin resistance, which results in increased concentrations of testosterone (T), which disturbs follicular growth and ovulation. This study aimed to assess PCOS women's clinical, endocrinological, and metabolic parameters concerning hyperandrogenism severity. Results: 314 women (mean age 27.3 ± 4.6; mean body mass index (BMI) 25.7 ± 5.6) with PCOS, were divided into terciles according to T concentrations: <0.64 ng/mL (group 1), 0.64 to 0.84 ng/mL (Group 2) and >0.84 ng/mL (group 3). The mean concentration of T in all women was 0.59 ng/mL and correlated negatively with the number of menstrual cycles per year (MPY) (r = −0.36; p < 0.0001) and positively with Ferriman-Gallway score (FG) (r = 0.33; p < 0.0001), luteinizing hormone (LH) (r = 0.19; p < 0.0001) and dehydroepiandrosterone sulfate (DHEAS) (r = 0.52; p < 0.0001). Positive correlation between BMI and hirsutism (r = 0.16; p < 0.0001), total cholesterol (TC) (r = 0.18; p < 0.0001), low-density lipoprotein (LDL) (r = 0.29; p < 0.0001), and triglycerides (TG) (r = 0.40; p < 0.0001) was demonstrated. The division into subgroups confirmed the lowest MPY, highest LH, and hirsutism in group 3. BMI, insulin sensitivity indices, and lipid profile parameters were not different between the three T subgroups. Conclusions: We found no correlation between testosterone levels and insulin sensitivity or dyslipidemia in women with PCOS. Metabolic abnormalities may contribute more significantly than hyperandrogenemia to PCOS development.
Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates
Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity
The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females, as well as the interaction between altered androgen levels and dietary restriction and excess, in particular the western-style diet that underlies significant human pathophysiology.
Nesfatin-1 and other hormone alterations in polycystic ovary syndrome
Endocrine, 2012
Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting 5-10 % of females of reproductive age. Based on the findings that PCOS is associated with obesity, metabolic disturbances and ovarian dysfunction and accounting for the observations that nesfatin-1 is an anorexigenic neuropeptide linked to insulin resistance and obesity, we postulated that nesfatin-1 administration may have beneficial effects for managing polycystic ovaries in rats. We aimed to investigate the effects of nesfatin-1 as a therapeutic approach in PCOS management. Materials and methods: 48 virgin female albino rats were divided into two main groups: Group I (Controls, n=24) and Group II (PCOS group, n=24) each group was divided into lean rats (group A) and obese rats (group B). Lean and obese rats in all the study groups either in control group or PCOS group were randomly subdivided into vehicle-treated group with 1 ml/kg/day of saline and nesfatin-1-treated group with a dose of 10 µg/kg/day of nesfatin-1. Body weight was recorded and food intake was calculated. Serum glucose, insulin, LH, FSH, Estradiol, Progesterone and Testosterone levels were measured. HOMA-IR was calculated. MalonylDiAldehyde (MDA), ovarian superoxide dismutase (SOD) and ovarian glutathione peroxidase (GPX) were measured. Histopathological examination was performed. Results: Nesfatin produced a significant inhibitory effect on body weight, food intake, glucose, insulin, HOMA-IR and LH level and a significant increase in FSH level. Also, nesfatin has a significant inhibitory effect on MDA and TNF-α and a significant stimulatory effect on SOX and GPx. Conclusion: our findings confirmed the potential therapeutic role of nesfatin in treatment of PCOS. Further studies should be conducted in human PCOS for application in clinical field.
Gynecological Endocrinology, 2015
Five beagles out of 11 dogs aged 7-10 years with benign prostatic hypertrophy (BPH) were implanted subcutaneously with pellets of the synthetic anti-androgen chlormadinone acetate (CMA) at a dose of 10 mg/kg bodyweight. The remaining six dogs (one beagle and five mongrel dogs) underwent bilateral orchidectomy. Changes in prostatic volume, histological findings in the prostate and the testis, and peripheral plasma levels of LH, testosterone and oestradiol-17~ (E 2) were assessed up until 24 and 4 weeks after CMA-implantation and orchidectomy, respectively. Measurements of the size of the prostate and biopsies of the prostate were performed by laparotomy. Mean prostatic volume had decreased to 71% and 41%, respectively, of its pretreatment volume, by 4 weeks after CMA-implantation and orchidectomy, and was 49% and 47%, respectively, ofpretreatment volume at 12 and 24 weeks after CMAimplantation. The clinical signs of BPH, e.g. haematuria, resolved within 2 weeks after either treatment. When the prostate was examined histologically 4 weeks after either treatment, hardly any evidence of active secretion (e.g. glandular epithelium projecting markedly into the lumen), was observed in CMA-implanted dogs, alveolar diameter and height of the glandular epithelium had decreased markedly and the glandular lumen had become very small in the orchidectomized dogs. By 12 weeks after CMAimplantation, degenerative and atrophic glands were observed in the prostate nearly the same as at 4 weeks after orchidectomy. In the testis the number of germ cells in the seminiferous tubules decreased markedly after CMA-implantation. The mean level of plasma LH at 4 weeks after orchidectomy had increased to 14.9 ng/ml, twice the value before operation. The mean levels of plasma testosterone and E 2 at 4 weeks after CMA-implantation had decreased to 0.7 ng/ml and 9 pg/ml from 1.5 ng/ml and 15 pg/ml, the values before treatment, respectively. CMA-implantation resulted in poor semen quality. The results indicate that CMA-implantation at a dose of 10 mg/kg results in the same prostate-shrinking effect as orchidectomy.
Insulin Resistance and Urolithiasis as a Challenge for a Dietitian
International Journal of Environmental Research and Public Health
Many obesity and diet-related diseases have been observed in recent years. Insulin resistance (IR), a state of tissue resistance to insulin due to its impaired function, is a common coexisting condition. The most important predisposing factors are excessive visceral fat and chronic low-grade inflammatory response. However, IR’s pathogenesis is not fully understood. Hence, the diagnosis of IR should be carried out carefully because many different diagnostic paths do not always give equivalent results. An additional disease that is often associated with IR is urolithiasis. The common feature of these two conditions is metabolic acidosis and mild inflammation. A patient diagnosed with IR and urolithiasis is a big challenge for a dietitian. It is necessary to check a thorough dietary history, make an appropriate anthropometric measurement, plan a full-fledged diet, and carry out the correct nutritional treatment. It is also essential to conduct proper laboratory diagnostics to plan nutr...
Clinical Nutrition Research
Polycystic ovary syndrome (PCOS) is a heterogeneous clinical syndrome. Recent studies examine different strategies to modulate its related complications. Chlorogenic acid, as a bioactive component of green coffee (GC), is known to have great health benefits. The present study aimed to determine the effect of GC on lipid profile, glycemic indices, and inflammatory biomarkers. Forty-four PCOS patients were enrolled in this randomized clinical trial of whom 34 have completed the study protocol. The intervention group (n = 17) received 400 mg of GC supplements, while the placebo group (n = 17) received the same amount of starch for six weeks. Then, glycemic indices, lipid profiles, and inflammatory parameters were measured. After the intervention period, no significant difference was shown in fasting blood sugar, insulin level, Homeostasis model assessment of insulin resistance index, low-density lipoprotein, high-density lipoprotein, Interleukin 6 or 10 between supplementation and placebo groups. However, cholesterol and triglyceride serum levels decreased significantly in the intervention group (p < 0.05). This research confirmed that GC supplements might improve some lipid profiles in women with PCOS. However, more detailed studies with larger sample sizes are required to prove the effectiveness of this supplement.
Journal of Endocrinology, Metabolism and Diabetes of South Africa, 2013
Objectives: Women with polycystic ovarian syndrome (PCOS) are at twice the risk of developing metabolic syndrome, compared to women from the general population. The aim of this study was to assess the prevalence of metabolic syndrome in the first-degree relatives (fathers) of patients suffering from PCOS. Design: This was a case control study. Setting and subjects: The study was conducted on 34 fathers of women with PCOS who presented at gynaecological clinics in Shiraz, Iran (as the case group), and 34 fathers of healthy women (as the control group). Outcomes measures: Metabolic syndrome was determined according to Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) indices. A blood sample was obtained to assay serum insulin, blood sugar, testosterone and lipoproteins. The data were analysed using independent t-test, Fisher's exact test and the chisquare test. Results: According to the ATP III index, the prevalence of metabolic syndrome was 29.35% in the fathers of the PCOS patients and 8.8% in the fathers of women in the control group (p-value < 0.05). According to the IDF index, this rate was 17.41 in the fathers of patients with PCOS (p-value < 0.05). According to the quantitative insulin sensitivity check and homeostasis model insulin resistance indices, the prevalence of insulin resistance, hypertension, type 2 diabetes and hypercholesterolaemia was higher in the fathers of patients with PCOS than in the control group, but the difference was not significant (p-value > 0.05). Conclusion: The fathers of the women with PCOS were at a higher risk of developing metabolic syndrome, hypertension, dyslipidaemia, impaired glucose tolerance and diabetes.
Scientific Reports
Vitamin E supplementation might have favorable effects on risk factors of polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to summarize the effects of vitamin E supplementation or vitamin E in combination with omega-3 or magnesium on PCOS. PubMed, Scopus, ISI Web of Science, Cochrane, Embase electronic databases, and Google scholar were searched for all available articles up to September 2022. Randomized controlled trials (RCTs) that examined the effect of vitamin E supplementation or vitamin E in combination with omega-3 or magnesium on lipid and glycemic profiles, anthropometric measurements, biomarkers of inflammation and oxidative stress, hormonal profile, and hirsutism score in patients with PCOS were included. Ten RCTs (with 504 participants) fulfilled the eligible criteria. Vitamin E supplementation or vitamin E in combination with omega-3 or magnesium in comparison to placebo could significantly reduce serum levels of TG (weighted mean differe...
Does Polycystic Ovary Syndrome Itself Have Additional Effect on Apelin Levels?
Obstetrics and Gynecology International, 2014
Objective. The present study was designed to compare serum levels of apelin between lean PCOS women and healthy women with regular menses.Study Design. A total of 30 lean patients with PCOS and 30 healthy subjects were included in this study. Serum apelin levels were compared between groups.Results. Serum apelin levels in lean PCOS patients were not significantly different from the control subjects.Conclusion. Our findings indicate that PCOS itself does not seem to change apelin levels. Further investigation on a large number of subjects will need to be conducted to prove the consistent or variable association in PCOS.
Journal of Endocrinological Investigation, 2008
Young, normotensive, and non-obese women with polycystic ovary syndrome (PCOS) may present abnormal hemodynamic alterations (HA). The purpose of this study was to investigate heart rate (HR), intima-media thickness (IMT), and diameter (DCCA) in the common carotid arteries (CCA), flow velocities, and resistance index in both extracranial carotid and vertebral arteries (VA), in the abdominal aorta (AO) and in the renal arteries (RA) in PCOS women and matched controls. This was a case-control study conducted at a tertiary University Hospital. We studied 53 PCOS women and 53 healthy matched volunteers as controls. The previously reported parameters were assessed using color Doppler ultrasonography. HR, IMT in the CCA, and peak systolic velocity in all examined arteries were significantly increased in PCOS women compared to controls. On the contrary , DCCA was significantly decreased in PCOS women compared to controls. End diastolic velocity (EDV) in both VA and RA, in the AO and in the left extracranial carotid system was significantly increased in the PCOS group compared to controls. Furthermore, the peripheral resistance (PR) of AO and right external carotid artery was also found to be increased while in both RA and in left VA, PR was decreased. No further statistical significant HA in EDV and PR were noted. The results of this study provide evidence for a mild hyperdynamic circulation in young, normotensive, non-obese women with PCOS compared to controls, indicating a mild sympathetic activation at an early age, which may be an underlying cause of hypertension and cardiovascular risk.
Cureus
Polycystic ovary syndrome (PCOS) is an endocrine disorder increasingly affecting women in the reproductive age group. The women usually present with menstruation irregularities, hirsutism, weight gain, and acne. There has been ongoing research about the increased risk of gynecological cancers in women with polycystic ovary syndrome compared to those without it. This review aimed to understand the risk of gynecological cancers, endometrial, ovarian, and breast cancer in PCOS, and to study in detail the underlying mechanisms involved. We searched PubMed and Google Scholar databases for studies and selected 10 articles from a total of 19,388 relevant articles. We found an increased risk of endometrial cancer in women with PCOS whereas the risk of ovarian and breast cancer was not increased. A recent study has even reported a reduced risk of ovarian cancer in genetically predicted PCOS. In understanding various medical conditions possibly leading to cancer in these women we found that hyperandrogenism, hyperinsulinemia, unopposed estrogen action, chronic inflammation, and dyslipidemia were major contributors. There is a need for more large-scale cohort studies which will take into consideration other factors leading to cancers in women with PCOS, such as smoking, alcohol, and family history, to substantiate the significance of these associations further. The interventions used to treat PCOS might also affect the risk of cancer and require further probing. This review is an attempt to analyze the risk of cancers of the reproductive system in females with PCOS in coherence with understanding the mechanisms leading to the respective cancers.
Assessment of Early Markers of Cardiovascular Risk in Polycystic Ovary Syndrome
European Endocrinology, 2021
P olycystic ovary syndrome (PCOS) is a heterogeneous syndrome, with long-term sequelae from birth to senescence. The long-term effects of PCOS are attributed to several metabolic aberrations ensuing the syndrome. In a systematic review of literature regarding the cardiovascular risk factors that accompany PCOS, we found that macrovascular function has been assessed by flow-mediated dilatation (FMD), microvascular function by venous occlusion plethysmography (VOP), and arterial structure by ultrasonographic assessment of intima-media thickness (IMT) usually of the carotid artery. Contradictory results have been reported; however, in most studies, endothelial dysfunction, an early marker of atherosclerosis assessed either by haemodynamic methods such as FMD or by biochemical methods such as endothelin-1 levels, was found to be impaired. VOP is a less-studied method, with few indices altered. IMT was found to be altered in most of the included studies, but the population was more heterogeneous. Inflammatory markers, including C-reactive protein, were also found to be altered in most studies. On the other hand, a number of interventions have been shown beneficial for the markers of cardiovascular risk, in the context of insulin-sensitizers. However, other interventions such as oral contraceptive pills or statins did not consistently show a similar beneficial effect. In summary, the early identification and eventual treatment of cardiovascular clinical and biochemical risk factors may be used in clinical practice to prevent potential 'silent' triggers of cardiovascular disease.