Role hyperleptinemia, insulin resistance and hyperestrogenemia in the development of ovarian failure in women with obesity

Actuality of the study. Ovarian insufficiency is present in more that 30% of reproductive age women. The role of leptine and insuin resistance in the pathogenesis of ovarian insufficiency is not yet established and has to be clarified. The aim of the study to investigate the role of hyperleptinemia, insulin resistance and hyperestrogenemia in the pathogenesis of ovarian insufficiency in obesity.Materials and methods. Fifty reproductive age women with BMI > 25,6 kg/m2 were studied. Ten healthy reproductive age women were included as controls. The plasma level of leprin, honadotropins, prolactin, insulin and sex steroid hormones assayed by immunoenzyme analysis, morning fasting blood glucose and the glucose level after glucose tolerance test, pelvic echography, “whole body” program of dual x-ray absorptiometry were studied in both patients and controls.Results. Thirty-six out of 50 women had signs of ovarian insufficiency. The presence and severity of ovarian insufficiency did not correlate with the level of leptin in blood or with insulin resistance. The positive correlation between oestradiol level and both presence and severity of ovarian insufficiency could be demonstrated.Conclusion. The results of our study do not support the hyperleptinemia and insulin resistance as the main cause of ovarian insufficiency in alimentary obesity. The most potential reason of anovulation in these women could be hyperoestrogenia due to increased conversion of androgens into oestrogenes in fat tissues and ovaria.

Download Full-text

The role of leptin in the pathogenesis of ovarian insufficiency in obesity women

Journal of obstetrics and women s diseases ◽

10.17816/jowd65318-24 ◽

2016 ◽

Vol 65 (3) ◽

pp. 18-24

Author(s):

Ekaterina М Riazantceva

Keyword(s):

Reproductive Age ◽

Blood Levels ◽

Obese Women ◽

Ovarian Dysfunction ◽

Ovarian Insufficiency ◽

Reproductive Age Women ◽

Alimentary Obesity ◽

Immunoenzymatic Assay ◽

Follicular Stimulating Hormone

Actuality. Ovarian insufficiency can be diagnosed in more than 30% of reproductive age women with obesity. The role of leptin in the pathogenesis of ovarian insufficiency in obesity is not well understood and needs to be detalised. The aim of the study: to ivestigate the role of leptin in the pathogenesis of ovarian insufficiency in obesity. Materials and methods. 50 reproductive age females with BMI > 26.5 kg/m2 were studied. 10 healthy reproductive age females were used as control. Blood levels of leptin, gonadotropins, prolactin, sex steroid hormones were measured by immunoenzymatic assay and pelvic echoscopy were performed in all studied patients and co ntrols. Results. 72% of obese women had signs of ovarian insufficiency, such as ovarian enlargement and increased antral follicular count. The level of leptin did not correlate with the presence or absence of ovarian insufficiency in our patient group. The positive correlation between leptin level and BMI, luteinizing hormone (LG) and oestradiol and negative correlation between leptin level and follicular stimulating hormone (FSH) were revealed. Conclusion. The results of our study do not support the hyperleptinemia as the main cause of ovarian dysfunction in alimentary obesity. The most potential reason of ovarian dysfunction in these women could be ovarian or non-ovarian origin hyperoestrogenia leading to premature LG piques, and, thus, disturbing folliculogenesis in ovaria.

Download Full-text

Endometriosis

10.2310/im.1005 ◽

2019 ◽

Author(s):

Valerie A Flores ◽

Hugh S Taylor

Keyword(s):

Pelvic Pain ◽

Treatment Options ◽

Reproductive Age ◽

Fertility Treatment ◽

Future Research ◽

Retrograde Menstruation ◽

Reproductive Age Women ◽

Aberrant Gene Expression ◽

Aberrant Gene

Endometriosis is a chronic, gynecologic disease affecting 6 to 10% of reproductive age women. Pelvic pain, dyspareunia, and infertility are the most common symptoms of endometriosis that can have a significant impact on patients’ lives. Although the etiology remains largely unknown, the role of estrogens in the development and growth of endometriosis is well characterized. Medical and surgical therapies are the two cornerstones of endometriosis management. Following diagnosis of endometriosis, treatment options will be dependent on patient preference (ie, seeking pain relief versus fertility treatment). Future research aimed at targeting altered molecular pathways in patients with endometriosis will hopefully help mitigate the burden of this debilitating disease. This review contains 5 figures, 7 tables, and 75 references. Key Words: aberrant gene expression, altered immunity, endometriosis, infertility, medical and surgical therapy, pelvic pain, retrograde menstruation, stem cells

Download Full-text

Obese Older Type 2 Diabetes Mellitus Patients with Muscle Insulin Resistance Benefit from an Enriched Protein Drink during Combined Lifestyle Intervention: The PROBE Study

Nutrients ◽

10.3390/nu12102979 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2979 ◽

Cited By ~ 1

Author(s):

Wilrike J. Pasman ◽

Robert G. Memelink ◽

Johan de Vogel-Van den Bosch ◽

Mark P. V. Begieneman ◽

Willem J. van den Brink ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Muscle Mass ◽

Lifestyle Intervention ◽

Tolerance Test ◽

Whole Body ◽

Physiological Data ◽

Oral Glucose ◽

Before And After

(1) Background: Recent research showed that subtypes of patients with type 2 diabetes may differ in response to lifestyle interventions based on their organ-specific insulin resistance (IR). (2) Methods: 123 Subjects with type 2 diabetes were randomized into 13-week lifestyle intervention, receiving either an enriched protein drink (protein+) or an isocaloric control drink (control). Before and after the intervention, anthropometrical and physiological data was collected. An oral glucose tolerance test was used to calculate indices representing organ insulin resistance (muscle, liver, and adipose tissue) and β-cell functioning. In 82 study-compliant subjects (per-protocol), we retrospectively examined the intervention effect in patients with muscle IR (MIR, n = 42) and without MIR (no-MIR, n = 40). (3) Results: Only in patients from the MIR subgroup that received protein+ drink, fasting plasma glucose and insulin, whole body, liver and adipose IR, and appendicular skeletal muscle mass improved versus control. Lifestyle intervention improved body weight and fat mass in both subgroups. Furthermore, for the MIR subgroup decreased systolic blood pressure and increased VO2peak and for the no-MIR subgroup, a decreased 2-h glucose concentration was found. (4) Conclusions: Enriched protein drink during combined lifestyle intervention seems to be especially effective on increasing muscle mass and improving insulin resistance in obese older, type 2 diabetes patients with muscle IR.

Download Full-text

MON-647 Mechanisms of Insulin Resistance in Skeletal Muscle in Women with PCOS

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.773 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Alba Moreno-Asso ◽

Luke C McIlvenna ◽

Rhiannon K Patten ◽

Andrew J McAinch ◽

Raymond J Rodgers ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Glucose Uptake ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Reproductive Age ◽

Whole Body ◽

Dependent Manner ◽

Cultured Myotubes ◽

Tgfβ Superfamily

Abstract Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder affecting metabolic, reproductive and mental health of 8-13% of reproductive-age women. Insulin resistance (IR) appears to underpin the pathophysiology of PCOS and is present in approximately 85% of women with PCOS. This underlying IR has been identified as unique from, but synergistic with, obesity-induced IR (1). Skeletal muscle accounts for up to 85% of whole body insulin-stimulated glucose uptake, however, in PCOS this is reduced about 27% when assessed by hyperinsulinemic euglycemic clamp (2). Interestingly, this reduced insulin-stimulated glucose uptake observed in skeletal muscle tissue is not retained in cultured myotubes (3), suggesting that environmental factors may play a role in this PCOS-specific IR. Yet, the molecular mechanisms regulating IR remain unclear (4). Previous work suggested that Transforming Growth Factor Beta (TGFβ) superfamily ligands may be involved in the metabolic morbidity associated with PCOS (5). In this study, we investigated the effects of TGFβ1 (1, 5ng/ml), and the Anti-Müllerian hormone (AMH; 5, 10, 30ng/ml), a novel TGFβ superfamily ligand elevated in women with PCOS, as causal factors of IR in cultured myotubes from women with PCOS (n=10) and healthy controls (n=10). AMH negatively affected glucose uptake and insulin signalling increasing p-IRS1 (ser312) in a dose-dependent manner in myotubes from both women with and without PCOS. AMH did not appear to activate the canonical TGFβ/BMP signalling pathway. Conversely, TGFβ1 had an opposite effect in both PCOS and control myotubes cultures, decreasing phosphorylation of IRS1 (ser312) and enhancing glucose uptake via Smad2/3 signalling. In conclusion, these results suggest that AMH may play a role in skeletal muscle IR observed in PCOS, however, further research is required to elucidate its mechanisms of action and broader impact in this syndrome. References: (1) Stepto et al. Hum Reprod 2013 Mar;28(3):777-784. (2) Cassar et al. Hum Reprod 2016 Nov;31(11):2619-2631. (3) Corbould et al., Am J Physiol-Endoc 2005 May;88(5):E1047-54. (4) Stepto et al. J Clin Endocrinol Metab, 2019 Nov 1;104(11):5372-5381. (5) Raja-Khan et al. Reprod Sci 2014 Jan;21(1):20-31.

Download Full-text

Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5368657 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Yanan Shi ◽

Dan Liu ◽

Jihong Yuan ◽

Lihui Yan ◽

Zhenfeng Zhan ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Er Stress ◽

Heart Diseases ◽

Fasting Blood Glucose ◽

Underlying Mechanism ◽

Hepatic Function ◽

Tolerance Test ◽

Oral Glucose ◽

Signal Sensitivity

Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.

Download Full-text

Analysis of candidate genes in Polish families with obesity

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2004.083 ◽

2004 ◽

Vol 42 (5) ◽

Cited By ~ 6

Author(s):

Malgorzata Malczewska-Malec ◽

Iwona Wybranska ◽

Iwona Leszczynska-Golabek ◽

Lukasz Partyka ◽

Jadwiga Hartwich ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

Body Mass ◽

Tolerance Test ◽

Whole Body ◽

Oral Glucose ◽

Sensitivity Index ◽

Model Assessment ◽

The Metabolic Syndrome

AbstractThis study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γThe 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated.The single gene mutations such as CWe conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

Download Full-text

Expression of FOXC2 in adipose and muscle and its association with whole body insulin sensitivity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00155.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. E799-E803 ◽

Cited By ~ 18

Author(s):

Gina B. Di Gregorio ◽

Rickard Westergren ◽

Sven Enerback ◽

Tong Lu ◽

Philip A. Kern

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Tolerance Test ◽

Intravenous Glucose Tolerance Test ◽

Whole Body ◽

Forkhead Transcription Factor ◽

Intravenous Glucose ◽

Insulin Resistant ◽

Diet Induced Obesity ◽

Tnf Α

FOXC2 is a winged helix/forkhead transcription factor involved in PKA signaling. Overexpression of FOXC2 in the adipose tissue of transgenic mice protected against diet-induced obesity and insulin resistance. We examined the expression of FOXC2 in fat and muscle of nondiabetic humans with varying obesity and insulin sensitivity. There was no relation between body mass index (BMI) and FOXC2 mRNA in either adipose or muscle. There was a strong inverse relation between adipose FOXC2 mRNA and insulin sensitivity, using the frequently sampled intravenous glucose tolerance test ( r = −0.78, P < 0.001). However, there was no relationship between muscle FOXC2 and any measure of insulin sensitivity. To separate insulin resistance from obesity, we examined FOXC2 expression in pairs of subjects who were matched for BMI but who were discordant for insulin sensitivity. Compared with insulin-sensitive subjects, insulin-resistant subjects had threefold higher levels of adipose FOXC2 mRNA ( P = 0.03). In contrast, muscle FOXC2 mRNA expression was no different between insulin-resistant and insulin-sensitive subjects. There was no association of adipose or muscle FOXC2 mRNA with either circulating or adipose-secreted TNF-α, IL-6, leptin, adiponectin, or non-esterified fatty acids. Thus adipose FOXC2 is more highly expressed in insulin-resistant subjects, and this effect is independent of obesity. This association between FOXC2 and insulin resistance may be related to the role of FOXC2 in PKA signaling.

Download Full-text

Glycated Albumin as Marker for Early Hyperglycemia Detection in Adolescent with β Thalassemia Major

The Indonesian Biomedical Journal ◽

10.18585/inabj.v13i3.1546 ◽

2021 ◽

Vol 13 (3) ◽

pp. 281-8

Author(s):

Dewinda Candrarukmi ◽

Annang Giri Moelyo ◽

Muhammad Riza

Keyword(s):

Diabetes Mellitus ◽

Characteristic Curve ◽

Glycated Albumin ◽

Fasting Blood Glucose ◽

Thalassemia Major ◽

Tolerance Test ◽

Oral Glucose ◽

Single Blind ◽

Endocrine Complications

BACKGROUND: Hyperglycemia is one of the most common endocrine complications in children with β thalassemia major. Though the current diagnostic marker either requires fasting, has low reproducibility, or it is not an accurate for thalassemia patients. Glycated albumin (GA) is a quick and easy alternative marker for hyperglycemia detection and monitoring of glycemic control. However to date, no studies have analyzed the role of GA value in detection of hyperglycemia in children with thalassemia major. This study analyzed the value of GA as an alternative screening marker for hyperglycemia detection in children with β thalassemia major.METHODS: A single-blind prospective diagnostic test was conducted in 9 to 18 years old children with β thalassemia major and who were treated at the Dr. Moewardi Regional General Hospital between October 1, 2018 and December 31, 2019. In a single, fasted study visit, height, weight, fasting blood glucose (FPG), GA, oral glucose tolerance test (OGTT) were measured. The area under a receiver operating characteristic curve (AUC) was used to determine the cut-off value at which hyperglycemia prediction (OGTT ≥140 mg/dL) display optimal sensitivity and specificity. RESULTS: Among the 53 children with β thalassemia major, 1 (1.9%) had diabetes mellitus and 4 (7.5%) had prediabetes based on their OGTT values. The median GA value in this study was 10.9% (range: 7.6–12.4%). GA had a low AUC (0.646, p=0.287) for hyperglycemia detection in pediatric patients with β thalassemia major. At a cut-off of 11.45%, GA demonstrated 60% sensitivity and 60.4% specificity.CONCLUSION: GA cannot be used as an alternative marker for hyperglycemia detection in children with β thalassemia major.KEYWORDS: hyperglycemia, diabetes mellitus, prediabetes, β thalassemia major, glycated albumin

Download Full-text

The Role of Angiopoietin-like Protein 3 and Fibroblast Growth Factor 21 to Lipolysis, Inflammation and Insulin Resistance in Indonesian Non-Diabetic Obese Male

The Indonesian Biomedical Journal ◽

10.18585/inabj.v2i2.117 ◽

2010 ◽

Vol 2 (2) ◽

pp. 33

Author(s):

Yani Lina ◽

Gatot Susilo Lawrence ◽

Andi Wijaya ◽

Suryani As'ad

Keyword(s):

Insulin Resistance ◽

Fasting Blood Glucose ◽

Feedback Mechanism ◽

Fibroblast Growth Factor 21 ◽

Low Grade ◽

Cross Sectional ◽

Negative Feedback Mechanism ◽

Two Factors ◽

Cross Sectional Design

BACKGROUND: Obesity is commonly associated with a systemic low grade inflammation and insulin resistance state. Although it is still being debated, increased lipolysis is known as one of the risk factors for inflammation and insulin resistance. Two factors already known to affect lipolysis are Angptl3, known as prolipolytic factor, and FGF21, known as antilipolytic factor. The aim of this study was to observe the role of Angptl3 and FGF21 to lipolysis, inflammation and insulin resistance in non diabetic obese male.METHODS: This was an observational study with cross sectional design. One hundred and thirty male subjects aged 30-60 years with non diabetic abdominal obesity characterized by waist circumference 97.32±5.63 cm and fasting blood glucose 90.19±8.78 mg/dL.RESULTS: The results of this study showed a correlation between Angptl3-FFA (r=0.203; p=0.021; R square=0.041; p=0.021), Angptl3-FABP4 (r=0.330; p=0.000; R square=0.109; p=0.000) and Angptl3-TNFα (r=0.288; p=0.001; R square=0.049; p=0.011). There was a correlation between FGF21-FABP4 (r=0.218, p=0.013; R square=0.047, p=0.013) and FGF21 HOMA-IR (r=0.308, p=0.000; R square=0.046, p=0.014).CONCLUSIONS: We conclude that Angptl3 may affect lipolysis and inflammation while FGF21 may affect lipolysis and insulin resistance. The increased FGF21 concentration might occur as a compensation (negative feedback mechanism) to reduce lipolysis and increase insulin sensitivity in non diabetic obese males. Further studies might be needed to observe Angptl3 and FGF21 profile in more severe obese population in Indonesia.KEYWORDS: obesity, lipolysis, inflammation, insulin resistance

Download Full-text

Role of oral inositol supplementation in women with polycystic ovarian syndrome

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20214648 ◽

2021 ◽

Vol 10 (12) ◽

pp. 4493

Author(s):

Najma Malik ◽

Navneet Dubey

Keyword(s):

Insulin Resistance ◽

Prospective Observational Study ◽

Oocyte Quality ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Medical College ◽

Good Medicine ◽

Ovarian Syndrome ◽

Rotterdam Criteria

Background: PCOS is one of the most common endocrine disorder in women of reproductive age, it affects about 5-10% of women of reproductive age. It is characterized by chronic anovulation, hyperandrogenism, and insulin resistance. 30-40% of PCOS women have impaired glucose tolerance.Methods: This was prospective observational study carried out on 100 patients of PCOS visiting outpatient Department of Obstetrics and Gynecology, BRD Medical College, Gorakhpur from 1st July 2018 to 30th June 2019. Patients were diagnosed as PCOS on basis of Rotterdam criteria. In these 100 patients, oral inositol 2 gm twice daily was given for 3 months to 6 months depending upon the response of the patient and patients were examined every 4 week for menstrual regularity, acne improvement, hirsutism, spontaneous ovulation and pregnancy.Results: With inositol supplementation, menstrual abnormality corrected in 80% cases, 45% cases having acne improved. Ovulation occurred in 75.5% cases and 66.6% cases conceived with inositol supplementation.Conclusions: Insulin resistance is the basic pathophysiology for PCOS hence inositol supplementation is supposed to be very good medicine for management of PCOS to improve insulin sensitivity. Inositol leads to improvement in regularity of menstrual cycle, insulin resistance, hyperandrogenic features like hirsutism, acne, restores ovulation and improves oocyte quality.

Download Full-text