Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome.

ObjectiveThe insulin-resistant state of the polycystic ovary syndrome (PCOS) was found to be associated with a decreased glucose transporter GLUT4 expression in the insulin target tissues. This study was performed to explore whether the well-known clinical, hormonal and metabolic efficacy of metformin or rosiglitazone treatment is reflected in the modulation of adipocyte GLUT4 mRNA expression in patients with PCOS.MethodsWe enrolled 35 women with PCOS. They received either metformin or rosiglitazone for 6 months. A history, blood samples for the measurement of androgens and s.c. adipose tissue samples were taken at baseline and end point. Quantification of GLUT4 mRNA expression in adipose tissue was performed using real-time quantitative PCR. Homeostasis model assessment (HOMAIR) score calculation was applied as a measure for insulin resistance (IR).ResultsGLUT4 mRNA expression in adipose tissue increased significantly in both groups (P<0.001). The increase was more pronounced in the rosiglitazone group (P=0.040). There was a statistically significant improvement of HOMAIRin both groups (P=0.008). After treatment, frequencies of menstrual bleeding were significantly higher (P<0.001) and serum total testosterone levels significantly lower in both groups (P=0.001).ConclusionsA 6-month therapy with insulin sensitizers resulted in marked improvement in adipose tissue GLUT4 mRNA expression in PCOS patients, rosiglitazone being more effective when compared with metformin. The augmentation of the insulin signal transduction was accompanied by a significant improvement of HOMAIR, menstrual pattern and androgen profile.

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Endotrophin as a novel marker in PCOS and its relation with other adipokines and metabolic parameters: a pilot study

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/20420188211049607 ◽

2021 ◽

Vol 12 ◽

pp. 204201882110496

Author(s):

Gurhan Guney ◽

Mine Islimye Taskin ◽

Ozgur Baykan ◽

Ertan Adali ◽

Selin Gul Tezcan ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Density Lipoprotein ◽

Resistance Index ◽

Total Testosterone ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Ovary Syndrome ◽

Significant Difference

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.

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Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.61.03.215 ◽

2015 ◽

Vol 61 (3) ◽

pp. 215-219 ◽

Cited By ~ 4

Author(s):

Margareth Chiharu Iwata ◽

Livia Porquere ◽

Isabel C. Espósito Sorpreso ◽

Edmund C. Baracat ◽

José Maria Soares Júnior

Keyword(s):

Insulin Resistance ◽

Oral Contraceptive ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Total Testosterone ◽

Model Assessment ◽

Cycle Index ◽

Androgen Excess ◽

Ovary Syndrome ◽

Improve Insulin Resistance

Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS) using metformin or combined oral contraceptive (COC) after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16); II-metformin (850mg 12/12h, n=16); III-COC plus metformin (n=9). Body mass index (BMI), acne (% of improvement), modified Ferriman-Gallway index and menstrual cycle index (MCI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), androstenedione (A) and homeostasis model assessment: insulin resistance (HOMA-IR) index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007). The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046). The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75), showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.

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Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje-12-0340 ◽

2012 ◽

Vol 167 (5) ◽

pp. 705-713 ◽

Cited By ~ 11

Author(s):

Tao Tao ◽

Shengxian Li ◽

Aimin Zhao ◽

Yanyun Zhang ◽

Wei Liu

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Subcutaneous Adipose Tissue ◽

Polycystic Ovary ◽

Mrna Abundance ◽

Model Assessment ◽

Ovary Syndrome ◽

Subcutaneous Adipose

Objective Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR. Methods The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR). Results The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity. Conclusion The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

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Polymorphisms of TCF7L2 gene in South Brazilian women with polycystic ovary syndrome: a cross-sectional study

Acta Endocrinologica ◽

10.1530/eje-13-0105 ◽

2013 ◽

Vol 169 (5) ◽

pp. 569-576 ◽

Cited By ~ 10

Author(s):

Ramon Bossardi Ramos ◽

Denusa Wiltgen ◽

Poli Mara Spritzer

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Cross Sectional Study ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Model Assessment ◽

Nucleotide Polymorphisms ◽

Sectional Study ◽

Ovary Syndrome ◽

Cross Sectional

ObjectiveTo assess whetherTCF7L2single nucleotide polymorphisms rs7903146 C/T and rs11196236 C/T are associated with polycystic ovary syndrome (PCOS) in South Brazilian women.DesignCross-sectional study.MethodsTwo hundred PCOS patients and 102 non-hirsute, ovulatory controls were genotyped by real-time PCR. Haplotypes were constructed from the combination of both polymorphisms. Frequencies were inferred using the PHASE 2.1.1 software.Results and conclusionsThe distribution of rs7903146 (PCOS, 54.4% CC; 28.5% CT; 17.1% TT; controls, 51.0% CC; 37.0% CT; 12.0% TT) and rs11196236 (PCOS, 4.3% CC; 33.5% CT; 62.2% TT; controls, 3.2% CC; 35.5% CT; 61.3% TT) was similar between the groups. rs7903146 and rs11196236 were not in linkage disequilibrium (|D′|=0.34;r2=0.07). PCOS participants were younger, with higher age-adjusted BMI, waist circumference, blood pressure, triglycerides, insulin, homeostasis model assessment index to estimate insulin resistance and total testosterone, and lower HDL-C and sex hormone binding globulin vs controls. In PCOS, no differences between genotypes and haplotypes were found for clinical and metabolic variables. However, for each T (rs7903146) and T (rs11196236) allele added to the haplotypes, a variation of 5.87 cm in waist (Ptrend=0.01), 10.7 mg/dl in total cholesterol (Ptrend=0.03), and 10.3 mg/dl in LDL-C (Ptrend=0.01) was recorded.TCF7L2variants are probably not implicated in PCOS development in South Brazilian women.

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Amelioration by quercetin of insulin resistance and uterine GLUT4 and ERα gene expression in rats with polycystic ovary syndrome (PCOS)

Reproduction Fertility and Development ◽

10.1071/rd18222 ◽

2019 ◽

Vol 31 (2) ◽

pp. 315 ◽

Cited By ~ 10

Author(s):

Asma Neisy ◽

Fatemeh Zal ◽

Atefeh Seghatoleslam ◽

Sanaz Alaee

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Glucose Transporter ◽

Specific Activity ◽

Polycystic Ovary ◽

Fasting Blood Glucose ◽

Model Assessment ◽

Ovary Syndrome ◽

Metabolic Systems

Insulin resistance (IR) and infertility are two major complications of polycystic ovary syndrome (PCOS), which are the results of changes in certain parts of the reproductive and metabolic systems. We aimed to observe the effect of quercetin on dehydroepiandrosterone (DHEA)-induced PCOS and insulin resistance in rats. All animals were divided into five groups and DHEA was used to induce PCOS. Bodyweight and ovarian morphology of all groups were observed. Fasting blood glucose and insulin levels were analysed. The homeostasis model assessment of insulin resistance (HOMA-IR) method was used for IR level determination. The expression of oestrogen receptor α (ERα) and glucose transporter 4 (GLUT4) genes in the uterus was examined by real-time polymerase chain reaction. Liver hexokinase (HK) and glucokinase (GK) activity was determined using spectrophotometry. Quercetin significantly improved the IR state in PCOS rats. PCOS resulted in a decrease in liver GK and an increase in liver HK specific activity, whereas quercetin increased both liver HK and GK activity. Our data also showed a significant reduction in uterine ERα and GLUT4 expression in the PCOS group, which was increased by quercetin. A remarkable effect of quercetin was the intensive reduction of PCOS-IR and significant induction of uterine GLUT4 and ERα gene expression; it could thus be a possible effective treatment for PCOS and its complications, IR and infertility.

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MRNA Expression of Adipocytokines and Glucose Transporter Type 4 (GLUT4) in Adipose Tissue in Women With and Without Polycystic Ovary Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1510 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A742-A743

Author(s):

Katarzyna Maria Ozga ◽

Magdalena Krzyczkowska Sendrakowska ◽

Tomasz Milewicz ◽

Marek Sanak ◽

Robert Jach

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Mrna Expression ◽

Polycystic Ovary ◽

Serum Amyloid ◽

Control Group ◽

Ovary Syndrome ◽

Glut 4 ◽

Serum Amyloid A1

Abstract Background: The main feature of polycystic ovary syndrome (PCOS) is hyperandrogenism, adipocytes hypertrophy and chronic low-grade inflammation. It is known that PCOS is closely linked to functional dysfunction in adipose tissue, which in turn are connected with metabolic disturbances such as insulin resistance. However, there is no complete characterization of the adipose tissue in women with PCOS. Aim: To compare the expression of adipocytokines between women with and without PCOS. Materials and Methods: The total number of twenty two participants were enrolled into the study. Study group included ten women with PCOS diagnosed according to the Rotterdam criteria, the control group- twelve women without PCOS. Approximately 3 g of tissue was excised from subcutaneous adipose tissue through a small incision in the suprapubic area. mRNA was isolated and gene expression profiling was performed including following genes: GLUT4, irisin, leptin, omentin, vaspin, adiponectin, visfastin, apelin, serum amyloid A1 and chemerin. Blood samples were taken between 3rd and 5th day of the menstrual cycle to evaluate serum hormonal levels. The oral glucose tolerance test (OGTT) was done simultaneously with the assessment of glucose and insulin plasma levels at 0, 60 and 120 minute. Results: Patients with PCOS presents different mRNA expression of adipocytokines compared with control group. There were statistically significant differences in irisin, leptin, omentin, visfastin, chemerin and serum amyloid A1 expression, that were higher in PCOS. GLUT-4 and adiponectin expression was significantly lower in PCOS patient compared to control. Due to an insufficient measurement of apelin and vaspin gene expression there were not included in following analysis. Conclusions: mRNA expression of adipocytokines in adipose tissue in women with and without polycystic ovary syndrome is different. In women with PCOS, there is a higher expression of genes for most of adipocytokines with lower for adiponectin and GLUT-4.

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Predicting Menstrual Recovery After Laparoscopic Sleeve Gastrectomy in Polycystic Ovary Syndrome Women With Obesity

10.21203/rs.3.rs-861231/v1 ◽

2021 ◽

Author(s):

Meili Cai ◽

Yuqin Zhang ◽

Jingyang Gao ◽

Diliqingna Dilimulati ◽

Ziwei Lin ◽

...

Keyword(s):

Sleeve Gastrectomy ◽

Polycystic Ovary Syndrome ◽

Laparoscopic Sleeve Gastrectomy ◽

Polycystic Ovary ◽

Preoperative Evaluation ◽

Total Testosterone ◽

Model Assessment ◽

Ovary Syndrome ◽

Homeostatic Model Assessment

Abstract Objectives: To investigate the recovery of menses in polycystic ovary syndrome (PCOS) women with obesity after laparoscopic sleeve gastrectomy (LSG), and to explore the predictors for menstrual recovery. Methods: A total of 88 PCOS patients with obesity and 76 control patients with obesity aged 18-45 years were enrolled between May 2013 and December 2020. Preoperative clinical characteristics, metabolic parameters and sex hormones were collected. Postoperative menstrual status, body weight and use of oral contraceptives were obtained through telephone follow-up. Results: Patients with PCOS were followed up for at least six months after surgery, and the mean follow-up time was 3.23 years. About 24.66% of patients with PCOS started their first menstruation after LSG within 7 days, and 79.52% patients had regular menstruation at six months after LSG. In logistic regression analyses, duration of PCOS ≤4.5 years (P=0.007), number of preoperative menstruation per year >4.0 times/year (P=0.045), homeostatic model assessment of insulin resistance (HOMA-IR) ≤7.3 (P=0.020) and total testosterone (TT) ≤1.5 nmol/L (P=0.029) at baseline were significantly associated with menstrual resumption in PCOS patients within 6 months after LSG. After adjusting confounders, combination of four clinical indices at baseline could effectively predict menstrual recovery in PCOS patients within 6 months after LSG (AUC=0.837, [95%CI: 0.735-0.939], P<0.001). Conclusion: Overall, the combination of PCOS duration, menstruations per year, HOMA-IR and TT at baseline could be used as an effective tool for the prediction of menstrual recovery in PCOS patients within 6 months after LSG, which can be applied in preoperative evaluation.

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Brown adipose tissue thermogenesis in women with polycystic ovary syndrome

Endocrine Abstracts ◽

10.1530/endoabs.49.gp135 ◽

2017 ◽

Cited By ~ 1

Author(s):

Soulmaz Shorakae ◽

Eveline Jona ◽

Courten Barbora de ◽

Gavin Lambert ◽

Elisabeth Lambert ◽

...

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Brown Adipose Tissue ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Physical Performance Regarding Handgrip Strength in Women with Polycystic Ovary Syndrome

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0040-1718953 ◽

2020 ◽

Vol 42 (12) ◽

pp. 811-819

Author(s):

Gislaine Satyko Kogure ◽

Victor Barbosa Ribeiro ◽

Flávia Ganoa de Oliveira Gennaro ◽

Rui Alberto Ferriani ◽

Cristiana Libardi Miranda-Furtado ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Physical Performance ◽

Lean Mass ◽

Polycystic Ovary ◽

Handgrip Strength ◽

Serum Levels ◽

Total Testosterone ◽

Dominant Hand ◽

Ovary Syndrome ◽

Pcos Group

Abstract Objective The present study aimed to investigate the physical performance of handgrip strength (HGS) in women with polycystic ovary syndrome (PCOS). Methods A case-control study that included 70 women with PCOS and 93 age-matched healthy women aged between 18 and 47 years with body mass index (BMI) between 18 Kg/m2–39.9 Kg/m2. The serum levels of total testosterone, androstenedione, insulin, estradiol, thyroid-stimulating hormone (TSH), prolactin, sex hormone-binding globulin (SHBG), and 17-hydroxyprogesterone (17-OHP) were measured. The free androgen index (FAI) and the homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. The body composition regions of interest (ROIs) were assessed by dual-energy X-ray absorptiometry (DXA), and the handgrip strength (HGS) was evaluated for both the dominant and the non-dominant hands with a manual Sammons Preston (Bolingbrook, IL, US) bulb dynamometer. Results Women with PCOS had high serum levels of total testosterone (p < 0.01), androstenedione (p = 0.03), and insulin (p < 0.01), as well as high FAI (p < 0.01) and HOMA-IR (p = 0.01) scores. Compared with the non-PCOS group, the PCOS group had greater total lean mass in the dominant hand (p < 0.03) and greater HGS in both the dominant and the non-dominant hands (p < 0.01). The HGS was correlated with lean mass (p < 0.01). Conclusion Women with PCOS have greater HGS. This may be associated with age and BMI, and it may be related to lean mass. In addition, the dominance effect on muscle mass may influence the physical performance regarding HGS in women with PCOS.

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Indirect Predictors of Visceral Adipose Tissue in Women with Polycystic Ovary Syndrome: A Comparison of Methods

Nutrients ◽

10.3390/nu13082494 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2494

Author(s):

Małgorzata Kałużna ◽

Magdalena Czlapka-Matyasik ◽

Aleksandra Bykowska-Derda ◽

Jerzy Moczko ◽

Marek Ruchala ◽

...

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Visceral Adipose Tissue ◽

Polycystic Ovary ◽

Age Groups ◽

Ovary Syndrome ◽

Women Subjects ◽

Pcos Group ◽

Total Body ◽

Visceral Adipose

Visceral adipose tissue (VAT) accumulation, is a part of a polycystic ovary syndrome (PCOS) phenotype. Dual-energy x-ray absorptiometry (DXA) provides a gold standard measurement of VAT. This study aimed to compare ten different indirect methods of VAT estimation in PCOS women. The study included 154 PCOS and 68 age- and BMI-matched control women. Subjects were divided into age groups: 18–30 y.o. and 30–40 y.o. Analysis included: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist/height 0.5 (WHT.5R), visceral adipose index (VAI), lipid accumulation product (LAP), and fat mass index (FMI). VAT accumulation, android-to-gynoid ratio (A/G), and total body fat (TBF) was measured by DXA. ROC analysis revealed that WHtR, WHT.5R, WC, BMI, and LAP demonstrated the highest predictive value in identifying VAT in the PCOS group. Lower cut-off values of BMI (23.43 kg/m2) and WHtR (0.45) were determined in the younger PCOS group and higher thresholds of WHtR (0.52) in the older PCOS group than commonly used. Measuring either: WHtR, WHT.5R, WC, BMI, or LAP, could help identify a subgroup of PCOS patients at high cardiometabolic risk. The current observations reinforce the importance of using special cut-offs to identify VAT, dependent on age and PCOS presence.

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