scholarly journals Association between Polymorphisms of OCT1 and Metabolic Response to Metformin in Women with Polycystic Ovary Syndrome

2019 ◽  
Vol 20 (7) ◽  
pp. 1720 ◽  
Author(s):  
Hui Chang ◽  
Yuan-Shuo Hsueh ◽  
Yung Cheng ◽  
Huang-Tz Ou ◽  
Meng-Hsing Wu
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Treatment Effectiveness ◽  
Metabolic Response ◽  
Polycystic Ovary ◽  
Organic Cation Transporter ◽  
Oral Glucose ◽  
Metformin Treatment ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Insulin Sensitizer

Insulin-sensitizer treatment with metformin is widely used in polycystic ovary syndrome (PCOS). However, the treatment effectiveness shows individual differences in PCOS patients. Organic cation transporter (OCT) 1 and 2 have been reported to mediate metformin transport in the liver and kidney, respectively. In this study, we investigated the association between the polymorphisms of OCT1 and OCT2 and the treatment effectiveness of metformin in PCOS patients. The single nucleotide polymorphisms (SNPs) of OCT1 (rs683369 and rs628031) and OCT2 (rs316019) were analyzed in 87 PCOS and 113 control women. Oral glucose tolerance tests (OGTTs), which represented metformin treatment response, were conducted at the start of treatment and after six-month treatment. The results demonstrated that the SNP frequencies of OCT1 and OCT2 were not associated with PCOS pathophysiology, and that the polymorphisms of OCT1 and OCT2 were not associated with the OGTT parameters at baseline. However, PCOS patients with the G allele of OCT1 rs683369 and/or with the A allele of OCT1 rs628031 had increased insulin sensitivity compared to those with wild-type genotype after receiving metformin treatment. Moreover, the interactions of metformin*SNP were significant in both OCT1 rs683369 (p < 0.001) and rs628031 (p = 0.001) during the treatment period. Taken together, genetic polymorphisms of OCT1 contributed to different metformin treatment responses, and further study is needed to establish personalized treatment programs using a pharmacogenomic algorithm approach in PCOS patients.

scholarly journals Liver Injury Indicating Fatty Liver but Not Serologic NASH Marker Improves under Metformin Treatment in Polycystic Ovary Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Susanne Tan ◽  
Nils Vollmar ◽  
Sven Benson ◽  
Jan-Peter Sowa ◽  
Lars P. Bechmann ◽  
...  
Keyword(s):  
Liver Injury ◽  
Polycystic Ovary Syndrome ◽  
Fatty Liver ◽  
Polycystic Ovary ◽  
Serum Marker ◽  
Metformin Treatment ◽  
Ovary Syndrome ◽  
Cytokeratin 18 ◽  
Insulin Sensitizer ◽  
Pcos Group

Objective. Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance (IR), key features of nonalcoholic steatohepatitis (NASH). Cytokeratin 18 fragments (M30) have been established as a serum marker for NASH. The insulin sensitizer metformin improves hepatic IR. This study evaluates the influence of MF on serologic NASH (sNASH) in patients with PCOS.Patients and Methods. In 89 patients, metabolic parameters, liver injury indicating fatty liver (LIFL), and M30 were assessed at baseline and after metformin treatment. Patients with initial IR were subdivided into dissolved (PCOS-exIR) and persistent IR (PCOS-PIR) after treatment and compared to an initially insulin sensitive PCOS group (PCOS-C).Results. Improvement of LIFL prevalence could be seen in PCOS-C and PCOS-exIR compared to PCOS-PIR (−19.4, resp., −12.0% versus 7.2%, Chi2= 29.5,P<0.001) without change in sNASH prevalence. In PCOS-PIR, ALT levels increased significantly accompanied by a nominal, nonsignificant M30 increase.Conclusions. Metformin improves LIFL in subgroups of patients with PCOS without influencing sNASH. This could either indicate a missing effect of metformin on NAFLD or slowed disease progression. Further studies are needed to elucidate NAFLD in the context of PCOS and potential therapeutic options.

scholarly journals Metabolic Response to Short-term Protein Supplementation in Reproductive-Aged Women with Polycystic Ovary Syndrome (PCOS) (P08-070-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Manisha Rao ◽  
Emily Zumbro ◽  
Morgan Dixon ◽  
Kayleigh Kaiser ◽  
Lily Sebastian ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
G Protein ◽  
Whey Protein ◽  
Repeated Measures ◽  
Metabolic Response ◽  
Polycystic Ovary ◽  
Vital Role ◽  
Protein Supplementation ◽  
Oral Glucose ◽  
Ovary Syndrome

Abstract Objectives Women with polycystic ovary syndrome (PCOS) are commonly insulin resistant, hyperinsulinemic and hyperglycemic, increasing their risk for development of other metabolic, cardiovascular and reproductive disturbances. Dietary whey protein may attenuate postprandial glycemic excursions due to its effect on the gut-brain axis. The aim of the study is to evaluate 7-day whey protein supplementation on metabolic parameters in young women with PCOS. Methods A repeated measures (RM) design was used. Three women with and six without PCOS (PCO and CON respectively) underwent three 150-min oral glucose tolerance tests (OGTT): (i) OGTT without protein preload, (ii) OGTT on first and (iii) seventh day of protein preload. Participants consumed 35 g protein daily with protein intake 30 min before carbohydrate load on the test days. Blood samples collected at −30 (fasting/pre-preload), 0 (pre-glucose), 15, 30, 60, 90, 120 and 150 min of OGTTs were analyzed for glucose, insulin, and incretins. (Participant recruitment, data collection and analyses in progress.) Results Mixed design RM - MANOVA indicates that day of test and time did not have a significant effect on glucose levels within and between groups (P ≥ .05). However, day (P = .027) and time (P = .047) had a significant impact on insulin concentrations in both, PCO and CON groups. Insulin was significantly higher at 30 min compared to −30 and 0 min timepoints (P = .016 and P = .032 respectively) on the first and seventh days of preload. Conclusions An insulinogenic response elicited by 35 g protein preload may blunt glycemic responses, moderating them throughout the test period in women with PCOS and age-matched healthy controls. Timing of supplementation may play a vital role in achieving long term glucose homeostasis in PCOS. Funding Sources Texas Woman's University Research Enhancement Program & Glanbia Nutritionals, Inc.

scholarly journals Organic Cation Transporter 1 Polymorphisms Predict the Metabolic Response to Metformin in Women with the Polycystic Ovary Syndrome

2010 ◽  
Vol 95 (10) ◽  
pp. E204-E208 ◽  
Author(s):  
Alessandra Gambineri ◽  
Federica Tomassoni ◽  
Daniela Ibarra Gasparini ◽  
Antonio Di Rocco ◽  
Vilma Mantovani ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Organic Cation ◽  
Metabolic Response ◽  
Polycystic Ovary ◽  
Organic Cation Transporter ◽  
Ovary Syndrome ◽  
Organic Cation Transporter 1

scholarly journals The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome

2006 ◽  
Vol 155 (5) ◽  
pp. 763-770 ◽  
Author(s):  
Susanne Hahn ◽  
Ulrich H Frey ◽  
Winfried Siffert ◽  
Susanne Tan ◽  
Klaus Mann ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Oral Glucose ◽  
Allele Carrier ◽  
Metformin Treatment ◽  
Ovary Syndrome ◽  
Α Subunit ◽  
The Common

Objective: Variants in the Gs protein α subunit gene (GNAS1) are known to be involved in the pathogenesis of several endocrine and metabolic disorders. To understand genetic determinants of androgen excess, insulin resistance, and obesity in polycystic ovary syndrome (PCOS), we investigated the effect of the common GNAS1 T393C polymorphism on the phenotype of German PCOS women. Design: Two hundred and seventy-eight PCOS women and 820 Caucasian controls were genotyped for the common T393C polymorphism in GNAS1. To this end, genomic DNA was amplified by PCR with specific oligonucleotides and genotypes were determined using the restriction enzyme FokI. In addition, we evaluated whether the T393C polymorphism had an influence on the response to 6 months metformin treatment in a subgroup of 105 PCOS women. Methods: Anthropometric variables, metabolic parameters including indices of insulin resistance measured by oral glucose tolerance testing, and endocrine biochemical as well as clinical parameters were measured in all PCOS subjects. Results: GNAS1 genotype distributions were not significantly different between PCOS women and controls. In PCOS women, no significant differences in endocrine clinical and biochemical variables were found between the genotypes. However, the C-allele carrier group had significantly higher mean body weight, body mass index, leptin levels, and higher indices of insulin resistance compared with women with GNAS1 TT-genotype. Metformin treatment significantly improved hyperandrogenism, menstrual cyclicity, body weight, and insulin resistance independent of GNAS1 genotype. The major determinant of weight loss was body weight before treatment. Conclusion: The T393C polymorphism is not associated with PCOS in Caucasian women, but may represent a genetic marker for increased susceptibility for obesity in this cohort.

Metformin Treatment Ameliorates Liver Injury Indicating Fatty Liver Polycystic Ovary Syndrome

2015 ◽  
Vol 53 (01) ◽  
Author(s):  
S Tan ◽  
N Vollmar ◽  
S Benson ◽  
LP Bechmann ◽  
G Gerken ◽  
...  
Keyword(s):  
Liver Injury ◽  
Polycystic Ovary Syndrome ◽  
Fatty Liver ◽  
Polycystic Ovary ◽  
Metformin Treatment ◽  
Ovary Syndrome

Genetic polymorphisms of reproductive hormones and their receptors in assisted reproduction technology for patients with polycystic ovary syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yulia A. Koloda ◽  
Yulia V. Denisova ◽  
Natalia M. Podzolkova
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Assisted Reproductive Technologies ◽  
Polycystic Ovary ◽  
Ovarian Response ◽  
Reproductive Technologies ◽  
Reproductive Hormones ◽  
Current Data ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Art Programs

Abstract Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of childbearing, which is defined by the accumulation of multiple, small fluid-filled ovarian cysts without the selection of a single dominant follicle. Most PCOS phenotypes are characterized by the absence of spontaneous ovulation, resistance toward ovulation inductors, the production of a large immature oocytes number, and the high prevalence of ovarian hyperstimulation syndrome, resulting in reduced assisted reproductive technologies (ART) programs effectiveness. The review analyses current data about the relationship between polymorphism genotypes of KISS genes, follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and their receptors genes, gonadotropin-releasing hormone (GnRH), estrogen, and progesterone receptors genes, the PCOS risk and the features of ovarian response to stimulation during ART cycles. The use of single nucleotide polymorphisms (SNPs) as prognostic markers of ART programs outcomes would provide a personalized approach to the drugs and doses choice for ovarian stimulation and significantly increase the chance of pregnancy.

scholarly journals Berberine Phospholipid Is an Effective Insulin Sensitizer and Improves Metabolic and Hormonal Disorders in Women with Polycystic Ovary Syndrome: A One-Group Pretest–Post-Test Explanatory Study

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3665
Author(s):  
Mariangela Rondanelli ◽  
Antonella Riva ◽  
Giovanna Petrangolini ◽  
Pietro Allegrini ◽  
Attilio Giacosa ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Sex Hormone ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Tnf Α ◽  
Post Test ◽  
Liver And Kidney ◽  
Kidney Functions

Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disease in females of reproductive age and is characterized by multifactorial unhealthy conditions related to hormonal unbalance and also to dysmetabolism and inflammation. Recently, increasing evidence has shown that natural plant-based products may play a role in PCOS management. The aim of this one-group pretest–post-test explanatory study was to evaluate, in normal–overweight PCOS women with normal menses, the effectiveness of berberine on: Insulin resistance (IR) by Homeostasis Model Assessment (HOMA); Inflammation by C-Reactive Protein (CRP), Tumor Necrosis Factor α (TNF-α); Lipid metabolism; Sex hormone profile and symptoms correlated to hyperandrogenism, such as acne, by Global Acne Grading System (GAGS) and Cardiff Acne Disability Index (CADI); Body composition by DXA. Finally, adverse effects were assessed by liver and kidney functions and creatine phosphokinase (CPK). All these parameters were collected at baseline and 60 days after supplementation with a new bioavailable and safe berberine formulation. Twelve females (aged 26.6 ± 4.9, BMI 25.3 ± 3.6) were supplied for 60 days with two tablets/day (550 mg/table) of the bioavailable berberine. Results showed a statistically significant decrease in HOMA, CRP, TNF-α, Triglycerides, testosterone, Body Mass Index (BMI), Visceral Adipose Tissue (VAT), fat mass, GAGS and CADI scores, and a statistically significant increase in sex hormone-binding globulin (SHBG). Liver and kidney functions and CPK are not statistically significantly different. Therefore, berberine can represent a safe novel dietary supplement, helpful in treatment strategy for PCOS.

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