Is the association between insulin resistance and diabetogenic haematopoietically expressed homeobox (HHEX) polymorphism (rs1111875) affected by polycystic ovary syndrome status?

2017 ◽  
Vol 29 (4) ◽  
pp. 670 ◽  
Author(s):  
F. Ramezani Tehrani ◽  
M. Zarkesh ◽  
M. Tohidi ◽  
F. Azizi ◽  
A. Zadeh-Vakili

Polycystic ovary syndrome (PCOS) is frequently accompanied by insulin resistance (IR). The aim of the present study was to investigate whether the genetic association between insulin resistance and two single nucleotide polymorphisms (SNPs), namely rs7903146 (C/T) in transcription factor 7-like 2 (TCF7L2) and rs1111875 (A/G) in haematopoietically expressed homeobox (HHEX), is affected by PCOS status in Iranian women. The study participants consisted of 582 women with PCOS (cases) referred to the Reproductive Endocrinology Research Center and 504 subjects without PCOS (controls), randomly selected from the Tehran Lipid and Glucose Study. Cases and controls were further subdivided to two groups according to IR status: those with and without IR. IR was identified on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.63. The SNPs in TCF7L2 and HHEX were genotyped by polymerase chain reaction–restriction fragment length polymorphism. There were no significant differences in the distribution of genotypes and alleles between cases and controls (P < 0.05). Among cases, the prevalence of the CC, CT and TT genotypes was 37.8%, 46.3% and 15.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 13.5%, 46.1% and 40.4%, respectively. In the control group, the prevalence of the CC, CT and TT genotypes was 32.2%, 53.9% and 13.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 11.3%, 48.6% and 40.0%, respectively. After adjustment for age and body mass index, the probability of IR was decreased by 49% among carriers of the A allele in the control group (95% confidence interval 0.33–0.78; P = 0.002). The findings of the present study suggest that the association between IR and diabetogenic polymorphisms may be affected by PCOS status.

2015 ◽  
Vol 172 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Rong Ju ◽  
Wei Wu ◽  
Juan Fei ◽  
Yufeng Qin ◽  
Qiuqin Tang ◽  
...  

ObjectiveTo assess whether single nucleotide polymorphisms of HSD17B5 (AKR1C3) (rs1937845 and rs12529) and HSD17B6 (rs898611) are associated with polycystic ovary syndrome (PCOS) in a Chinese population.DesignA case–control study was conducted to investigate the relation between HSD17B5 and HSD17B6 polymorphisms and PCOS.MethodsIn this study, 335 patients with PCOS and 354 controls were recruited. The genotypes of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) were detected by the TaqMan method.Results and conclusionsWe found that the genotypic frequencies of the rs1937845 polymorphism were different in subjects with PCOS compared with control, with the CT genotype being more commonly found in patients with PCOS than in controls (P=0.005). We observed a significantly 1.74-fold higher risk of CT genotype in the polymorphism rs1937845 in women with PCOS vs the control group (adjusted odds ratio (OR), 1.74; 95% CI=1.19–2.54; P=0.005). A similar, significant 1.47-fold higher risk (adjusted OR, 1.47; 95% CI=1.07–2.03; P=0.018) was demonstrated for T allele of polymorphism rs1937845 associated with PCOS. In patients with PCOS, the rs12529 (G>C) and rs1937845 (C>T) polymorphisms were strongly associated with the high level of testosterone. The TT carriers of polymorphism rs1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P=0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in genotype or allele distributions of the polymorphisms rs12529 of HSD17B5 and rs898611 of HSD17B6 between patients with PCOS and controls. Additionally, the two polymorphisms of HSD17B5 are associated with hyperandrogenemia in patients with PCOS. In conclusion, our findings showed a significant statistical association between HSD17B5 rs1937845 and PCOS risk in Chinese women. The CT genotype and T allele frequency are influenced significantly to a higher extent in patients with PCOS than controls. Further studies are needed to confirm the results and find out the exact molecular mechanism of the polymorphism on the risk of hyperandrogenemia and PCOS.


2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Ewelina Kolan′ska-Dams ◽  
Joanna Boinska ◽  
Maciej W. Socha

Introduction: Central obesity appears to play a major role in the pathogenesis of metabolic disorders in polycystic ovary syndrome. Insulin resistance and carbohydrate disorders are associated with dysfunctional secretion of various adipokines by the adipose tissue. Objectives: This study aimed to evaluate leptin, apelin, and visfatin against a background of carbohydrate metabolism parameters in patients diagnosed de novo with polycystic ovary syndrome (PCOS). Material and methods: The study group consisted of 40 patients with PCOS (mean age, 29 years) diagnosed in accordance with the American Society for Reproductive Medicine criteria from 2003. The control group consisted of 37 clinically healthy women (mean age, 26 years). All controls had regular menses and no clinical or biochemical signs of hyperandrogenism. Concentrations of leptin, apelin, visfatin, and insulin were measured by immunoenzymatic methods. Glucose concentrations were determined using spectrophotometry. Results: Significantly higher concentrations of leptin, insulin, homeostatic model assessment for insulin resistance (HOMA-IR) index, and the immunoreactive insulin (IRI)/glucose index were found in the PCOS group than in the control group. Notably, the concentration of apelin was over five times lower in the PCOS group than in the control group. In patients with PCOS, a positive correlation was found between the concentrations of insulin and leptin and concentrations of leptin and IRI/glucose. Patients of the PCOS group with body mass index (BMI) ≥  25 had significantly higher values of leptin, insulin, HOMA-IR index, and IRI/glucose index than patients of the PCOS group with normal BMI. In the PCOS group, a positive correlation was found between BMI and leptin concentration (r = 0.7176; p < 0.0001) and carbohydrate metabolism, such as insulin (r = 0.5524; p = 0.0003), glucose (r = 0.3843; p = 0.0157), HOMA-IR (r = 0.5895; p < 0.0001), and IRI/glucose (r = 0.3872; p = 0.0163). These findings were not observed in the control group. Conclusions: (1) Increased leptin concentration observed in women diagnosed de novo with PCOS as well as positive correlations between leptin and HOMA-IR, and IRI/glucose and BMI may indicate a potential role of leptin in the reduction of tissue sensitivity to insulin. (2) Significantly lower apelin concentration in the PCOS group (>5 fold) than in the control group, associated with a concomitant increase in leptin, may also contribute to carbohydrate metabolism disorders occurring in the course of PCOS.


2020 ◽  
Vol 9 (3) ◽  
pp. 732 ◽  
Author(s):  
Aleksandra Maria Polak ◽  
Agnieszka Adamska ◽  
Anna Krentowska ◽  
Agnieszka Łebkowska ◽  
Justyna Hryniewicka ◽  
...  

Insulin resistance and hyperandrogenemia observed in polycystic ovary syndrome (PCOS) are associated with metabolic disturbances and could be connected with body composition pattern. To date, several studies defining the parameters of body composition using dual energy X-ray absorptiometry (DXA) method in the group of PCOS patients have been published, however, without the analysis in different phenotypes. The aim of the present study was to investigate the relationships between serum androgens concentration, insulin resistance and distribution of fat mass using DXA method in various PCOS phenotypes according to the Rotterdam criteria. We examined 146 women: 34 (38%) had PCOS phenotype A, 20 (23%) phenotype B, 20 (23%) phenotype C and 15 (16%) phenotype D (with mean age of each phenotype 25 years), and 57 control subjects (mean age of 25.5 years). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Serum concentrations of testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEA-S) were assessed and free androgen index (FAI) was calculated. In phenotypes A, B and C, we observed higher FAI in comparison to the control group (all p < 0.01). Serum concentrations of androstenedione and DHEA-S were higher in phenotypes A and C in comparison to the control group (all p < 0.01). However, only in phenotype A we found higher visceral adipose tissue (VAT) mass and android/gynoid ratio (A/G ratio) in comparison to the control group (all p < 0.01). In phenotype A, we observed connection of VAT with FAI (r = 0.58, p < 0.01). Accordingly, A/G ratio was related with FAI in all phenotypes (all p < 0.05). Additionally, in phenotype C, A/G ratio was related to serum concentrations of DHEA-S and androstenedione (r = 0.46, p = 0.03; r = 0.53, p = 0.01, respectively). We also found connections of HOMA-IR with VAT and A/G ratio in all phenotypes (all p < 0.05). Women with phenotype A had higher amount of VAT and A/G ratio in comparison to the control group. Serum concentration of androgens and insulin resistance are connected with VAT and A/G ratio in normoandrogenic and hyperandrogenic PCOS phenotypes.


BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e027498 ◽  
Author(s):  
Yan Li ◽  
Lihui Hou ◽  
Yingji Wang ◽  
Liangzhen Xie ◽  
Meiwei Zhang ◽  
...  

IntroductionApproximately 5%–20% of reproductive women suffer from polycystic ovary syndrome (PCOS). Auricular points acupressure (AA) may serve as alternative management for PCOS for its benefits in both physical and psychological well-being. However, the effects of AA for insulin resistance (IR) in overweight/obese PCOS women have not been confirmed.Methods and analysisThe present study is designed as a randomised, placebo-controlled pilot trial to evaluate the effectiveness and safety of AA in treating IR in women with PCOS. A total of 60 eligible PCOS subjects will be randomised into an intervention group (AA group) and a control group (sham AA group) in a ratio of 1:1. Magnetic beads will be taped to the auricular points by the same senior acupuncture specialist from the First Affiliated Hospital, Heilongjiang University of Chinese Medicine. The treatment will last for 12 weeks. Primary outcome measure will be changes in homeostasis model assessment of IR between baseline and after 3 months of AA/sham AA treatment. Secondary outcomes include hormonal profile, weight, waist/hip circumference, body mass index, blood pressure, Ferriman-Gallwey score, acne and the assessment of health-related quality of life. Outcome measures are collected at baseline and the end of treatment visit.Ethics and disseminationThe protocol has been approved by the ethics committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine (HZYLLKY201800301). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications.Trial registration numberNCT03546595; Pre-results.


2020 ◽  
Author(s):  
yonghui jiang ◽  
yue liu ◽  
zhiheng yu ◽  
ping yang ◽  
lei xie ◽  
...  

Abstract Objective Polycystic ovary syndrome (PCOS) can be divided into different subtypes, including insulin resistance (IR) and hyperandrogenism (HA). Asprosin is a novel hormone associated with IR; however, the role of asprosin in women with PCOS has not been investigated. Thus, the aim of this study was to investigate the relationship between serum asprosin levels and PCOS subtypes. Methods Ninety-three women with PCOS and 77 healthy women as controls were selected for this study. Clinical and laboratory data were compared between the PCOS group and the control group. The PCOS group was further divided into subgroups: 1) women with or without HA (PCOS HA and PCOS NHA, respectively); 2) women with or without IR (PCOS IR and PCOS NIR, respectively). Serum asprosin was measured by ELISA. Results Serum asprosin levels showed no significant difference between the PCOS and control groups. However, it was significantly lower in the PCOS HA and IR groups compared to the respective PCOS NHA and NIR groups (P < .05). In the PCOS group, serum asprosin was negatively correlated with body mass index, luteinizing hormone, testosterone, basal antral follicles, fasting insulin, Homeostatic Model Assessment of Insulin Resistance, and triglycerides. After adjusting for BMI, the correlations were not significant and asprosin was only positively correlated with prolactin (r = 0.426, P < .001). Conclusions Our study shows that women with PCOS HA or IR exhibit significantly lower serum asprosin levels compared to controls, and the lower asprosin level directly correlated with PRL level.


2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110317
Author(s):  
Chenyun Miao ◽  
Qingge Guo ◽  
Xiaojie Fang ◽  
Yun Chen ◽  
Ying Zhao ◽  
...  

Objective This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration. Results A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = –0.37; 95% confidence interval –0.69, –0.05) and serum insulin (standardized mean difference = –0.66; 95% confidence interval –1.19, –0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar. Conclusions Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.


Author(s):  
Daniel A Dumesic ◽  
Ayli Tulberg ◽  
Megan McNamara ◽  
Tristan R Grogan ◽  
David H Abbott ◽  
...  

Abstract Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective To examine whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Design Prospective cohort study. Setting Academic center. Patients Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls. Intervention(s) Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy. Main Outcome Measure(s) Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.


2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Gurhan Guney ◽  
Mine Islimye Taskin ◽  
Ozgur Baykan ◽  
Ertan Adali ◽  
Selin Gul Tezcan ◽  
...  

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.


Author(s):  
Cristina Benetti-Pinto ◽  
Vanessa Piccolo ◽  
Daniela Yela ◽  
Heraldo Garmes

Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 – 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥ 2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.


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