Insulin Resistance In PCOS Research Articles

A Comparative Study of Serum Adiponectin and Insulin Resistance In Patients With Polycystic Ovary Syndrome

Objective: To assess correlation between serum adiponectin levels and insulin resistance in patients with Polycystic ovary syndrome. Study Design: Comparative Cross-Sectional study. Place and Duration of Study: PNS Hafeez Hospital, Islamabad Pakistan, and Multidisciplinary Lab-I, Department of Biochemistry, Army Medical College Rawalpindi, Pakistan from Feb 2018 to Jan 2019. Methodology: Three groups (35 females each) were formed from selected one hundred and five females (puberty till 25 years) who had Polycystic ovary syndrome. After overnight fast, blood samples were collected to measure serum levels of insulin and adiponectin. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was used to calculate insulin resistance. Results: The over-weight PCOS subgroup displayed lowest serum adiponectin level (8.73±2.13 mg/L; 13.87±3.60 mg/L in normal weight PCOS and 15.09±3.07 mg/L in controls). There was statistical significance of serum Fasting Blood Glucose (mmol/L, p=0.002), serum Insulin (mIU/L; p=0.003) andserum Adiponectin levels (mg/L; p˂0.001) and HOMA-IR (p<0.001) among three groups. The over-weight PCOS subgroup presented with highest HOMA-IR (1.71±0.19; 1.35±0.25 in normal weight PCOS subgroup and 1.12±0.26 in controls). There is negative correlation between serum adiponectin and HOMA-IR with r= -0.46. Conclusion: In PCOS-affected females, HOMA-IR correlates inversely with serum adiponectin levels, signifying that abdominal adiposity indirectly favors insulin resistance in PCOS through decrease in adiponectin secretion. Serum adiponectin level is negatively associated with severity of IR in PCOS.

Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.

Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. In recent years, inositols have emerged as potential treatment options for PCOS, but confidence in the available evidence supporting their use is limited. We comprehensively searched PubMed, Embase, and Cochrane databases for RCTs comparing the use of combined metformin and inositol versus metformin alone in women with PCOS. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of <0.05 was deemed as statistically significant. Six RCTs and 388 patients were included in the analysis, with follow-up ranging from 3 to 6 months. Combination therapy was significantly associated with improved menstrual cycle regularity (RR 1.56; 95% CI 1.01 to 2.41; p = 0.04), and lower values of modified Ferriman-Gallwey score (MD -0.97; 95% CI -1.53 to -0.40; p < 0.01) and LH/FSH ratios (MD -0.13; 95% CI -0.24 to -0.03; p = 0.01). Differences in acne (p = 0.58), body mass index (p = 0.13), fasting blood glucose (p = 0.07) and HOMA-IR (p = 0.25) were not statistically significant. In this meta-analysis of RCTs, combination therapy was associated with cycle regularization and reduction in hirsutism and LH/FSH ratio compared to metformin monotherapy. Further studies are needed to clarify the true benefits of the use of inositol in PCOS treatment.

CAPN2 correlates with insulin resistance states in PCOS as evidenced by multi-dataset analysis

ObjectiveIR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies.MethodsWe retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR scores as a phenotypic marker. Gene refinement was executed through the LASSO, SVM, and Boruta feature selection algorithms. qPCR was carried out on selected samples to confirm findings. We predicted both miRNA and lncRNA targets using the ENCORI database, which facilitated the construction of a ceRNA network. Lastly, a drug-target network was derived from the CTD.ResultsThirteen genes related to insulin resistance in PCOS were identified via WGCNA analysis. LASSO, SVM, and Boruta algorithms further isolated CAPN2 as a notably upregulated gene, corroborated by biological verification. The ceRNA network involving lncRNA XIST and hsa-miR-433-3p indicated a possible regulatory link with CAPN2, supported by ENCORI database. Drug prediction analysis uncovered seven pharmacological agents, most being significant regulators of the endocrine system, as potential candidates for addressing insulin resistance in PCOS.ConclusionsThis study highlights the pivotal role of CAPN2 in insulin resistance within the context of PCOS, emphasizing its importance as both a critical biomarker and a potential therapeutic target. By identifying CAPN2, our research contributes to the expanding evidence surrounding the CAPN family, particularly CAPN10, in insulin resistance studies beyond PCOS. This work enriches our understanding of the mechanisms underlying insulin resistance, offering insights that bridge gaps in the current scientific landscape.

Exercise to Combat the Effect of Insulin Resistance in PCOS: A Narrative Review

Abstract: PCOS is a complex multigenic condition influenced by significant epigenetic and environmental variables, including nutrition and lifestyle. IR is found in roughly 80% of obese women with PCOS and 30–40% of lean women. IR is an impairment of insulin to mediate metabolism in skeletal muscle, adipocytes and liver. Following weight gain, the severity of IR in women with PCOS increases. IR affects many PCOS women who are not overweight, and minor weight loss improves clinical results in those with near-normal body weight. The effect of exercise on IS is optimized through glucose transport and metabolism. Exercise is the first-line treatment for PCOS. Moderate intensity (60–70% VO2max; comparable to 75–80% HRmax) and high-intensity aerobic exercise (heart rate &gt;80%) improves IR in women with PCOS. These exercises are performed for at least 30 minutes per session and 3–5 days per week. A single bout of exercise (2–72 hours postexercise) can improve IS immediately. Exercise improves IS and glycemic management as well as helps in lowering the abdominal fat. Therefore, exercise performed on a regular basis can help improve insulin resistance in women with PCOS.

“A Cross Sectional Study on Association between Serum Vitamin D Status and Insulin Resistance in Polycystic Ovarian Syndrome”

Polycystic ovarian syndrome is a common cause of ovarian dysfunction in women with anovulation world wide.50-70% of patients with PCOS exhibit metabolic abnormalities, including poor glucose tolerance and hyperinsulinemia. The prevalence of vitamin D deficiency in women with PCOS is about 67-85 per cent, with serum concentrations of 25(OH) D &lt;20 ng/ml. It is suggested that there is an association between serum levels of vitamin D and metabolic parameters in women with PCOS, including fasting glucose levels, fasting insulin, insulin resistance, high blood pressure, lipid disorders, obesity, fertility and other clinical and laboratory- related parameters associated with PCOS. Given the high prevalence of vitamin D deficiency in the south Indian population, less number of studies, inconclusive studies, especially in the population of women with PCOS, as well as evidence from recent studies indicating a link between vitamin D levels with lab parameters, this study aimed to assess the relationship between vitamin D deficiency and insulin resistance in PCOS. Pearsons correlation showed 0.034 between HOMA IR and vitamin d levels indicating that vitamin d deficiency is associated with more HOMA IR values, the more insulin resistance. Pearsons correlation showed 0.05 between fasting insulin levels and vitamin d levels indicating the vitamin d deficiency is associated with more fasting insulin levels, the more insulin resistance. No significant relation is seen with fasting glucose insulin levels (Pearsons correlation value &gt;0.05). In the study, it was found that a high percentage of PCOS women were vitamin D deficient. The study also showed a significant difference in the values of some clinical and metabolic parameters such as waist circumference, fasting insulin, HOMA-IR, BMI between PCOS women with and without vitamin D deficiency; however, no linear correlation was found between serum levels of vitamin D and baseline variables, except for HOMA IR values, fasting insulin levels, BMI, G120. In conclusion, our data confirm an association between vitamin D deficiency and Insulin resistance in patients with PCOS. Thus, vitamin D supplementation could be a beneficial treatment of PCOS women to abolish insulin resistance and regulate menstrual irregularities.

Association between insulin resistance and abnormal menstrual cycle in Chinese patients with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, which is characterized by insulin resistance (IR) and menstrual cycle disorders. IR is thought of as a pivotal cause of PCOS and related comorbidities. However, the link between IR and abnormal menstrual cycles in PCOS should be further studied. In this study, we clarified the dose–response relationship between IR and abnormal menstrual cycles in patients with PCOS.ResultsIn this retrospective study including 140 patients with PCOS, we found that there was a dose–response relationship between the increased HOMA-IR index and the level of menstrual cycle disorders (1.61 [95%CI: 1.37–1.85] for normal menstruation, 2.02 [95%CI: 1.61–2.44] for oligomenorrhea, 2.35 [95%CI:1.96–2.75] for amenorrhea, P for trend = 0.003). Further stratification analyses showed that this dose–response relationship was more evident in the patients who were younger, had higher BMI, higher AFC numbers, elevated levels of testosterone, anti-Müllerian hormone, inhibin B, and prolactin levels, and had a lower progestogen level.ConclusionsOur study has established an association between IR and abnormal menstrual cycles in patients with PCOS, which can be affected by age, BMI, and hormone levels. Our results might be helpful for further prevention and treatment of amenorrhea in PCOS.

Molecular studies of CAPN-10 gene (rs2975760) and its association with Insulin Resistance in Polycystic Ovarian Syndrome of Iraqi women

Objectives: To explore an association between CAPN10, SNP-44 (rs2975760) with IR condition in women with PCOS.&#x0D; Methods: A study included 120 participants of which 68 women have PCOS subdivide according to their body mass index (BMI) into 45 obese (BMI≥30) and 23 non-obese (BMI&lt;30). The remaining 52 represent the control group who were apparently healthy women with normal weight and normal menstrual cycle. Patients with PCOS were selected from the Infertility Department, Gynecology and Obstetrics Teaching Hospital, Kerbala Health Directorate / Kerbala-Iraq between Nov., 2021 and June, 2022. Diagnosis of PCOS is based on 2 of 3 findings: oligo/anovulation, hyperandrogenism, polycystic ovaries in ultrasound (Rotterdam criteria). Patients were interviewed and examined for weight, height, waist circumference, and hip circumference. Venous blood samples were collected at 9 AM after an overnight fast. IR was assessed by calculating homeostatic model assessment of insulin resistance (HOMA-IR) using the formula (fasting glucose mg/dl x fasting insulin µU/ml)/405, taking normal value &lt;2.7. Genotypes of CAPN10, SNP-44 has been identified using Allele-specific polymerase chain reaction (AS-PCR) technique.&#x0D; Results: The prevalence of IR based on HOMA-IR was (80%) in obese PCOS and (48%) in non-obese PCOS women. CAPN10, SNP-44 has been reconstructed and analyzed in patients and controls. Genotypes of 45 obese PCOS subjects (TT, N=26; TC, N=12; and CC, N=7), 23 non-obese PCOS subjects (TT, N=15; TC, N=6; and CC, N=2) and control subjects (TT, N=39; TC, N=11; and CC, N=2) were identified. The genotype distribution was statistically different between obese PCOS women and controls (OR=5.25, P=0.048). The association of SNP-44 allele with IR status was detected. HOMA-IR was greater in CC (10.54 ± 1.29, 9.88 ± 1.41) than in TT (3.30 ± 1.52, P&lt;0.001; 2.82 ± 1.45, P&lt;0.001) and TC (3.76 ± 1.58, P&lt;0.001; 4.10 ±1.57, P&lt;0.05) in obese PCOS and non-obese PCOS subjects respectively.&#x0D; Conclusion: In obese PCOS, the C allele was associated with higher insulin secretion and HOMA-IR compared with the T allele. The increased HOMA-IR is an indicator of IR. In this scenario, the C allele might be involved in the pathophysiology of insulin resistance in PCOS.

180-LB: Plasma miRNAs May Be Associated with Waist Circumference and Insulin Resistance among Women with Polycystic Ovary Syndrome—Pilot Study

Background: Insulin resistance (IR) and central obesity are common in PCOS, but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of tissue gene expression that may contribute to the pathogenesis of IR and central adiposity in PCOS. Methods: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n=11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR) -adjusted cutoff p&amp;lt;0.1 to adjust for multiple testing. We used the miRDB’s Gene Ontology (GO) tool to identify predicted pathways for top hits. Results: Participants were 27.9 years old on average with mean BMI 32.5 kg/m2. At an FDR&amp;lt;0.1, lower levels of miR-1294 were associated with higher waist circumference (β = -0.10, FDR=0.095) . While no miRNAs were associated with HOMA-IR at our predetermined cut off, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at p&amp;lt;0.01 (Table 1) . Pathways identified in the GO analysis of miR-1294 include “negative regulation of insulin receptor signaling” (p=0.019) . Conclusions: Plasma miRNAs may be associated with IR and central obesity among PCOS patients. Disclosure P. Wander: None. D. Enquobahrie: None. T. Bammler: None. J. Macdonald: None. S. Srinouanprachanh: None. T. Kaleru: None. D. Khakpour: None. S. Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas, Insulet Corporation, Insulet Corporation. Funding NIDDK (K08103945)

Association of galactose and insulin resistance in polycystic ovary syndrome: A case-control study

SummaryBackgroundPolycystic ovary syndrome (PCOS) is closely linked to metabolic disorders. Recent reports have identified galactose as having strong associations with metabolic disorders, however, the correlation between galactose and PCOS remains largely unknown.MethodsThe serum galactose levels of 104 patients with PCOS and 98 controls were measured, and their relationships with several metabolic parameters were analyzed. The study took place at the Center for Reproductive Medicine at Shengjing Hospital of China Medical University, Shenyang, China from July 13 to Oct 20, 2020. The relationships between serum galactose and PCOS as well as PCOS-related insulin resistance were investigated via logistic regression analyses, and the performance of serum galactose as a potential biomarker for PCOS was evaluated using receiver operating characteristic curve analysis.FindingsHigher serum galactose levels were observed in the patients with PCOS than in the controls (p = 0.001). There was still a correlation between circulating galactose levels and PCOS after adjusting for covariates (p = 0.002; odds ratio (OR), 1.133; 95% confidence interval (CI) 1.047–1.227). Serum galactose levels were shown to be most closely related to the fasting serum insulin level (r = 0.370, p = 0.001) and were higher in the insulin-resistant subgroup than in the non-insulin-resistant subgroup of patients with PCOS (p = 0.001). There was no difference in serum galactose levels between the insulin-resistant and non-insulin-resistant subgroups of women in the control group (p > 0.05). Furthermore, higher serum galactose levels were shown to be associated with insulin resistance in PCOS (p = 0.004; OR, 26.017; 95% CI, 2.907–232.810). The area under the curve for galactose-mediated prediction of PCOS was 80.0%, with a sensitivity of 71.0% and a specificity of 86.4%.InterpretationHigher circulating galactose levels correlate with PCOS and PCOS-related insulin resistance; therefore, it may serve as a potential biomarker for patients with PCOS. These findings require further validation in a study with a larger sample size.FundingNational Natural Science Foundation of China (No. 82,071,607 and 32,100,691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151,039); Key Research and Development Program of Liaoning Province (NO. 2,018,225,062); Outstanding Scientific Fund of Shengjing Hospital (No. 202,003).

Evaluation of the inhibitory potentials of selected compounds from Costus spicatus (Jacq.) rhizome towards enzymes associated with insulin resistance in polycystic ovarian syndrome: an in silico study

BackgroundPolycystic ovary syndrome (PCOS) is a chronic endocrine disorder prevalent in premenopausal women and is characterized by a range of physiological and biochemical abnormalities which may include reproductive, endocrine, and metabolic alterations such as insulin resistance. Insulin resistance is the hallmark of PCOS as it predisposes the affected subjects to a higher risk of impaired glucose tolerance and type 2 diabetes mellitus (T2DM). In this study, the inhibitory activities of phytosterols and saccharides from aqueous extract of Costus spicatus rhizome were investigated against phosphoenolpyruvate carboxykinase (PEPCK), α-amylase, β-glucosidase, and fructose 1,6-biphosphatase (FBPase) in silico as potential novel therapeutic targets for T2DM-associated-PCOS. Phytochemical constituents of the plant were determined using gas chromatography-mass spectrophotometry (GC-MS), while molecular docking of the compounds with PEPCK, α-amylase, β-glucosidase, and FBPase was conducted using Vina. Thereafter, the binding modes were determined using Discovery Studio Visualizer, 2020. ResultsGCMS analysis of an aqueous extract of Costus spicatus rhizome revealed the presence of three compounds with a higher binding affinity for all enzymes studied compared to metformin. The compounds also interacted with key amino acid residues crucial to the enzyme’s activities. This study identified Lyxo-d-manno-nononic-1,4-lactone as potential multi-target inhibitors of PEPCK, α-amylase, β-glucosidase, and FBPase with reasonable pharmacokinetic properties and no significant toxicity. ConclusionThese compounds can be explored as potential therapeutic agents for the management of insulin resistance in PCOS, subject to further experimental validation.

An Analysis of PCOS Disease Prediction Model Using Machine Learning Classification Algorithms

Background: Polycystic ovary syndrome is commonly known as PCOS and it is surprising that it affects up to 18% of women in reproductive age. PCOS is the most usually occurring hormone-related disorder. Some of the symptoms of PCOS are irregular periods, increased facial and body hair growth, attain more weight, darkening of skin, diabetes and trouble conceiving (infertility). It also came into light that patients suffering from PCOS also possess a range of metabolic abnormalities. Due to metabolic abnormalities, some disorder may occur which increase the risk of insulin resistance, type 2 diabetes and impaired glucose tolerance (a sign of prediabetes). Family members of women suffering from PCOS are also at higher hazardous level for developing the same metabolic abnormalities. Obesity and overweight status contribute to insulin resistance in PCOS. Objective: In the modern era, there are several new technologies available to diagnose PCOS and one of them is Machine learning algorithms because they are exposed to new data. These algorithms learn from past experiences to produce reliable and repeatable decisions. In this article, Machine learning algorithms are used to identify the important features to diagnose PCOS. Methods: Several classification algorithms like Support vector machine (SVM), Logistic Regression, Gradient Boosting, Random Forest, Decision Tree and K-Nearest Neighbor (KNN) are uses well organized test datasets for classify huge records. Initially a dataset of 541 instances and 41 attributes has been taken to apply the prediction models and a manual feature selection is done over it. Results: After the feature selection, a set of 12 attributes has been identified which plays a crucial role in diagnosing PCOS. Conclusion: There are several researches progressing in the direction of diagnosing PCOS but till now the relevant features are not identify for the same.

THE EFFECT OF OBESITY ON PREGNANCY COMPLICATION RISKS IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

PCOS is known to raise the risk of pregnancy complications, including gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP) as compared to controls. These increased risks are likely related to the intrinsic insulin resistance in PCOS, and the magnitude of insulin resistance is primarily related to obesity. Lean women with PCOS are minimally at risk for cardiovascular disease due to the mild nature of their insulin resistance. Therefore, we have studied the risk of pregnancy complication in women with PCOS and BMI≥30 kg/m2 as compared to women with PCOS and BMI<30 using a national database.

Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model-Based Study.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types in the ovary and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS.

Corrigendum to: "Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell Function".

Corrigendum to: "Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell Function".

Circulating vaspin levels and nutritional status and insulin resistance in polycystic ovary syndrome.

The study aimed to assess the associations between circulating vaspin levels and nutritional status (assessed on tha basis of BMI) as well as insulin resistance in PCOS. Eighty-seven PCOS women, 48 obese and 39 normal weight, were enrolled in the cross-sectional study. Seventy-two Non-PCOS women, 41 obese and 31 normal weight, constituted a control group. Body mass, height and waist circumference as well as body composition by bioimpedance were measured. In the morning (16h after the last meal) we determined: serum glucose, insulin, androgens, gonadotropin (LH, FSH) and sex hormone-binding globulin (SHBG) as well as plasma vaspin levels. Standard HOMA-IR formula was used to assess insulin resistance (IR). Plasma vaspin levels were significantly lower in PCOS, both normal weight and obese, than in Non-PCOS groups. Vaspin levels were similar in normal weight and obese PCOS subgroups. There was no association between plasma vaspin levels and anthropometric parameters in PCOS group. While in Non-PCOS group a negative correlation between plasma vaspin levels and body mass (r = -0.26; p < 0.05) was found. We did not observe correlations between plasma vaspin levels and serum glucose and insulin concentrations as well as HOMA-IR values, however, in multivariable, stepwise backward regression waist circumference and HOMA-IR values explained 18.0% of plasma vaspin levels variability in the study subjects. PCOS occurrence is associated with decreased vaspin levels. The influence of nutritional status on vaspin level observed in Non-PCOS is abolished in PCOS women, possibly by more severe insulin resistance.

Metabolic Analysis in Women with Polycystic Ovary Highlight Specific Biomarkers of Insulin Resistance

The aim of the paper is to detect insulin resistance (IR) biomarkers via metabolomics. It is important to understand the PCOS pathophysiology, diagnosis measures and, subsequently, to improve treatment type and time of IR in PCOS. In most cases, almost half of the women with PCOS have IR which is triggered by inflammation, glucotoxicity and lipotoxicity. In this work was conducted a systematic review of all the papers that used metabolomics for detecting IR biomarkers in PCOS women. The exclusion criteria were: reviews, study population with women bellow 18 years of age, studies including animals and articles not in English, remaining 4 records. The results from the literature shown that phosphatidylcholines were decreased in IR PCOS women when compared to controls. Nonetheless, trans-2-hexenoylcoa, linoleic acid, leucine, myristic acid and palmitic acid regarding lipid metabolism and tyrosine, lysine, phenylalanine a-aminoadipic acid regarding amino acid metabolism were also corelated to IR in PCOS women when compared with healthy or IR controls. Lactate was the only increased metabolite related to glucose metabolism in IR PCOS women. Metabolic alteration in PCOS women with IR when are compared with controls and results that those are brought by both PCOS and IR. Lyso-phosphatidylcholine have an important pro-inflammatory and altered insulin signaling effect, both alterations being considered hallmarks of PCOS women. Serine hyperphosphorylation of the receptor accentuates IR by decreasing the signaling of insulin receptor. Moreover, high levels of lactate correlated with IR in PCOS women may indicate high muscle glycolysis, hepatic glucose production and peripheral glucose uptake. IR biomarkers in PCOS women were evidenced by metabolomics technique.

Metabolic Analysis in Women with Polycystic Ovary Highlight Specific Biomarkers of Insulin Resistance

The aim of the paper is to detect insulin resistance (IR) biomarkers via metabolomics. It is important to understand the PCOS pathophysiology, diagnosis measures and, subsequently, to improve treatment type and time of IR in PCOS. In most cases, almost half of the women with PCOS have IR which is triggered by inflammation, glucotoxicity and lipotoxicity. In this work was conducted a systematic review of all the papers that used metabolomics for detecting IR biomarkers in PCOS women. The exclusion criteria were: reviews, study population with women bellow 18 years of age, studies including animals and articles not in English, remaining 4 records. The results from the literature shown that phosphatidylcholines were decreased in IR PCOS women when compared to controls. Nonetheless, trans-2-hexenoylcoa, linoleic acid, leucine, myristic acid and palmitic acid regarding lipid metabolism and tyrosine, lysine, phenylalanine a-aminoadipic acid regarding amino acid metabolism were also corelated to IR in PCOS women when compared with healthy or IR controls. Lactate was the only increased metabolite related to glucose metabolism in IR PCOS women. Metabolic alteration in PCOS women with IR when are compared with controls and results that those are brought by both PCOS and IR. Lyso-phosphatidylcholine have an important pro-inflammatory and altered insulin signaling effect, both alterations being considered hallmarks of PCOS women. Serine hyperphosphorylation of the receptor accentuates IR by decreasing the signaling of insulin receptor. Moreover, high levels of lactate correlated with IR in PCOS women may indicate high muscle glycolysis, hepatic glucose production and peripheral glucose uptake. IR biomarkers in PCOS women were evidenced by metabolomics technique. Keywords: Polycystic ovary syndrome, insulin resistance, metabolomics, women, plasma, metabolism, biomarkers

Treatment with Metformin and Combination of Metformin Plus Pioglitazone on Serum Levels of IL-6 and IL-8 in Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Elevated serum levels of inflammatory mediators in conditions such as PCOS reflect a low-grade chronic inflammation and this has been attributed to be associated with insulin-resistance in PCOS. Therefore, insulin-sensitizing agents are suggested to improve both reproductive as well as metabolic aspects of PCOS. This study aimed to compare the effects of metformin taken alone with that of a combination of metformin and pioglitazone on menstrual cycle, hormonal parameters, insulin resistance, and inflammatory biomarkers in women with PCOS. One hundred and six women with PCOS participated in the study. All subjects were randomized into two-arm intervention groups (Arm 1 and 2). Participants in Arm-1 received metformin (500 mg BD) daily while those in Arm-2 a combination of metformin (500 mg BD) and pioglitazone (15 mg BD) for 12 wks. Serum levels of IL-6 and IL-8 were measured using ELISA whereas insulin resistance was assessed using HOMA-IR. At baseline women with PCOS had significantly elevated circulating concentrations of IL-6 and IL-8. Treatment decreased IL-6 in both the groups, however, only the combination group showed a significant decrease (p=0.005). Serum IL-8 level had a significant decrease after treatment in both groups (p <0.001). HOMA-IR and insulin levels also decreased in both the groups (both p <0.001). Testosterone, FSH, and prolactin significantly decreased in both groups. LH also decreased in both groups, however, the change was significant only in the combination group (p=0.013). Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.

Estradiol/testosterone and estradiol/androstenedione indexes and nutritional status in PCOS women – A pilot study

ObjectiveThe aim of the study was to analyze interrelations between estradiol/testosterone (E2/T) and estradiol/androstenedione (E2/A) indexes and nutritional status, insulin resistance in PCOS. Study designA cross-sectional study involved 76 PCOS (41 obese) and 67 Non-PCOS (40 obese) women. Anthropometric parameters and body composition were assessed. In fasting state of serum glucose, androgens, estradiol, FSH, LH, SHBG and insulin were measured. E2/T and E2/A indexes and the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. ResultsThe values of E2/T and E2/A indexes were significantly lower in the PCOS than Non-PCOS subjects, but did not differ significantly between the obese and normal weight groups. The lowest E2/T and E2/A values were observed in the normal weight PCOS group. Multivariable regression analyses revealed that the presence of PCOS was the major factor affecting both the log10 E2/T (β = −0.16) and log10 E2/A (β = −0.15) indexes. In addition, log10 E2/A index variability was explained by percentage of body fat (β = 0.57). HOMA-IR was not among the explanatory factors in all above models. CommentThe E2/A index is more affected by nutritional status than E2/T index. The lower value of both indices in PCOS women with normal body mass suggest that aromatase activity in PCOS are related to nutritional status.

Modern approaches to diagnostics of hyperandrogenism distributed forms in reproductive aged women

Гіперандрогенія (ГА) характеризується підвищеними рівнями циркулюючих андрогенів та/або наявністю клінічних проявів їх біологічних ефектів. Частота ГА в жіночій популяції в середньому становить 8%. Підвищення рівнів андрогенів може бути зумовлене різними, не завжди відомими факторами і реалізовуватися за допомогою різних механізмів. Присутність ГА в жінок чинить негативний вплив на фертильність і обмін речовин. За походженням ГА поділяють на істинні наднирникові або яєчникові; периферичні/рецепторні; ятрогенні; транспортні; вторинні. ГА супроводжує досить широкий спектр захворювань і станів. Більшість захворювань супроводжуються змішаними формами ГА, коли є основне джерело і додаткові або вторинні. Внесок тих чи інших джерел ГА при змішаних формах може змінюватися з плином часу і в залежності від впливу екзогенних або ендогенних факторів. Часто важливою складовою ГА є переважання вільної форми тестостерону за рахунок зниженого синтезу глобуліну, що зв’язує статеві стероїди. Все це диктує необхідність диференційованого підходу до лабораторної діагностики ГА при різних захворюваннях, особливо при порушенні жіночої фертильності. До поширених ГА, що впливають на жіночу фертильність і пов’язані з підвищеними пожиттєвими метаболічними ризиками, належать: синдром полікістозних яєчників (СПКЯ), некласичні форми вродженої гіперплазії кори наднирників (є першою патологією для диференціальної діагностики при обстеженні пацієнтки з підозрою на СПКЯ), стани, що супроводжуються оліго-/ановуляцією і вторинною ГА (гіперпролактинемія, гіперкортицизм, гіпотиреоз тощо). На сьогоднішній день рекомендовано користуватися наступним визначенням СПКЯ, що полягає у поєднанні щонайменше двох із трьох критеріїв – оліго-/ановуляція; полікістозний морфотип яєчників; клінічна та/або біохімічна ГА. Лабораторна діагностика СПКЯ включає: дослідження для виключення інших причин ГА та оліго-/ановуляції (диференціальна діагностика СПКЯ); дослідження для підтвердження діагнозу СПКЯ відповідно до критеріїв (визначення біохімічної ГА); додаткові дослідження для діагностики СПКЯ, особливо нормоандрогенних форм; дослідження для діагностики метаболічних ускладнень СПКЯ.