Cited by 81Ovarian function and disordersAdipokines, Inflammation, and Metabolic DiseasesGenetic and Kidney Cyst Diseases

Circulating Adipokine Levels in Nonobese Women with Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis

Open access
Lin, Kainan, Sun, Xiaoting, Wang, Xiao, Wang, Hanchu, Chen, Xia·2021·Frontiers in Endocrinology

Published version of a preprint

Abstract

Levels of circulating adipokines in nonobese polycystic ovary syndrome (PCOS) patients have been reported in many studies. However, the results are inconsistent. The aim of this meta-analysis is to assess whether the levels of circulating adipokines are changed in nonobese PCOS relative to nonobese healthy controls. To identify eligible studies, a literature research was performed in the PubMed, Embase, and Web of Science databases without restricting by region, journal, or language. A total of 81 studies met the eligibility criteria. The meta-analysis showed that the circulating level of adiponectin (standardized mean difference [SMD]: -0.95; 95% CI: -1.36 to -0.53) was significantly decreased in nonobese PCOS patients. In contrast, the circulating levels of chemerin (SMD: 1.13; 95% CI: 0.08 to 2.18), leptin (SMD: 0.47; 95% CI: 0.13 to 0.81), resistin (SMD: 0.45; 95% CI: 0.03 to 0.88), and visfatin (SMD: 1.38; 95% CI: 0.68 to 2.09) were significantly increased in nonobese PCOS patients. There were no significant changes in the circulating levels of apelin (SMD: 0.32; 95% CI: -1.34 to 1.99), irisin (SMD: 1.01; 95% CI: -0.68 to 2.70), omentin (SMD: -0.37; 95% CI: -1.05 to 0.31), or vaspin (SMD: 0.09; 95% CI: -0.14 to 0.32). Thus, scientific evidence suggests that the circulating adipokine levels are altered in nonobese PCOS patients compared to nonobese healthy controls. Therefore, independent of the degree of obesity, dysregulated circulating adipokine levels might play important roles in the occurrence and development of PCOS.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis found that circulating adipokine levels are altered in nonobese women with PCOS compared with nonobese controls: adiponectin is decreased, while chemerin, leptin, resistin, and visfatin are increased. The authors suggest dysregulated adipokines may play roles in PCOS independent of obesity.

Key findings

  • Adiponectin was significantly decreased in nonobese PCOS patients (SMD: -0.95; 95% CI: -1.36 to -0.53; P<0.00001; 30 studies, n=2565).
  • Chemerin (SMD: 1.13; 95% CI: 0.08 to 2.18; P=0.03), leptin (SMD: 0.47; 95% CI: 0.13 to 0.81; P=0.007), resistin (SMD: 0.45; 95% CI: 0.03 to 0.88; P=0.03), and visfatin (SMD: 1.38; 95% CI: 0.68 to 2.09; P=0.0001) were significantly increased.
  • No significant changes were found for apelin (SMD: 0.32; 95% CI: -1.34 to 1.99; P=0.70), irisin (SMD: 1.01; 95% CI: -0.68 to 2.70; P=0.24), omentin (SMD: -0.37; 95% CI: -1.05 to 0.31; P=0.29), or vaspin (SMD: 0.09; 95% CI: -0.14 to 0.32; P=0.43).
  • Egger’s test suggested possible publication bias for resistin (P=0.004) and visfatin (P=0.018); trim-and-fill corrected SMDs did not differ from uncorrected values.

Methods

  • Systematic review and meta-analysis reported according to PRISMA and MOOSE; PubMed, Embase, and Web of Science were searched without region, journal, or language restrictions for studies published before July 2019.
  • Eligible studies defined PCOS by Rotterdam or compatible criteria and excluded obese women (BMI ≥30.0), reviews, nonhuman studies, conference proceedings, studies without controls, and studies without extractable mean ± SD data.
  • Meta-analysis used Review Manager 5.3 to calculate standardized mean differences (SMDs) with 95% CIs, with Cochran’s Q and I² for heterogeneity; STATA 15.0 was used for Egger’s test and trim-and-fill when publication bias was detected.

Limitations

  • The paper states that PCOS diagnostic criteria varied across studies; obesity definitions differed by region (e.g., WHO BMI >30 vs. China BMI >28), so some obese patients may not have been excluded; adipokine measurement methods varied; and androgen effects on adipokine levels were not ruled out.
  • The text inconsistently reports the number of included studies: the abstract says 81 studies met eligibility, while the Results say 71 studies (2495 PCOS patients and 2520 controls) met criteria, and the Characteristics section again says 81 included studies.
  • High heterogeneity was evident for several adipokines (e.g., adiponectin I²=95%, chemerin I²=96%, irisin I²=97%, omentin I²=89%, resistin I²=91%, visfatin I²=96%), and publication bias was possible for resistin and visfatin.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fendo.2020.537809

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 41 cited sources checked · 0 supported · 0 flagged

  • Findingreasoning

    71 studies (comprising 2495 PCOS patients and 2520 controls) met the eligibility criteria.

    “Thus, 71 studies (comprising 2495 PCOS patients and 2520 controls) met our eligibility criteria.”
    Quote in the paperSubstantial claim
  • Findingown data

    PCOS was significantly associated with an increased chemerin level (SMD: 1.13; 95% CI: 0.08 to 2.18; P=0.03).

    “PCOS was significantly associated with an increased chemerin level (SMD: 1.13; 95% CI: 0.08 to 2.18; P=0.03).”
    • Also stated in: § Abstract · plain
      “In contrast, the circulating levels of chemerin (SMD: 1.13; 95% CI: 0.08 to 2.18), leptin (SMD: 0.47; 95% CI: 0.13 to 0.81), resistin (SMD: 0.45; 95% CI: 0.03 to 0.88), and visfatin (SMD: 1.38; 95% CI: 0.68 to 2.09) were significantly increased in nonobese PCOS patients.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no significant association between PCOS and apelin (SMD: 0.32; 95% CI: -1.34 to 1.99; P=0.70).

    “There was no significant association between PCOS and apelin (SMD: 0.32; 95% CI: -1.34 to 1.99; P=0.70).”
    • Also stated in: § Abstract · plain
      “There were no significant changes in the circulating levels of apelin (SMD: 0.32; 95% CI: -1.34 to 1.99)”
    Quote in the paperNot a substantial claim
  • Findingown data

    PCOS was significantly associated with a decreased adiponectin level (SMD: -0.95; 95% CI: -1.36 to -0.53; P<0.00001).

    “PCOS was significantly associated with a decreased adiponectin level (SMD: -0.95; 95% CI: -1.36 to -0.53; P<0.00001).”
    • Also stated in: § Abstract · plain
      “The meta-analysis showed that the circulating level of adiponectin (standardized mean difference [SMD]: -0.95; 95% CI: -1.36 to -0.53) was significantly decreased in nonobese PCOS patients.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no significant association between PCOS and irisin (SMD: 1.01; 95% CI: -0.68 to 2.70; P=0.24).

    “There was no significant association between PCOS and irisin (SMD: 1.01; 95% CI: -0.68 to 2.70; P=0.24).”
    • Also stated in: § Abstract · plain
      “There were no significant changes in the circulating levels of apelin (SMD: 0.32; 95% CI: -1.34 to 1.99), irisin (SMD: 1.01; 95% CI: -0.68 to 2.70), omentin (SMD: -0.37; 95% CI: -1.05 to 0.31), or vaspin (SMD: 0.09; 95% CI: -0.14 to 0.32).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 30
  • May combine two claims. 16
  • The quote only partly states this claim. 1
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    A total of 81 studies met the eligibility criteria.

    “A total of 81 studies met the eligibility criteria.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Funnel plots indicated observable publication bias for leptin and visfatin, but not obviously asymmetric for adiponectin and resistin.

    “Regarding adiponectin and resistin, the shape of the funnel plots was not obviously asymmetric. However, regarding leptin and visfatin, the funnel plots indicated observable publication bias ( Figures 5A–D ).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Findingown data

    There was significant heterogeneity among studies for visfatin (I2 = 96%; P<0.00001).

    “there was significant heterogeneity among the studies (I 2 = 96%; P<0.00001).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The obesity rate among PCOS patients is significantly increased, suggesting obesity may be related to the occurrence and symptoms of PCOS.

    “Research has shown that the obesity rate among PCOS patients is significantly increased, which suggests that obesity may be related to the occurrence and symptoms of PCOS (3).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Joham, 2016, Polycystic Ovary Syndrome, Obesity, and Pregnancy, Semin Reprod Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dysregulation of adipokines may lead to endocrine diseases.

    “As adipokines are involved in many critical physiological processes in the body, dysregulation of adipokines may lead to endocrine diseases (5).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Havel, 2002, Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin, Curr Opin Lipidol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fat tissue is a crucial endocrine tissue in the body.

    “Fat tissue, which we often think of as a storage site for energy, is a crucial endocrine tissue in the body (4).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Holst, 2002, New factors in the regulation of adipose differentiation and metabolism, Curr Opin Lipidol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    PCOS patients commonly have metabolic complications, such as type 2 diabetes, insulin resistance (IR), and adipose tissue dysfunction.

    “PCOS patients commonly have metabolic complications, such as type 2 diabetes, insulin resistance (IR), and adipose tissue dysfunction (7–9).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] Legro, 1999, Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [8] Stepto, 2013, Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp, Hum Reprod source

      Not checked in the free run.

    • cites [9] Spritzer, 2015, Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome, Reprod (Cambridge Engl) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Adipokines play an essential role in the pathogenesis of obesity and obesity-related diseases.

    “Additionally, research has shown that adipokines play an essential role in the pathogenesis of obesity and obesity-related diseases (6).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Chen, 2019, Serum CTRP3 Levels In Obese Children: A Potential Protective Adipokine Of Obesity, Insulin Sensitivity And Pancreatic β Cell Function, Diabetes Metab Syndr Obes Targets Ther source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The possibility of publication bias was assessed by visual inspection of a funnel plot and Egger's test.

    “The possibility of publication bias was assessed by visual inspection of a funnel plot and Egger’s test.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Study design and conductown data

    There were no significant differences in age between the PCOS patients and the controls in any of the studies, so the influence of age on the results can be excluded.

    “As there were no significant differences in age between the PCOS patients and the controls in any of the studies, we can exclude the influence of age on the results.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The Cochrane Collaboration tool was used to assess the risk of bias in the included studies.

    “We used the Cochrane Collaboration tool to assess the risk of bias in the included studies.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Disagreements between the two reviewers were resolved by discussion and, if necessary, consultation with a third reviewer.

    “Disagreements between the two reviewers were resolved by discussion and, if necessary, consultation with a third reviewer.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    Many studies show that there are changes in adipokine levels in obese PCOS patients, indicating that adipokines may play a role in obese PCOS patients.

    “Many studies show that there are changes in adipokine levels in obese PCOS patients, indicating that adipokines may play a role in obese PCOS patients (14, 15).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Itoh, 2013, The role of serum adiponectin levels in women with polycystic ovarian syndrome, Clin Exp Obstet Gynecol

      Not checked in the free run.

    • cites [15] Kumawat, 2018, Role of serum Leptin, insulin and other hormones in women with Polycystic ovarian syndrome, Indian J Clin Biochem source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Two reviewers independently reviewed the studies and determined whether they met the eligibility criteria.

    “Two reviewers independently reviewed the studies and determined whether they met the eligibility criteria.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    This systematic review and meta-analysis was designed according to PRISMA and MOOSE guidelines.

    “This systematic review and meta-analysis was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (16) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines (17).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Knobloch, 2009, Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and publication bias, J Craniomaxillofac Surg

      Not checked in the free run.

    • cites [17] Stroup, 2000, Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group, JAMA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Each risk-of-bias domain was independently evaluated by two reviewers, and disagreements were resolved by discussion.

    “Each domain was independently evaluated (as having a high, low, or unclear risk of bias) by two reviewers, and disagreements were resolved by discussion.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Adipose tissue dysfunction can lead to changes in adipokine levels.

    “Adipose tissue dysfunction can lead to changes in adipokine levels (13).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Maury, 2010, Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome, Mol Cell Endocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    Combining study findings is an attractive option to enhance the credibility of the evidence.

    “Combining study findings is an attractive option to enhance the credibility of the evidence (22).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] DerSimonian, 1986, Meta-analysis in clinical trials, Controlled Clin Trials source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Many different sets of criteria are used for the identification of PCOS, so the diagnosis of PCOS is associated with heterogeneity.

    “First, many different sets of criteria are used for the identification of PCOS, so the diagnosis of PCOS is associated with heterogeneity.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The literature search was comprehensive and did not apply region, journal, or language restrictions.

    “Our literature search was comprehensive, and we did not apply any region, journal, or language restrictions that would limit the assessment of the relationships between the adipokine levels and PCOS.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Many different methods are used to determine adipokine levels in blood, which may have led to deviations among studies.

    “Third, many different methods are used to determine the adipokine levels in the blood, which may have led to some deviations among the studies.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Study design and conductreasoning

    Not all obese PCOS patients may have been excluded, so obesity may have influenced the results.

    “Given this, not all obese PCOS patients (e.g., based on the less stringent criteria of BMI >28) may have been excluded, so obesity may have influenced the results.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Publication bias was not assessed for apelin, chemerin, irisin, omentin, or vaspin because the Cochrane Handbook states that the test for publication bias yields unreliable results when <10 studies are included.

    “We did not assess the publication bias for apelin, chemerin, irisin, omentin, or vaspin, as the Cochrane Handbook for Systematic Reviews of Interventions (www.cochranehandbook.org) states that the test for publication bias yields unreliable results when <10 studies are included.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cochrane Handbook for Systematic Reviews of Interventions

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The corrected and uncorrected SMD values for resistin and visfatin did not differ, suggesting publication bias did not affect the final results.

    “We used the trim-and-fill method and recalculated our pooled SMD values for resistin and visfatin, and the corrected and uncorrected SMD values did not differ, which suggested that publication bias did not affect the final results.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Study design and conductreasoning

    The meta-analysis increased statistical power by pooling results of single studies, and the total number of subjects was sufficiently large to support more robust conclusions.

    “Despite these limitations, our meta-analysis increased the statistical power by pooling the results of single studies, which meant that the total number of subjects was sufficiently large to support more robust conclusions.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    The included studies for apelin are homogeneous and their results are accurate.

    “However, the analysis of apelin shows no heterogeneity, indicating that the included studies are homogeneous and the study results are accurate.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Interpretationcitation

    Low serum adiponectin levels may cause insulin resistance in women with PCOS.

    “In particular, we need to consider the role of low serum adiponectin levels in causing IR in women with PCOS as adiponectin (i) decreases muscle triglyceride content, (ii) regulates the insulin receptor, (iii) activates peroxisome proliferator-activated receptor α (PPARα) to increase fatty acid oxidation, (iv) reduces hepatic glucose production by activating protein kinases, (v) increases fat ox”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Kadowaki, 2005, Adiponectin and adiponectin receptors, Endocr Rev source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The occurrence of PCOS is closely related to hyperandrogenism.

    “1) Hyperandrogenism: the occurrence of PCOS is closely related to hyperandrogenism (26).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Wang, 2018, High level of C-type natriuretic peptide induced by hyperandrogen-mediated anovulation in polycystic ovary syndrome mice, Clin Sci (Lond Engl 1979) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Type 2 diabetes is almost 10 times more common in PCOS patients than in the normal population.

    “Type 2 diabetes is almost 10 times more common in PCOS patients than in the normal population, and glucose intolerance is 30%–50% higher in obese PCOS patients (50).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Jakubowicz, 2012, The link between polycystic ovarian syndrome and type 2 diabetes: preventive and therapeutic approach in Israel, Isr Med Assoc J

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Glucose intolerance is 30%-50% higher in obese PCOS patients.

    “Type 2 diabetes is almost 10 times more common in PCOS patients than in the normal population, and glucose intolerance is 30%–50% higher in obese PCOS patients (50).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Jakubowicz, 2012, The link between polycystic ovarian syndrome and type 2 diabetes: preventive and therapeutic approach in Israel, Isr Med Assoc J

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Metformin might alleviate symptoms and treat PCOS by correcting abnormal levels of certain adipokines, such as resistin, visfatin, irisin, and chemerin.

    “Metformin might alleviate the symptoms and treat PCOS by correcting the abnormal levels of certain adipokines, such as resistin, visfatin, irisin, and chemerin levels (18, 52–54).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [18] Foda, 2019, Serum chemerin levels in Polycystic Ovary Syndrome after metformin therapy, Diabetes Metab Syndr source

      Not checked in the free run.

    • cites [52] Tarkun, 2010, Impact of treatment with metformin on adipokines in patients with polycystic ovary syndrome, Eur Cytokine Netw source

      Not checked in the free run.

    • cites [53] Ozkaya, 2010, Effect of metformin on serum visfatin levels in patients with polycystic ovary syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [54] Li, 2015, Elevated Circulating Levels of Irisin and the Effect of Metformin Treatment in Women With Polycystic Ovary Syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Resistin gene 420 C→G and 299 G→A polymorphisms are positively associated with the incidence of PCOS in Indian women.

    “A study of women in India shows that the resistin gene 420 C→G (promoter region) and 299 G→A polymorphisms are positively associated with the incidence of PCOS (with the heterozygous CG genotype, regarding the former polymorphism, being more common in PCOS patients than controls) (19).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Nambiar, 2016, Association of adiponectin and resistin gene polymorphisms in South Indian women with polycystic ovary syndrome, Eur J Obstet Gynecol Reprod Biol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hyperandrogenemia and abdominal obesity are the main causes of low serum adiponectin levels in PCOS patients.

    “In addition, hyperandrogenemia and abdominal obesity are the main causes of low serum adiponectin levels in PCOS patients, which may explain the link between the former two factors and the IR experienced by PCOS patients (as decreased adiponectin may cause IR) (44).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Escobar-Morreale, 2006, Adiponectin and resistin in PCOS: a clinical, biochemical and molecular genetic study, Hum Reprod (Oxford Engl) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Vaspin gene rs2236242 polymorphism is significantly different between PCOS patients and controls (OR: 0.59; 95% CI: 0.37 to 0.95; P=0.03).

    “Another study shows that vaspin gene rs2236242 polymorphism is significantly different between PCOS patients and controls (odds ratio: 0.59; 95% CI: 0.37 to 0.95; P=0.03).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Kohan, 2014, Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk, Gene source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Chemerin and CMKLR1 recruit immune cells to injury sites and might affect the occurrence and development of inflammation.

    “Chemerin and CMKLR1 (which is expressed on immature dendritic cells, myeloid dendritic cells, macrophages, and natural killer cells) were later shown to recruit immune cells to injury sites and might affect the occurrence and development of inflammation (37, 38).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [37] Bondue, 2011, ChemR23 Dampens Lung Inflammation and Enhances Anti-viral Immunity in a Mouse Model of Acute Viral Pneumonia, PLoS Pathog source

      Not checked in the free run.

    • cites [38] Benjamin, Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Adiponectin gene polymorphisms may increase susceptibility to PCOS, as the T allele studied is significantly reduced in PCOS patients compared with controls (OR: 0.72; 95% CI: 0.52 to 0.99; P=0.047).

    “A Finnish study suggests that adiponectin gene polymorphisms may increase susceptibility to PCOS as the T allele studied is significantly reduced in PCOS patients compared to controls (odds ratio: 0.72; 95% CI: 0.52 to 0.99; P=0.047) (42).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Heinonen, 2005, Associations between two single nucleotide polymorphisms in the adiponectin gene and polycystic ovary syndrome, Gynecol Endocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The proinflammatory adipokine chemerin promotes chemotaxis of immature dendritic cells and macrophages via its receptor CMKLR1.

    “The proinflammatory adipokine chemerin was discovered to promote the chemotaxis of immature dendritic cells and macrophages via its receptor CMKLR1 (36).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Wittamer, 2003, Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids, J Exp Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    High leptin levels may lead to insulin resistance in nonobese PCOS patients by promoting four events: inhibition of phosphoenolpyruvate carboxykinase, fat deposition in skeletal muscle cells, fat breakdown and free fatty acid production, and direct inhibition of basal and glucose-stimulated insulin secretion.

    “High leptin levels may lead to IR in nonobese PCOS patients by promoting the following events: (i) inhibition of phosphoenolpyruvate carboxykinase, causing decreased hepatic glucose oxidation and increased hepatic glycogen reserve; (ii) fat deposition in skeletal muscle cells; (iii) fat breakdown and free fatty acid production; and (iv) direct inhibition of basal insulin secretion and glucose-stim”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] Tan, 2008, Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome - Ex vivo and in vivo regulation of omentin-1 by insulin and glucose, Diabetes source

      Not checked in the free run.

    • cites [34] Barzilai, 1997, Leptin selectively decreases visceral adiposity and enhances insulin action, J Clin Invest source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Metformin may also alleviate PCOS symptoms by reducing high testosterone levels.

    “Relatedly, metformin may also alleviate PCOS symptoms via reducing high testosterone levels (56).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Sharma, 2019, Efficacy of Metformin in the Treatment of Acne in Women with Polycystic Ovarian Syndrome: A Newer Approach to Acne Therapy, J Clin Aesthet Dermatol

      Not checked in the free run.

39 of 39
  • The paper relies on this without support.

    Studies on adipokine levels in nonobese PCOS patients have been inconsistent.

    “However, studies on adipokine levels in nonobese PCOS patients have been inconsistent.”
  • The paper relies on this without support.

    It is not known whether the changes in adipokines are related directly to PCOS, to obesity, or to both.

    “Moreover, it is not known whether the changes in adipokines are related directly to PCOS, to obesity, or to both.”
  • The paper relies on this without support.

    The mechanism of PCOS has not been determined.

    “However, the mechanism of PCOS has not been determined.”
  • The paper relies on this without support.

    No prior systematic review or meta-analysis has quantified the levels of nine adipokines in nonobese PCOS patients.

    “To our knowledge, this is the first systematic review and meta-analysis quantifying the levels of nine adipokines in nonobese PCOS patients.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Apelin heterogeneity is described in opposite ways

    Minor

    The discussion includes apelin among outcomes with significant heterogeneity, then says the apelin analysis shows no heterogeneity.

  • Visfatin study count differs between the results and bias test

    Minor

    The results say 26 studies compared visfatin levels, whereas the Egger-test table lists 15 visfatin studies. This leaves unclear how many studies support the reported visfatin analysis.

  • Included-study count is reported as both 71 and 81

    Minor

    The study-selection calculation yields 71 included studies (284 minus 203 minus 10), but the abstract and subsequent sections report 81. The paper does not reconcile the ten-study difference.

3 of 3

The citation lists haven’t been fetched yet

References 59 · Cited by 81

Research works printed but not linked: 1

  1. Lim, 2012, Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis, Hum Reprod Update, 18, 10.1093/humupd/dms030 · DOI · Paper page

Authors
Lin, K., Sun, X., Wang, X., Wang, H., & Chen, X.
Affiliations
First Affiliated Hospital of Wenzhou Medical University (CN)
Corresponding author
  • Wang, Hanchu
  • Chen, Xia
Venue
Frontiers in Endocrinology
Published
2021-01-07
Volume
11
Pages
537809-537809
ISSN
1664-2392 (ISSN-L)
OpenAlex
W3118630608
Cited by
81
References
59
Citations by year
2026: 13 · 2025: 12 · 2024: 13 · 2023: 14 · 2022: 22 · 2021: 7
FWCI
2.30
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Wenzhou Municipal Science and Technology Bureau (Y20180271)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
polycystic ovary syndrome, adipokines, non-obese women, adiponectin, chemerin, leptin, resistin, visfatin, apelin, irisin, omentin, vaspin
MeSH terms
Female, Humans, Obesity, Polycystic Ovary Syndrome, Adipokines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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