title: Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis.
abstract: OBJECTIVE
  It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC.
  
  
  METHODS
  We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by Newcastle-Ottawa scale. Random-effects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC.
  
  
  RESULTS
  Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n = 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04-52.85, p = 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n = 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08-0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n = 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20-2.06, p = 0.02). There was moderate-to-high heterogeneity among the included studies.
  
  
  CONCLUSIONS
  Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMA-IR values.
authors.affiliation: School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima 9, Peru; Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, 44195 USA. Electronic address: adrianhernandezdiaz@gmail.com.
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Hernandez
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH, 44106 USA. Electronic address: lepiscean@gmail.com.
authors.forename: Vinay
authors.initials: V
authors.lastname: Pasupuleti
authors.affiliation: Faculty of Human Medicine, Postgraduate Section, Universidad de San Martin de Porres, Lima 12, Peru. Electronic address: vbeniteszapata@gmail.com.
authors.forename: Vicente A
authors.initials: VA
authors.lastname: Benites-Zapata
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH, 44106 USA. Electronic address: tpriyaleela@gmail.com.
authors.forename: Priyaleela
authors.initials: P
authors.lastname: Thota
authors.affiliation: Medicine Institute Center for Value Based Care Research, Cleveland Clinic, Cleveland, OH, 44195 USA. Electronic address: abhishekdp@gmail.com.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Deshpande
authors.affiliation: Department of Obstetrics and Gynecology, University of Zaragoza Faculty of Medicine and Lozano Blesa University Hospital, Domingo Miral s/n, Zaragoza 50009, Spain. Electronic address: faustino.perez@unizar.es.
authors.forename: Faustino R
authors.initials: FR
authors.lastname: Perez-Lopez
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D016009:Chi-Square Distribution; D016889:Endometrial Neoplasms / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008019:Life Style; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin
keywords: Endometrial cancer; Insulin resistance; Meta-analysis