title: Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes.
abstract: OBJECTIVE
  To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes.
  
  
  METHODS
  Two observational prospective cohort studies.
  
  
  METHODS
  Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively.
  
  
  METHODS
  Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997.
  
  
  RESULTS
  During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes.
  
  
  CONCLUSIONS
  IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.
authors.affiliation: Department of Medicine, Helsinki University Hospital, Helsinki, Finland. kari.luotola@helsinki.fi
authors.forename: K
authors.initials: K
authors.lastname: Luotola
authors.forename: A
authors.initials: A
authors.lastname: Pietilä
authors.forename: T
authors.initials: T
authors.lastname: Zeller
authors.forename: L
authors.initials: L
authors.lastname: Moilanen
authors.forename: M
authors.initials: M
authors.lastname: Kähönen
authors.forename: M S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Y A
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: S
authors.initials: S
authors.lastname: Blankenberg
authors.forename: A
authors.initials: A
authors.lastname: Jula
authors.forename: M
authors.initials: M
authors.lastname: Perola
authors.forename: V
authors.initials: V
authors.lastname: Salomaa
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D002097:C-Reactive Protein