title: A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women.
abstract: BACKGROUND
  Inflammatory cytokines, including tumor necrosis factor alpha, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations.
  
  
  METHODS
  Among 82,069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor alpha receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease.
  
  
  RESULTS
  After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor alpha receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups.
  
  
  CONCLUSIONS
  These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.
authors: Department of Epidemiology, University of California, Los Angeles, CA 90095-1772, USA. siminliu@ucla.edu
authors: Simin
authors: S
authors: Liu
authors: Lesley
authors: L
authors: Tinker
authors: Yiqing
authors: Y
authors: Song
authors: Nader
authors: N
authors: Rifai
authors: Denise E
authors: DE
authors: Bonds
authors: Nancy R
authors: NR
authors: Cook
authors: Gerardo
authors: G
authors: Heiss
authors: Barbara V
authors: BV
authors: Howard
authors: Gokhan S
authors: GS
authors: Hotamisligil
authors: Frank B
authors: FB
authors: Hu
authors: Lewis H
authors: LH
authors: Kuller
authors: JoAnn E
authors: JE
authors: Manson
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications; D015850:Interleukin-6 / Q000097:blood*; D008593:Menopause; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein