title: Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women.
abstract: Elevated circulating levels of soluble adhesion molecules as markers of endothelial dysfunction have been related to insulin resistance and its associated metabolic abnormalities. However, their associations with type 2 diabetes remain inconclusive. We conducted a prospective nested case-control study to examine the associations between plasma levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) and diabetes risk among 82,069 initially healthy women aged 50-79 years from the Women's Health Initiative Observational Study. During a median follow-up of 5.9 years, 1,584 incident diabetes case subjects were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood draw, and follow-up time. Baseline median levels of the biomarkers were each significantly higher among case subjects than among control subjects (E-selectin, 49 vs. 37 ng/ml; ICAM-1, 324 vs. 280 ng/ml; and VCAM-1, 765 vs. 696 ng/ml [all P values <0.001]). After adjustment for risk factors, the relative risks of diabetes among women in the highest quartile versus those in the lowest quartile were 3.46 for E-selectin (95% CI 2.56-4.68; P for trend <0.0001), 2.34 for ICAM-1 (1.75-3.13; P for trend <0.0001), and 1.48 for VCAM-1 (1.07-2.04; P for trend = 0.009). E-selectin and ICAM-1 remain significant in each ethnic group. In conclusion, higher levels of E-selectin and ICAM-1 were consistently associated with increased diabetes risk in a multiethnic cohort of U.S. postmenopausal women, implicating an etiological role of endothelial dysfunction in the pathogenesis of type 2 diabetes.
authors: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Yiqing
authors: Y
authors: Song
authors: JoAnn E
authors: JE
authors: Manson
authors: Lesley
authors: L
authors: Tinker
authors: Nader
authors: N
authors: Rifai
authors: Nancy R
authors: NR
authors: Cook
authors: Frank B
authors: FB
authors: Hu
authors: Gokhan S
authors: GS
authors: Hotamisligil
authors: Paul M
authors: PM
authors: Ridker
authors: Beatriz L
authors: BL
authors: Rodriguez
authors: Karen L
authors: KL
authors: Margolis
authors: Albert
authors: A
authors: Oberman
authors: Simin
authors: S
authors: Liu
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology*; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D012306:Risk; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014652:Vascular Diseases / Q000150:complications*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1