Circulating Levels of Endothelial Adhesion Molecules and Risk of Diabetes in an Ethnically Diverse Cohort of Women
Yiqing Song 1 ,
JoAnn E. Manson 1 2 3 ,
Lesley Tinker 4 ,
Nader Rifai 5 ,
Nancy R. Cook 1 3 ,
Frank B. Hu 2 3 ,
Gokhan S. Hotamisligil 6 ,
Paul M. Ridker 1 ,
Beatriz L. Rodriguez 7 8 9 ,
Karen L. Margolis 10 ,
Albert Oberman 11 and
Simin Liu 1 3 12 13
1 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
2 the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
3 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
4 Fred Hutchinson Cancer Research Center, Seattle, Washington
5 Children's Hospital, Harvard Medical School, Boston, Massachusetts
6 Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts
7 Department of Public Health Sciences and Epidemiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu,
Hawaii
8 Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii
9 Pacific Health Research Institute, Honolulu, Hawaii
10 HealthPartners Research Foundation, Minneapolis, Minnesota
11 Division of Preventive Medicine, Department of Medicine, School of Medicine, University of Alabama, Birmingham, Alabama
12 Department of Epidemiology, School of Public Health, University of California, Los Angeles, California
13 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
Address correspondence and reprint requests to Dr. Simin Liu, Department of Epidemiology, UCLA School of Public Health, Box
951772, 650 Charles E. Young Dr. South, Los Angeles, CA 90095. E-mail: siminliu{at}ucla.edu
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.
CRP, C-reactive protein
CVD, cardiovascular disease
HOMA-IR, insulin resistance index estimated using the homeostasis model assessment
ICAM-1, intercellular adhesion molecule-1
VCAM-1, vascular cell adhesion molecule-1
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 27 March 2007. DOI: 10.2337/db07-0250.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0250 .
Accepted March 20, 2007.
Received February 20, 2007.
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Circulating Levels of Endothelial Adhesion Molecules and Risk of Diabetes in an Ethnically Diverse Cohort of Women

10.2337/db07-0250