The lack of utility of circulating biomarkers of inflammation and endothelial dysfunction for type 2 diabetes risk prediction among postmenopausal women: the Women's Health Initiative Observational Study.
BACKGROUND
Recent studies have linked plasma markers of inflammation and endothelial dysfunction to type 2 diabetes mellitus (DM) development. However, the utility of these novel biomarkers for type 2 DM risk prediction remains uncertain.


METHODS
The Women's Health Initiative Observational Study (WHIOS), a prospective cohort, and a nested case-control study within the WHIOS of 1584 incident type 2 DM cases and 2198 matched controls were used to evaluate the utility of plasma markers of inflammation and endothelial dysfunction for type 2 DM risk prediction. Between September 1994 and December 1998, 93 676 women aged 50 to 79 years were enrolled in the WHIOS. Fasting plasma levels of glucose, insulin, white blood cells, tumor necrosis factor receptor 2, interleukin 6, high-sensitivity C-reactive protein, E-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were measured using blood samples collected at baseline. A series of prediction models including traditional risk factors and novel plasma markers were evaluated on the basis of global model fit, model discrimination, net reclassification improvement, and positive and negative predictive values.


RESULTS
Although white blood cell count and levels of interleukin 6, high-sensitivity C-reactive protein, and soluble intercellular adhesion molecule 1 significantly enhanced model fit, none of the inflammatory and endothelial dysfunction markers improved the ability of model discrimination (area under the receiver operating characteristic curve, 0.93 vs 0.93), net reclassification, or predictive values (positive, 0.22 vs 0.24; negative, 0.99 vs 0.99 [using 15% 6-year type 2 DM risk as the cutoff]) compared with traditional risk factors. Similar results were obtained in ethnic-specific analyses.


CONCLUSIONS
Beyond traditional risk factors, measurement of plasma markers of systemic inflammation and endothelial dysfunction contribute relatively little additional value in clinical type 2 DM risk prediction in a multiethnic cohort of postmenopausal women.
Chao
Chun
C
Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, USA.
Song
Yiqing
Y
Cook
Nancy
N
Tseng
Chi-Hong
CH
Manson
JoAnn E
JE
Eaton
Charles
C
Margolis
Karen L
KL
Rodriguez
Beatriz
B
Phillips
Lawrence S
LS
Tinker
Lesley F
LF
Liu
Simin
S
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008875:Middle Aged; D017698:Postmenopause; D011237:Predictive Value of Tests; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D018570:Risk Assessment; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D019040:E-Selectin; D007328:Insulin; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein