Biomedical Engineering Reference
In-Depth Information
ICAM-1, were strong independent predictors of type 2 diabetes in populations
with diverse ethnic backgrounds. h is chapter aims to summarize both clinical and
epidemiological studies relating plasma levels of endothelial adhesion molecules
to diabetes mellitus and interpret these data in the context of emerging biological
evidence. h e available evidence indicates that elevated circulating levels of some,
but not all, markers correlate not only with prediabetic insulin resistance and
type 2 diabetes, but also with complications in both type 1 and type 2 diabetes.
Future studies are warranted to evaluate the clinical utility of endothelial markers
in comprehensively assessing and managing the development and prognosis of
diabetes in the context of other diabetes biomarkers and traditional risk factors.
INTRODUCTION
Endothelial dysfunction has been closely related to insulin resistance, implicating
its etiologic role in the development of type 2 diabetes as well as diabetic
complications (Price and Loscalzo 1999, Ross 1999). Endothelial function
can readily be measured by circulating levels of endothelial soluble adhesion
molecules. In response to several inl ammatory cytokines, endothelial cells secrete
cellular adhesion molecules including E-selectin, intercellular adhesion molecule
1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) on the cell surface
(Price and Loscalzo 1999, Ross 1999). Soluble forms of these molecules are released
from shedding or proteolytic cleavage from the endothelial cell surface and may
rel ect over-expression of their respective membrane-bound forms (Price and
Loscalzo 1999). Measurable levels of these soluble cellular adhesion molecules have
modest but also meaningful correlations with the direct assessment of endothelial
function and are thus considered useful indicators of endothelial dysfunction/
activation.
Epidemiological evidence, primarily from cross-sectional studies, has shown
that an elevation in circulating levels of E-selectin, ICAM-1, and VCAM-1 is
associated with not only prediabetic insulin resistance, obesity, hypertension, and
dyslipidemia among non-diabetic individuals but also type 2 diabetes patients
with or without vascular complications (Schram and Stehouwer, 2005). However,
these cross-sectional or retrospective studies cannot establish the time-to-event
sequence for the associations observed. Few prospective studies have specii cally
examined the relationship between levels of endothelial adhesion molecules and the
development of diabetes mellitus. Findings from several well-designed prospective
studies suggested that elevated levels of soluble adhesion molecules, especially
E-selectin, independently predicted risk of type 2 diabetes among initially non-
diabetic individuals. Such i ndings have been coni rmed in an ethnically diverse
cohort of US post-menopausal women.
