Biomedical Engineering Reference
In-Depth Information
type 2 diabetes in women with history of GDM. Nevertheless, further research is
warranted to characterize the longitudinal changes of circulating endothelial cell
adhesion molecules during pregnancy and to compare the levels of these molecules
between GDM pregnancy and normoglycemic pregnancy.
IMPLICATIONS AND CONCLUSIONS
h ere are many important questions that must be answered before we formally
incorporate measures of circulating adhesion molecules into diabetes risk
prediction and treatment. First, endothelial dysfunction is a multifaceted process,
and measurement of the three soluble adhesion molecules (i.e., E-selectin,
ICAM-1, and VCAM-1) may not fully rel ect the extent to which the vasculature
has been altered by endothelial dysfunction. Soluble forms of these molecules
are released from either passive shedding or active proteolytic cleavage from the
endothelial cell surface (Price and Loscalzo 1999). h e mechanisms regulating the
release and clearance of soluble endothelial adhesion molecules are more likely
to be variable for dif erent adhesion molecules and remain incompletely dei ned.
Second, additional research is needed to elucidate the physiological functions
of soluble cellular adhesion molecules in circulation. h ird, elevated plasma
CRP levels may be a marker of an inl ammatory component associated with a
cluster of metabolic risk factors. Whether endothelial adhesion molecules have a
direct causal impact on the multifactorial etiology of CVD and diabetes and the
extent of such an impact remain elusive. h e non-specii c nature of endothelial
dysfunction among insulin-resistant individuals with and without diabetes, and
among patients with and without vascular complications, makes circulating
cellular adhesion molecules less than ideal as a marker of diabetes or diabetic
complications. Fourth, circulating levels of endothelial markers were assessed
only once and had varying coei cients of variation. For example, the observed
random measurement errors, especially for VCAM-1, may partially explain the
null i ndings for VCAM-1 with diabetes in some studies. Fit h, owing to the lack
of accurate assessment of preclinical atherosclerosis such as carotid artery intima-
media thickness or coronary calcii cation, we cannot completely rule out the
possibility that elevation in circulating adhesion molecule levels may be secondary
to the presence of preclinical atherosclerosis, which is highly prevalent in both
prediabetic individuals and diabetic patients. Finally, there is a notable lack of
data from prospective studies regarding the practical clinical and public health
signii cance of incorporating endothelial biomarker measurements into diabetes
prevention, diagnosis and treatment, including type 1 and type 2 diabetes and
GDM. Although careful consideration should be given to the incremental value of
adding endothelial biomarker measures, more research in this area is needed.
In conclusion, epidemiological evidence for a relationship between circulating
levels of endothelial adhesion molecules and type 1 and type 2 diabetes and their
complications is substantial, although most previous studies have been cross-
