The incidence and characteristics of silent cerebral infarction in elderly diabetic patients: association with serum-soluble adhesion molecules

Abstract

It has been widely accepted that the initial steps in the formation of atherosclerotic lesions involve the adherence of circulating leukocytes to dysfunctional endothelium and their subsequent transmigration into the arterial intima [1±3]. The recruitment of leukocytes into the tissues is dependent on a multistep cascade of events mediated by distinct adhesion molecules such as the selectin family, immunoglobulin superfamily and integrin family [3,4]. Substantially, vascular cell adhesion molecule-1 (VCAM-1) has been found in rabbit atherosclerotic lesions [5] and intercellular adhesion molecule-1 (ICAM-1) has been expressed in human atherosclerotic plaques [6] and carotid bifurcations [7]. Also, the soluble form of adhesion molecules has recently been found in serum and increased levels have been re- Diabetologia (1998) Summary The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p < 0.05, p < 0.001, and p < 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p < 0.01 and p < 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p < 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI. [Diabetologia (1998) 41: 911±917]

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

“…The risk increase did not vary with time. In accordance with previous studies, we showed sVCAM-1 levels to be significantly associated with male sex, age, fasting insulin levels, vWF level, the presence of type 2 diabetes, hypertension, and microalbuminuria, and, inversely, with levels of total, LDL, and HDL cholesterol and estimates of glomerular filtration rate (18,(20)(21)(22)27,37). These variables, however, did not materially affect the association between sVCAM-1 levels and risk of cardiovascular mortality (Ta b l e 3).…”

“…In accordance with previous findings (20,(24)(25)(26)(27)(28)(29), we demonstrated levels of sVCAM-1 to be higher among diabetic than among nondiabetic subjects, suggesting a stronger stimulation of VCAM-1 synthesis among diabetic as compared with nondiabetic subjects. In an environment with long-standing high glucose concentrations, lipids and proteins will undergo nonenzymatic glycation and oxidation, resulting in the successive formation of successively reversible Amadori products (such as GHb) and irreversible metabolites, so-called advanced glycated end products (AGEs) (48,49).…”

“…Increased levels thus may reflect progressive formation of atherosclerotic lesions (14,17). In addition, recent cross-sectional studies showed sVCAM-1 concentration to be positively associated with carotid artery intima-media thickness (18)(19)(20) and with the severity of peripheral arterial disease assessed by angiography (18,21). In prospective studies, however, high levels of sVCAM-1 could not be demonstrated to be associated with risk of cardiovascular events (22,23), which is in contrast with findings on other adhesion molecules, such as intercellular adhesion molecule 1 and E-selectin (22,24).…”

“…Most (20,(25)(26)(27)(28)(29), but not all (30,31), studies have shown sVCAM-1 levels to be increased among type 2 diabetic subjects as compared with nondiabetic subjects, and sVCAM-1 levels have been shown to be independently associated with carotid artery intima-media thickness in type 2 diabetes patients (29). In view of these considerations, we investigated the association of sVCAM-1 concentration and risk of cardiovascular and all-cause mortality among nondiabetic and type 2 diabetic subjects in a prospective, populationbased cohort study.…”

Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects

“…Elevated levels of various cellular adhesion molecules including E-selectin and vascular cell adhesion molecule 1 (VCAM-1) are considered putative markers of endothelial dysfunction. These cellular adhesion molecules are typically elevated in individuals at risk for T2DM, and they are elevated further in diabetic patients who have had silent cerebral infarction (Kawamura et al 1998). A recent longitudinal study in T2DM patients (Stehouwer et al, 2002) indicated that endothelial dysfunction and inflammation progress together over time, each influencing the other and creating a vicious downward spiral.…”