Plasma Soluble Intercellular Adhesion Molecule 1 Levels Are Increased in Type 2 Diabetic Patients with Nephropathy

Abstract

Background/Aim: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic complications is still a matter of debate. This study was performed to investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in patients with type 2 diabetes mellitus. Methods: Ninety-three patients (24 males and 69 females) with type 2 diabetes mellitus were included into the study. Fifty patients had nephropathy, and 43 were free from nephropathy. Fifty healthy subjects (14 males and 36 females) served as the control group (group 1). Twenty-five of the diabetic patients had microalbuminuria (group 2), 25 had macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group 4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting. Results: The mean plasma sICAM-1 levels were not different in the 93 diabetic patients as compared with the healthy controls (392.7 ± 119.5 vs. 350.1 ± 90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the diabetic patients with nephropathy than in those without nephropathy (430.3 ± 78.2 vs. 368.2 ± 122.5 ng/ml, p = 0.03) and in the controls (430.3 ± 78.2 vs. 350.1 ± 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups 2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 ± 129.2 vs. 427.2 ± 113.7 ng/ml and 368.2 ± 122.5 vs. 350.1 ± 90.2 ng/ml, respectively). Conclusions: The plasma sICAM-1 levels in patients with type 2 diabetes mellitus are not significantly different from those in nondiabetic subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the development of nephropathy in patients with type 2 diabetes mellitus.

Therapeutic Potential of Angiostatin in Diabetic Nephropathy

“…In the early stage of DN, several proinflammatory factors such as MCP-1, TNF-␣, ICAM-1, and IL-18, have been found to be upregulated (21)(22)(23). MCP-1 is a major chemokine inducing monocyte migration and differentiation to macrophages, which augment ECM production and interstitial fibrosis in diabetic kidney (17,43,44).…”

“…Accumulating evidence suggests that inflammation plays a crucial role in DN (17)(18)(19)(20). Upregulated expression of proinflammatory cytokines, such as TNF-␣, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and IL-18, is closely associated with renal functional damage (21)(22)(23)(24). Knockout of ICAM-1 abolished diabetes-induced increase in urinary albumin excretion (UAE), glomerular hypertrophy, and mesangial matrix expansion, suggesting that inflammation may be partially responsible for the renal injury in diabetes (19).…”

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

“…Soluble forms of ICAM1 and VCAM1 have been found to enter the systemic circulation, as a result of proteolytic cleavage at the cell surface, releasing the extracellular domain. Indeed, sICAM1 and sVCAM1 levels are higher in insulin resistance, obesity and type 2 diabetes (Guler et al 2002, Leinonen et al 2003, Kent et al 2004. There is also evidence indicating that women with GDM develop endothelial dysfunction during pregnancy (Knock et al 1997), and despite returning to NGT, endothelial dysfunction is still evident in women 1-year post GDM pregnancy (Pleiner et al 2007).…”

Serum Interleukin-18 Levels Are Associated With Nephropathy and Atherosclerosis in Japanese Patients With Type 2 Diabetes

“…Furthermore, IL-18 leads to production of other proinflammatory molecules, including IL-8, IL-1␤, TNF-␣, and intercellular adhesion molecule-1 (20,22), from mononuclear cells and macrophages. These molecules are known to increase in type 2 diabetes (4,5,30) and may contribute to maintain microinflammation in renal tissues of patients with type 2 diabetes. Microalbuminuria, hs-CRP, and other proinflammatory markers are known to be associated with cardiovascular diseases.…”