Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus

To better understand potential associations of circulating adhesion molecules (cAMs) with diabetic microangiopathy, circulating serum concentrations of intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), and endothelial leukocyte adhesion molecule-1 (cELAM-1) were determined in patients with insulin-dependent diabetes mellitus (IDDM) (n=70) presenting with varying degree of metabolic control and status of diabetic late complications, and were compared with age-matched healthy subjects (n=70) in a cross-sectional study. Concentrations of cICAM-1 and cVCAM-1 were elevated in IDDM vs. age-matched controls (cICAM-1: 276+/-71 vs. 212+/-57 ng/mL; P <0.0001; cVCAM-1: 781+/-245 vs. 615+/-151 ng/mL; P <0.0001), whereas cELAM-1 did not differ between the groups (cELAM-1: 50+/- 25 vs. 46+/-23 ng/mL, P=0.31). The levels of cVCAM-1 were more markedly elevated in IDDM patients with diabetic retinopathy (n=32) than in those without (n=38) (cVCAM-1: 848+/-281 vs. 724+/-197 ng/mL, P <0.05), as well as in patients with micro- or macroalbuminuria (n=10) vs. those without (n=60) (cVCAM-1: 947+/-256 ng/mL vs. 753+/-234 ng/mL, P <0.05), whereas no difference in cICAM-1 and cELAM-1 was apparent regarding the clinical status of diabetic microangiopathy. No correlations were found between hemoglobin A(1c) and cAMs in the individual subgroups of patients and healthy subjects. Interestingly, however, low density lipoprotein cholesterol correlated with cVCAM-1 (r=0.38, P=0.03) in IDDM patients with diabetic microangiopathy (n=33), but not in healthy controls or patients without microangiopathy (n=37). Analyzing the pooled data of diabetic patients and healthy subjects (n=140), concentrations of cICAM-1 were markedly related to cVCAM-1 (r=0.45, P <0.0001) and cELAM-1 (r=0.31, P <0.0002), whereas cVCAM-1 was related less to cELAM-1 (r=0.19, P=0.03), respectively. We conclude that, irrespective of actual metabolic control, serum concentrations of cICAM-1 and cVCAM-1 but not cELAM-1 are elevated in patients with IDDM, reflecting ongoing endothelial cell stimulation and leukocyte activation. More specifically, more marked elevation of cVCAM-1 may even hint at clinically manifest diabetic microangiopathy.