Serum Concentrations of Soluble Vascular Cell Adhesion Molecule-1 and E-Selectin Are Elevated in Insulin-Resistant Patients With Type 2 Diabetes

It is well known that soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) levels are elevated in patients with type 2 diabetes (1,2,3). Previous studies suggest that hyperglycemia, hyperinsulinemia, or insulin resistance may be responsible for the elevation of adhesion molecules (4,5,6). However, to our knowledge, the relation between soluble adhesion molecules and directly measured insulin sensitivity has not been studied in patients with type 2 diabetes. To investigate the direct association between insulin resistance and the elevation of soluble adhesion molecules, we performed a case-control study. Serum concentrations of sICAM-1, sVCAM-1, and sE-selectin were compared in insulin-sensitive and insulin-resistant patients who were matched for age, sex, BMI, duration of diabetes, and glycemic control (HbA_1c). Insulin sensitivity was assessed by the K index of short insulin tolerance test (K_ITT) (7). Briefly, a bolus of regular insulin (0.1 unit/kg) was infused, and blood samples were collected at 3, 6, 9, 12, and 15 min after infusion. K_ITT was calculated using the following formula: K_ITT = 0.693/t_1/2 (8). Patients whose K_ITT values were <2.00% per min were diagnosed as having insulin resistance, and those with K_ITT values >3.00% per min were defined as insulin-sensitive. Serum concentrations of sICAM-1, sVCAM-1, and sE-selectin were measured by enzyme-linked immunosorbent assay kits (R&D Systems, Minneapolis, MN). Data were compared with Student’s t test or contingency table analysis.

A total of 37 insulin-sensitive patients (24 men and 13 women, mean ± SEM of K_ITT = 3.82 ± 0.12% per min) and 37 insulin-resistant patients (24 men and 13 women, mean K_ITT = 1.47 ± 0.06% per min) were compared. The age (61 ± 2 vs. 62 ± 2 years, P = 0.51, respectively), BMI (23.2 ± 0.5 vs. 24.3 ± 0.7 kg/m², P = 0.22, respectively), duration of diabetes (6 ± 1 vs. 7 ± 1 years, P = 0.59, respectively), and HbA_1c levels (8.9 ± 0.2 vs. 9.1 ± 0.3%, P = 0.66, respectively) were comparable between the two groups. The percentage of insulin therapy (21.6 vs. 37.8%, P = 0.20, respectively), presence of retinopathy (18.9 vs. 10.8%, P = 0.52, respectively), and presence of coronary artery disease (8.1 vs. 18.9%, P = 0.31, respectively) did not differ between the two groups. Concerning the lipid profile, insulin-sensitive patients had significantly lower serum triglyceride levels than insulin-resistant patients (1.0 ± 0.1 vs. 1.5 ± 0.1 mmol/l, P < 0.01, respectively). sICAM-1 levels were comparable between the two groups (166.5 ± 11.9 vs. 186.2 ± 1 0.5 ng/ml, P = 0.22, respectively). In contrast, levels of sVCAM-1 and sE-selectin in insulin-sensitive patients were significantly lower than those of insulin-resistant patients (sVCAM-1 683 ± 23 vs. 813 ± 44 ng/ml, P = 0.01; and sE-selectin 48.9 ± 4.0 vs. 81.5 ± 5.7 ng/ml, P < 0.01, respectively). Because HbA_1c levels in insulin-sensitive and -resistant patients were comparable, the significant elevation of sVCAM-1 and sE-selectin in insulin-resistant patients may be independent of the plasma glucose level. Thus, in type 2 diabetic patients, insulin resistance is associated with an elevation in sVCAM-1 and sE-selectin. Increased levels of sVCAM-1 and sE-selectin may partly explain the predisposition of insulin-resistant type 2 diabetic patients to atherosclerotic vascular disease.