Relation between glycaemic control, hyperinsulinaemia and plasma concentrations of soluble adhesion molecules in patients with impaired glucose tolerance or Type II diabetes

Aims/hypothesis. Increased plasma concentrations of circulating adhesion molecules in patients with Type II (non-insulin-dependent) diabetes mellitus could be associated with the increased cardiovascular risk in these patients. However, it is controversial whether increased adhesion molecule plasma concentrations are primarily related to hyperglycaemia or to hyperinsulinaemia. Methods. We evaluated the plasma concentrations of soluble E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) at baseline and during euglycaemic hyperinsulinaemic clamp in three different groups without additional cardiovascular risk factors: group A (control group), 28 healthy volunteers with normal glucose tolerance; group B, 24 subjects with fasting hyperinsulinaemia, normal fasting glucose but impaired glucose tolerance; group C, 32 patients with Type II diabetes, fasting hyperinsulinaemia and chronic hyperglycaemia. Results. Plasma soluble E-selectin, ICAM-1, and VCAM-1 concentrations were higher (p < 0.05) in patients with Type II diabetes (group C) compared with the other groups. The adhesion molecule concentrations correlate with the fasting plasma glucose (r = 0.59, p < 0.001), the 2-h OGTT plasma glucose (r = 0.70, p < 0.01), and the HbA_1c value (r = 0.61, p < 0.05). The E-selectin but not the ICAM-1 and VCAM-1 plasma concentrations correlated with the fasting insulin concentrations (r = 0.62, p < 0.05) or the whole body glucose uptake (r = 0.59, p < 0.05) in the clamp. The hyperinsulinaemia during the euglycaemic hyperinsulinaemic clamp had no significant effect on the plasma concentrations of E-selectin, ICAM-1, and VCAM-1 in all three groups. Conclusion/interpretation. Our results suggest that increased E-selectin concentrations are related to hyperglycaemia, hyperinsulinaemia and insulin resistance, whereas increased ICAM-1 and VCAM-1 plasma concentrations in patients with Type II diabetes are rather related to hyperglycaemia than to hyperinsulinaemia or insulin resistance.