E-SELECTIN PLASMA-CONCENTRATION IS INFLUENCED BY GLYCEMIC CONTROL IN NIDDM PATIENTS - POSSIBLE ROLE OF OXIDATIVE STRESS

Although elevated levels of soluble E-selectin and intercellular cell adhesion molecules-1 (ICAM-1) have been reported in non-insulin-depend ent diabetes mellitus (NIDDM), it is not clear by what mechanism this elevation occurs and whether or not it is related to glycaemic control . In this study we analyse: 1) the relation of glycaemic control with the concentrations of E-selectin, vascular cell adhesion molecules-1 ( VCAM-1) and ICAM-1 in NIDDM patients; 2) whether metabolic control can affect the oxidative stress (as measured by plasma hydroperoxide conc entration and susceptibility of LDL to in vitro oxidation) and hence t he adhesion molecule plasma concentrations. Thirty-four (19 males and 15 females) poorly controlled NIDDM patients were studied. All paramet ers were evaluated at the beginning of the study and after 90 days of dietary and pharmacological treatment. The treatment decreased HbA(1C) (p < 0.001), E-selectin (p < 0.001), plasma hydroperoxides (p < 0.003 ) and the susceptibility of LDL to in vitro oxidation (lag phase) (p < 0.0001). Before treatment HbA(1C), lag phase and lipid hydroperoxides correlated with E-selectin plasma concentration (r = 0.51, -0.57 and 0.54, respectively, p < 0.01). There was also a correlation between Hb A(1C) and lag phase (p < 0.01) and between HbA(1C) and lipid hydropero xides (p < 0.01). In addition, the variations of HbA(1C), lag phase an d lipid hydroperoxide values correlated with those for E-selectin conc entration after 90 days' treatment (r = 0.54, -0.64 and 0.61, respecti vely, p < 0.01). In multiple linear correlation analysis, however, the partial correlation coefficients of HbA(1C) (basal and variations) wi th E-selectin concentration (basal and variations) fell to non-signifi cant values (r = 0.12 and 0.25, respectively) when LDL lag phase and p lasma hydroperoxides were kept constant. The results indicate that the improvement of metabolic control in NIDDM patients is associated with a decrease of E-selectin plasma levels; they also suggest that glycae mic control per se is not directly implicated in determining E-selecti n plasma concentration; glycaemic control could affect E-selectin conc entration through its effect on oxidative stress.