Relation between soluble adhesion molecules and insulin sensitivity in type 2 diabetic individuals - Role of adipose tissue

OBJECTIVE - The purpose of this study was to explore the relation between i nsulin resistance and plasma levels of soluble adhesion molecules and to ex amine the effects of acute hyperinsulinemia on these molecules in type 2 di abetic individuals. RESEARCH DESIGN AND METHODS - Intercellular adhesion molecule (ICAM)-1, vas cular cell adhesion molecule (VCAM)-1, and E- and P-selectin plasma concent rations were measured in 36 nonobese type 2 diabetic patients without cardi ovascular disease and in 7 healthy subjects. Insulin sensitivity was assess ed by a 4-h euglycemic (similar to5 mmol/l)-hyperinsulinemic (similar to 30 0 pmol/l) clamp performed in combination with [H-3]3-D-glucose infusion. RESULTS - Diabetic subjects were insulin resistant but did not show plasma concentrations of adhesion molecules that were significantly higher than co ntrol subjects. in diabetic subjects, plasma ICAM-1 and E-selectin were neg atively correlated with total glucose disposal during the insulin clamp (r = -0.432, P < 0.01; and r = -0.375, P < 0.05, respectively), whereas plasma VCAM-1 and P-selectin were not. Plasma ICAM-1 as well as E- and P-selectin were positively correlated with BMI, total body fat (TBF), and waist girth (P < 0.05-0.001). In multiple regression analyses, the relation of plasma ICAM-1 and E-selectin with insulin sensitivity was lost after adjustment fo r potential confounders, including HbA(1c), blood pressure, and/or LDL chol esterol. In these analyses, BMI was the only independent predictor of plasm a ICAM-1 (R-2 = 0.244, P < 0.002), whereas TBF Was the only independent pre dictor of plasma E-selectin (R2 = 0.202, P = 0.01). The 4-h insulin infusio n during the glucose clamp did not significantly change plasma levels of ad hesion molecules. CONCLUSIONS - Overall adiposity, rather than insulin resistance, may be a d eterminant of plasma levels of ICAM-1 and E-selectin in type 2 diabetic ind ividuals. In these patients, acute hyperinsulinemia does not exert any sign ificant effect on plasma adhesion molecules. These findings support the pos sibility that adipose tissue releases one or more factors that may adversel y affect endothelial function on one hand and insulin sensitivity on the ot her.