Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation.

AIMS/HYPOTHESIS: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by oxidised LDL.

SUBJECTS AND METHODS

Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by oxidised LDL.

RESULTS

Oxidised LDL inhibited endothelium-dependent vasodilation (maximal relaxation [Emax] = 58.2+/-14.6 vs 99.3+/-5.2% for incubation without any lipoprotein, p < 0.0001). HDL from control subjects significantly reduced the inhibitory effect of oxidised LDL on vasodilatation (Emax = 77.6+/-12.9 vs 59.5+/-7.7%, p < 0.001), whereas HDL from type 2 diabetic patients had no effect (Emax = 52.4+/-20.4 vs 57.2+/-18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3+/-2.2 vs 3.1+/-1.4%, p < 0.01) and was highly inversely correlated to Emax for oxidised LDL+HDL in type 2 diabetic patients (r = -0.71, p < 0.005).

CONCLUSIONS/INTERPRETATION: In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.