Low-density lipoprotein postsecretory modification, monocyte function, andcirculating adhesion molecules in type 2 diabetic patients with and without macrovascular complications - The effect of alpha-tocopherol supplementation

Background-Although diabetes confers an increased propensity toward acceler ated atherogenesis, data are lacking on monocyte activity in typo 2 diabeti c patients with (DM2-MV) and without (DM2) macrovascular disease compared w ith control subjects, Thus, we tested whether (1) postsecretory modificatio ns of LDL (glycation and oxidation), monocyte proatherogenic activity, and circulating levels of soluble cell adhesion molecules (sCAMs) are more pron ounced in DM2-MV than in DM2 and control subjects and (2) RRR-alpha-tocophe rol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 gro ups (n=25 per group). Methods and Results-Although LDL glycation was increased in both diabetic g roups compared with control subjects, AT therapy had no significant effect on glycation, AT therapy significantly decreased LDL oxidizability in all 3 groups. Diabetic n monocytes released significantly more superoxide anion (O-2(-)) and interleukin-1 beta (IL-1 beta) and exhibited greater adhesion to endothelium than control subjects. AT therapy significantly decreased th e release of O-2(-), IL-1 beta, tumor necrosis factor-alpha, and monocyte-e ndothelium adhesion in all 3 groups. There was no significant difference be tween the 2 diabetic groups for any of the above parameters. sICAM levels w ere significantly elevated in both diabetic groups compared with controls. AT therapy resulted in a significant decrease in sCAMs. Conclusions-This is the first demonstration of increased IL-1 beta secretio n and increased adhesion of monocytes to endothelium from normotriglyceride mic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.