(Circulation. 2000;102:191.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Low-Density Lipoprotein Postsecretory Modification, Monocyte Function, and Circulating Adhesion Molecules in Type 2 Diabetic Patients With and Without Macrovascular Complications
The Effect of 
-Tocopherol Supplementation
From the Division of Clinical Biochemistry and Human Metabolism (S.D., I.J.) and Center for Human Nutrition (I.J.), Departments of Pathology (S.D., I.J.) and Internal Medicine (I.J.), University of Texas Southwestern Medical Center, Dallas.
Correspondence to I. Jialal, MD, PhD, Director, Division of Clinical Biochemistry and Human Metabolism, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-9073. E-mail jialal.i{at}pathology.swmed.edu
Background—Although diabetes
confers an increased propensity toward accelerated atherogenesis, data
are lacking on monocyte activity in type 2 diabetic patients with
(DM2-MV) and without (DM2) macrovascular disease compared with control
subjects. Thus, we tested whether (1) postsecretory modifications of
LDL (glycation and oxidation), monocyte proatherogenic activity, and
circulating levels of soluble cell adhesion molecules (sCAMs) are more
pronounced in DM2-MV than in DM2 and control subjects and (2)
RRR-
-tocopherol (AT) therapy, 1200 IU/d for 3 months,
has a similar effect in the 3 groups (n=25 per group).
Methods and Results—Although LDL glycation was increased in both
diabetic groups compared with control subjects, AT therapy had no
significant effect on glycation. AT therapy significantly decreased LDL
oxidizability in all 3 groups. Diabetic monocytes released
significantly more superoxide anion (O2-) and
interleukin-1ß (IL-1ß) and exhibited greater adhesion to
endothelium than control subjects. AT therapy
significantly decreased the release of O2-,
IL-1ß, tumor necrosis factor-, and
monocyte-endothelium adhesion in all 3 groups. There
was no significant difference between the 2 diabetic groups for any of
the above parameters. sICAM levels were 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-1ß secretion and increased adhesion of monocytes to endothelium from normotriglyceridemic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.
Key Words: vitamins • diabetes • cells • cell adhesion molecules • proteins
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