Monocyte and neutrophil adhesion molecule expression during acute hyperglycemia and after antioxidant treatment in type 2 diabetes and control patients.
OBJECTIVE
We hypothesized that acute hyperglycemia (an independent cardiovascular risk factor) increases the expression of proatherogenic leukocyte adhesion molecule in type 2 diabetes and controls and that the expression of these adhesion molecules would be antioxidant sensitive.


RESULTS
Twenty-three type 2 diabetes patients and 13 control patients underwent two oral glucose tolerance tests 14 days apart and took placebo or 800 IU daily of oral alpha tocopherol between tests. Monocyte and neutrophil expression of adhesion molecules Mac-1, LFA-1 and 3, ICAM-1, and VLA-4 were measured at 0, 120, and 240 minutes by using laser flow cytometry. Baseline adhesion molecule expression did not differ between groups, but there was a rapid, highly significant increase (P<0.0001) in the intensity of monocyte Mac-1 expression after a glucose load in both groups. Alpha-tocopherol supplementation reduced only Mac-1 expression in the diabetes group (P=0.03).


CONCLUSIONS
Acute glycemic excursions of any degree cause highly significant, rapid increases in monocyte Mac-1 expression in type 2 diabetes patients and controls. Mac-1 mediates leukocyte vascular infiltration and is prothrombotic. These data suggest a mechanism for the link between glycemic excursions and increased vascular event rates.
Bertram Diabetes Research Unit, Department of Diabetes & Endocrinology, Norfolk and Norwich University Hospital NHS Trust, Colney, Norwich, UK. mike.sampson@norfolk-norwich.thenhs.com
M J
MJ
Sampson
I R
IR
Davies
J C
JC
Brown
K
K
Ivory
D A
DA
Hughes
D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D018968:CD58 Antigens / Q000096:biosynthesis / Q000097:blood; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000150:complications; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000097:blood; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000097:blood; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use
D000975:Antioxidants; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D015850:Interleukin-6; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D024502:alpha-Tocopherol