Role of hyperglycemia in nitrotyrosine postprandial generation.
OBJECTIVE
Recently, much attention has been paid to the possibility that postprandial hyperglycemia may be a cardiovascular risk factor in diabetes. Oxidative stress has been involved in the pathogenesis of diabetic complications, and increased plasma levels of nitrotyrosine, a product of peroxynitrite action, have been found in the plasma of diabetic subjects. The aim of the present study was to evaluate whether postprandial hyperglycemia is accompanied by nitrotyrosine generation and, if so, to explore a possible direct role of hyperglycemia in such a phenomenon.


METHODS
A total of 23 type 2 diabetic patients and 15 matched normal healthy subjects were recruited for this study. Two different tests were performed in diabetic patients: a standard meal preceded by regular insulin (0.15 units/kg body wt) or insulin aspart (0.15 units/kg body wt) to achieve different levels of postprandial hyperglycemia. The meal test was also performed in healthy control subjects. At 0 min and 1, 2, 4, and 6 h after each meal, blood glucose, triglyceride, and nitrotyrosine levels were measured.


RESULTS
Fasting nitrotyrosine was significantly increased in diabetic patients and was further increased during both meal tests in diabetic subjects but not normal subjects. As compared with regular insulin, aspart administration significantly reduced the area under the curve of both glycemia (P < 0.04) and nitrotyrosine (P < 0.03), whereas that of triglycerides was not significantly affected by the treatment.


CONCLUSIONS
This study shows a direct correlation between postprandial hyperglycemia and the production of nitrotyrosine, a marker of oxidative stress, in patients with type 2 diabetes.
Ceriello
Antonio
A
Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy. antonio.ceriello@dpmsc.uniud.it
Quagliaro
Lisa
L
Catone
Barbara
B
Pascon
Roberta
R
Piazzola
Marta
M
Bais
Bruno
B
Marra
Giampiero
G
Tonutti
Laura
L
Taboga
Claudio
C
Motz
Enrico
E
D015415:Biomarkers; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D014280:Triglycerides; C002744:3-nitrotyrosine; D014443:Tyrosine