Role of Hyperglycemia in Nitrotyrosine Postprandial Generation
- Antonio Ceriello, MD1,
- Lisa Quagliaro, PHD2,
- Barbara Catone, MD1,
- Roberta Pascon, MD1,
- Marta Piazzola, DS1,
- Bruno Bais, MD1,
- Giampiero Marra, MD3,
- Laura Tonutti, MD4,
- Claudio Taboga, MD4 and
- Enrico Motz, MD1
- 1Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy
- 2Morpurgo Hofman Research Laboratory on Aging, Udine, Italy
- 3Novo Nordisk S.p.A., Rome, Italy
- 4Diabetology Unit, Udine General Hospital, Udine, Italy
Abstract
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.
RESEARCH DESIGN AND 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.
- AUCA, area under the curve after the administration of aspart insulin
- AUCR, area under the curve after the administration of regular insulin
- CVD, cardiovascular disease
- ELISA, enzyme-linked immunosorbent assay
- NO, nitric oxide
- NT, nitrotyrosine
- O2−, superoxide anion
- TNM, tetranitromethane
Footnotes
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Address correspondence and reprint requests to Dr. Antonio Ceriello, Chair of Internal Medicine, University of Udine, P.le S. Maria della Misericordia, 33100 Udine, Italy. E-mail: antonio.ceriello{at}dpmsc.uniud.it.
Received for publication 5 November 2001 and accepted in revised form 3 May 2002.
A.C. is a paid consultant for Novo Nordisk Italy.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE
