Simultaneous Control of Hyperglycemia and Oxidative Stress Normalizes Endothelial Function in Type 1 Diabetes
- Antonio Ceriello, MD1,
- Sudhesh Kumar, MD1,
- Ludovica Piconi, BSC2,
- Katerine Esposito, MD3 and
- Dario Giugliano, MD3
- 1Centre of Excellence in Diabetes and Endocrinology, University Hospital of Coventry and Warwickshire, Warwick Medical School, University of Warwick, Coventry, U.K., the
- 2Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
- 3Division of Metabolic Diseases, Center of Excellence for Cardiovascular Diseases, University of Naples SUN, Naples, Italy
- Address correspondence and reprint requests to Prof. Antonio Ceriello, Warwick Medical School, Clinical Science Research Institute, Clinical Science Building, University Hospital–Walsgrave Campus, Clifford Bridge Road, Coventry CV2 2DX, U.K. E-mail: antonio.ceriello{at}warwick.ac.uk
Abstract
OBJECTIVE—Previous studies have shown that in type 1 diabetes endothelial dysfunction persists even when glycemia is normalized. Moreover, oxidative stress has recently been demonstrated to be the mediator of hyperglycemia-induced endothelial dysfunction.
RESEARCH DESIGN AND METHODS—Thirty-six type 1 diabetic patients and 12 control subjects were enrolled. The diabetic patients were divided into three groups. The first group was treated for 24 h with insulin, achieving a near-normalization of glycemia. After 12 h of this treatment, vitamin C was added for the remaining 12 h. The second group was treated for 24 h with vitamin C. After 12 h of this treatment, insulin was started, with achievement of near-normalization of glycemia for the remaining 12 h. The third group was treated for 24 h with both vitamin C and insulin, achieving near-normalization of glycemia.
RESULTS—Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. However, a combination of insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels.
CONCLUSIONS—This study suggests that long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations in endothelial cells, which may contribute to endothelial dysfunction by increased oxidative stress even when hyperglycemia is normalized.
- AGE, advanced glycation end product
- ELISA, enzyme-linked immunosorbent assay
- FMD, flow-mediated vasodilatation
- NO, nitric oxide
- NOS, nitric oxide synthase
- PARP-1, poly(ADP-ribose) polymerase-1
- PKC, protein kinase C
- TNM, tetranitromethane
Footnotes
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All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted November 22, 2006.
- Received October 4, 2006.
- DIABETES CARE
