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Telmisartan Shows an Equivalent Effect of Vitamin C in Further Improving Endothelial Dysfunction After Glycemia Normalization in Type 1 Diabetes

¹ Centre of Excellence in Diabetes and Endocrinology, University Hospital of Coventry and Warwickshire, Warwick Medical School, University of Warwick, Coventry, U.K.
² Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
³ Division of Metabolic Diseases, Center of Excellence for Cardiovascular Diseases, Second 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

OBJECTIVE— Long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations of endothelial function by increased oxidative stress, even when glycemia is normalized.

RESEARCH DESIGN AND METHODS— In this study, 36 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, achieving a 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. The same protocols were performed after 1 month of telmisartan or placebo.

RESULTS— Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels. Telmisartan significantly improved basal endothelial function and decreased nitrotyrosine plasma levels. In patients treated with telmisartan, a near normalization of both flow-mediated vasodilation and oxidative stress was achieved when glycemia was normalized, whereas adding vitamin C infusion did not show further effect on endothelial function or nitrotyrosine plasma levels.

CONCLUSIONS— These data indicate that combining the normalization of glycemia with an antioxidant can normalize endothelial function in type 1 diabetic patients and that telmisartan works as an antioxidant like vitamin C.

Abbreviations: CVD, cardiovascular disease • FMD, flow-mediated dilation • NF-B, nuclear factor-B

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