Simultaneous control of hyperglycemia and oxidative stress normalizes endothelial function in type 1 diabetes.

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.