Background. Endothelial dysfunction and increased inflammation are precursors of cardiovascular disease in type 1 diabetes (T1D) and occur even in adolescents with T1D. The goal of this study was to determine the relationship of endothelial dysfunction to various measures of glycemia. Research Design and Methods. Forearm blood flow (FBF, venous occlusion plethysmography) was measured before and after 5？min of upper arm vascular occlusion in 17 adolescents with uncomplicated type 1 diabetes. Endothelial function was assessed as postocclusion FBF and forearm vascular resistance (FVR, mean arterial pressure/FBF). Fasting glucose, 72 hour mean glucose and standard deviation from continuous glucose monitoring, hemoglobin A1c, and hemoglobin A1c by duration area under the curve were used to assess immediate, short-term, and intermediate- and long-term glycemia. Results. Postocclusion FBF ( , ) negatively correlated and postocclusion FVR positively correlated ( , ) with hemoglobin A1c levels. FVR was positively associated with log 3 day mean glucose ( , ). Postocclusion FBF ( versus ？mL/dL/min, mean ± SE, ) tended to be lower and FVR ( versus ？mmHg？dL？min/mL, ) was significantly higher in subjects with hemoglobin A1c above the median (8.3%) compared to those with lower hemoglobin A1c levels. Conclusions. These results demonstrate that poor intermediate-term glycemic control is associated with impaired endothelial function. 1. Background Vascular endothelial dysfunction contributes to the development of both macrovascular and microvascular complications in type 1 diabetes (T1D) and there is considerable evidence that patients with T1D have increased endothelial stress/injury and reduced endothelial repair. Recent studies have indicated that adolescents with T1D have impaired flow mediated vasodilation, as measured using either brachial artery ultrasound or venous occlusion plethysmography [1–6]. Flow mediated vasodilation is due to endothelial nitric oxide release and thus is an effective measure of endothelial function. Beyond this, there is good evidence of impaired endothelial repair capacity in T1D. Studies in mice indicate that animals with streptozotocin-induced diabetes have impaired vascular repair following hindlimb ischemia [7]. Similarly, vascular repair is impaired in control animals following transplantation of bone marrow derived stem cells from diabetic animals compared to those receiving cells from healthy animals [8]. Both studies indicated that progenitor cell counts were reduced in diabetic animals. Studies in humans have generally indicated
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