Arterioles from Bariatric Patients with Diabetes Have Blunted Responses to Insulin but not Acetylcholine

Abstract

Obesity and type‐2 diabetes are associated with cardiovascular disease and endothelial dysfunction of which the mechanisms leading to aberrant insulin‐dependent vasodilation are incompletely understood. As not all obese individuals are diabetic, we hypothesize that reduced insulin‐dependent vasodilation is a specific endothelial dysfunction independent of the degree of obesity that accompanies the presence of overall insulin resistance. We tested this hypothesis in jejunal submucosal arterioles obtained from bariatric patients undergoing Roux‐en‐Y proximal gastric bypass surgery. Patients were 49±2 years old with a body mass index (BMI) of 48.5±2.4 Kg/m2. No differences in age or BMI were found between diabetics (n=22) and non‐diabetics (n=30). Maximal arteriolar responses to KCl, phenylephrine, acetylcholine, or sodium nitroprusside were not significantly different between diabetics and non‐diabetics. In contrast, insulin‐dependent vasodilation was smaller in diabetics (40.4±6.4 vs. 61.9±8.8%, respectively). This suggests that a blunted insulin‐vasodilation response is a form of endothelial dysfunction not correlated with BMI in type‐2 diabetes. The blunted‐response to insulin occurring in the absence of an abnormal acetylcholine‐induced dilation suggest that the mechanism responsible for the blunted insulin response is upstream of nitric oxide synthase activation.