Endothelial Function Varies According to Insulin Resistance Disease Type Short Title: Insulin Resistance and Vascular Function

Objective: We examined the relationship between insulin resistance and vascular function in three insulin resistant states (type 2 diabetes mellitus, non-HIV lipodystrophic diabetes, and non-diabetic polycystic ovary syndrome (PCOS)) and in healthy controls. Research Design and Methods: The population included 12 women with type 2 diabetes, 6 with lipodystrophic diabetes, 10 with polycystic ovary syndrome, and 19 healthy female subjects. Metabolic measures included insulin sensitivity by the homeostasis model assessment, lipids, free fatty acids, and adiponectin. High-resolution B mode ultrasound was used to determine endothelium-dependent and –independent vasodilation. Results: Type 2 diabetic, liposdystrophic, and polycystic ovary syndrome subjects were insulin resistant compared with control subjects (p = 0.001). Flow mediated vasodilation (FMD) was reduced in diabetic subjects (3.4 ± 1.3%), compared with control (7.3 ± 1.1%) but not in lipodystrophic (7.7 ± 1.2%) or polycystic ovary syndrome subjects (9.9 ± .7%) (p = 0.005). Nitroglycerin-mediated vasodilation (NMD) was attenuated in both diabetic (15.2 ± 2.0%) and lipodystrophic subjects (16.7 ± 3.6%) compared to healthy control subjects (24.6 ± 2.4%) and polycystic ovary syndrome subjects (23.2 ± 1.8%)(p = 0.019). Neither insulin resistance, free fatty acids, adiponectin, nor C-reactive protein associated with vascular dysfunction. Conclusions: Among these different types of patients with insulin resistance, we found abnormal endothelium-dependent vasodilation only in the patients with type 2 diabetes. We postulate that variations in the mechanism of insulin resistance may affect endothelial function differently than glucose homeostasis.