This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This is a randomized, non-blinded, comparative study that will evaluate the effects of Exenatide on endothelial function and arterial stiffness. 60 subjects with poorly controlled diabetes on either Metformin, a Sulfonylurea, or both, with type 2 diabetes will be randomized to treatment with either Exenatide of Lantus insulin. They will have a baseline evaluation prior to starting treatment, which will include: flow mediated dilation, to evaluate the endothelial-dependent vasodilation, pulse wave analysis to assess arterial stiffness, and response to nitroglycerin to evaluate endothelial-independent vasodilation. These tests will be performed both before and after a meal tolerance test, along with laboratory markers: endothelial function, inflammation and oxidative stress, at various time points over the course of three hours. Subjects will then be randomized to treatment with Exenatide or Lantus. Exenatide dose will be increased after 4 weeks, and Lantus dose will be titrated every other week to achieve the target fasting blood glucose. After 12 weeks, subjects will return for repeat baseline studies, as well as a meal tolerance test, with repeat studies and laboratory evaluation afterwards. The primary endpoints will be endothelial-dependent vasodilation, endothelial-independent vasodilation and arterial stiffness. Secondary endpoints will include the markers of inflammation, endothelial function and oxidative stress.
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