Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes ( ZQL007)

Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes ( ZQL007)

The primary objective of this study is to examine whether exercise training alone, liraglutide treatment alone or exercise training plus liraglutide treatment increases cardiac and muscle capillary blood volume, improves vascular function in the larger conduit vessels, and enhances insulin's metabolic action in humans with Type 2 diabetes. Subjects will be randomized to one of the three groups: exercise training, liraglutide treatment, and exercise + liraglutide. They will be studied at the baseline and then after 16 weeks of intervention.

Our hypothesis is that sustained activation of the GLP-1 receptor with Liraglutide or exercise training will enhance microvascular perfusion, promote angiogenesis, and improve microvascular response to insulin in muscle, leading to increased muscle delivery of oxygen and nutrients and increased exercise tolerance in subjects with type 2 diabetes.

Inclusion Criteria:

• Age 21-60
• A1C ≤ 8.5%
• Never on GLP-1RA (eg: exenatide, liraglutide) or DPP4I ( eg: Sitaglipton)
• On stable dose of oral hypoglycemic agents >4 months
• On stable dose of other medications for >4 months

Exclusion Criteria:

• Taking Insulin
• Smoking presently or in the past 6 months
• BP >160/90
• BMI >35
• Family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome
• History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease.
• Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease
• Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI).
• Pregnant or breastfeeding.
• Known hypersensitivity to perflutren (contained in Definity)