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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Type2 Diabetes

Intervention / Treatment
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* Other: Exercise
* Drug: Liraglutide


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Alone<br>16 weeks of treatment | Other: Exercise<br>* 16 weeks of treatment<br>|
| Experimental: Liraglutide alone<br>16 weeks of treatment | Drug: Liraglutide<br>* 16 weeks of Liraglutide<br>|
| Experimental: Exercise + Liraglutide<br>16 weeks of treatment | Other: Exercise<br>* 16 weeks of treatment<br>Drug: Liraglutide<br>* 16 weeks of Liraglutide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular Blood Volume - change from baseline | measured at baseline and 16 weeks | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Augmentation Index - change from baseline | measured at baseline and 16 weeks | 16 weeks | 
| Flow Mediated Dilation - change from baseline | measured at baseline and 16 weeks | 16 weeks | 
| Pulse Wave Velocity - change from baseline | measured at baseline and 16 weeks | 16 weeks | 
| Post Ischemic Flow Velocity-Change from baseline | measured at baseline and 16 weeks | 16 weeks | 
| Insulin Sensitivity-Change from baseline | measured at baseline and 16 weeks | 16 weeks |