Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome

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 skeletal muscle microvascular blood volume, improves vascular function of the conduit vessels, and enhances insulin's metabolic action in humans with Metabolic Syndrome. Subjects will be randomized to one of the 4 groups: control, exercise training, liraglutide treatment, and exercise + liraglutide. They will be studied at the baseline and then after 24 weeks of intervention.

Detailed Description
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Our hypothesis is that sustained activation of the GLP-1 receptor with Liraglutide and exercise training each will enhance microvascular insulin responses and angiogenesis in both cardiac and skeletal muscle to increase muscle insulin delivery and action and the combination of both is more effective than either alone in adults with metabolic syndrome.

Official Title
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Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: Liraglutide
* Other: Exercise training
* Drug: Liraglutide + Exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥21 and ≤60 years old. Body mass index >25 and ≤35 kg/m2 and is weight stable (<5 kg weight change in the past 6 months). BMI is limited to ≤35 kg/m2 for easier vascular access and cardiac imaging. Meet 3 of 5 National Cholesterol Education Program Adult Treatment Panel III Metabolic Syndrome criteria: Increased waist circumference (≥102 cm in men; ≥88 cm in women) Elevated triglycerides (≥150 mg/dl) Reduced HDL-cholesterol (<40mg/dl in men, <50 mg/dl in women) High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic) Elevated fasting glucose (≥100 mg/dl) Subject may participate if on the following drugs, provided the drug doses have been stable for at least 3 months. Ace inhibitor ARB HMG CoA reductase inhibitor Beta blocker Calcium channel blockers Alpha-adrenergic antagonist Statin Exclusion Criteria: A diagnosis of any type of diabetes or history of diabetes medication use Recently active (>20 min of moderate/high intensity exercise, 2 times/week) Subjects who are smokers or who have quit smoking <5 years Subjects with hypertriglyceridemia (>400 mg/dl) or hypercholesterolemia (>260 mg/dl) Subjects with BP>160/90 Subjects with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or malignancy Pregnant (as evidenced by positive pregnancy test) or nursing women Subjects with contraindications to participation in an exercise training program Allergic to perflutren A prior use of Liraglutide

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>24 weeks of treatment | Other: Exercise training<br>* 24 weeks of Exercise training<br>|
| Experimental: Liraglutide Alone<br>24 weeks of treatment | Drug: Liraglutide<br>* 24 weeks of Liraglutide<br>|
| Experimental: Exercise + Liraglutide<br>24 weeks f treatment | Drug: Liraglutide + Exercise training<br>* 24 weeks of Liraglutide + Exercise training<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 24 weeks | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Augmentation Index - change from baseline | measured at baseline and 24 weeks | 24 weeks | 
| Flow Mediated Dilation | measured at baseline and 24 weeks | 24 weeks | 
| Pulse Wave Velocity | measured at baseline and 24 weeks | 24 weeks | 
| Post Ischemic Flow Velocity - change from baseline | measured at baseline and 24 weeks | 24weeks | 
| Insulin Sensitivity - change from baseline | measured at baseline and 24 weeks | 24 weeks |