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

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

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.

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.

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