Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome

In our protocol, we will study vascular function using pulse wave velocity (PWV) augmentation index (AI), flow mediated dilation (FMD) and contrast enhanced ultrasound (CEU) as well as insulin sensitivity (euglycemic clamp) in 50 adults with metabolic syndrome, age 18-60 years. They will each be studied 4 times,before and after two 12-wk interventions (randomly assigned) as follows: 1) Placebos and 2) Metformin . This is a cross-over design.

Inclusion criteria

• Age 18-60

• No smoking the past 6 months
• Normal screening labs or no clinically significant values-except those listed below
• Must have 3 of the following 4 characteristics established by NCEP-AHA-NHLBI

• Males waist circumference greater than 40 inches, females greater than 35 inches
• Blood pressure greater than 130/85 or on treatment with one or more antihypertensive agent
• Fasting plasma triglycerides >150 or HDL <40 (males) <50 (females)
• Fasting blood sugar >100 but <126
• Subject may participate if on the following drugs, provided the drugs can remain at stable doses throughout the 12 week treatment interval.

• Ace inhibitor
• ARB
• HMG CoA reductase inhibitor
• Beta blocker
• Calcium channel blockers
• Alpha-adrenergic antagonist

Exclusion criteria

• Smoking presently or in the past 6 months
• HbA1c ≥ 6.5
• Glucocorticoids-eg: prednisone, dexamethasone
• Any known sensitivity or intolerance to Metformin
• Any chronic GI disorders such as Irritable Bowel Syndrome or Crohns disease
• History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease.
• History of malignant or metabolic disorders including diabetes
• Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI)
• Hypersensitivity to perflutren (contained in Definity)
• Pregnant or breastfeeding