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

Study Overview
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Brief Summary
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The purpose of this study is to look at how insulin (a hormone that helps the cells get energy from sugar) in our body affects blood vessels (elasticity in the bigger blood vessels and blood flow in the smaller blood vessels in the arm) and how Metformin (a drug that makes you more sensitive to insulin) affects insulin's action on the blood vessels.

Detailed Description
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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.

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

Conditions
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Metabolic Syndrome, Insulin Sensitivity

Intervention / Treatment
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* Drug: Placebos
* Drug: metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>12 weeks of Placebo tablet 3 x daily | Drug: Placebos<br>* A 12 week single blind placebos<br>* Other names: inactive substance;|
| Experimental: Metformin<br>12 weeks of Metformin tablet 850 mg 3 x daily | Drug: metformin<br>* A 12 week single blind metformin<br>* Other names: glucophage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow Mediated Dilation - Endothelial Function | brachial artery ultrasonography % flow-mediated dilatation (FMD) for assessing endothelial function before and after an insulin clamp to assess insulin's effect on the vasculature | before and after 12 weeks on placebo or metformin |