Insulin Sensitivity, Metabolic Syndrome
Conditions
Brief summary
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
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.
Interventions
DRUGPlacebos
A 12 week single blind placebos
DRUGmetformin
A 12 week single blind metformin
Sponsors
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow Mediated Dilation - Endothelial Function | before and after 12 weeks on placebo or metformin | 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 |
Countries
United States
Participant flow
Pre-assignment details
6 subjects failed the screening. 2 subjects voluntarily withdrew.
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Then Metformin 12 weeks of Placebo tablet 3 x daily, then a 8 week washout, then 12 weeks Metformin tablet 3 X daily | 6 |
| Metformin, Then Placebo 12 weeks of Metformin tablet 850 mg 3 x daily, then 8 week washout , then 12 weeks Placebo tablet 3X daily | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Placebo, Then Metformin | Metformin, Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 9 Participants |
| Region of Enrollment United States | 6 participants | 5 participants | 11 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
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
Time frame: before and after 12 weeks on placebo or metformin
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pre and Post Placebo 12 Weeks | Flow Mediated Dilation - Endothelial Function | 6.1 percentage of artery dilation | Standard Error 1.1 |
| Pre and Post Metformin 12 Weeks | Flow Mediated Dilation - Endothelial Function | 6.2 percentage of artery dilation | Standard Error 1.1 |
p-value: >0.05t-test, 2 sided