Insulin Resistance, Metabolic Syndrome
Conditions
Brief summary
Insulin resistance is a common condition that can lead to type 2 diabetes. One of the commonly prescribed diabetes medications, called rosiglitazone, works by decreasing insulin resistance. Rosiglitazone appears to work on fat cells. Animal studies suggest that rosiglitazone may work by increasing blood vessel growth in fat cells. The purpose of this research is to see if rosiglitazone also increases blood vessel growth in human fat cells. The investigators will compare results from before and after being on rosiglitazone for 6 weeks.
Detailed description
Adipocytes play a crucial role in the control of metabolic homeostasis, by sequestering excess calories in the form of triglycerides, and secreting cytokines that control systemic fuel utilization. Sustained excess calorie consumption results in adipocyte hypertrophy and hyperplasia, and like any expanding tissue, requires increased capillary expansion to nourish the enlarged adipose tissue mass. Recent reports indicate that decreased capillary density in adipose tissue of obese individuals correlates with insulin resistance, suggesting that an imbalance of angiogenesis and adipogenesis may underlie this condition. To determine whether improvement in insulin sensitivity is related to changes in adipose tissue capillary development, we conducted a randomized, double-blind, placebo-controlled trial to determine capillary density, angiogenic growth potential, and metabolic parameters in healthy human volunteers before and after treatment with rosiglitazone, a potent insulin sensitizer.
Interventions
DRUGRosiglitazone
One 8mg capsule daily for 6 weeks.
DRUGPlacebo
One capsule daily for 6 weeks.
Sponsors
GlaxoSmithKline
University of Massachusetts, Worcester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Overweight but otherwise in good general health. 2. Age 18 - 55 years. 3. Normal glucose tolerance. 4. Stable weight with BMI (27-44). 5. Stable medication use for the preceding month. 6. BP \< 150/90. 7. Negative pregnancy test (\*HCG), if female and of childbearing potential. 8. Practicing, and willing to continue to practice appropriate contraception throughout the study if a female of childbearing potential.
Exclusion criteria
1. Serious medical illness. 2. Pregnancy. 3. Tobacco use within the past 6 months. 4. Prior or current treatment with a thiazolidinedione. 5. Patients who have received an investigational drug in the past 30 days. 6. Use of systemic corticosteroids. 7. Known or suspected allergy to Rosiglitazone or any component of the preparation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adipose Tissue Capillary Sprout Formation | 8 weeks | Adipose tissue collected at 8 weeks was cut into \ 1mm pieces which were embedded in individual wells of a 96 well plate containing growth factor depleted Matrigel. Wells were filled with media supplemented with endothelial growth factors, replaced every second day. Values for each patient are expressed as the difference in the average number of capillary branches (sprouts) formed by each of approximately 50 explants between day 14 and day 7. The number of branches forming on the periphery (defined as at least three cells in a branch structure) was counted by two investigators at day 7 and 14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Adiponectin | 8 weeks | Adiponectin concentrations in serum were measured in ng/ml, in both arms at baseline and at 8 weeks, i.e. 2 weeks after stopping drug or placebo treatment |
Countries
United States
Participant flow
Recruitment details
dates of recruitment January 2007 to January 2010
Participants by arm
| Arm | Count |
|---|---|
| Rosiglitazone One 8mg capsule daily for 6 weeks. | 20 |
| Placebo One capsule daily for 6 weeks. | 15 |
| Total | 35 |
Baseline characteristics
| Characteristic | Placebo | Rosiglitazone | 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 | 15 Participants | 20 Participants | 35 Participants |
| Age Continuous | 40.2 years STANDARD_DEVIATION 10.23 | 39.25 years STANDARD_DEVIATION 2.42 | 40.09 years STANDARD_DEVIATION 10.43 |
| Region of Enrollment United States | 15 participants | 20 participants | 35 participants |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 25 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 15 |
| serious Total, serious adverse events | 0 / 20 | 0 / 15 |
Outcome results
Primary
Adipose Tissue Capillary Sprout Formation
Adipose tissue collected at 8 weeks was cut into \ 1mm pieces which were embedded in individual wells of a 96 well plate containing growth factor depleted Matrigel. Wells were filled with media supplemented with endothelial growth factors, replaced every second day. Values for each patient are expressed as the difference in the average number of capillary branches (sprouts) formed by each of approximately 50 explants between day 14 and day 7. The number of branches forming on the periphery (defined as at least three cells in a branch structure) was counted by two investigators at day 7 and 14.
Time frame: 8 weeks
Population: The number of subjects was based on the power of calculations in being able to demonstrate a difference from baseline in fat tissue microvasculature, change in HOMA2 and serum adiponectin after 6 weeks of rosiglitazone intake in all groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone | Adipose Tissue Capillary Sprout Formation | 143.5 number of capillary sprouts | Standard Deviation 41.12 |
| Placebo | Adipose Tissue Capillary Sprout Formation | 122.1 number of capillary sprouts | Standard Deviation 43.88 |
Secondary
Serum Adiponectin
Adiponectin concentrations in serum were measured in ng/ml, in both arms at baseline and at 8 weeks, i.e. 2 weeks after stopping drug or placebo treatment
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone | Serum Adiponectin | 28.56 ng/ml | Standard Error 2.89 |
| Placebo | Serum Adiponectin | 14.64 ng/ml | Standard Error 2.86 |