Diabetes, Insulin Resistance, Metabolic Syndrome
Conditions
Keywords
Growth hormone antagonism
Brief summary
Growth hormone is well known to cause changes in glucose regulation. People with Laron syndrome are born without the growth hormone receptor and are protected from diabetes. Mice who are engineered without the growth hormone receptor are similarly protected from diabetes. Conversely, people who have excessive amounts of growth hormone, such as patients with acromegaly, have an increased risk for type 2 diabetes. In acromegaly patients, treatment with pegvisomant, a medication that reduces insulin like growth factor-1 by blocking the growth hormone receptor, significantly improves insulin resistance. Pegvisomant has not been explored as a possibility for the treatment of type 2 diabetes or insulin resistance in people without acromegaly. In this study, the investigators hope to study the metabolic effects of pegvisomant on people who have insulin resistance but not diabetes. Pegivosmant is expected to improve insulin resistance in the liver, fat and muscle as well as decrease serum free fatty acids.
Interventions
DRUGpegvisomant
Pegvisomant 20 mg subcutaneously Qday will be administered by the study subject for 28 days during this study.
Sponsors
San Francisco General Hospital
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI between 18-35 * Homeostatic model assessment - insulin resistance (HOMA-IR) \>2.77 * Able to administer daily subcutaneous injections of pegvisomant
Exclusion criteria
* Pregnancy * Breastfeeding in the last 6 months * Liver function tests greater than 3x the upper limits of normal * unstable diet over the last 3 months * unstable weight over the last 6 months * unstable lipid lowering regimen * diabetes - type 1 or type 2 * History of major gastrointestinal surgery * History of pancreatic, liver, biliary, or intestinal disease * Fasting blood glucose \>126 * Fasting triglycerides\>500 * A1c\>6.5
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 28 days | Investigators will measure insulin sensitivity via hyperinsulinemic euglycemic clamp prior to the initiation of the study medication and then again at the end of the 28 days to evaluate the effect of pegvisomant on insulin sensitivity and reported as HOMA-IR. HOMA-IR was derived from fasting insulin and fasting glucose by the calculation: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lipolysis | 28 days | Treatment with pegvisomant is expected to alter lipolysis. To assess this investigators will do fasting and steady state stable isotope measurements prior to treatment with pegvisomant and at day 28 after treatment with pegvisomant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pegvisomant Arm pegvisomant: Pegvisomant 20 mg subcutaneously Qday will be administered by the study subject for 28 days during this study. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Pegvisomant Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 56.5 years STANDARD_DEVIATION 3.6 |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Insulin Sensitivity
Investigators will measure insulin sensitivity via hyperinsulinemic euglycemic clamp prior to the initiation of the study medication and then again at the end of the 28 days to evaluate the effect of pegvisomant on insulin sensitivity and reported as HOMA-IR. HOMA-IR was derived from fasting insulin and fasting glucose by the calculation: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5
Time frame: 28 days
Population: Patients were compared after treatment to their own baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegvisomant Arm | Insulin Sensitivity | Baseline HOMA-IR | 3.06 units on a scale | Standard Deviation 1.46 |
| Pegvisomant Arm | Insulin Sensitivity | HOMA-IR after 28 days of treatment | 3.33 units on a scale | Standard Deviation 2.76 |
Secondary
Lipolysis
Treatment with pegvisomant is expected to alter lipolysis. To assess this investigators will do fasting and steady state stable isotope measurements prior to treatment with pegvisomant and at day 28 after treatment with pegvisomant.
Time frame: 28 days
Population: Ra glycerol reported
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegvisomant Arm | Lipolysis | Ra glycerol fasting state baseline | 0.20 mg/kg/min | Standard Deviation 0.07 |
| Pegvisomant Arm | Lipolysis | Ra glycerol fasting state after 28 days of peg | 0.21 mg/kg/min | Standard Deviation 0.02 |
| Pegvisomant Arm | Lipolysis | Ra glycerol steady state baseline | -0.01 mg/kg/min | Standard Deviation 0.2 |
| Pegvisomant Arm | Lipolysis | Ra glycerol steady state treatment 28 days peg | 0.4 mg/kg/min | Standard Deviation 0.2 |