Insulin Resistance, Obesity
Conditions
Keywords
obesity
Brief summary
The purpose of this study is to learn more about how insulin resistance (inability to process glucose correctly resulting in mildly elevated glucose levels) affects the hormone ghrelin.
Detailed description
Insulin resistance suppresses fasting ghrelin levels and impairs postprandial ghrelin suppression. Improved insulin sensitivity with a thiazolidinedione will raise ghrelin levels, enhance meal-related suppression, but not change the ratio of total to active ghrelin or result in an alteration of ghrelin structure.
Interventions
DRUGplacebo
treatment with placebo for 3 months
DRUGpioglitazone
treatment with 30mg daily for two weeks then 45mg every day with pioglitazone for three months
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 80, weight stable for at least 3 months * At lifetime maximal body weight and impaired glucose tolerance (ICT) by the World Health ORganization criteria: * fasting plasma glucose level of 100- 125mg/dL or * plasma glucose level between 140 to 149mg/dL following a 75gram oral glucose load
Exclusion criteria
* Actively losing weight * Smokers * Alcohol consumption \> 2 drinks/day * Prescription drug use * Recreational drug use * Type 2 Diabetes * Conditions that contraindicate treatment with pioglitazone such as CHF, impaired liver or kidney function or known sensitivity to pioglitazone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total and Active Ghrelin Levels | 0 and 3 months | The primary outcome of this study will be the comparison of ghrelin suppressibility (total and acylated) in response to meals obese subjects before and after 3-months therapy with a thiazolidinedione. |
Countries
United States
Participant flow
Recruitment details
Subjects will be recruited to participate in this aim from the Portland-Vancouver area through postings on the OHSU website, recruitment from previous studies, and advertisements in local newspapers. Original study recruitment dates were 2009 to 2013.
Pre-assignment details
Following consent, patients undergo screening for entry criteria using blood work and an oral glucose tolerance test. Participants are excluded if they did not have impaired glucose tolerance and/or a contraindication to using a thiazolidinedione (pioglitazone or Actos), such as heart failure or abnormal liver studies.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Treatment with placebo for 3 months before spectroscopy, hyperinsulinemic-euglycemic clamp, control diet, blood sampling.
placebo: treatment with placebo for 3 months | 3 |
| Pioglitizone Treatment with pioglitazone for 3 months before hyperinsulinemic-euglycemic clamp, control diet with blood sampling and spectroscopy.
pioglitazone: treatment with 30mg daily for two weeks then 45mg every day with pioglitazone for three months | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Pioglitizone | Total | Placebo |
|---|---|---|---|
| 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 | 3 Participants | 6 Participants | 3 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 5.5 | 37 years STANDARD_DEVIATION 5.7 | 34 years STANDARD_DEVIATION 5 |
| 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 | 0 Participants | 0 Participants | 0 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 | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 6 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Total and Active Ghrelin Levels
The primary outcome of this study will be the comparison of ghrelin suppressibility (total and acylated) in response to meals obese subjects before and after 3-months therapy with a thiazolidinedione.
Time frame: 0 and 3 months
Population: This aim was terminated early due to a shortage of funds and no samples were analyzed. There is no data to report