Diabetes, Impaired Glucose Tolerance (IGT)
Conditions
Keywords
Impaired glucose tolerance (IGT), Diabetes
Brief summary
This research study will examine brain glucose metabolism after an overnight fast to determine the effect of exenatide on brain glucose metabolism and lipid metabolism.
Detailed description
This study will elucidate if exenatide has an effect on brain glucose metabolism. This will be accomplished by measuring the rate of glucose binding in various brain regions by Positron Emission Tomography (PET) after glucose load with exenatide injection and compare it with placebo injection measured in the same subject. The changes will be compared with peripheral and hepatic glucose metabolism and lipolysis.
Interventions
DRUGExenatide
Exenatide (5mcg) was administered in random order 30 min before OGTT-PET study, crossover study
DRUGPlacebo
Placebo was administered in random order 30 min before OGTT-PET study in the same subject
Sponsors
Amylin Pharmaceuticals, LLC.
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males age 18-65 years old 2. Patients must have Body Mass Index (BMI) between 25 and 40 kg/m2 3. 2-hour glucose concentration above 140mg/dl after 75g glucose load, ie, having impaired glucose tolerance or newly diagnosed type 2 diabetes. 4. Patients must have BMI of 25-40 kg/m2 5. Patients must have no known severe liver or kidney disease, cancer, neurologic, psychiatric or systemic disease, ability to understand the study. 6. Only patients whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included. 7. Patients must have the following laboratory values: * Hematocrit ≥ 34 vol% * Serum creatinine\* ≤ 1.5 mg/dl in males and * Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT): ≤ 2.5 times upper limit of normal * Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT): ≤ 2.5 times upper limit of normal * Alkaline phosphatase ≤ 2.5 times upper limit of normal * If serum creatinine is ≤ 1.5 mg/dl in males, the PI can grant an exception and not exclude the patient if the Glomerular filtration rate (GFR) is \>70 ml/min
Exclusion criteria
Patients are excluded from participation in the study if they meet any of the following criteria: 1. Patients with major chronic illness (cancer, liver, kidney, cardiovascular disease) 2. Patients with BMI over 40 and under 25 3. Patient with age below 18 yrs and over 65 yrs 4. Female subjects 5. Patients with type 1 diabetes 6. Patients treated for type 2 diabetes 7. Subjects with normal glucose tolerance (NGT)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Exenatide on Brain (Total Gray Matter) Glucose Metabolism | 120 minutes after exenatide or placebo injection | To study the acute effect of exenatide on brain glucose metabolism after the glucose load. Brain glucose uptake will be determined from serial FDG PET-imaging, by using graphical methods to quantify both global and regional results. The results obtained after Exenatide injection will be compared with the ones obtained after injection of placebo in the same subject. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Exenatide on the Liver and Adipose Tissue Glucose Uptake | 60 minutes after exenatide or placebo injection | we evaluated the acute effects of exenatide on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PET With Exenatide vs Placebo Injection All subjects will receive the same intervention with Exenatide and placebo. Exenatide or placebo will be administered in random order, (i.e. first or second before OGTT-PET study).
In the first study IGT male subjects will be randomized to exenatide or placebo injection before OGTT-PET study. In the second study the same subjects will receive placebo or exenatide respectively before OGTT-PET study. The results obtained after Exenatide injection will be compared with the ones obtained after injection of placebo in the same subject. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | PET With Exenatide vs Placebo Injection |
|---|---|
| 2 hour plasma glucose concentration | 177 mg/dl STANDARD_DEVIATION 11 |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 6 |
| BMI (Body Mass Index) | 29 kg/m^2 STANDARD_DEVIATION 3 |
| Fasting plasma glucose | 114 mg/dl STANDARD_DEVIATION 3 |
| HbA1c | 5.6 % of total hemoglobin STANDARD_DEVIATION 0.1 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Effect of Exenatide on Brain (Total Gray Matter) Glucose Metabolism
To study the acute effect of exenatide on brain glucose metabolism after the glucose load. Brain glucose uptake will be determined from serial FDG PET-imaging, by using graphical methods to quantify both global and regional results. The results obtained after Exenatide injection will be compared with the ones obtained after injection of placebo in the same subject.
Time frame: 120 minutes after exenatide or placebo injection
Population: We studied, in the same subject, the acute effect of injection of exenatide vs placebo on brain glucose metabolism (CMRglu) after the glucose load. We used FDG PET-imaging to quantify global and regional results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Effect of Exenatide or Placebo on CMRglu | Effect of Exenatide on Brain (Total Gray Matter) Glucose Metabolism | total gray matter CMRglu after Exenatide | 0.14 μmol/(ml*min) | Standard Error 0.02 |
| Effect of Exenatide or Placebo on CMRglu | Effect of Exenatide on Brain (Total Gray Matter) Glucose Metabolism | total gray matter CMRglu after Placebo | 0.10 μmol/(ml*min) | Standard Error 0.01 |
Secondary
Effect of Exenatide on the Liver and Adipose Tissue Glucose Uptake
we evaluated the acute effects of exenatide on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake.
Time frame: 60 minutes after exenatide or placebo injection
Population: Outcome data was not collected