Acute Effect of Exenatide on Brain Glucose Metabolism

Phase 4

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

Males age 18-65 years old
Patients must have Body Mass Index (BMI) between 25 and 40 kg/m2
2-hour glucose concentration above 140mg/dl after 75g glucose load, ie, having impaired glucose tolerance or newly diagnosed type 2 diabetes.
Patients must have BMI of 25-40 kg/m2
Patients must have no known severe liver or kidney disease, cancer, neurologic, psychiatric or systemic disease, ability to understand the study.
Only patients whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.
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:

Patients with major chronic illness (cancer, liver, kidney, cardiovascular disease)
Patients with BMI over 40 and under 25
Patient with age below 18 yrs and over 65 yrs
Female subjects
Patients with type 1 diabetes
Patients treated for type 2 diabetes
Subjects with normal glucose tolerance (NGT)

Arm && Interventions

Group	Intervention	Description
Exenatide first, then Placebo	Exenatide	Exenatide 5mcg was injected subcutaneously 30 min before Oral Glucose Tolerance Test (OGTT)-PET study. The same subject was studied again a few weeks later with the same protocol with Placebo injection.
Exenatide first, then Placebo	Placebo	Exenatide 5mcg was injected subcutaneously 30 min before Oral Glucose Tolerance Test (OGTT)-PET study. The same subject was studied again a few weeks later with the same protocol with Placebo injection.
Placebo first, then Exenatide	Placebo	Placebo was injected subcutaneously 30 min before OGTT-PET study. The same subject was studied again a few weeks later with the same protocol with injection of Exenatide 5mcg .
Placebo first, then Exenatide	Exenatide	Placebo was injected subcutaneously 30 min before OGTT-PET study. The same subject was studied again a few weeks later with the same protocol with injection of Exenatide 5mcg .

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.