Effect of Exenatide on Liver and Heart Fat and Inflammation
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to examine the effect of exenatide on liver and heart
      (myocardial) fat and inflammation.
    

Detailed description: 
      Type 2 diabetics and insulin resistant individuals have an excess of fat in the liver which
      is not attributable to alcohol or other known causes of liver disease, a condition defined as
      nonalcoholic fatty liver disease (NAFLD). The fatty liver is insulin resistant. Individuals
      with a fatty liver are more likely to have excess intra-abdominal fat as well as a reduction
      in circulating plasma adiponectin levels. We have previously shown that type 2 diabetes and
      its associated Non Alcoholic Fatty Liver Disease (NAFLD) is characterized by increased
      hepatic fat content, decreased circulating adiponectin levels, and hepatic and peripheral
      (muscle) insulin resistance. Weight loss in humans with Non Alcoholic Fatty Liver Disease is
      associated with a decrease in hepatic fat content. Exenatide, an incretin based anti-diabetes
      therapy, enhances glucose-dependent insulin secretion and glucose-dependent suppression of
      inappropriately high glucagon secretion, improves glycemic control in patients with type 2
      diabetes and is associated with weight loss. In rodent studies, exenatide reduces hepatic and
      myocardial fat and reduces vascular inflammation independent of changes in weight. Exenatide
      has also been shown to increase plasma adiponectin levels in humans and rodents. Furthermore
      type 2 diabetics are characterized by an increase in both hepatic and myocardial fat and left
      ventricular dysfunction, particularly diastolic dysfunction. However, the effect of exenatide
      therapy on liver and myocardial fat content, as well as left ventricular function in patients
      with type 2 diabetes has not been previously studied.
    

Intervention name(s): Exenatide; Glipizide
Intervention type(s): Drug; Drug
Intervention description(s): Type 2 diabetic subjects will be randomized to receive either Exenatide 10 micrograms twice daily injected subcutaneously or glipizide 5 mg twice daily orally for 6 months. All subjects will receive baseline measurements of fasting plasma glucose, free fatty acids, plasma adipocytokines, plasma lipids, and glycosylated hemoglobin (HbA1c) as well as measurement of liver and myocardial fat content and left ventricular function with magnetic resonance imaging/spectroscopy. All subjects will also undergo measurements of monocyte inflammatory proteins at baseline. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, adipocytokines, HbA1c, monocyte inflammation, as well as hepatic/myocardial fat content determination and left ventricular function at the end of the 6 months.; Type 2 diabetic subjects will be randomized to receive either Exenatide 10 micrograms twice daily injected subcutaneously or glipizide 5 mg twice daily orally for 6 months. All subjects will receive baseline measurements of fasting plasma glucose, free fatty acids, plasma adipocytokines, plasma lipids, and glycosylated hemoglobin (HbA1c) as well as measurement of liver and myocardial fat content and left ventricular function with magnetic resonance imaging/spectroscopy. All subjects will also undergo measurements of monocyte inflammatory proteins at baseline. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, adipocytokines, HbA1c, monocyte inflammation, as well as hepatic/myocardial fat content determination and left ventricular function at the end of the 6 months.
Other intervention name(s): Byetta; Glucotrol
Intervention MeSH terms: Exenatide; Glipizide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes