Effect Of Exenatide Treatment on Liver Fat Content in Patients With Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to examine the effect of exenatide, an anti-diabetes medication,
      on liver fat and blood levels of proteins that influence liver fat.
    

Detailed description: 
      Obesity is characterized as generalized expansion of all adipose tissue depots, an increase
      in tissue lipid content, and dyslipidemia, insulin resistance, and type 2 diabetes. The
      adipocyte functions not only as a storage depot for fat but as an endocrine organ that
      releases hormones in response to specific extracellular stimuli or changes in metabolic
      status. These secreted proteins, carry out a variety of diverse functions, and they have been
      referred to collectively as adipokines. The adipokines have been postulated to play important
      roles in the pathogenesis of insulin resistance, hypertension, disorders of coagulation,
      dyslipidemia, and glucose intolerance, abnormalities associated with insulin resistance
      syndrome.

      These observations are of considerable interest because recent studies have provided evidence
      that increased hepatic fat content is an important determinant of hepatic insulin resistance
      in type 2 diabetic patients. Fatty liver is common in type 2 diabetic patients. The
      mechanisms responsible for the increase in hepatic fat content are unclear. It has been
      suggested that fatty liver results from accelerated fatty acid mobilization from expanded
      visceral fat stores and their deposition in the liver as well as decreased hepatic fatty acid
      oxidation. Weight loss in humans with Non Alcoholic Fatty Liver Disease (NAFLD) is associated
      with a decrease in hepatic fat content. In addition, thiazolidinediones have been shown to
      reduce hepatic fat content and improve hepatic insulin sensitivity in patients with type 2
      diabetes as well as in non-diabetic patients with NAFLD. The thiazolidinediones initiate
      their action by binding the peroxisome proliferator activator receptors (PPAR) , which
      primarily are located on adipocytes. Treatment of insulin-resistant mice as well as type 2
      diabetic patients with insulin sensitizing PPAR activators, such as thiazolidinediones, and
      increases plasma adiponectin levels. Indirect evidence suggests that adiponectin might
      mediate some of the insulin-sensitizing effects of PPAR agonists.

      Exenatide, a Glucagon Like Peptide-1 (GLP-1) receptor agonist approved for treatment of type
      2 diabetes, elicited dose-dependent reductions in body weight in association with improved
      glycemic control in type 2 diabetic patients. In animal models of obesity, exenatide reduces
      hepatic fat. However, the effect of exenatide treatment in combination with a
      thiazolidinedione on liver fat content and plasma adipocytokines levels in patients with type
      2 diabetes remains to be investigated.
    

Intervention name(s): Exenatide; Pioglitazone
Intervention type(s): Drug; Drug
Intervention description(s): Type 2 diabetic subjects will be randomized to receive exenatide 10 micrograms injected subcutaneously twice daily for 12 months. Prior to randomization, all subjects will receive baseline measurements of fasting plasma glucose, plasma adipocytokines, Free Fatty Acids, insulin, plasma lipids, and HbA1c as well as measurement of liver fat content with magnetic resonance spectroscopy. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, insulin and adipocytokines as well as hepatic fat content determination at the end of the 12 month treatment period.; Type 2 diabetic subjects will be randomized to receive pioglitazone 45 mg daily orally for 12 months. Prior to randomization, all subjects will receive baseline measurements of fasting plasma glucose, plasma adipocytokines, Free Fatty Acids, insulin, plasma lipids, and HbA1c as well as measurement of liver fat content with magnetic resonance spectroscopy. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, insulin and adipocytokines as well as hepatic fat content determination at the end of the 12 month treatment period.
Other intervention name(s): Byetta; Actos
Intervention MeSH terms: Pioglitazone; Exenatide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes