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Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance

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ClinicalTrials.gov Identifier: NCT00108615
Recruitment Status : Completed
First Posted : April 18, 2005
Last Update Posted : April 25, 2008
Sponsor:
Information provided by:
VA Office of Research and Development

Study Description
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Brief Summary:
Subjects with impaired glucose tolerance will be randomized to receive pioglitazone or metformin for 10 weeks. Measurements of insulin sensitivity, body composition, glucose tolerance, and muscle lipid accumulation will be performed. Adipose tissue and muscle biopsies are performed. The goal of the study is to determine whether the lipotoxiciy of impaired glucose tolerance is ameliorated by pioglitazone.

Condition or disease Intervention/treatment Phase
Glucose Metabolism Disorders Diabetes Drug: Metformin Drug: Pioglitazone Radiation: CT scans Procedure: Oral glucose tolerance test Phase 4

Detailed Description:

The progression to type 2 diabetes represents an evolution, which results from a vicious cycle where both glucotoxicity and lipotoxicity act to reduce insulin secretion and insulin action. Lipotoxicity is a new concept, which refers to overaccumulation of lipids in non-adipose tissue reflecting increased free fatty acid delivery. Increased fat content of skeletal muscle and islet cell is associated with insulin resistance and impaired pancreatic -cell function respectively in animal models. Whether lipotoxicity is the link between obesity and diabetes, in humans, and whether reducing intracellular fat content will improve insulin secretion and sensitivity in humans is not known. In this study, we will focus on obese subjects with impaired glucose tolerance (IGT) who have not yet developed glucose toxicity. We will examine insulin secretion, insulin action, hepatic glucose production, and muscle lipid metabolism in response to two insulin sensitizers with two different modes of action. We propose that thiazolidinediones will improve cell function by reversing lipotoxicity as reflective in reduced muscle lipid accumulation.

Hypothesis 1. In subjects with impaired glucose tolerance, who are insulin resistant and also have an insulin secretory defect, thiazolidinediones, but not biguanides, improve cell function.

Hypothesis 2. In subjects with impaired glucose tolerance, thiazolidinediones, but not biguanides, decrease the accumulation of fat in non-adipose tissues including muscle, pancreas, liver and myocardium.

Specific Aim 1. Fifty subjects with impaired glucose tolerance will be recruited and randomized to pioglitazone or metformin treatment

Specific Aim 2. cell function will be evaluated by measuring changes in acute insulin response to glucose and non-glucose secretagogues in subjects with IGT and it will be compared in response to treatment with pioglitazone versus metformin.

Specific Aim 3. The muscle fat content will be evaluated as the surrogate measure for lipotoxicity and overaccumulation of fat in non-adipose tissue. From the muscle biopsy specimens, we will measure the amount of intramyocellular triglyceride before and after treatment with pioglitazone versus metformin.

Specific Aim 4. Adipose tissue cytokine expression is associated with changes in muscle lipid accumulation.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
Study Start Date : January 2004
Actual Primary Completion Date : April 2007
Actual Study Completion Date : December 2007
Arms and Interventions
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Arm Intervention/treatment
Experimental: 1
pioglitazone
 Drug: Metformin
Drug: Pioglitazone
Radiation: CT scans
To measure changes in adipose tissue volumes

Procedure: Oral glucose tolerance test
To detect a change in glucose tolerance
Active Comparator: 2
metformin
 Drug: Metformin
Drug: Pioglitazone
Radiation: CT scans
To measure changes in adipose tissue volumes

Procedure: Oral glucose tolerance test
To detect a change in glucose tolerance


Outcome Measures
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Primary Outcome Measures :
  1. Effects of pioglitazone and metformin on ectopic lipid accumulation [ Time Frame: 4 yr ]

Secondary Outcome Measures :
  1. Effects of pioglitazone and metformin on beta cell responsiveness [ Time Frame: 4 yr ]

Eligibility Criteria
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Ages Eligible for Study:   35 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Impaired glucose tolerance
  • Body mass index (BMI) of 28-38

Exclusion Criteria:

  • Heart disease
  • Renal disease
  • Liver disease
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00108615


Locations
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United States, Arkansas
Central Arkansas Veterans HCS
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
US Department of Veterans Affairs
Investigators
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Principal Investigator: Philip A Kern, MD Central Arkansas Veterans HCS
More Information
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Publications of Results:

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Responsible Party: Kern, Philip - Principal Investigator, Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00108615     History of Changes
Other Study ID Numbers: CLIN-013-0S3
First Posted: April 18, 2005    Key Record Dates
Last Update Posted: April 25, 2008
Last Verified: April 2008
Additional relevant MeSH terms:
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Glucose Intolerance
Metabolic Diseases
Glucose Metabolism Disorders
Hyperglycemia
 Metformin
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs