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
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Condition or disease | Intervention/treatment | Phase |
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Glucose Metabolism Disorders Diabetes | Drug: Metformin Drug: Pioglitazone Radiation: CT scans Procedure: Oral glucose tolerance test | Phase 4 |
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 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 |
Arm | Intervention/treatment |
---|---|
Experimental: 1
pioglitazone
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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
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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 |
- Effects of pioglitazone and metformin on ectopic lipid accumulation [ Time Frame: 4 yr ]
- Effects of pioglitazone and metformin on beta cell responsiveness [ Time Frame: 4 yr ]

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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 |
Inclusion Criteria:
- Impaired glucose tolerance
- Body mass index (BMI) of 28-38
Exclusion Criteria:
- Heart disease
- Renal disease
- Liver disease

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
United States, Arkansas | |
Central Arkansas Veterans HCS | |
Little Rock, Arkansas, United States, 72205 |
Principal Investigator: | Philip A Kern, MD | Central Arkansas Veterans HCS |
Responsible Party: | Kern, Philip - Principal Investigator, Department of Veterans Affairs |
ClinicalTrials.gov Identifier: | NCT00108615 |
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 |
Metabolic Diseases Glucose Intolerance Glucose Metabolism Disorders Hyperglycemia |
Metformin Pioglitazone Hypoglycemic Agents Physiological Effects of Drugs |