Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
Overview[ - collapse ][ - ]
Purpose | 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. |
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Condition | Glucose Metabolism Disorders Diabetes |
Intervention | Drug: Metformin Drug: Pioglitazone Drug: Metformin Drug: Pioglitazone Radiation: CT scans Procedure: Oral glucose tolerance test |
Phase | Phase 4 |
Sponsor | Department of Veterans Affairs |
Responsible Party | Department of Veterans Affairs |
ClinicalTrials.gov Identifier | NCT00108615 |
First Received | April 15, 2005 |
Last Updated | April 23, 2008 |
Last verified | April 2008 |
Tracking Information[ + expand ][ + ]
First Received Date | April 15, 2005 |
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Last Updated Date | April 23, 2008 |
Start Date | January 2004 |
Estimated Primary Completion Date | December 2007 |
Current Primary Outcome Measures | Effects of pioglitazone and metformin on ectopic lipid accumulation [Time Frame: 4 yr] [Designated as safety issue: No] |
Current Secondary Outcome Measures | Effects of pioglitazone and metformin on beta cell responsiveness [Time Frame: 4 yr] [Designated as safety issue: No] |
Descriptive Information[ + expand ][ + ]
Brief Title | Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance |
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Official Title | Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance |
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. |
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 Type | Interventional |
Study Phase | Phase 4 |
Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science |
Condition |
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Intervention | Drug: Metformin Drug: 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 |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Completed |
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Estimated Enrollment | 48 |
Estimated Completion Date | December 2007 |
Estimated Primary Completion Date | April 2007 |
Eligibility Criteria | Inclusion Criteria: - Impaired glucose tolerance - Body mass index (BMI) of 28-38 Exclusion Criteria: - Heart disease - Renal disease - Liver disease |
Gender | Both |
Ages | 35 Years |
Accepts Healthy Volunteers | Accepts Healthy Volunteers |
Contacts | Not Provided |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT00108615 |
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Other Study ID Numbers | CLIN-013-0S3 |
Has Data Monitoring Committee | Yes |
Information Provided By | Department of Veterans Affairs |
Study Sponsor | Department of Veterans Affairs |
Collaborators | Not Provided |
Investigators | Principal Investigator: Philip A Kern, MD Central Arkansas Veterans HCS |
Verification Date | April 2008 |
Locations[ + expand ][ + ]
Central Arkansas Veterans HCS | Little Rock, Arkansas, United States, 72205 |
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