Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance

April 23, 2008 updated by: US Department of Veterans Affairs
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

48

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Central Arkansas Veterans HCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • Heart disease
  • Renal disease
  • Liver disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Effects of pioglitazone and metformin on ectopic lipid accumulation
Time Frame: 4 yr
4 yr

Secondary Outcome Measures

Outcome Measure
Time Frame
Effects of pioglitazone and metformin on beta cell responsiveness
Time Frame: 4 yr
4 yr

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Department of Veterans Affairs

Investigators

  • Principal Investigator: Philip A Kern, MD, Central Arkansas Veterans HCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Primary Completion (Actual)

April 1, 2007

Study Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

April 15, 2005

First Submitted That Met QC Criteria

April 15, 2005

First Posted (Estimate)

April 18, 2005

Study Record Updates

Last Update Posted (Estimate)

April 25, 2008

Last Update Submitted That Met QC Criteria

April 23, 2008

Last Verified

April 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLIN-013-0S3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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