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.
ConditionGlucose Metabolism Disorders
Diabetes
InterventionDrug: Metformin
Drug: Pioglitazone
Drug: Metformin
Drug: Pioglitazone
Radiation: CT scans
Procedure: Oral glucose tolerance test
PhasePhase 4
SponsorDepartment of Veterans Affairs
Responsible PartyDepartment of Veterans Affairs
ClinicalTrials.gov IdentifierNCT00108615
First ReceivedApril 15, 2005
Last UpdatedApril 23, 2008
Last verifiedApril 2008

Tracking Information[ + expand ][ + ]

First Received DateApril 15, 2005
Last Updated DateApril 23, 2008
Start DateJanuary 2004
Estimated Primary Completion DateDecember 2007
Current Primary Outcome MeasuresEffects of pioglitazone and metformin on ectopic lipid accumulation [Time Frame: 4 yr] [Designated as safety issue: No]
Current Secondary Outcome MeasuresEffects of pioglitazone and metformin on beta cell responsiveness [Time Frame: 4 yr] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleEffects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
Official TitleEffects 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 TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Condition
  • Glucose Metabolism Disorders
  • Diabetes
InterventionDrug: 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)
  • Experimental: 1
    pioglitazone
  • Active Comparator: 2
    metformin

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment48
Estimated Completion DateDecember 2007
Estimated Primary Completion DateApril 2007
Eligibility Criteria
Inclusion Criteria:

- Impaired glucose tolerance

- Body mass index (BMI) of 28-38

Exclusion Criteria:

- Heart disease

- Renal disease

- Liver disease
GenderBoth
Ages35 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00108615
Other Study ID NumbersCLIN-013-0S3
Has Data Monitoring CommitteeYes
Information Provided ByDepartment of Veterans Affairs
Study SponsorDepartment of Veterans Affairs
CollaboratorsNot Provided
Investigators Principal Investigator: Philip A Kern, MD Central Arkansas Veterans HCS
Verification DateApril 2008

Locations[ + expand ][ + ]

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