Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00108615
Status:
COMPLETED
Last Update Posted:
2008-04-25
First Post:
2005-04-15
Brief Title:
Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
Status:
COMPLETED
Status Verified Date:
2008-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None