Integrating the Genetic and Metabolic Faces of Obesity

Study Overview
=================
Brief Summary
-----------------
The goal of this study is to determine why some obese individuals develop insulin resistance and others do not. We hypothesize that an impairment in differentiation of fat cells (adipocytes) is responsible for the development of insulin resistance in select obese individuals. This study will evaluate obese individuals at baseline with respect to characteristics of adipocytes, including gene expression, and will then entail randomizing subjects to either weight loss or treatment with an insulin sensitizing drug (pioglitazone). Changes in insulin resistance will be associated with changes in adipocyte morphology and gene expression.

Detailed Description
-----------------
Healthy overweight/obese individuals will be screened for insulin resistance. Both insulin resistant individuals and insulin sensitive individuals (to serve as controls) will be eligible to enroll. Fat cel biopsy and CT scan of the abdomen is required at baseline and after an intervention with either weight loss or pioglitazone (drug to improve insulin resistance). Subjects will repeat insulin resistance test after the intervention as well. Subjects will learn much about their metabolism in this study, and will have an opportunity to improve their insulin resistance.

Official Title
-----------------
Integrating the Genetic and Metabolic Faces of Obesity

Conditions
-----------------
Obesity, Insulin Resistance, Metabolic Syndrome

Intervention / Treatment
-----------------
* Behavioral: weight loss
* Drug: thiazolidinedione


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: nondiabetic defined as fasting plasma glucose < 126 mg/dL body mass index 27 to 35 kg/m2 no major organ diseases able to come to Stanford for regular clinical research center visits English speaking or has own translator Exclusion Criteria: pregnancy/lactation history of eating disorder or major psychiatric illness allergy to thiazolidenedione elevation of liver enzymes (> 2.5 times upper normal limit)

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pioglitazone<br>IR and IS subjects will be randomized to pioglitazone 45 mg daily for 16 wks for comparison with dietary weight loss intervention | Drug: thiazolidinedione<br> <br> |
| Experimental: Dietary Weight Loss<br>IR and IS subjects will be randomized to dietary weight loss for 16 wks for comparison to pioglitazone intervention | Behavioral: weight loss<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipose Cell Size Distribution |  | 2005-2012 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipose Tissue Gene Expression |  | 2005-2013 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, insulin resistance, thiazolidinedione, weight loss, adipose tissue, metabolic syndrome, diabetes prevention, cardiovascular disease prevention