Integrating the Genetic and Metabolic Faces of Obesity

Stanford University

Status and phase: Completed; Phase 1

Conditions: Insulin Resistance; Obesity; Metabolic Syndrome

Treatments: Drug: thiazolidinedione; Behavioral: weight loss

Study type: Interventional

Funder types: Other

Identifiers

NCT00285844

RDK071309

Details and patient eligibility

About

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.

Full 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.

Enrollment: 88 patients

Sex: All

Ages: 30 to 65 years old

Volunteers: Accepts Healthy Volunteers

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 thiazolidinedione
• elevation of liver enzymes (> 2.5 times upper normal limit)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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88 participants in 2 patient groups

pioglitazone

Experimental group

Description:

IR and IS subjects will be randomized to pioglitazone 45 mg daily for 16 wks for comparison with dietary weight loss intervention

Treatment:

Drug: thiazolidinedione

Dietary Weight Loss

Experimental group

Description:

IR and IS subjects will be randomized to dietary weight loss for 16 wks for comparison to pioglitazone intervention

Treatment:

Behavioral: weight loss