Clinical trial NCT00285844: Integrating the Genetic and Metabolic Faces of Obesity
Official title: Integrating the Genetic and Metabolic Faces of Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insulin Resistance
Obesity
Metabolic Syndrome
Keywords: obesity
insulin resistance
thiazolidinedione
weight loss
adipose tissue
metabolic syndrome
diabetes prevention
cardiovascular disease prevention
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2006-02-02
Enrollment: 88
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Adipose Cell Size Distribution
timeFrame: 2005-2012
Secondary outcomes:
measure: Adipose Tissue Gene Expression
timeFrame: 2005-2013
Other outcomes:
measure: Insulin-Mediated Glucose Uptake
timeFrame: 2005-2012
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Tracey McLaughlin, MD, MS
role: STUDY_DIRECTOR
References:
citation: McLaughlin T, Liu LF, Lamendola C, Shen L, Morton J, Rivas H, Winer D, Tolentino L, Choi O, Zhang H, Hui Yen Chng M, Engleman E. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler Thromb Vasc Biol. 2014 Dec;34(12):2637-43. doi: 10.1161/ATVBAHA.114.304636. Epub 2014 Oct 23.
citation: McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011 Nov;96(11):E1756-60. doi: 10.1210/jc.2011-0615. Epub 2011 Aug 24.
citation: McLaughlin T, Deng A, Yee G, Lamendola C, Reaven G, Tsao PS, Cushman SW, Sherman A. Inflammation in subcutaneous adipose tissue: relationship to adipose cell size. Diabetologia. 2010 Feb;53(2):369-77. doi: 10.1007/s00125-009-1496-3. Epub 2009 Oct 9.
citation: McLaughlin T, Deng A, Gonzales O, Aillaud M, Yee G, Lamendola C, Abbasi F, Connolly AJ, Sherman A, Cushman SW, Reaven G, Tsao PS. Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women. Diabetologia. 2008 Dec;51(12):2303-8. doi: 10.1007/s00125-008-1148-z. Epub 2008 Sep 30.