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Regional Fat Depots and Insulin Resistance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01336777
Recruitment Status : Unknown
Verified December 2013 by Tracey McLaughlin, Stanford University.
Recruitment status was:  Active, not recruiting
First Posted : April 18, 2011
Last Update Posted : December 3, 2013
University of California
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Tracey McLaughlin, Stanford University

Brief Summary:
The biological basis for insulin resistance associated with obesity is unknown. By studying equally-overweight/obese individuals who are either insulin resistant or insulin sensitive, the investigators will compare characteristics of fat tissue to test several hypotheses: 1) impaired differentiation and fat storage in the subcutaneous fat depot characterize insulin resistant individuals, who have, as a result, fat in other tissues like liver and muscle, as well as more fat circulating in the blood; 2) inflammation is greater in visceral and/or subcutaneous adipose tissue depots in insulin resistant individuals as compared with insulin sensitive individuals.

Condition or disease
Obesity Insulin Resistance Diabetes Mellitus Type 2

Detailed Description:

Insulin resistance (IR) is a major contributor to obesity-related morbidities such as diabetes and cardiovascular disease. While obesity is associated with IR, the biological basis for this association is unclear, and not all obese individuals are IR. The once-popular portal hypothesis, which states that lipolysis from VAT in particular accounts for IR, has been questioned because VAT contributes only 15% of the total systemic free fatty acid (FFA) flux. Other proposed mechanisms linking obesity to IR include inflammation, adiponectin, and ectopic fat. It is unclear whether VAT mass is more closely linked to IR than is subcutaneous adipose tissue (SAT) mass. Furthermore, evidence linking differential biological activity to IR in VAT or SAT is indirect, largely derived from studies comparing lean to obese or VAT to SAT without evaluation of IR. Thus, the purpose of this study is to investigate the biological mechanisms by which SAT and/or VAT contribute to IR. Specifically, the investigators will explore two related hypotheses- that impaired adipocyte differentiation in SAT is related to IR, ectopic fat deposition and expansion of VAT depot, and that inflammation in VAT is associated with IR. Utilizing adipose cell size/distribution obtained by Beckman Coulter Multisizer, gene expression via quantitative PCR, in-vivo quantification of IR via a modified insulin suppression test, and CT scans of abdomen/thigh, our specific aims are to:

  1. Confirm that impairment of adipocyte differentiation in SAT is associated with IR by comparing cell size characteristics and differentiation markers in IR and IS subjects undergoing elective surgery;
  2. Test the hypothesis that the same relationship will not be seen in VAT;
  3. Demonstrate that VAT mass is expanded in the presence of impaired differentiation of adipocytes in SAT;
  4. Demonstrate that intramuscular fat is related to both IR and impaired differentiation of adipocytes in SAT using cell size characteristics and differentiation markers;
  5. Demonstrate that increased inflammation in omental fat is associated with IR independent of obesity using inflammation markers (gene and protein).

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Heterogeneity of Fat Depots
Study Start Date : August 2009
Estimated Primary Completion Date : August 2014
Estimated Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin

Insulin resistant group
there is no intervention
Insulin sensitive group
There is no intervention

Primary Outcome Measures :
  1. Adipose Cell Size [ Time Frame: 3 years ]
    Harvest adipose tissue from human biopsy. Prepare for cell size analysis using Beckman Multisizer Coulter Counter

Secondary Outcome Measures :
  1. Macrophage density [ Time Frame: 3 years ]
    Human adipose tissue will be formalin-fixed and paraffin-blocked for immunohistochemical analysis to identify macrophage number and pattern

  2. Gene Expression [ Time Frame: 3 years ]
    Adipose tissue from humans will be frozen and RNA prepared for measurement of relative expression of genes related to adipose cell differentiation, fat storage, and inflammation

Biospecimen Retention:   Samples With DNA
adipose tissue samples will be frozen for gene expression analysis.

Information from the National Library of Medicine

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Ages Eligible for Study:   39 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy, nondiabetic volunteers will be recruited from Stanford's General Surgery Preoperative Clinic, Stanford's Bariatric Surgery Clinic, and nonsurgical volunteers who respond to local newspaper advertisements.

Inclusion Criteria:

  • No major organ disease
  • Fasting blood glucose < 126 mg/dL
  • BMI 25-35 kg/m2
  • Nonpregnant/nonlactating

Exclusion Criteria:

  • pregnancy/lactation
  • major organ disease
  • drugs that influence insulin resistance
  • unstable body weight or active weight loss program
  • outside BMI range or age range
  • diabetic by fasting glucose criteria 126 mg/dL or higher

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01336777

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United States, California
Stanford University
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
University of California
National Institutes of Health (NIH)

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Tracey McLaughlin, Associate Professor, Stanford University Identifier: NCT01336777     History of Changes
Other Study ID Numbers: 1R01DK080436 ( U.S. NIH Grant/Contract )
First Posted: April 18, 2011    Key Record Dates
Last Update Posted: December 3, 2013
Last Verified: December 2013

Keywords provided by Tracey McLaughlin, Stanford University:
adipocyte differentiation
insulin resistance
visceral fat
regional fat depots

Additional relevant MeSH terms:
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Diabetes Mellitus
Insulin Resistance
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs