Adipose Tissue Response to Overfeeding in Insulin Resistance-Prone vs. Insulin Sensitive Humans

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Stanford University
Sponsor:
Information provided by (Responsible Party):
Tracey McLaughlin, Stanford University
ClinicalTrials.gov Identifier:
NCT02084641
First received: March 12, 2013
Last updated: March 9, 2014
Last verified: March 2014
  Purpose

Obesity has become an epidemic worldwide. Data from our laboratory and others demonstrate that most of the excess morbidity from obesity is related to insulin resistance (IR). While total adiposity correlates with insulin resistance, not all obese individuals are IR. When obese IR individuals lose weight in response to caloric restriction, even moderate loss of body fat results in improved insulin sensitivity (IS). With massive weight loss, either dietary or surgical, even the most IR individuals can completely reverse their insulin resistance. But why is one individual IR at a BMI of 26 and another IS at a BMI of 35? There must be differences in the manner in which adipose cells/tissue respond to caloric excess and weight gain. One potentially unifying hypothesis with regard to obesity-associated insulin resistance is that those individuals who fail to respond to caloric excess/obesity with adequate adipocyte differentiation and expanded subcutaneous fat storage capacity develop increased circulating FFAs, ectopic fat deposition, stress on adipocytes, triggering localized and systemic inflammation and ultimately insulin resistance in skeletal muscle.

Clearly, the best way to examine the human response to obesity is to challenge overweight individuals with the need to store excess triglyceride in adipose tissue. Specific aims are:

  1. Test the hypothesis that impaired adipogenesis and fat storage capacity are associated with insulin resistance by comparing 1) cell size distribution; 2) gene markers of adipose cell differentiation; 3) differentiation of isolated preadipocytes in IR-prone vs IS individuals subjected to caloric excess.
  2. Determine if circulating (daylong FFA, two-stage Insulin Suppression Test) and ectopic fat (MRI liver, CT abdomen) are worsened to a greater degree in IR-prone vs IS individuals subjected to caloric excess.
  3. Determine whether differences in inflammation and/or innate or adaptive immune response are associated with insulin resistance by comparing differences in resident dendritic cells, macrophages and their activation profiles, changes in T-cell subpopulations, and other inflammatory mediators in IR-prone vs IS individuals who are subjected to caloric excess via overfeeding.
  4. Exploratory: Evaluate IR-prone vs IS individuals for evidence of hypoxia and insufficient angiogenic response in response to caloric excess.

Condition Intervention
Insulin Resistance
Obesity
Other: Over feeding

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Adipose Tissue Response to Overfeeding in Insulin Resistance-Prone vs. Insulin Sensitive Humans

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Subcutaneous adipose cell triglyceride storage capacity/differentiation [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    this will be quantified by measuring: 1) adipose cell size distribution; 2) gene markers of adipose cell differentiation; 3) differentiation of isolated preadipocytes in IR-prone vs IS individuals subjected to caloric excess; in vivo triglyceride synthesis using stable isotope methods


Secondary Outcome Measures:
  • Ectopic fat [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Fat deposited in liver (MRI), visceral (intraabdominal) abdominal (CT) versus subcutaneous abdominal and thigh fat (CT)


Other Outcome Measures:
  • Adipose tissue and systemic inflammation: both innate or adaptive immune response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Flow cytometry will be used to quantitate, in both adipose tissue and plasma, populations of dendritic cells, T-cell subpopulations, and macrophages


Estimated Enrollment: 45
Study Start Date: September 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin resistant and insulin sensitive
Both groups will be given the same intervention and then outcomes compared between groups
Other: Over feeding
Study participants will be given low saturated fat snacks, an additional 750-1000 calories to gain 6-8 lbs over 4 weeks

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

BMI 25-35 kg/m2 Healthy adults Age 35-65 Weight stable Nondiabetic

Exclusion Criteria:

Major organ disease such as heart, kidney, liver Malignancy Inflammatory conditions (eg. lupus, rheumatoid arthritis, Crohn's disease) Eating disorder h/o bariatric surgery or liposuction use of blood thinners such as Coumadin (aspirin is ok)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02084641

Contacts
Contact: Colleen Craig, MD 650-736-2056
Contact: Dalia Perelman, RD 650-723-6713

Locations
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Craig, MD    650-736-2056      
Contact: Lamendola, NP    650-736-2056      
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Tracey McLaughlin, MD Stanford University
  More Information

No publications provided

Responsible Party: Tracey McLaughlin, Associate Professor, Stanford University
ClinicalTrials.gov Identifier: NCT02084641     History of Changes
Other Study ID Numbers: 20281
Study First Received: March 12, 2013
Last Updated: March 9, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Stanford University:
ectopic fat
obesity
triglyceride storage
adipocyte
overfeeding
intrahepatic fat
adipocyte proliferation
inflammation
macrophage

Additional relevant MeSH terms:
Insulin Resistance
Obesity
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014