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

NCT ID: NCT02084641

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2016-08-31

Brief Summary

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.

Conditions

Insulin Resistance; Obesity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Insulin resistant

Both groups will be given the same intervention and then outcomes compared between groups

Group Type: EXPERIMENTAL

Over feeding

Intervention Type: OTHER

Study participants will be given low saturated fat snacks, an additional 750-1000 calories to gain 6-8 lbs over 4 weeks

Insulin Sensitive

Both groups will be given the same intervention and then outcomes compared between groups

Group Type: EXPERIMENTAL

Over feeding

Intervention Type: OTHER

Study participants will be given low saturated fat snacks, an additional 750-1000 calories to gain 6-8 lbs over 4 weeks

Interventions

Over feeding

Study participants will be given low saturated fat snacks, an additional 750-1000 calories to gain 6-8 lbs over 4 weeks

Intervention Type: OTHER

Eligibility 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)

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Tracey McLaughlin

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tracey McLaughlin, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Countries

United States

Other Identifiers

20281

Identifier Type: -

Identifier Source: org_study_id