Understanding the Relationship Between Inflammation and Insulin Resistance in the Adipose Tissue

Immunomodulatory Role of Eosinophils in Determining Inflammation and Insulin Sensitivity in Human Adipose Tissue- Aims 1&2

This study is being done to better understand the relationship between inflammation and insulin resistance in your Adipose (fat) Tissue .

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Resistance
• Intervention / Treatment: Procedure: Fat biopsy during scheduled abdominal surgery; Procedure: Fat Aspiration; Dietary supplement: Fish Oil Supplement

Detailed Description

This study is being done to determine whether eosinophils (a type of white blood cell) play an important role in human fat metabolism and inflammation.

This study is being done to determine if fish oil supplement could play a role in reducing inflammation and improving insulin sensitivity in your fat tissue.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Lean, healthy person with a body mass index (BMI) of 25 or less, or you are obese, BMI between 30 and 50, and non-diabetic.

Lean healthy controls will not be on any medication and will be undergoing elective abdominal surgery excluding those involving acute inflammation (i.e. acute cholecystitis, bowel perforation, or diverticulitis).

Obese, non-diabetic subjects will have a BMI between 30 and 50 and be taking no medications affecting glucose metabolism or lipid metabolism. These subjects will be identified from a pool of patients undergoing an elective abdominal surgical procedure such as inguinal hernia repair, laparoscopic Nissen fundoplication, planned cholecystectomy, but also bariatric surgery.

Volunteers will not be taking corticosteroid therapy or have a history of asthma, COPD or atopic syndrome. All subjects will undergo a medical history intake and a physical examination followed by an OGTT to confirm normal glucose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lean or Obese, Non-Diabetic; To determine whether eosinophil content of adipose tissue is related to insulin sensitivity. We will use euglycemic clamps, fat biopsy (obtained during a scheduled abdominal surgery) and fat aspiration for analysis of subcutaneous (Sc) and omental (OM) adipose tissue from obese, insulin resistant and lean, insulin sensitive volunteers to test the hypothesis that, as in mice, eosinophil content in human subcutaneous and omental white adipose tissue, inversely correlates with body weight, with skeletal muscle and hepatic insulin sensitivity.	Procedure: Fat biopsy during scheduled abdominal surgery; Physical exam including blood work, an EKG and bioimpedance testing. An oral glucose tolerance test. Insulin infusion. Fat tissue biopsy during a scheduled abdominal surgery.; Other Names: Fat Aspiration; Tissue Biopsy; Procedure: Fat Aspiration; Physical exam including blood work, an EKG and bioimpedance testing. An oral glucose tolerance test. Insulin infusion. Subcutaneous fat tissue biopsy.; Other Names: Fat Sample; Adipose Tissue
Experimental: Fish oil supplementation; Determine whether, in adipose tissue, levels of, anti-inflammatory molecules correlate with insulin sensitivity and whether these levels are altered by a treatment designed to promote resolution of inflammation. Volunteers will take a fish oil supplement for three months.	Procedure: Fat Aspiration; Physical exam including blood work, an EKG and bioimpedance testing. An oral glucose tolerance test. Insulin infusion. Subcutaneous fat tissue biopsy.; Other Names: Fat Sample; Adipose Tissue; Dietary supplement: Fish Oil Supplement; Fish Oil supplementation for three months.; Other Names: Dietary Supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eosinophil content in adipose tissue	Eosinophils number will be measured by flow cytometry in subcutaneous and visceral fat of lean vs obese, non-diabetic volunteers	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between eosinophils content and body mass index (BMI)	Measure as a linear regression between BMI (kg/m2) and eosinophils number in the fat	baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in insulin sensitivity	Measured by euglycemic-hyperinsulinemic clamp taken before and after fish oil supplementation	Baseline, post fish oil supplementation (approximately 3 months)
Change in plasma inflammatory cytokines	Measured by Elisa reported in pg/mL before and after fish oil supplementation	Baseline, post fish oil supplementation (approximately 3 months)
Change in plasma inflammatory adipokines	Measured by Elisa reported in pg/mL before and after fish oil supplementation	Baseline, post fish oil supplementation (approximately 3 months)
Change in adipose tissue inflammatory markers	Measured by mRNA levels of pro-inflammatory markers before and after fish oil supplementation	Baseline, post fish oil supplementation (approximately 3 months)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Elena Anna De Filippis, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: September 17, 2014
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimate): March 4, 2015

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Obesity; Insulin Resistance
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Inflammation; Insulin Resistance
• Other Study ID Numbers: 14-001288