Bariatric Surgery And Adipose Inflammation Dysfunction and Type 2 Diabetes Mellitus

NCT ID: NCT01882036

Last Updated: 2023-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2018-07-10

Brief Summary

The focus of this proposal is to define the mechanism by which bariatric surgery acutely improves insulin sensitivity. Our central hypothesis is that drastically reduced caloric intake early after Bariatric surgery improves the pro-inflammatory profile of macrophages, which in turn improves insulin sensitivity and glucose homeostasis.

Detailed Description

Bariatric surgery quickly improves tissue specific insulin sensitivity. Changes in glucose metabolism are seen within days after surgery, prior to any significant weight loss--raising the question of a difference between dietary restriction and early food intake after surgery. A major factor in the development of insulin resistance is obesity. It has been noted that by 3 months following Roux-en Y gastric bypass surgery in obese patients with (T2DM), fasting glucose and insulin levels are improved independent of weight loss, insulin resistance in muscle is lowered, and that the pro-inflammatory profile of resident microphages is lowered improving insulin sensitivity.

The focus of this proposal is to define the mechanism by which bariatric surgery improves impacts insulin sensitivity. Our long-term goal is to correlate these changes with direct measures of adipose tissue insulin resistance to develop novel immunotherapies towards reducing insulin resistance without surgery.

Our central hypothesis is that gastrointestinal rearrangement by various mechanisms impacts adipose tissue and improves the pro-inflammatory profile of macrophages improving insulin sensitivity and glucose homeostasis. To test this hypothesis we propose the following aims:

Specific Aim 1. Recruit a patient population and measure insulin sensitivity using homeostatic model assessment (HOMA) to measure insulin resistance (IR), cytokines, incretins, and serum adipokines in morbidly obese patients • prior to and 7-10 days following bariatric surgery while on a hypocaloric diet (surgery group) and •prior to and 7-10 days while following hypocaloric diet similar to bariatric surgery (diet group). Subjects will be assigned to the two arms; subjects assigned to the hypocaloric diet may be offered bariatric surgery after completion of the diet.

Specific Aim 2.

• Profile inflammatory macrophages, T cells and secreted factors in subcutaneous and visceral adipose tissue of patients prior to and following RYGB and hypocaloric diet treatments. • prior to and 7-10 days following surgery
• prior to and 7-10 days following hypocaloric diet similar to bariatric surgery

Specific Aim 3.

Assess the effects of bariatric surgery on ROS (reactive oxygen species) production, expression of transcription factors and enzymes of mitochondrial biogenesis, tissue FABP4, and biomarkers of oxidative stress and protein carbonylation in patients prior to and following surgery and in control diet subjects maintained on hypocaloric diet.

Specific Aim 4.

Determine the impact of bariatric surgery on lipolysis and the role of TLQP-21 (a genetically derived peptide that increases energy expenditure and prevents the early phase of diet-induced obesity).

Conditions

Type 2 Diabetes Mellitus; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gastric Bypass w/ matched hypocaloric diet

Group Type: ACTIVE_COMPARATOR

Gastric Bypass w/ matched hypocaloric diet

Intervention Type: PROCEDURE

Roux en Y Gastric Bypass with Hypocaloric liquid diet for 10 days

Hypocaloric Diet

Group Type: ACTIVE_COMPARATOR

Hypocaloric diet

Intervention Type: OTHER

Hypocaloric liquid diet for 10 days

Interventions

Gastric Bypass w/ matched hypocaloric diet

Roux en Y Gastric Bypass with Hypocaloric liquid diet for 10 days

Intervention Type: PROCEDURE

Hypocaloric diet

Hypocaloric liquid diet for 10 days

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Candidate for RYGB gastric bypass with insurance approval.

2. Willing to accept randomization to either immediate surgery, or delayed surgery after diet study.

3. Willing to undergo two sessions of testing before, and ten days after surgery (or initiation of dietary intervention).

4. BMI 35-45kg/m2

5. Pre-diabetes (ADA criteria) or T2DM with HbA1c< 8%.

Exclusion Criteria

1. T1DM.

2. Serious illness such as cancer, active chronic infection, cardiovascular disease greater that New York Heart Association class 2, chronic renal failure, chronic lung disease.

3. Inflammatory or celiac intestinal disease.

4. Untreated thyroid disease.

5. Serious psychiatric disease.

6. Excessive alcohol use.

7. Illicit drug use. -

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sayeed Ikramuddin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

SURG-2018-26725

Identifier Type: -

Identifier Source: org_study_id