Bariatric Surgery And Adipose Inflammation Dysfunction and Type 2 Diabetes Mellitus

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01882036
First received: June 21, 2012
Last updated: May 4, 2015
Last verified: May 2015
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Insulin Resistance
Procedure: Gastric Bypass w/ matched hypocaloric diet
Other: Hypocaloric diet
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Roux-en-Y Gastric Bypass on Mitochondrial Dysfunction and Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Measure homeostasis model assessment i.e. estimated change in insulin resistance (HOMA-IR) index [ Time Frame: Seven days before and 10 days following RYGB or hypocaloric diet similar to RYGB patients ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: November 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gastric Bypass w/ matched hypocaloric diet Procedure: Gastric Bypass w/ matched hypocaloric diet
Roux en Y Gastric Bypass with Hypocaloric liquid diet for 10 days
Active Comparator: Hypocaloric Diet Other: Hypocaloric diet
Hypocaloric liquid diet for 10 days

Detailed Description:

One of the effects of bariatric surgery on Mitochondrial Dysfunction and Type 2 diabetes is the improvement in fasting glucose and insulin levels following the Roux en Y gastric bypass (RYGB) independent of weight loss. 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 the RYGB as it relates to insulin resistance. 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 glucose homeostasis in patients with Type 2 diabetes (T2DM). 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 drastically reduced caloric intake early after RYGP 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 RYGB surgery while on a hypocaloric diet (surgery group) and •prior to and 7-10 days while following hypocaloric diet similar to RYGB (diet group). Subjects will be randomly assigned to the two arms; subjects assigned to the hypocaloric diet will be offered RYGB after completion of the diet.

Specific Aim 2.

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

Specific Aim 3.

Assess the effects of RYGB on ROS (reactive oxygen species) production, expression of transcription factors and enzymes of mitochondrial biogenesis, and biomarkers of oxidative stress and protein carbonylation in patients prior to and following RYGB surgery and in 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).

Rationale: Lipolysis is a central feature of adipocyte biology. It is currently unclear if bariatric surgery can modulate basal and stimulated lipolysis in adipocytes. Additionally, Bartlomucci had demonstrated that the murine (mouse) version of TLQP-21 enhances lipolysis in adipocytes. Batolomucci has shown that the human version of TLQP-21 shows a lower biological activity on its human receptor compared to the mouse version.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. -
  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: NCT01882036

Contacts
Contact: JOYCE L SCHONE, RD 612-273-4860 jschone1@fairview.org
Contact: Stanley E E. Williams, PhD 612 6253265 willi004@umn.edu

Locations
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Joyce L Schone, RD    612-273-4860    jschone1@fairview.org   
Contact: Stanley E E. Williams, PhD    612 6253265    willi004@umn.edu   
Principal Investigator: Sayeed Ikramuddin, MD         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
American Diabetes Association
Investigators
Principal Investigator: Sayeed Ikramuddin, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01882036     History of Changes
Other Study ID Numbers: 0908M70742
Study First Received: June 21, 2012
Last Updated: May 4, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Endocrine System Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases

ClinicalTrials.gov processed this record on August 27, 2015