Bariatric Surgery And Adipose Inflammation Dysfunction and Type 2 Diabetes Mellitus
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|ClinicalTrials.gov Identifier: NCT01882036|
Recruitment Status : Active, not recruiting
First Posted : June 20, 2013
Last Update Posted : July 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Mellitus Insulin Resistance||Procedure: Gastric Bypass w/ matched hypocaloric diet Other: Hypocaloric diet||Not Applicable|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Effects of Roux-en-Y Gastric Bypass on Mitochondrial Dysfunction and Type 2 Diabetes Mellitus|
|Study Start Date :||November 2011|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
|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
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01882036
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Sayeed Ikramuddin, MD||University of Minnesota - Clinical and Translational Science Institute|