Bariatric Surgery And Adipose Inflammation Dysfunction and Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus; Insulin Resistance
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
Study type: Interventional

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).
    

Intervention name(s): Gastric Bypass w/ matched hypocaloric diet; Hypocaloric diet
Intervention type(s): Procedure; Other
Intervention description(s): Roux en Y Gastric Bypass with Hypocaloric liquid diet for 10 days; Hypocaloric liquid diet for 10 days
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment