Effect of Bariatric Surgery on Tissue-specific Glucose Uptake

Obesity is associated with an impairment in postprandial glucose disposal, which is an important risk factor for type 2 diabetes (T2D). Weight loss improves postprandial glycemic control. The difficulty in achieving successful weight loss by using lifestyle therapy (diet and physical activity) has led to an increased interest in bariatric surgery, which is the most effective available weight loss therapy. Moreover, bariatric surgery procedures that bypass the upper gastrointestinal tract, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), have profound effects on glycemic control and cause remission in a large percentage of people with T2D. However, the effect of RYGB and SG surgery on postprandial glucose disposal among key metabolic organs has not been investigated and compared. The goal of this study is to provide a comprehensive evaluation of whole-body and tissue-specific glucose metabolism after consuming a mixed meal in lean people and people with obesity, before and after 20-35% weight loss induced by RYGB or SG surgery. Glucose uptake (GU) will be assessed by using: i) a combination of oral and intravenous stable isotopically-labeled glucose tracers to assess the delivery of ingested glucose into the systemic circulation and whole-body glucose disposal rate; and ii) positron emission tomography (PET) with magnetic resonance (MR) imaging to assess muscle, subcutaneous and visceral adipose tissue, liver, small intestine, and pancreas GU.