Mechanisms of Glycemic Improvement After Gastrointestinal Surgery

Mechanisms of Glycemic Improvement After Gastrointestinal Surgery

This study is designed as a prospective clinical trial aimed at investigating the mechanisms behind observed improvements in type 2 diabetes mellitus (T2DM) following bariatric surgery. The majority of patients with T2DM who are undergoing Roux-en-Y gastric bypass (RYGB) surgery, in particular, experience complete remission of T2DM almost immediately post-surgery. This response occurs before significant weight loss is possible. To assess the mechanisms involved with disease resolution, the investigators propose a study to evaluate patients at the UW Medical Center (UWMC) who have T2DM and are undergoing RYGB with G (gastronomy)-tube placement as part of their clinical care. The investigators are interested in this sub-population as the G-tube allows us the unique opportunity to evaluate glycemic control and insulin response following delivery or exclusion of nutrients to the otherwise bypassed portion of the gastrointestinal tract. The investigators hypothesize that nutrient delivery to the proximal GI tract will reverse RYGB-mediated improvements in glucose homeostasis, possibly in association with changes in nutrient-regulated gut peptides involved in glucose control.

Roux-en-Y gastric bypass surgery causes complete, durable remission of type 2 diabetes (T2DM) in 84% of cases, typically within a few days to weeks after surgery. Mounting evidence indicates that this dramatic phenomenon results from effects beyond those related to weight loss and reduced caloric intake alone. The mechanisms mediating the weight-independent anti-diabetes impact of RYGB are unknown, and elucidating them could lead to new diabetes medicines. Human subjects will undergo frequently sampled I.V. glucose tolerance tests (FS-IVGTT) and tracer-enhanced hyperinsulinemic/euglycemic clamps (to measure insulin secretion and sensitivity) before RYBG and 3 times in the first six weeks afterward, during which the proximal small bowel will either be excluded from nutrient contact or exposed to nutrients delivered through an indwelling gastric cannula. We hypothesize that nutrient delivery to the proximal GI tract will reverse RYGB-mediated improvements in glucose homeostasis, possibly in association with changes in nutrient-regulated gut peptides involved in glucose control. Our study will allow us to test the upper intestinal hypothesis rigorously in man, and whether the hypothesis is confirmed or refuted, we will gain valuable new insights into the mechanisms of improved glucose control early after RYGB.

Inclusion Criteria:

• Age 18 years or greater and planning to undergo RYGB at UWMC
• Ability to speak English and communicate effectively with research staff
• Ability to return for follow-up visits at UWMC
• Adequate IV access
• A G-tube is planned as part of the bariatric surgical procedure
• Documented T2DM (fasting plasma glucose >125 mg/dL) that is treated with lifestyle efforts or by taking acceptable oral medications

Exclusion Criteria:

• Informed consent not obtained
• Unlikely to comply with the protocol
• Current HbA1c >8.5% or fasting blood glucose >180 mg/dL
• Serum creatinine >1.7 mg/dL
• Use of unacceptable diabetes medications at baseline