Mechanisms of Glycemic Improvement After Gastrointestinal Surgery
| Status: | Completed |
|---|---|
| Conditions: | Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2010 |
| End Date: | June 2015 |
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.
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.
(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
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