Foregut Exclusion Enhances Incretin and Insulin Secretion After Roux-en-Y Gastric Bypass in Adults With Type 2 Diabetes

Author:

Kirwan John P123,Axelrod Christopher L1243ORCID,Kullman Emily L1,Malin Steven K1,Dantas Wagner S2,Pergola Kathryn24,del Rincon Juan Pablo1,Brethauer Stacy A5,Kashyap Sangeeta R6,Schauer Philip R53

Affiliation:

1. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH,USA

2. Integrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA,USA

3. Bariatric and Metabolic Institute, Pennington Biomedical Research Center, Baton Rouge, LA,USA

4. Department of Translational Services, Pennington Biomedical Research Center, Baton Rouge, LA,USA

5. Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio,USA

6. Department of Endocrinology and Metabolism, Cleveland Clinic, Cleveland, Ohio,USA

Abstract

Abstract Introduction Patients with type 2 diabetes experience resolution of hyperglycemia within days after Roux-en-Y gastric bypass (RYGB) surgery. This is attributed, in part, to enhanced secretion of hindgut factors following exclusion of the gastric remnant and proximal intestine during surgery. However, evidence of the mechanisms of remission remain limited due to the challenges of metabolic evaluation during the early postoperative period. The purpose of this investigation was to determine the role of foregut exclusion in the resolution of type 2 diabetes after RYGB. Methods Patients with type 2 diabetes (n = 15) undergoing RYGB had a gastrostomy tube (G-tube) placed in their gastric remnant at time of surgery. Patients were randomized to receive a mixed meal tolerance test via oral or G-tube feeding immediately prior to and 2 weeks after surgery in a repeated measures crossover design. Plasma glucose, insulin, C-peptide, incretin responses, and indices of meal-stimulated insulin secretion and sensitivity were determined. Results Body weight, fat mass, fasting glucose and insulin, and circulating lipids were significantly decreased 2 weeks after surgery. The glycemic response to feeding was reduced as a function of total area under the curve but not after adjustment for the reduction in fasting glucose. Oral feeding significantly enhanced insulin and incretin secretion after RYGB, which was entirely ablated by G-tube feeding. Conclusion Foregut exclusion accounts for the rise in incretin and insulin secretion but may not fully explain the early improvements in glucose metabolism after RYGB surgery.

Funder

NIH

National Center for Research Resources

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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