What question did this study set out to answer?

This study investigates how insulin secretion dynamics differ in post-RYGB patients who experience hypoglycemia compared to those who do not.

June 7, 2026

3041-LB: Insulin Secretion Dynamics after Roux-en-Y Gastric Bypass and Their Association with Post-bariatric Hypoglycemia

Key Points

This study investigates how insulin secretion dynamics differ in post-RYGB patients who experience hypoglycemia compared to those who do not.
Insulin secretion parameters were measured during a mixed-meal tolerance test.
Three cohorts were analyzed: 11 controls, 18 post-RYGB without hypoglycemia, and 20 with hypoglycemia.
Data was modeled using a forcing-function strategy to identify key parameters.
Models captured experimental data well with RMSE values indicating varied performance across groups.
Post-RYGB patients showed faster meal absorption and reduced insulin clearance compared to controls.
Meal-driven insulin secretion increased after surgery in post-RYGB patients without hypoglycemia, while glucose-driven secretion decreased only in those without PBH.

Abstract

Introduction and Objective: Roux-en-Y gastric bypass (RYGB) is an effective treatment for obesity and type 2 diabetes but may lead to post-bariatric hypoglycemia (PBH). This study investigates how insulin secretion dynamics differ between post-RYGB patients with and without hypoglycemia by identifying key model parameters. Methods: Insulin secretion parameters were identified using plasma glucose, insulin, and C-peptide concentrations during a mixed-meal tolerance test in three cohorts from clinical study NCT04428866: 11 controls, 18 post-RYGB without hypoglycemia, and 20 post-RYGB with hypoglycemia. Model identification used a forcing-function strategy. Results: Models adequately captured experimental data across groups, with joint insulin-C-peptide normalized RMSE of 0.60 (0.28) in Controls, 0.84 (0.18) in RYGB-noPBH, and 0.92 (0.36) in RYGB-PBH. Post-RYGB subjects exhibited faster meal absorption (lower τ) and reduced insulin clearance (lower γ) vs. controls. Meal-driven insulin secretion (β) increased after surgery, whereas glucose-driven secretion (a) decreased in RYGB subjects without PBH but remained unchanged in those with PBH (Figure 1). Conclusion: PBH appears to arise when meal-driven insulin secretion increases while glucose-driven secretion remains unchanged. Findings can be incorporated into in-silico platforms to support development and testing of therapeutic strategies for PBH. Disclosure E. Mohammadi: None. A. El Fathi: Research Support; Current; Tandem Diabetes Care, Inc. Research Support; Ended; Novo Nordisk A/S. L. Pei: None. H. Saeed: None. M.E. Patti: Other - My institution receives research funding for clinical trial.; Current; Recordati S.p.A, Amylyx. Other - Data Safety Monitoring Board; Current; Fractyl Health, Inc. B. Kovatchev: Research Support; Current; Dexcom, Inc. Other - Patent royalties handled by the UVA Licensing and Ventures Group; Current; Dexcom, Inc. Research Support; Current; Tandem Diabetes Care, Inc. Other - Patent royalties handled by the UVA Licensing and Ventures Group; Current; Tandem Diabetes Care, Inc. Research Support; Ended; Novo Nordisk. Other - Patent royalties handled by the UVA Licensing and Ventures Group; Ended; Novo Nordisk, Sanofi. M. Breton: Research Support; Current; Tandem Diabetes Care, Inc. Advisory Panel; Current; Tandem Diabetes Care, Inc. Other - IP royalties; Current; Tandem Diabetes Care, Inc. Research Support; Current; Dexcom, Inc. Other - IP royalties; Current; Dexcom, Inc. Speaker's Bureau; Current; Sinocare, Tandem Diabetes Care, Inc. Other - IP royalties; Current; Sanofi. Research Support; Ended; Novo Nordisk. Other - IP royalties; Ended; Novo Nordisk. Consultant; Current; Boydsense, Roche Diabetes Care. Funding National Institutes of Health (R01DK137518)

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