Does GLP-1 cause post-bariatric hypoglycemia: 'Computer says no'

Ysanne M. Pasveer, Ömrüm Aydin, Albert K. Groen, Abraham S. Meijnikman, Max Nieuwdorp, Victor E.A. Gerdes, Natal A.W. van Riel (Corresponding author)

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Samenvatting

BACKGROUND AND OBJECTIVE: Patients who underwent Roux-en-Y Gastric Bypass surgery for treatment of obesity or diabetes can suffer from post-bariatric hypoglycemia (PBH). It has been assumed that PBH is caused by increased levels of the hormone GLP-1. In this research, we elucidate the role of GLP-1 in PBH with a physiology-based mathematical model.

METHODS: The Eindhoven Diabetes Simulator (EDES) model, simulating postprandial glucose homeostasis, was adapted to include the effect of GLP-1 on insulin secretion. Parameter sensitivity analysis was used to identify parameters that could cause PBH. Virtual patient models were created by defining sets of models parameters based on 63 participants from the HypoBaria study cohort, before and one year after bariatric surgery.

RESULTS: Simulations with the virtual patient models showed that glycemic excursions can be correctly simulated for the study population, despite heterogeneity in the glucose, insulin and GLP-1 data. Sensitivity analysis showed that GLP-1 stimulated insulin secretion alone was not able to cause PBH. Instead, analyses showed the increased transit speed of the ingested food resulted in quick and increased glucose absorption in the gut after surgery, which in turn induced postprandial glycemic dips. Furthermore, according to the model post-bariatric increased rate of glucose absorption in combination with different levels of insulin sensitivity can result in PBH.

CONCLUSIONS: Our model findings implicate that if initial rapid improvement in insulin sensitivity after gastric bypass surgery is followed by a more gradual decrease in insulin sensitivity, this may result in the emergence of PBH after prolonged time (months to years after surgery).

Originele taal-2Engels
Artikelnummer108424
Aantal pagina's9
TijdschriftComputer Methods and Programs in Biomedicine
Volume257
Vroegere onlinedatum19 sep. 2024
DOI's
StatusE-publicatie vóór gedrukte publicatie - 19 sep. 2024

Financiering

NvR, AKG and MN acknowledge funding by EC FP7 Health (RESOLVE, Grant agreement ID: 305707 ) and the Dutch Research Council (NWO Complexity in Health and Nutrition , project number 645.001.003). NvR also acknowledges the Dutch Research Council for funding the DiaGame project (project number 628.011.027) and the Centre for Unusual Collaborations of the alliance TU/e, WUR, UU, UMC Utrecht . MN is supported by a personal ZONMW-VICI grant 2020 ( 09150182010020 ).

FinanciersFinanciernummer
Nederlandse Organisatie voor Wetenschappelijk Onderzoek628.011.027, 645.001.003
ZonMw : Dutch Organisation for Health Research and Development09150182010020

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