American Diabetes Association
3 files

Bariatric surgery alters the postprandial recovery from hypoglycemia mediated by cholinergic signal 

posted on 2023-07-19, 19:27 authored by Marzieh Salehi, Devjit Tripathy, Richard Peterson, Henri Honka, Samantha Pezzica, Ralph DeFronzo, Amalia Gastaldelli


Roux-en-Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) increase prandial insulin and glucagon secretion but reduce the endogenous glucose production (EGP) response to hypoglycemia compared to non-operated controls (CN), suggesting that parasympathetic nervous system (PNS) plays a role. Here, we investigated the effect of acute PNS blockade on the post-meal counterregulatory response to insulin-induced hypoglycemia in GB and SG compared to CN. Glucose kinetics and islet-cell secretion were measured in 9 non-diabetic subjects with GB, 7 with SG, and 5 CN during hyperinsulinemic hypoglycemic clamp (~3.2mM) combined with meal ingestion on two separate days with and without intravenous atropine infusion. Glucose and hormonal levels were similar at baseline and during steady state hypoglycemia before meal ingestion in 3 groups and unaffected by atropine. Atropine infusion diminished prandial systemic appearance of ingested glucose (RaO) by 30%, EGP by 40%, and glucagon response to hypoglycemia by 90%, in controls. In GB or SG, blocking PNS had no effect on the RaO or meal-induced hyperglucagonemia, but increased EGP in SG without any effect in GB (p<0.05 interaction). These findings indicate that cholinergic signal contributes to the recovery from hypoglycemia by meal consumption in humans. However, bariatric surgery dissipates PNS-mediated physiologic responses to hypoglycemia in the fed state. 


This work was supported by grants from the National Institute of Health, DK105379 (MS) and in part by National Center for Advancing Translational Sciences, National Institute of Health grant UL1 TR002645. A.G. acknowledges the financial support from the European Union’s Horizon 2020 Research and Innovation Programme for the project “Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy” (SOPHIA). SOPHIA has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 875534. This Joint Undertaking received support from the European Union’s Horizon 2020 research and innovation program, EFPIA, T1D Exchange, JDRF, and Obesity Action Coalition. The communication reflects the author's view. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein.


Usage metrics



    Ref. manager