Despite the increasing prevalence of postbariatric hypoglycemia (PBH), a late metabolic
complication of bariatric surgery, our understanding of its diverse manifestation
To contrast parameters of glucose-insulin homeostasis in two distinct phenotypes of
PBH (mild vs. moderate hypoglycemia) based on nadir plasma glucose.
Twenty-five subjects with PBH following gastric bypass surgery (age 41±12years, BMI
28.1±6.1kg/m2) received 75g of glucose with frequent blood sampling for glucose, insulin, C-peptide
and GLP-1. Based on nadir plasma glucose (</≥50mg/dL), subjects were grouped into
Level 1 and Level 2 PBH groups. Beta-cell function (BCF), GLP-1 exposure (λ), beta-cell
sensitivity to GLP-1 (π), potentiation of insulin secretion by GLP-1 (PI), first-pass
hepatic insulin extraction (HE), insulin sensitivity (SI) and rate of glucose appearance
(Ra) were calculated using an oral model of GLP-1 action coupled with the oral minimal
Nadir glucose was 43.3±6.0mg/dL (mean±SD) and 60.1±9.1mg/dL in Level 2 and Level 1-PBH,
respectively. Insulin exposure was significantly higher in Level 2 vs. Level 1 (p=0.004).
Mathematical modelling revealed higher BCF in Level 2 vs. Level 1 (34.3 vs. 18.8 10-9*min-1, p=0.003). Despite an increased GLP-1 exposure in Level 2 compared to Level 1 PBH
(50.7 vs. 31.9pmol*L-1*min*102, p=0.021), no significant difference in PI was observed (p=0.204). No significant
differences were observed for HE, Ra and SI.
Our results suggest that higher insulin exposure in PBH patients with lower postprandial
nadir glucose values mainly relate to a higher responsiveness to glucose-, rather
Received in revised form:
In Press Journal Pre-Proof
Funding: Swiss National Science Foundation (PCEGP3_186978), MIUR (Italian Minister for Education) under the initiative “Departments of Excellence” (Law 232/2016) and University of Padova DOR (Project Networking 2019), Diabetes Center Berne.
Disclosure summary: Authors have nothing to disclose. No competing financial interests exist.
Acknowledgments: We are grateful to all study participants for their time and efforts. We thank Nina Omlin (medical student), Sandra Tenisch, and Nicole Truffer (study nurses at the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism) for their assistance in patient care and data collection. We thank Laura Goetschi for providing administrative support. GLP-1 concentrations were measured at Medics Laboratory, Berne.
Authors have nothing to disclose. No competing financial interests exist.
All datasets analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.
DH, MS, CDM and LB designed the retrospective analysis. AT, VL, JM and SJ conducted the study visits. LB and TPS conceptualized laboratory analyses. CK performed the sample workup and analytical measurements. DH, MS and CDM analysed the data and produced the display items. DH, MS, CDM and LB interpreted the results and wrote the manuscript. All authors critically reviewed the manuscript and approved its final version. CDM and LB are the guarantor of this work and take main responsibility for the integrity and accuracy of the data.
This work was accepted for an oral presentation at the 81st Scientific Sessions of the American Diabetes Association (June 25-29, 2021).
© 2022 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.