The Journal of Clinical Endocrinology & Metabolism, 2021, Vol. 106, No. 2, 364–371 doi:10.1210/clinem/dgaa854 Clinical Research Article 364 https://academic.oup.com/jcem ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Clinical Research Article Acceleration of Gastric Emptying by Insulin- Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia Tejaswini Arunachala Murthy, 1,2 Jacqueline Grivell, 1 Seva Hatzinikolas, 1 Lee-anne S Chapple, 1,2 Marianne J Chapman, 1,2 Julie E Stevens, 3 Charles-Henri Malbert, 4 Christopher K Rayner, 1,5 Michael Horowitz, 1,6 Karen L Jones, 1,6 and Chinmay S Marathe 1,6 1 Adelaide Medical School, University of Adelaide, Adelaide, 5000, Australia, 2 Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia, 5005, 3 RMIT, Melbourne, 3000, Australia, 4 INRA, Saint-Gilles, 35590, France, 5 Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, 5005, Australia; and 6 Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, 5005, Australia ORCiD numbers: 0000-0002-1155-5816 (K. L. Jones); 0000-0002-8086-2449 (C. S. Marathe). Abbreviations: AUC, area under the curve; CV, coefficient of variation; GLP-1, glucagon-like peptide-1; HbA1c, glycated hemoglobin A1c; T1D, type 1 diabetes; T2D, type 2 diabetes. Received: 21 August 2020; Editorial Decision: 17 November 2020; First Published Online: 24 November 2020; Corrected and Typeset: 18 December 2020. Abstract  Context: Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized “non-severe” hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. “Marked” hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of “mild” hypoglycemia (3.0- 3.9 mmol/L) is unknown. Objective: To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L (“marked”) and 3.6 mmol/L (“mild”), on gastric emptying in health. Design, Setting, and Subjects: Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m 2 ) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. Results: Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during Downloaded from https://academic.oup.com/jcem/article/106/2/364/5999194 by guest on 01 January 2024