Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans

Authors

Shana O. Warner, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Yufei Dai, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Nicole Sheanon, Department of Pediatrics, Division of Pediatric Endocrinology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Michael V. Yao, Department of Pediatrics, Division of Endocrinology, University of New Mexico, Albuquerque, New Mexico, USA
Rebecca L. Cason, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Shahriar Arbabi, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Shailendra B. Patel, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Diana Lindquist, Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
Jason J. Winnick, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Document Type

Article

Publication Date

6-22-2023

Abstract

Fasting is associated with increased susceptibility to hypoglycemia in people with type 1 diabetes, thereby making it a significant health risk. To date, the relationship between fasting and insulin-induced hypoglycemia has not been well characterized, so our objective was to determine whether insulin-independent factors, such as counterregulatory hormone responses, are adversely impacted by fasting in healthy control individuals. Counterregulatory responses to insulin-induced hypoglycemia were measured in 12 healthy people during 2 metabolic studies. During one study, participants ate breakfast and lunch, after which they underwent a 2-hour bout of insulin-induced hypoglycemia (FED). During the other study, participants remained fasted prior to hypoglycemia (FAST). As expected, hepatic glycogen concentrations were lower in FAST, and associated with diminished peak glucagon levels and reduced endogenous glucose production (EGP) during hypoglycemia. Accompanying lower EGP in FAST was a reduction in peripheral glucose utilization, and a resultant reduction in the amount of exogenous glucose required to maintain glycemia. These data suggest that whereas a fasting-induced lowering of glucose utilization could potentially delay the onset of insulin-induced hypoglycemia, subsequent reductions in glucagon levels and EGP are likely to encumber recovery from it. As a result of this diminished metabolic flexibility in response to fasting, susceptibility to hypoglycemia could be enhanced in patients with type 1 diabetes under similar conditions.

Publication Title

JCI Insight

ISSN

2379-3708

Volume

8

Issue

12

DOI

10.1172/jci.insight.169789

Recommended Citation

Warner SO, Dai Y, Sheanon N, Yao MV, Cason RL, Arbabi S, Patel SB, Lindquist D, Winnick JJ. Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans. JCI Insight. 2023 Jun 22;8(12):e169789. doi: 10.1172/jci.insight.169789. PMID: 37166980.