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

JCI Insight · 9 authors, 4 centres

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TL;DR

This study investigated the effect of a 22-hour fast on glucagon and glucose metabolism in healthy humans. It found that fasting lowered glucagon levels and endogenous glucose production under both normal and low blood sugar conditions.

Full summary

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The central result was that fasting reduced hepatic glycogen content by 42%, which was associated with lower glucagon levels and diminished endogenous glucose production under both euglycemic and hypoglycemic conditions. The glucagon response to hypoglycemia itself did not differ between treatments. Limitations include the study of healthy individuals rather than those with type 1 diabetes, assessment of only a single fasting day, and an uneven sex distribution. The findings suggest fasting may increase hypoglycemia susceptibility in humans through an insulin-independent reduction in the counterregulatory hormone response.

STUDY TYPE

other

SPECIALTY

endocrinology

SUMMARISED BY

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100% · A

ORIGINAL PAPER

PMC10371233

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

JCI Insight

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ABSTRACT

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. Keywords: Endocrinology Keywords: Diabetes

CITATION EXPORT

Shana O Warner, Yufei Dai, Nicole Sheanon et al.. Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans. JCI Insight. (2023). https://doi.org/10.1172/jci.insight.169789

AUTHORS

9 · 4 CENTRES

Shana O Warner, Yufei Dai, Nicole Sheanon, Michael V Yao, Rebecca L Cason, Shahriar Arbabi, Shailendra B Patel, Diana Lindquist, Jason J Winnick

1Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
2Department of Pediatrics, Division of Pediatric Endocrinology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
3Department of Pediatrics, Division of Endocrinology, University of New Mexico, Albuquerque, New Mexico, USA.
4Imaging Research Center, Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA.

Shana O Warner, Yufei Dai, Nicole Sheanon et al.. Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans. JCI Insight. (2023). https://doi.org/10.1172/jci.insight.169789