Development and Evaluation of a Glucagon Sensitivity Test in Individuals With and Without Hepatic Steatosis

What Was Tested

In this not phased trial, researchers set out to test Glucagon for fatty liver & elevated liver enzymes.

Glucagon is secreted from pancreatic alpha-cells in response to protein-rich meals and during hypoglycemia.

A physiological feedback system exists between the liver and the pancreatic alpha cells termed the liver-alpha cell axis and signifies the role between amino acid-stimulated glucagon secretion and glucagon-stimulated amino acid metabolism.

It had 1 arm (groups): Measuring glucagon sensitivity in humans (experimental).

Participants will be subjected to two experimental days.

The registry classes the interventions as diagnostic test.

More on the Plan

Amino acids administered orally or intravenously stimulate glucagon secretion from the pancreas and in turn, glucagon is a powerful stimulus for hepatic amino acid turnover through transcriptional (long-term) and non- transcriptional (acute) mechanisms.

Some amino acids are more potent in stimulating glucagon secretion (glucagonotropic amino acids), including alanine, and the glucagon-alanine index is currently used as a surrogate marker for the hepatic actions of glucagon on ureagenesis.

The fate of amino acid turnover depends on both glucagon and insulin dynamics by stimulating amino acid catabolism and synthesis, respectively.

Studying the effects of glucagon in individuals with type 1 diabetes will allow one to differentiate between the combined effects of glucagon and insulin compared to the effects of glucagon alone.

Who Took Part

Enrollment: 65 actual participants took part.

It was open to people of any sex aged from 25 years up to 65 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: BMI = 18.6-25 kg/m2. Male or female. 25-65 years of age.

The full record lists 3 inclusion and 45 exclusion criteria; among the exclusions: diabetes (ada criteria); amino acid-related diseases such as phenylketonuria; kidney disease.

How the Study Was Run

The set-up was single-group and open-label.

Nothing was hidden in this open-label Glucagon study: the fatty liver & elevated liver enzymes participants and staff both knew the treatment.

Everyone received the same intervention, so there was no separate comparison group inside the trial.

It started in 2021-05-27 with completion listed for 2023-10-21.

It ran at 1 site in Denmark.

Its stated primary purpose is basic science.

What Was Measured

The main thing measured (primary outcome): Differences in the calculated GLUSENTIC index between individuals with or without MASLD without diabetes.

It also tracked 23 secondary outcomes, for example Simple linear regression between hepatic steatosis (%) and the GLUSENTIC index, ROC curve analysis to evaluate cut-off value for GLUSENTIC index, Differences in the glucagon-alanine index, Differences in plasma levels of amino acids during the amino acid tolerance test (determined by baseline corrected AUC), Differences in plasma levels of total amino acids and alanine following an overnight fast and Baseline corrected AUC for glucagon after a bolus injection of glucagon.

What This Means in Plain Language

Put simply, this is a not phased trial of Glucagon in 65 people with fatty liver & elevated liver enzymes.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Glucagon compound page, Fatty liver & elevated liver enzymes research.