Glucagon resistance in individuals with obesity and hepatic steatosis can be measured using the GLUSENTIC test and index

Sasha A. S. Kjeldsen, Michael M. Richter, Nicole J. Jensen, Malin S. D. Nilsson, Niklas Heinz, Janus D. Nybing, Frederik H. Linden, Erik Høgh-Schmidt, Mikael P. Boesen, Thomas L. Andersen, Helle H. Johannesen, Samuel A. J. Trammell, Trisha J. Grevengoed, Sten Madsbad, Hendrik Vilstrup, Frank Vinholt Schiødt, Andreas Møller, Elias B. Rashu, Kirsten Nørgaard, Signe SchmidtLise L. Gluud, Steen B. Haugaard, Jens J. Holst, Jørgen Rungby, Nicolai J Wewer Albrechtsen*

*Corresponding author af dette arbejde

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Abstract

Increased plasma levels of glucagon (hyperglucagonaemia) promote diabetes development but is also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance towards amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, consisting of two study days: a glucagon injection and measurements of plasma amino acids, and an infusion of mixed amino acids and subsequent calculation of the GLUSENTIC index (primary outcome measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The delta-decline in total amino acids was 49% lower in MASLD following exogenous glucagon (p=0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (p<0.0001), but not T1D (p>0.99). In contrast, glucagon-induced glucose increments were similar in controls and MASLD (p=0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD.

OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind73
Udgave nummer10
Sider (fra-til)1716–1727
Antal sider12
ISSN0012-1797
DOI
StatusUdgivet - 2024

Bibliografisk note

© 2024 by the American Diabetes Association.

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