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. 2024 Oct 1;73(10):1641-1647.
doi: 10.2337/db24-0305.

Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis

Magnus F G Grøndahl  1 , Andreas H Lange  1 , Malte P Suppli  1 , Jonatan I Bagger  1   2 , Mira Thing  3 , Lise L Gluud  3 , Dea H Kofod  4   5 , Mads Hornum  4   5 , Gerrit van Hall  6   7 , Samuel A J Trammell  7 , Trisha J Grevengoed  7 , Bolette Hartmann  7 , Jens J Holst  7   8 , Tina Vilsbøll  1   2   4 , Mikkel B Christensen  1   4   9   10 , Asger B Lund  1   2   4 , Filip K Knop  1   2   4   11
Affiliations

Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis

Magnus F G Grøndahl et al. Diabetes. .

Abstract

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A-C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) compared with both individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] min) compared with individuals with cirrhosis (5.7 [5.2;6.3] min, P = 0.002) and control individuals (5.7 [5.2;6.3] min, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, CKD, but not liver cirrhosis, leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.

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Conflict of interest statement

Duality of Interest. A.B.L. is on the speaker’s bureau of and/or has received research support from Sanofi, Boehringer Ingelheim, Novo Nordisk, and AstraZeneca. B.H. is a cofounder of Bainan Biotech. J.I.B. has received lecture fees from Novo Nordisk. J.J.H. was on the advisory panel of, consultant for, in the speaker’s bureau of, and/or has received research support from AstraZeneca, GlaxoSmithKline, Hamni, Intarcia, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, and Zealand Pharma. F.K.K. has been on the advisory panel of, consultant for, in the speaker’s bureau of, and/or received research support from 89bio, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gubra, Novo Nordisk, Merck Sharp & Dohme, Sanofi, Structure Therapeutics, Zealand Pharma, and Zucara, and is cofounder of and minority shareholder in Antag Therapeutics and currently employed by Novo Nordisk. M.F.G.G. has received lecture fees and travel compensation from Novo Nordisk Denmark A/S, is a minority shareholder of Zealand Pharma A/S, and is cofounder of Medvaegt ApS. M.H. has received speaker and consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk, Vifor, and GSK within the last 3 years. T.V. is on the advisory panel for, consultant for, in the speaker’s bureau of, and/or has received research support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Gilead, GSK, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Glucagon levels before, during, and after a 1-h exogenous glucagon infusion (4 ng/kg/min, shaded area) in participants with liver cirrhosis (n = 16) and CKD (n = 16) and matched healthy control participants (n = 16). Data are plotted as mean ± SEM. ***Significant difference (P = 0.001) in steady-state glucagon levels between the CKD group and the two other groups.
Figure 2
Figure 2
Plasma insulin (A), C-peptide (B), glucose (C), glucose Ra (D), glucose Rd (E), total amino acids (F), and triglycerides (G) before, during, and after a 1-h exogenous glucagon infusion (4 ng/kg/min, shaded area) in participants with liver cirrhosis (n = 16) and chronic kidney disease (n = 16) and healthy matched control participants (n = 16). Data are plotted as means ± SEM.
See this image and copyright information in PMC

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