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

• Published in: Diabetes (New York, N.Y.) Vol. 73; no. 10; pp. 1641 - 1647
• Main Authors: Grøndahl, Magnus F G, Lange, Andreas H, Suppli, Malte P, Bagger, Jonatan I, Thing, Mira, Gluud, Lise L, Kofod, Dea H, Hornum, Mads, van Hall, Gerrit, Trammell, Samuel A J, Grevengoed, Trisha J, Hartmann, Bolette, Holst, Jens J, Vilsbøll, Tina, Christensen, Mikkel B, Lund, Asger B, Knop, Filip K
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.10.2024
• Subjects: Adult; Aged; Case-Control Studies; Female; Glucagon - blood; Glucagon - metabolism; Humans; Liver Cirrhosis - metabolism; Male; Metabolic Clearance Rate; Metabolism; Middle Aged; Renal Insufficiency, Chronic - metabolism
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db24-0305

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.