TY - JOUR

T1 - Glucagon Clearance is Preserved in Type 2 Diabetes

AU - Grøndahl, Magnus F. G.

AU - Lund, Asger

AU - Bagger, Jonatan I.

AU - Petersen, Tonny S

AU - Wewer Albrechtsen, Nicolai J

AU - Holst, Jens J

AU - Vilsbøll, Tina

AU - Christensen, Mikkel B

AU - Knop, Filip K

N1 - © 2021 by the American Diabetes Association.

PY - 2022

Y1 - 2022

N2 - Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity. Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T½) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed. Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T½ Individuals with obesity had neither a significantly decreased MCR, T½, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.

AB - Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity. Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T½) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed. Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T½ Individuals with obesity had neither a significantly decreased MCR, T½, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.

U2 - 10.2337/db21-0024

DO - 10.2337/db21-0024

M3 - Journal article

C2 - 34702780

VL - 71

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

M1 - db210024

ER -