Markers of Glucagon Resistance Improve With Reductions in Hepatic Steatosis and Body Weight in Type 2 Diabetes
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Markers of Glucagon Resistance Improve With Reductions in Hepatic Steatosis and Body Weight in Type 2 Diabetes. / Kjeldsen, Sasha A S; Thomsen, Mads N; Skytte, Mads J; Samkani, Amirsalar; Richter, Michael M; Frystyk, Jan; Magkos, Faidon; Hansen, Elizaveta; Thomsen, Henrik S; Holst, Jens J; Madsbad, Sten; Haugaard, Steen B; Krarup, Thure; Wewer Albrechtsen, Nicolai J.
In: Journal of the Endocrine Society, Vol. 7, No. 11, bvad122, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Markers of Glucagon Resistance Improve With Reductions in Hepatic Steatosis and Body Weight in Type 2 Diabetes
AU - Kjeldsen, Sasha A S
AU - Thomsen, Mads N
AU - Skytte, Mads J
AU - Samkani, Amirsalar
AU - Richter, Michael M
AU - Frystyk, Jan
AU - Magkos, Faidon
AU - Hansen, Elizaveta
AU - Thomsen, Henrik S
AU - Holst, Jens J
AU - Madsbad, Sten
AU - Haugaard, Steen B
AU - Krarup, Thure
AU - Wewer Albrechtsen, Nicolai J
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2023
Y1 - 2023
N2 - CONTEXT: Hyperglucagonemia may develop in type 2 diabetes due to obesity-prone hepatic steatosis (glucagon resistance). Markers of glucagon resistance (including the glucagon-alanine index) improve following diet-induced weight loss, but the partial contribution of lowering hepatic steatosis vs body weight is unknown.OBJECTIVE: This work aimed to investigate the dependency of body weight loss following a reduction in hepatic steatosis on markers of glucagon resistance in type 2 diabetes.METHODS: A post hoc analysis was conducted from 2 previously published randomized controlled trials. We investigated the effect of weight maintenance (study 1: isocaloric feeding) or weight loss (study 2: hypocaloric feeding), both of which induced reductions in hepatic steatosis, on markers of glucagon sensitivity, including the glucagon-alanine index measured using a validated enzyme-linked immunosorbent assay and metabolomics in 94 individuals (n = 28 in study 1; n = 66 in study 2). Individuals with overweight or obesity with type 2 diabetes were randomly assigned to a 6-week conventional diabetes (CD) or carbohydrate-reduced high-protein (CRHP) diet within both isocaloric and hypocaloric feeding-interventions.RESULTS: By design, weight loss was greater after hypocaloric compared to isocaloric feeding, but both diets caused similar reductions in hepatic steatosis, allowing us to investigate the effect of reducing hepatic steatosis with or without a clinically relevant weight loss on markers of glucagon resistance. The glucagon-alanine index improved following hypocaloric, but not isocaloric, feeding, independently of macronutrient composition.CONCLUSION: Improvements in glucagon resistance may depend on body weight loss in patients with type 2 diabetes.
AB - CONTEXT: Hyperglucagonemia may develop in type 2 diabetes due to obesity-prone hepatic steatosis (glucagon resistance). Markers of glucagon resistance (including the glucagon-alanine index) improve following diet-induced weight loss, but the partial contribution of lowering hepatic steatosis vs body weight is unknown.OBJECTIVE: This work aimed to investigate the dependency of body weight loss following a reduction in hepatic steatosis on markers of glucagon resistance in type 2 diabetes.METHODS: A post hoc analysis was conducted from 2 previously published randomized controlled trials. We investigated the effect of weight maintenance (study 1: isocaloric feeding) or weight loss (study 2: hypocaloric feeding), both of which induced reductions in hepatic steatosis, on markers of glucagon sensitivity, including the glucagon-alanine index measured using a validated enzyme-linked immunosorbent assay and metabolomics in 94 individuals (n = 28 in study 1; n = 66 in study 2). Individuals with overweight or obesity with type 2 diabetes were randomly assigned to a 6-week conventional diabetes (CD) or carbohydrate-reduced high-protein (CRHP) diet within both isocaloric and hypocaloric feeding-interventions.RESULTS: By design, weight loss was greater after hypocaloric compared to isocaloric feeding, but both diets caused similar reductions in hepatic steatosis, allowing us to investigate the effect of reducing hepatic steatosis with or without a clinically relevant weight loss on markers of glucagon resistance. The glucagon-alanine index improved following hypocaloric, but not isocaloric, feeding, independently of macronutrient composition.CONCLUSION: Improvements in glucagon resistance may depend on body weight loss in patients with type 2 diabetes.
U2 - 10.1210/jendso/bvad122
DO - 10.1210/jendso/bvad122
M3 - Journal article
C2 - 37818402
VL - 7
JO - Endocrine Research Communications
JF - Endocrine Research Communications
SN - 0743-5800
IS - 11
M1 - bvad122
ER -
ID: 379585866