Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach

Jeremy Basset-Sagarminaga; Tineke van de Weijer; Evi Koene; Yvonne M. H. Op den Kamp-Bruls; Esther Phielix; Kim Brouwers; Sam Springer; Edvin Johansson; Lars Johansson; Fotis Kotasidis; Paul Deak; Joachim E. Wildberger; Roel Wierts; Iina Laitinen; Patricia Iozzo; Patrick Schrauwen; Vera B. Schrauwen-Hinderling

doi:10.1016/j.diabres.2025.112288

Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach

Jeremy Basset-Sagarminaga, Tineke van de Weijer, Evi Koene, Yvonne M. H. Op den Kamp-Bruls, Esther Phielix, Kim Brouwers, Sam Springer, Edvin Johansson, Lars Johansson, Fotis Kotasidis, Paul Deak, Joachim E. Wildberger, Roel Wierts, Iina Laitinen, Patricia Iozzo, Patrick Schrauwen^*, Vera B. Schrauwen-Hinderling^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

<bold>Objective: </bold>Accumulation of fat in the liver is associated with hepatic insulin resistance, as evidenced by a reduced insulin-induced suppression of endogenous glucose production (EGP). However, suppression of EGP has been proposed to be mainly a reflection of indirect insulin action.Hepatic glucose uptake in the postprandial state is another aspect of hepatic insulin sensitivity, which is seldom investigated. Here we sought to examine if hepatic steatosis is associated with a reduced hepatic glucose uptake under conditions of hyperglycemia and hyperinsulinemia. <bold>Methods: </bold>In this cross-sectional study, 15 participants with a range of liver fat content (0.9-18 %) as assessed by H-1-MRSwere recruited. Whole-body insulin sensitivity and insulin-induced suppression of EGP were measured by a two-step euglycemic-hyperinsulinemic clamp. A hyperglycemic-hyperinsulinemic clamp was used to measure hepatic and tissue-specific glucose uptake using a dynamic whole-body F-18-FDG PET protocol. <bold>Results: </bold>Under conditions of hyperglycemic-hyperinsulinemia, hepatic glucose uptake correlated strongly and inversely with liver fat content (r = -0.756, p < 0.001). Hepatic glucose uptake also correlated with insulin-stimulated EGP suppression (r = 0.616, p = 0.015). Adipose tissue insulin sensitivity was negatively associated with liver fat content and positively with hepatic, skeletal muscle, and adipose tissue glucose uptake. <bold>Conclusion: </bold>We show that another aspect of hepatic insulin resistance, namely the ability of insulin to stimulate hepatic glucose uptake under hyperglycemic conditions, is negatively associated with hepatic fat content. This suggests that hepatic glucose uptake is another factor that may be important in Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) and the risk for type 2 diabetes, and needs further investigation.

Original language	English
Article number	112288
Number of pages	9
Journal	Diabetes Research and Clinical Practice
Volume	225
DOIs	https://doi.org/10.1016/j.diabres.2025.112288
Publication status	Published - 1 Jul 2025

Keywords

18F-FDG PET imaging
Adipose tissue insulin sensitivity
Endogenous glucose production (EGP)
Hepatic fat content
Hepatic glucose uptake
Hyperglycemic-hyperinsulinemic clamp
Hepatic insulin resistance
Metabolic dysfunction Associated Steatotic
Liver Disease (MASLD)
Tissue-specific glucose uptake
Type 2 diabetes risk
INSULIN-RESISTANCE
LIVER
DISEASE
METABOLISM
QUANTIFICATION
CLAMP
RISK

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Basset-Sagarminaga, J., van de Weijer, T., Koene, E., den Kamp-Bruls, Y. M. H. O., Phielix, E., Brouwers, K., Springer, S., Johansson, E., Johansson, L., Kotasidis, F., Deak, P., Wildberger, J. E., Wierts, R., Laitinen, I., Iozzo, P., Schrauwen, P., & Schrauwen-Hinderling, V. B. (2025). Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach. Diabetes Research and Clinical Practice, 225, Article 112288. https://doi.org/10.1016/j.diabres.2025.112288

@article{4c634a139bae48cb93c392c956e5ffc7,

title = "Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach",

abstract = "Objective: Accumulation of fat in the liver is associated with hepatic insulin resistance, as evidenced by a reduced insulin-induced suppression of endogenous glucose production (EGP). However, suppression of EGP has been proposed to be mainly a reflection of indirect insulin action.Hepatic glucose uptake in the postprandial state is another aspect of hepatic insulin sensitivity, which is seldom investigated. Here we sought to examine if hepatic steatosis is associated with a reduced hepatic glucose uptake under conditions of hyperglycemia and hyperinsulinemia. Methods: In this cross-sectional study, 15 participants with a range of liver fat content (0.9-18 \%) as assessed by H-1-MRSwere recruited. Whole-body insulin sensitivity and insulin-induced suppression of EGP were measured by a two-step euglycemic-hyperinsulinemic clamp. A hyperglycemic-hyperinsulinemic clamp was used to measure hepatic and tissue-specific glucose uptake using a dynamic whole-body F-18-FDG PET protocol. Results: Under conditions of hyperglycemic-hyperinsulinemia, hepatic glucose uptake correlated strongly and inversely with liver fat content (r = -0.756, p < 0.001). Hepatic glucose uptake also correlated with insulin-stimulated EGP suppression (r = 0.616, p = 0.015). Adipose tissue insulin sensitivity was negatively associated with liver fat content and positively with hepatic, skeletal muscle, and adipose tissue glucose uptake. Conclusion: We show that another aspect of hepatic insulin resistance, namely the ability of insulin to stimulate hepatic glucose uptake under hyperglycemic conditions, is negatively associated with hepatic fat content. This suggests that hepatic glucose uptake is another factor that may be important in Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) and the risk for type 2 diabetes, and needs further investigation.",

keywords = "18F-FDG PET imaging, Adipose tissue insulin sensitivity, Endogenous glucose production (EGP), Hepatic fat content, Hepatic glucose uptake, Hyperglycemic-hyperinsulinemic clamp, Hepatic insulin resistance, Metabolic dysfunction Associated Steatotic, Liver Disease (MASLD), Tissue-specific glucose uptake, Type 2 diabetes risk, INSULIN-RESISTANCE, LIVER, DISEASE, METABOLISM, QUANTIFICATION, CLAMP, RISK",

author = "Jeremy Basset-Sagarminaga and \{van de Weijer\}, Tineke and Evi Koene and \{den Kamp-Bruls\}, \{Yvonne M. H. Op\} and Esther Phielix and Kim Brouwers and Sam Springer and Edvin Johansson and Lars Johansson and Fotis Kotasidis and Paul Deak and Wildberger, \{Joachim E.\} and Roel Wierts and Iina Laitinen and Patricia Iozzo and Patrick Schrauwen and Schrauwen-Hinderling, \{Vera B.\}",

year = "2025",

month = jul,

day = "1",

doi = "10.1016/j.diabres.2025.112288",

language = "English",

volume = "225",

journal = "Diabetes Research and Clinical Practice",

issn = "0168-8227",

publisher = "Elsevier Ireland Ltd",

}

Basset-Sagarminaga, J, van de Weijer, T , Koene, E , den Kamp-Bruls, YMHO , Phielix, E, Brouwers, K, Springer, S, Johansson, E, Johansson, L, Kotasidis, F, Deak, P, Wildberger, JE , Wierts, R, Laitinen, I, Iozzo, P, Schrauwen, P & Schrauwen-Hinderling, VB 2025, 'Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach', Diabetes Research and Clinical Practice, vol. 225, 112288. https://doi.org/10.1016/j.diabres.2025.112288

Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach. / Basset-Sagarminaga, Jeremy; van de Weijer, Tineke ; Koene, Evi et al.
In: Diabetes Research and Clinical Practice, Vol. 225, 112288, 01.07.2025.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach

AU - Basset-Sagarminaga, Jeremy

AU - van de Weijer, Tineke

AU - Koene, Evi

AU - den Kamp-Bruls, Yvonne M. H. Op

AU - Phielix, Esther

AU - Brouwers, Kim

AU - Springer, Sam

AU - Johansson, Edvin

AU - Johansson, Lars

AU - Kotasidis, Fotis

AU - Deak, Paul

AU - Wildberger, Joachim E.

AU - Wierts, Roel

AU - Laitinen, Iina

AU - Iozzo, Patricia

AU - Schrauwen, Patrick

AU - Schrauwen-Hinderling, Vera B.

PY - 2025/7/1

Y1 - 2025/7/1

N2 - Objective: Accumulation of fat in the liver is associated with hepatic insulin resistance, as evidenced by a reduced insulin-induced suppression of endogenous glucose production (EGP). However, suppression of EGP has been proposed to be mainly a reflection of indirect insulin action.Hepatic glucose uptake in the postprandial state is another aspect of hepatic insulin sensitivity, which is seldom investigated. Here we sought to examine if hepatic steatosis is associated with a reduced hepatic glucose uptake under conditions of hyperglycemia and hyperinsulinemia. Methods: In this cross-sectional study, 15 participants with a range of liver fat content (0.9-18 %) as assessed by H-1-MRSwere recruited. Whole-body insulin sensitivity and insulin-induced suppression of EGP were measured by a two-step euglycemic-hyperinsulinemic clamp. A hyperglycemic-hyperinsulinemic clamp was used to measure hepatic and tissue-specific glucose uptake using a dynamic whole-body F-18-FDG PET protocol. Results: Under conditions of hyperglycemic-hyperinsulinemia, hepatic glucose uptake correlated strongly and inversely with liver fat content (r = -0.756, p < 0.001). Hepatic glucose uptake also correlated with insulin-stimulated EGP suppression (r = 0.616, p = 0.015). Adipose tissue insulin sensitivity was negatively associated with liver fat content and positively with hepatic, skeletal muscle, and adipose tissue glucose uptake. Conclusion: We show that another aspect of hepatic insulin resistance, namely the ability of insulin to stimulate hepatic glucose uptake under hyperglycemic conditions, is negatively associated with hepatic fat content. This suggests that hepatic glucose uptake is another factor that may be important in Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) and the risk for type 2 diabetes, and needs further investigation.

AB - Objective: Accumulation of fat in the liver is associated with hepatic insulin resistance, as evidenced by a reduced insulin-induced suppression of endogenous glucose production (EGP). However, suppression of EGP has been proposed to be mainly a reflection of indirect insulin action.Hepatic glucose uptake in the postprandial state is another aspect of hepatic insulin sensitivity, which is seldom investigated. Here we sought to examine if hepatic steatosis is associated with a reduced hepatic glucose uptake under conditions of hyperglycemia and hyperinsulinemia. Methods: In this cross-sectional study, 15 participants with a range of liver fat content (0.9-18 %) as assessed by H-1-MRSwere recruited. Whole-body insulin sensitivity and insulin-induced suppression of EGP were measured by a two-step euglycemic-hyperinsulinemic clamp. A hyperglycemic-hyperinsulinemic clamp was used to measure hepatic and tissue-specific glucose uptake using a dynamic whole-body F-18-FDG PET protocol. Results: Under conditions of hyperglycemic-hyperinsulinemia, hepatic glucose uptake correlated strongly and inversely with liver fat content (r = -0.756, p < 0.001). Hepatic glucose uptake also correlated with insulin-stimulated EGP suppression (r = 0.616, p = 0.015). Adipose tissue insulin sensitivity was negatively associated with liver fat content and positively with hepatic, skeletal muscle, and adipose tissue glucose uptake. Conclusion: We show that another aspect of hepatic insulin resistance, namely the ability of insulin to stimulate hepatic glucose uptake under hyperglycemic conditions, is negatively associated with hepatic fat content. This suggests that hepatic glucose uptake is another factor that may be important in Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) and the risk for type 2 diabetes, and needs further investigation.

KW - 18F-FDG PET imaging

KW - Adipose tissue insulin sensitivity

KW - Endogenous glucose production (EGP)

KW - Hepatic fat content

KW - Hepatic glucose uptake

KW - Hyperglycemic-hyperinsulinemic clamp

KW - Hepatic insulin resistance

KW - Metabolic dysfunction Associated Steatotic

KW - Liver Disease (MASLD)

KW - Tissue-specific glucose uptake

KW - Type 2 diabetes risk

KW - INSULIN-RESISTANCE

KW - LIVER

KW - DISEASE

KW - METABOLISM

KW - QUANTIFICATION

KW - CLAMP

KW - RISK

U2 - 10.1016/j.diabres.2025.112288

DO - 10.1016/j.diabres.2025.112288

M3 - Article

SN - 0168-8227

VL - 225

JO - Diabetes Research and Clinical Practice

JF - Diabetes Research and Clinical Practice

M1 - 112288

ER -

Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18 F-FDG PET approach

Abstract

Keywords

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