TY - JOUR
T1 - [18F]FDG Uptake in Adipose Tissue Is Not Related to Inflammation in Type 2 Diabetes Mellitus
AU - Reijrink, Melanie
AU - de Boer, Stefanie A.
AU - Antunes, Ines F.
AU - Spoor, Daan S.
AU - Heerspink, Hiddo J.L.
AU - Lodewijk, Monique E.
AU - Mastik, Mirjam F.
AU - Boellaard, Ronald
AU - Greuter, Marcel J.W.
AU - Benjamens, Stan
AU - Borra, Ronald J.H.
AU - Slart, Riemer H.J.A.
AU - Hillebrands, Jan Luuk
AU - Mulder, Douwe J.
N1 - Funding Information:
This study was supported by the Boehringer Ingelheim (Alkmaar, the Netherlands). Boehringer Ingelheim was not involved in the design and results of the study; collection, management, analysis and interpretation of data, writing of the report or the decision to submit the paper for publication. M.R. and S.B. were supported by the MD/PhD program of the Graduate School of Medical Sciences (GSMS) - UMCG. Acknowledgements
Funding Information:
We wish to thank the study participants, the general practitioner practices, R.A. Pol and P.H.J. Hemmer from the UMCG, Department of Surgery and M.G. Piersma-Wichers and H.L. Lutgers from CERTE Groningen.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Purpose: 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake is a marker of metabolic activity and is therefore used to measure the inflammatory state of several tissues. This radionuclide marker is transported through the cell membrane via glucose transport proteins (GLUTs). The aim of this study is to investigate whether insulin resistance (IR) or inflammation plays a role in [18F]FDG uptake in adipose tissue (AT). Procedures: This study consisted of an in vivo clinical part and an ex vivo mechanistic part. In the clinical part, [18F]FDG uptake in abdominal visceral AT (VAT) and subcutaneous AT (SAT) was determined using PET/CT imaging in 44 patients with early type 2 diabetes mellitus (T2DM) (age 63 [54–66] years, HbA1c [6.3 ± 0.4 %], HOMA-IR 5.1[3.1–8.5]). Plasma levels were measured with ELISA. In the mechanistic part, AT biopsies obtained from 8 patients were ex vivo incubated with [18F]FDG followed by autoradiography. Next, a qRT-PCR analysis was performed to determine GLUT and cytokine mRNA expression levels. Immunohistochemistry was performed to determine CD68+ macrophage infiltration and GLUT4 protein expression in AT. Results: In vivo VAT [18F]FDG uptake in patients with T2DM was inversely correlated with HOMA-IR (r = − 0.32, p = 0.034), and positively related to adiponectin plasma levels (r = 0.43, p = 0.003). Ex vivo [18F]FDG uptake in VAT was not related to CD68+ macrophage infiltration, and IL-1ß and IL-6 mRNA expression levels. Ex vivo VAT [18F]FDG uptake was positively related to GLUT4 (r = 0.83, p = 0.042), inversely to GLUT3 (r = − 0.83, p = 0.042) and not related to GLUT1 mRNA expression levels. Conclusions: In vivo [18F]FDG uptake in VAT from patients with T2DM is positively correlated with adiponectin levels and inversely with IR. Ex vivo [18F]FDG uptake in AT is associated with GLUT4 expression but not with pro-inflammatory markers. The effect of IR should be taken into account when interpreting data of [18F]FDG uptake as a marker for AT inflammation.
AB - Purpose: 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake is a marker of metabolic activity and is therefore used to measure the inflammatory state of several tissues. This radionuclide marker is transported through the cell membrane via glucose transport proteins (GLUTs). The aim of this study is to investigate whether insulin resistance (IR) or inflammation plays a role in [18F]FDG uptake in adipose tissue (AT). Procedures: This study consisted of an in vivo clinical part and an ex vivo mechanistic part. In the clinical part, [18F]FDG uptake in abdominal visceral AT (VAT) and subcutaneous AT (SAT) was determined using PET/CT imaging in 44 patients with early type 2 diabetes mellitus (T2DM) (age 63 [54–66] years, HbA1c [6.3 ± 0.4 %], HOMA-IR 5.1[3.1–8.5]). Plasma levels were measured with ELISA. In the mechanistic part, AT biopsies obtained from 8 patients were ex vivo incubated with [18F]FDG followed by autoradiography. Next, a qRT-PCR analysis was performed to determine GLUT and cytokine mRNA expression levels. Immunohistochemistry was performed to determine CD68+ macrophage infiltration and GLUT4 protein expression in AT. Results: In vivo VAT [18F]FDG uptake in patients with T2DM was inversely correlated with HOMA-IR (r = − 0.32, p = 0.034), and positively related to adiponectin plasma levels (r = 0.43, p = 0.003). Ex vivo [18F]FDG uptake in VAT was not related to CD68+ macrophage infiltration, and IL-1ß and IL-6 mRNA expression levels. Ex vivo VAT [18F]FDG uptake was positively related to GLUT4 (r = 0.83, p = 0.042), inversely to GLUT3 (r = − 0.83, p = 0.042) and not related to GLUT1 mRNA expression levels. Conclusions: In vivo [18F]FDG uptake in VAT from patients with T2DM is positively correlated with adiponectin levels and inversely with IR. Ex vivo [18F]FDG uptake in AT is associated with GLUT4 expression but not with pro-inflammatory markers. The effect of IR should be taken into account when interpreting data of [18F]FDG uptake as a marker for AT inflammation.
KW - Adipose tissue
KW - Diabetes
KW - GLUT
KW - Insulin resistance
KW - [F]FDG
UR - http://www.scopus.com/inward/record.url?scp=85090310491&partnerID=8YFLogxK
U2 - 10.1007/s11307-020-01538-0
DO - 10.1007/s11307-020-01538-0
M3 - Article
C2 - 32886301
AN - SCOPUS:85090310491
VL - 23
SP - 117
EP - 126
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
SN - 1536-1632
IS - 1
ER -