[18F]FDG Uptake in Adipose Tissue Is Not Related to Inflammation in Type 2 Diabetes Mellitus

Melanie Reijrink; Stefanie A de Boer; Ines F Antunes; Daan S Spoor; Hiddo J L Heerspink; Monique E Lodewijk; Mirjam F Mastik; Ronald Boellaard; Marcel J W Greuter; Stan Benjamens; Ronald J H Borra; Riemer H J A Slart; Jan-Luuk Hillebrands; Douwe J Mulder

doi:10.1007/s11307-020-01538-0

[¹⁸F]FDG Uptake in Adipose Tissue Is Not Related to Inflammation in Type 2 Diabetes Mellitus

Mol Imaging Biol. 2021 Feb;23(1):117-126. doi: 10.1007/s11307-020-01538-0. Epub 2020 Sep 4.

Authors

Melanie Reijrink¹, Stefanie A de Boer², Ines F Antunes³, Daan S Spoor³, Hiddo J L Heerspink⁴, Monique E Lodewijk⁵, Mirjam F Mastik⁵, Ronald Boellaard^{3

6}, Marcel J W Greuter^{7

8}, Stan Benjamens³, Ronald J H Borra^{3

8

9}, Riemer H J A Slart^{3

10}, Jan-Luuk Hillebrands⁵, Douwe J Mulder²

Affiliations

¹ Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, HP AA41, Hanzeplein 1, 9700RB, Groningen, The Netherlands. m.reijrink@umcg.nl.
² Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, HP AA41, Hanzeplein 1, 9700RB, Groningen, The Netherlands.
³ Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁶ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center-VU Medical Center, Amsterdam, the Netherlands.
⁷ Department of Robotics and Mechatronics Biomedical Technology and Technical Medicine (MIRA), University of Twente, Enschede, the Netherlands.
⁸ Department of Radiology, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁹ Department of Diagnostic Radiology, Medical Imaging Centre of Southwest Finland, University of Turku, Turku University Hospital, Turku, Finland.
¹⁰ Department of Biomedical Photonic Imaging, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands.

Abstract

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.

Keywords: Adipose tissue; Diabetes; GLUT; Insulin resistance; [18F]FDG.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / metabolism*
Aged
Antigens, CD / metabolism
Antigens, Differentiation, Myelomonocytic / metabolism
Diabetes Mellitus, Type 2 / pathology*
Female
Fluorodeoxyglucose F18 / metabolism*
Glucose Transporter Type 4 / metabolism
Humans
Inflammation / pathology*
Intra-Abdominal Fat / metabolism
Male
Middle Aged
Subcutaneous Fat / metabolism

Substances

Antigens, CD
Antigens, Differentiation, Myelomonocytic
CD68 antigen, human
Glucose Transporter Type 4
Fluorodeoxyglucose F18