PMID- 32886301 OWN - NLM STAT- MEDLINE DCOM- 20210825 LR - 20210825 IS - 1860-2002 (Electronic) IS - 1536-1632 (Print) IS - 1536-1632 (Linking) VI - 23 IP - 1 DP - 2021 Feb TI - [(18)F]FDG Uptake in Adipose Tissue Is Not Related to Inflammation in Type 2 Diabetes Mellitus. PG - 117-126 LID - 10.1007/s11307-020-01538-0 [doi] AB - PURPOSE: 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]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 [(18)F]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, [(18)F]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 [(18)F]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 [(18)F]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 [(18)F]FDG uptake in VAT was not related to CD68(+) macrophage infiltration, and IL-1ss and IL-6 mRNA expression levels. Ex vivo VAT [(18)F]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 [(18)F]FDG uptake in VAT from patients with T2DM is positively correlated with adiponectin levels and inversely with IR. Ex vivo [(18)F]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 [(18)F]FDG uptake as a marker for AT inflammation. FAU - Reijrink, Melanie AU - Reijrink M AUID- ORCID: 0000-0001-9447-7333 AD - Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, HP AA41, Hanzeplein 1, 9700RB, Groningen, The Netherlands. m.reijrink@umcg.nl. FAU - de Boer, Stefanie A AU - de Boer SA AD - Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, HP AA41, Hanzeplein 1, 9700RB, Groningen, The Netherlands. FAU - Antunes, Ines F AU - Antunes IF AD - Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Spoor, Daan S AU - Spoor DS AD - Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Lodewijk, Monique E AU - Lodewijk ME AD - Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Mastik, Mirjam F AU - Mastik MF AD - Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Boellaard, Ronald AU - Boellaard R AD - Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. AD - Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center-VU Medical Center, Amsterdam, the Netherlands. FAU - Greuter, Marcel J W AU - Greuter MJW AD - Department of Robotics and Mechatronics Biomedical Technology and Technical Medicine (MIRA), University of Twente, Enschede, the Netherlands. AD - Department of Radiology, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Benjamens, Stan AU - Benjamens S AD - Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Borra, Ronald J H AU - Borra RJH AD - Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. AD - Department of Radiology, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. AD - Department of Diagnostic Radiology, Medical Imaging Centre of Southwest Finland, University of Turku, Turku University Hospital, Turku, Finland. FAU - Slart, Riemer H J A AU - Slart RHJA AD - Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. AD - Department of Biomedical Photonic Imaging, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands. FAU - Hillebrands, Jan-Luuk AU - Hillebrands JL AD - Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Mulder, Douwe J AU - Mulder DJ AD - Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, HP AA41, Hanzeplein 1, 9700RB, Groningen, The Netherlands. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200904 PL - United States TA - Mol Imaging Biol JT - Molecular imaging and biology JID - 101125610 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD68 antigen, human) RN - 0 (Glucose Transporter Type 4) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) SB - IM MH - Adipose Tissue/*metabolism MH - Aged MH - Antigens, CD/metabolism MH - Antigens, Differentiation, Myelomonocytic/metabolism MH - Diabetes Mellitus, Type 2/*pathology MH - Female MH - Fluorodeoxyglucose F18/*metabolism MH - Glucose Transporter Type 4/metabolism MH - Humans MH - Inflammation/*pathology MH - Intra-Abdominal Fat/metabolism MH - Male MH - Middle Aged MH - Subcutaneous Fat/metabolism PMC - PMC7782394 OTO - NOTNLM OT - Adipose tissue OT - Diabetes OT - GLUT OT - Insulin resistance OT - [18F]FDG COIS- The authors declare that they have no conflict of interest. EDAT- 2020/09/05 06:00 MHDA- 2021/08/26 06:00 PMCR- 2020/09/04 CRDT- 2020/09/05 06:00 PHST- 2020/06/15 00:00 [received] PHST- 2020/08/27 00:00 [accepted] PHST- 2020/08/21 00:00 [revised] PHST- 2020/09/05 06:00 [pubmed] PHST- 2021/08/26 06:00 [medline] PHST- 2020/09/05 06:00 [entrez] PHST- 2020/09/04 00:00 [pmc-release] AID - 10.1007/s11307-020-01538-0 [pii] AID - 1538 [pii] AID - 10.1007/s11307-020-01538-0 [doi] PST - ppublish SO - Mol Imaging Biol. 2021 Feb;23(1):117-126. doi: 10.1007/s11307-020-01538-0. Epub 2020 Sep 4.