[18F]FDG Uptake in Adipose Tissue Is Not Related to Inflammation in Type 2 Diabetes Mellitus.,Molecular Imaging and Biology

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[18F]FDG Uptake in Adipose Tissue Is Not Related to Inflammation in Type 2 Diabetes Mellitus.
Molecular Imaging and Biology ( IF 3.0 ) Pub Date : 2020-09-04 , DOI: 10.1007/s11307-020-01538-0
Melanie Reijrink ₁ , Stefanie A de Boer ₁ , Ines F Antunes ₂ , Daan S Spoor ₂ , Hiddo J L Heerspink ₃ , Monique E Lodewijk ₄ , Mirjam F Mastik ₄ , Ronald Boellaard _{2,

5} , Marcel J W Greuter _{6,

7} , Stan Benjamens ₂ , Ronald J H Borra _{2,

7,

8} , Riemer H J A Slart _{2,

9} , Jan-Luuk Hillebrands ₄ , Douwe J Mulder ₁

Affiliation

Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, HP AA41, Hanzeplein 1, 9700RB, Groningen, The Netherlands.
Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center-VU Medical Center, Amsterdam, the Netherlands.
Department of Robotics and Mechatronics Biomedical Technology and Technical Medicine (MIRA), University of Twente, Enschede, the Netherlands.
Department of Radiology, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Diagnostic Radiology, Medical Imaging Centre of Southwest Finland, University of Turku, Turku University Hospital, Turku, Finland.
Department of Biomedical Photonic Imaging, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands.

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.

中文翻译：

[18F] 脂肪组织中的 FDG 摄取与 2 型糖尿病的炎症无关。

目的

2-脱氧-2- [ ¹⁸ F]氟- d -葡萄糖（[ ¹⁸ F] FDG）摄取的代谢活性的标记物，并因此被用于测量若干组织的炎症状态。这种放射性核素标记物通过葡萄糖转运蛋白 (GLUT) 转运通过细胞膜。本研究的目的是调查胰岛素抵抗 (IR) 或炎症是否在脂肪组织 (AT)中 [ ¹⁸ F] FDG 摄取中起作用。

程序

该研究由体内临床部分和离体机械部分组成。在临床部分，[ ¹⁸ F] FDG摄取腹部内脏AT（VAT）和皮下AT（SAT）使用PET / CT成像在44名早期患者2型糖尿病（T2DM）（63年龄[54-66确定] 年，HbA1c [6.3 ± 0.4 %]，HOMA-IR 5.1[3.1–8.5]）。用ELISA测量血浆水平。在机械部分，从 8 名患者获得的 AT 活组织检查与 [ ¹⁸ F] FDG离体孵育，然后进行放射自显影。接下来，进行 qRT-PCR 分析以确定 GLUT 和细胞因子 mRNA 表达水平。进行免疫组织化学以确定 CD68 ⁺ AT中的巨噬细胞浸润和GLUT4蛋白表达。

结果

T2DM 患者体内VAT [ ¹⁸ F] FDG 摄取与 HOMA-IR 呈负相关 ( r = − 0.32, p = 0.034)，与脂联素血浆水平呈正相关 ( r = 0.43, p = 0.003)。VAT 中的离体[ ¹⁸ F] FDG 摄取与 CD68 ⁺巨噬细胞浸润以及 IL-1ß 和 IL-6 mRNA 表达水平无关。体外VAT [ ¹⁸ F] FDG 摄取与 GLUT4 呈正相关（r = 0.83，p = 0.042），与 GLUT3 呈负相关（r = − 0.83，p = 0.042）并且与 GLUT1 mRNA 表达水平无关。