Abstract
Purpose2-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).ProceduresThis 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.ResultsIn 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.ConclusionsIn 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.
Highlights
Abdominal obesity is strongly associated with the development of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and premature mortality, and represents a rapidly growing threat for public health [1, 2]
Adipose Tissue [18F]FDG Uptake In patients with T2DM, visceral AT (VAT)-SUVmean was significantly higher than subcutaneous AT (SAT)-SUVmean (0.62 [0.56–0.72] vs 0.36 [0.32–0.39], p G 0.001)
VATSUVmean was inversely associated with HOMA-insulin resistance (IR) (r = − 0.32, p = 0.034), while SAT-SUVmean was not associated with HOMA-IR (r = − 0.13, p = 0.40) (Fig. 1a)
Summary
Abdominal obesity is strongly associated with the development of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and premature mortality, and represents a rapidly growing threat for public health [1, 2]. Adipose tissue (AT) does provide storage of lipids and functions as an endocrine organ with adipocytes that are able to secrete pro-inflammatory (e.g., interleukin (IL)-6, IL-1ß) and anti-inflammatory (e.g., adiponectin) cytokines, mediators known as adipokines [3]. Macrophages and other immune-cells are distributed throughout the AT, and able to produce pro-inflammatory cytokines. Inflammatory processes are an important component of the development of CVD and, pro- and anti-inflammatory adipokines play a major role in the relation of AT and CVD risk [4]. AT macrophage infiltration plays an important role in the development of insulin resistance (IR) and, T2DM [7]. An increased VAT inflammatory state with exaggerated adipokine production might contribute to an increased risk for developing CVD in T2DM [8,9,10,11]. Inflammation is suspected to play a central role in AT dysfunction, to our knowledge, no validated in vivo method to assess the local inflammatory state of AT is currently available
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
