The difference between steroid diabetes mellitus and type 2 diabetes mellitus: a whole-body 18F-FDG PET/CT study

Abstract

Aims Steroid diabetes mellitus (SDM) is a metabolic syndrome caused by an increase in glucocorticoids, and its pathogenesis is unclear. 18F-FDG PET/CT can reflect the glucose metabolism of tissues and organs under living conditions. Here, PET/CT imaging of SDM and type 2 diabetes mellitus (T2DM) rats was used to visualize changes in glucose metabolism in the main glucose metabolizing organs and investigate the pathogenesis of SDM. Methods SDM and T2DM rat models were established. During this time, PET/CT imaging was used to measure the %ID/g value of skeletal muscle and liver to evaluate glucose uptake. The pancreatic, skeletal muscle and liver were analyzed by immunohistochemistry. Results SDM rats showed increased fasting blood glucose and insulin levels, hyperplasia of islet α and β cells, increased FDG uptake in skeletal muscle accompanied by an up-regulation of PI3Kp85α, IRS-1, and GLUT4, no significant changes in liver uptake, and that glycogen storage in the liver and skeletal muscle increased. T2DM rats showed atrophy of pancreatic islet β cells and decreased insulin levels, significantly reduced FDG uptake and glycogen storage in skeletal muscle and liver. Conclusions The pathogenesis of SDM is different from that of T2DM. The increased glucose metabolism of skeletal muscle may be related to the increased compensatory secretion of insulin. Glucocorticoids promote the proliferation of islet α cells and cause an increase in gluconeogenesis in the liver, which may cause increased blood glucose.

Steroids May Be Associated With Extensive Skeletal Muscle Uptake of 18F-FDG

“…For the patients in whom well-known causes of ESMU were excluded, the incidence of ESMU was 0.259% (23/8866 scans) overall, 0.230% (12/5211 scans) in men, and 0.301% (11/3655 scans) in women. Our study demonstrated that ESMU may be associated with steroid administration history in humans, which was also observed in an animal study using rats 2 . In addition, we found that the mean SUV max of the measured skeletal muscle tended to decrease with the increase in the number of days elapsed since the last steroid administration (Fig.…”

“…Our study demonstrated that ESMU may be associated with steroid administration history in humans, which was also observed in an animal study using rats. 2 In addition, we found that the mean SUV max of the measured skeletal muscle tended to decrease with the increase in the number of days elapsed since the last steroid administration (Fig. 3).…”

“…11 Because 18 F-FDG has similar biochemical properties to glucose, it enters myocytes using a glucose transporter on the plasma membrane, is phosphorylated by hexokinase to 6-PO 4 -18 F-FDG, and remains in the myocytes. 2 Thus, elevated blood insulin levels lead to diffuse FDG uptake in skeletal muscle. 12,13 Qingqing Zhao et al reported that the pathogenesis of steroid diabetes mellitus differs from that of type 2 diabetes mellitus in rats, where glucocorticoids cause the proliferation of islet α cells and induce hyperglucagonemia, which leads to increased blood glucose levels and compensatory hyperplasia of islet β cells, 14,15 and β cells cause a compensatory increase in insulin secretion, resulting in a hyperinsulinemic state, which in turn causes upregulation (increased expression) of GLUT4 and increased FDG uptake in skeletal muscle.…”

“…There, glucose is transferred from the blood into muscle cells, increasing glucose accumulation in the muscle and decreasing blood glucose levels 11 . Because 18 F-FDG has similar biochemical properties to glucose, it enters myocytes using a glucose transporter on the plasma membrane, is phosphorylated by hexokinase to 6-PO 4 - 18 F-FDG, and remains in the myocytes 2 . Thus, elevated blood insulin levels lead to diffuse FDG uptake in skeletal muscle 12,13 …”

“…Moreover, it has been reported that steroid administration is associated with increased skeletal muscle FDG uptake in rats. 2 In the present study, we examined the association between skeletal muscle FDG uptake and steroid administration in humans when the previously known factors were not applicable.…”