The effect of dapagliflozin treatment on epicardial adipose tissue volume

Takao Sato, Yoshifusa Aizawa, Sho Yuasa, Shohei Kishi, Koichi Fuse, Satoshi Fujita, Yoshio Ikeda, Hitoshi Kitazawa, Minoru Takahashi, Masahito Sato, Masaaki Okabe, Takao Sato, Yoshifusa Aizawa, Sho Yuasa, Shohei Kishi, Koichi Fuse, Satoshi Fujita, Yoshio Ikeda, Hitoshi Kitazawa, Minoru Takahashi, Masahito Sato, Masaaki Okabe

Abstract

Background: Glycosuria produced by sodium-glucose co-transporter-2 (SGLT-2) inhibitors is associated with weight loss. SGLT-2 inhibitors reportedly might reduce the occurrence of cardiovascular events. Epicardial adipose tissue (EAT) is a pathogenic fat depot that may be associated with coronary atherosclerosis. The present study evaluated the relationship between an SGLT-2 inhibitor (dapagliflozin) and EAT volume.

Methods: In 40 diabetes mellitus patients with coronary artery disease (10 women and 30 men; mean age of all 40 patients was 67.2 ± 5.4 years), EAT volume was compared prospectively between the dapagliflozin treatment group (DG; n = 20) and conventional treatment group (CTG; n = 20) during a 6-month period. EAT was defined as any pixel that had computed tomography attenuation of - 150 to - 30 Hounsfield units within the pericardial sac. Metabolic parameters, including HbA1c, tumor necrotic factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) levels, were measured at both baseline and 6-months thereafter.

Results: There were no significant differences at baseline of EAT volume and HbA1c, PAI-1, and TNF-α levels between the two treatment groups. After a 6-month follow-up, the change in HbA1c levels in the DG decreased significantly from 7.2 to 6.8%, while body weight decreased significantly in the DG compared with the CTG (- 2.9 ± 3.4 vs. 0.2 ± 2.4 kg, p = 0.01). At the 6-month follow-up, serum PAI-1 levels tended to decline in the DG. In addition, the change in the TNF-α level in the DG was significantly greater than that in the CTG (- 0.5 ± 0.7 vs. 0.03 ± 0.3 pg/ml, p = 0.03). Furthermore, EAT volume significantly decreased in the DG at the 6-month follow-up compared with the CTG (- 16.4 ± 8.3 vs. 4.7 ± 8.8 cm3, p = 0.01). Not only the changes in the EAT volume and body weight, but also those in the EAT volume and TNF-α level, showed significantly positive correlation.

Conclusion: Treatment with dapagliflozin might improve systemic metabolic parameters and decrease the EAT volume in diabetes mellitus patients, possibly contributing to risk reduction in cardiovascular events.

Keywords: Diabetes mellitus; Epicardial adipose tissue; SGLT-2 inhibitor.

Figures

Fig. 1
Fig. 1
Measurement of epicardial adipose tissue (EAT) volumes with multislice CT. a 3D image. EAT area was measured on each axial image from the lower surface of left pulmonary artery origin to the left ventricular apex, and total EAT volume was obtained from multiplying total EAT areas by the slice thickness. b Axial images. A region of interest (ROI) was manually placed along the visceral pericardium (left and middle panel). EAT was extracted on an axial image (green) (right panel)
Fig. 2
Fig. 2
The correlation between the change in EAT volume and those in body weight or inflammatory marker (TNF-α). a A positive significant correlation was observed between the changes in EAT volume and body weight. b A positive significant correlation was observed between the changes in EAT volume and TNF-α level

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