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.
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.
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.
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.
Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, Sata M. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2013;33:1077–84. CrossRefPubMed
Okamoto A, Yokokawa H, Sanada H, Naito T. Changes in levels of biomarkers associated with adipocyte function and insulin and glucagon kinetics during treatment with dapagliflozin among obese type 2 diabetes mellitus patients. Drugs RD. 2016;16:255–61. CrossRef
Honda Y, Imajo K, Kato T, Kessoku T, Ogawa Y, Tomeno W, Kato S, Mawatari H, Fujita K, Yoneda M, Saito S, Nakajima A. The selective SGLT2 inhibitor ipragliflozin has therapeutic effect on nonalcoholic steatohepatitis in mice. PLoS ONE. 2016. https://doi.org/10.1371/journal.pone.0146337.
Bolinder J, Ljunggren Ö, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012;97:1020–31. CrossRefPubMed
Dutour A, Abdesselam I, Ancel P, Kober F, Mrad G, Darmon P, Ronsin O, Pradel V, Lesavre N, Martin JC, Jacquier A, Lefur Y, Bernard M, Gaborit B. Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: prospective randomized clinical trial using magnetic resonance imaging and spectroscopy. Diabetes Obes Metab. 2016;18:882–91. CrossRefPubMed
Xu L, Nagata N, Nagashimada M, Zhuge F, Ni Y, Chen G, Mayoux E, Kaneko S, Ota T. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing M2 macrophages in diet-induced obese mice. EBioMedicine. 2017;20:137–49. CrossRefPubMedPubMedCentral
Bouchi R, Terashima M, Sasahara Y, Asakawa M, Fukuda T, Takeuchi T, Nakano Y, Murakami M, Minami I, Izumiyama H, Hashimoto K, Yoshimoto T, Ogawa Y. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017;16:32. CrossRefPubMedPubMedCentral
Fukuda T, Bouchi R, Terashima M, Sasahara Y, Asakawa M, Takeuchi T, Nakano Y, Murakami M, Minami I, Izumiyama H, Hashimoto K, Yoshimoto T, Ogawa Y. Ipragliflozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: a pilot study. Diabetes Ther. 2017;8:851–61. CrossRefPubMedPubMedCentral
Díaz-Rodríguez E, Agra RM, Fernández ÁL, Adrio B, García-Caballero T, González-Juanatey JR, Eiras S. Novel effects of dapagliflozin on epicardial adipose tissue with insulin resistance, high levels of inflammatory chemokines production and low differentiation ability. Cardiovasc Res. 2017. https://doi.org/10.1093/cvr/cvx186. PubMed
Komiya C, Tsuchiya K, Shiba K, Miyachi Y, Furuke S, Shimazu N, Yamaguchi S, Kanno K, Ogawa Y. Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction. PLoS ONE. 2016;11:e0151511. https://doi.org/10.1371/journal.pone.0151511. CrossRefPubMedPubMedCentral
Hayashi T, Fukui T, Nakanishi N, Yamamoto S, Tomoyasu M, Osamura A, Ohara M, Yamamoto T, Ito Y, Hirano T. Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin. Cardiovasc Diabetol. 2017;16:8. CrossRefPubMedPubMedCentral
St-Pierre AC, Cantin B, Dagenais GR, Mauriège P, Bernard PM, Després JP, Lamarche B. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 2005;25:553–9. CrossRefPubMed
Sacks HS, Fain JN, Cheema P, Bahouth SW, Garrett E, Wolf RY, Wolford D, Samaha J. Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: changes associated with pioglitazone. Diabetes Care. 2011;34:730–3. CrossRefPubMedPubMedCentral
Iacobellis G, Mohseni M, Bianco S. Liraglutide causes massive and rapid reduction of cardiac fat independent of weight loss in type 2 diabetes. In: The proceedings of 75th American Diabetes Association, Scientific Sessions, LBA-5785, Boston, USA, 2015.
Bonner C, Kerr-Conte J, Gmyr V, Queniat G, Moerman E, Thévenet J, Beaucamps C, Delalleau N, Popescu I, Malaisse WJ, Sener A, Deprez B, Abderrahmani A, Staels B, Pattou F. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21:512–7. CrossRefPubMed
Mahabadi AA, Berg MH, Lehmann N, Kälsch H, Bauer M, Kara K, Dragano N, Moebus S, Jöckel KH, Erbel R, Möhlenkamp S. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol. 2013;61:1388–95. CrossRefPubMed
Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013;14(382):941–50. CrossRef
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