Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study.
Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study.
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DOI：
10.1186/s12933-017-0516-8
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发表时间：
2017-03-03
影响因子：
9.3
通讯作者：
Ogawa Y
中科院分区：
文献类型：
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作者：
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
心外膜脂肪（EF）的积累与增加的心脏代谢风险和冠状动脉事件相关，独立于传统的心血管危险因素。因此，EF容量（EFV）的减少可能与降低心脏代谢风险和未来心血管事件有关。钠-葡萄糖共转运蛋白-2 （SGLT2）抑制剂可降低2型糖尿病患者的体脂，包括内脏脂肪和心血管事件。然而，SGLT2抑制剂是否能降低EFV仍不清楚。HbA1c 6.5-9.0%、体重指数(BMI, kg/m2)≥25.0的2型糖尿病患者入组。参与者每天服用蔗糖格列净2.5毫克，并且耐受剂量增加到每天5.0毫克。磁共振成像测量EFV[中位数（四分位间距），cm3]。主要终点是12周时EFV的下降。在基线和12周时测定腹部计算机断层扫描测量的内脏脂肪面积（VFA, cm2）和肝脏衰减指数（LAI），以及全身双能x线吸收仪测量的骨骼肌指数（SMI）和体脂（%）。19例患者（平均年龄：55±12岁，女性占26%）完成了本研究。鲁西格列净治疗可显著降低12周EFV[117（96-136）至111 (88-134),p = 0.048]。12周时，糖格列净显著降低了体重、BMI、收缩压和舒张压、HbA1c、空腹血糖、胰岛素、稳态模型评估-胰岛素抵抗（HOMA-IR）、甘油三酯、SMI和体脂。EFV的降低与c反应蛋白的降低呈显著相关（r = 0.493, p = 0.019）。糖格列净治疗后VFA和LAI均未显著降低。未观察到严重的不良事件。我们的数据表明，在改善日本2型糖尿病患者的全身微炎症和减轻体重的同时，鲁西格列净可以降低EFV。服用SGLT2抑制剂后肌肉质量的减少可能需要特别注意。试用注册：min.ac.jp, UMIN000019072
Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV. Type 2 diabetic patients with HbA1c 6.5–9.0% and body mass index (BMI, kg/m2) ≥25.0 were enrolled in this single arm pilot study. Participants were administered luseogliflozin 2.5 mg daily and the dosage was tolerated to be increased up to 5.0 mg daily. EFV [median (interquartile range), cm3] was measured by magnetic resonance imaging. Primary endpoint was the decrease in EFV at 12 weeks. Visceral fat area (VFA, cm2) and liver attenuation index (LAI) measured by the abdominal computed tomography, and skeletal muscle index (SMI) and body fat (%) measured by the whole body dual-energy X-ray absorptiometry were also determined at baseline and at 12 weeks. Nineteen patients (mean age: 55 ± 12 years; 26% female) completed this study. Luseogliflozin treatment significantly reduced EFV at 12 weeks [117 (96–136) to 111 (88–134), p = 0.048]. The body weight, BMI, systolic and diastolic blood pressure, HbA1c, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, SMI, and body fat were significantly reduced by luseogliflozin at 12 weeks. The reduction of EFV was significantly correlated with the reduction of C-reactive protein (r = 0.493, p = 0.019). Neither VFA nor LAI were significantly reduced by the luseogliflozin treatment. No severe adverse events were observed. Our data suggest that luseogliflozin could reduce the EFV in parallel with the improvement of systemic micro-inflammation and the reduction of body weight in Japanese patients with type 2 diabetes. The reduction of muscle mass after the administration of SGLT2 inhibitors may require a particular attention. Trial registration umin.ac.jp, UMIN000019072