Goto Yuka, Otsuka Yoshie, Ashida Kenji, Nagayama Ayako, Hasuzawa Nao, Iwata Shimpei, Hara Kento, Tsuruta Munehisa, Wada Nobuhiko, Motomura Seiichi, Tajiri Yuji, Nomura Masatoshi
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan.
Division of Endocrinology and Metabolism, Diabetes Center, Kurume Medical Center, Kokubu-machi, Kurume-city, Fukuoka, Japan.
Endocr Connect. 2020 Jul;9(7):599-606. doi: 10.1530/EC-20-0082.
It is currently unclear whether sodium-glucose co-transporter 2 (SGLT2) inhibitor administration can improve the insulin sensitivity as well as rapidly reduce plasma glucose concentrations in humans during the early phase of treatment initiation. This study aimed to investigate the effect of SGLT2 inhibitor on insulin sensitivity in the early phase of treatment initiation.
This single-center, open label, and single-arm prospective study recruited 20 patients (14 men) with type 2 diabetes mellitus (T2DM). We examined the patients' metabolic parameters before and 1 week after SGLT2 inhibitor (10 mg/day of empagliflozin) administration. The glucose infusion rate (GIR) was evaluated using the euglycemic hyperinsulinemic glucose clamp technique. Changes in laboratory and anthropometric parameters before and after SGLT2 inhibitor administration were analyzed according to the change in the GIR. The BMI, body fat amount, skeletal muscle amount, systolic blood pressure, and triglyceride level significantly decreased along with the treatment, while urinary glucose level and log GIR value significantly increased. Notably, changes in the GIR after SGLT2 inhibitor administration, which indicated improvement in peripheral insulin sensitivity, were negatively correlated with T2DM duration and positively with reduction in fluctuation of daily plasma glucose profiles before and after treatment.
SGLT2 inhibitor improved insulin sensitivity in the skeletal muscle independent of anthropometric changes. Patients with short duration of T2DM and insulin resistance can be good candidates for short-term SGLT2 inhibitor administration to improve insulin sensitivity in the skeletal muscle.
目前尚不清楚在开始治疗的早期阶段,给予钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是否能改善胰岛素敏感性以及迅速降低人体血浆葡萄糖浓度。本研究旨在探讨SGLT2抑制剂在治疗开始早期对胰岛素敏感性的影响。
这项单中心、开放标签、单臂前瞻性研究招募了20例2型糖尿病(T2DM)患者(14例男性)。我们在给予SGLT2抑制剂(恩格列净10毫克/天)之前和之后1周检查了患者的代谢参数。使用正常血糖高胰岛素葡萄糖钳夹技术评估葡萄糖输注率(GIR)。根据GIR的变化分析SGLT2抑制剂给药前后实验室和人体测量参数的变化。随着治疗,体重指数、体脂肪量、骨骼肌量、收缩压和甘油三酯水平显著降低,而尿葡萄糖水平和log GIR值显著升高。值得注意的是,SGLT2抑制剂给药后GIR的变化表明外周胰岛素敏感性改善,与T2DM病程呈负相关,与治疗前后每日血浆葡萄糖曲线波动的降低呈正相关。
SGLT2抑制剂改善骨骼肌胰岛素敏感性,与人体测量变化无关。T2DM病程短且有胰岛素抵抗的患者可能是短期给予SGLT2抑制剂以改善骨骼肌胰岛素敏感性的良好候选者。