Hayashi Toshiyuki, Fukui Tomoyasu, Nakanishi Noriko, Yamamoto Saki, Tomoyasu Masako, Osamura Anna, Ohara Makoto, Yamamoto Takeshi, Ito Yasuki, Hirano Tsutomu
Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
Reagent R&D department, Denka Seiken Co., Ltd., Nihonbashi Mitsui Tower, 1-1, Nihonbashi-Muromachi 2-chome, Chuo-ku, Tokyo, 103-8338, Japan.
Cardiovasc Diabetol. 2017 Jan 13;16(1):8. doi: 10.1186/s12933-016-0491-5.
The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies.
This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. Small dense (sd) LDL-C, large buoyant (lb) LDL-C, HDL2-C, and HDL3-C levels were determined using our established homogeneous assays. Statistical comparison of blood parameters before and after treatment was performed using the paired t test.
Dapagliflozin and sitagliptin comparably decreased HbA1c (0.75 and 0.63%, respectively). Dapagliflozin significantly decreased body weight, systolic blood pressure, plasma triglycerides and liver transaminases, and increased adiponectin; sitagliptin did not alter these measurements. LDL-C and apolipoprotein (apo) B were not significantly changed by dapagliflozin, whereas HDL-C and apo AI were increased. Dapagliflozin did not alter concentrations of LDL-C, but sd LDL-C decreased by 20% and lb LDL-C increased by 18%. Marked elevation in lb LDL-C (53%) was observed in individuals (n = 20) whose LDL-C was elevated by dapagliflozin. However, sd LDL-C remained suppressed (20%). Dapagliflozin increased HDL2-C by 18% without affecting HDL3-C. Sitagliptin did not alter plasma lipids or lipoprotein subspecies.
A SGLT-2 inhibitor, dapagliflozin suppresses potent atherogenic sd LDL-C and increased HDL2-C, a favorable cardiometabolic marker. Although LDL-C levels are elevated by treatment with dapagliflozin, this was due to increased concentrations of the less atherogenic lb LDL-C. However, these findings were not observed after treatment with dipeptidyl peptidase-4 inhibitor, sitagliptin. Trial registration UMIN Clinical Trials Registry (UMIN000020984).
据报道，钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂可使低密度脂蛋白（LDL）和高密度脂蛋白（HDL）胆固醇（C）均升高。本研究旨在确定SGLT-2抑制剂如何影响LDL和HDL-C亚类。
这项单中心、开放标签、随机、前瞻性研究纳入了80例正在服用口服降糖药的2型糖尿病患者。患者被分配接受达格列净（n = 40）或西他列汀（n = 40）作为附加治疗。在干预前和干预12周后采集空腹血样。使用我们建立的均相分析法测定小而密（sd）LDL-C、大而轻（lb）LDL-C、HDL2-C和HDL3-C水平。采用配对t检验对治疗前后的血液参数进行统计学比较。
达格列净和西他列汀降低糖化血红蛋白（HbA1c）的效果相当（分别为0.75%和0.63%）。达格列净显著降低体重、收缩压、血浆甘油三酯和肝转氨酶，并增加脂联素；西他列汀未改变这些指标。达格列净对LDL-C和载脂蛋白（apo）B无显著影响，而HDL-C和apo AI升高。达格列净未改变LDL-C浓度，但sd LDL-C降低了20%，lb LDL-C升高了18%。在LDL-C因达格列净而升高的个体（n = 20）中观察到lb LDL-C显著升高（53%）。然而，sd LDL-C仍受到抑制（20%）。达格列净使HDL2-C升高了18%，而未影响HDL3-C。西他列汀未改变血浆脂质或脂蛋白亚类。
SGLT-2抑制剂达格列净可抑制具有强致动脉粥样硬化作用的sd LDL-C，并升高HDL2-C，HDL2-C是一种有利的心脏代谢标志物。虽然达格列净治疗会使LDL-C水平升高，但这是由于致动脉粥样硬化作用较弱的lb LDL-C浓度增加所致。然而，二肽基肽酶-4抑制剂西他列汀治疗后未观察到这些结果。试验注册号：日本大学医学情报网临床试验注册中心（UMIN000020984）。
