Jiang Aijun, Feng Zhanrong, Yuan Lu, Zhang Ying, Li Qian, She Yuqing
Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, 21006, Jiangsu, China.
Department of Endocrinology, Shuyang Hospital of Traditional Chinese Medicine, 28 Shanghai Middle Road, Shuyang, Suqian, Jiangsu, China.
Diabetol Metab Syndr. 2021 Mar 25;13(1):34. doi: 10.1186/s13098-021-00652-5.
Asprosin, a novel adipokine that raises glucose levels and stimulates appetite, has been proved to be pathologically increased in populations predisposed to type 2 diabetes mellitus (T2DM), obesity, and cardiovascular diseases. The mechanisms of sodium-glucose co-transporter-2 (SGLT2) inhibitors for hypoglycemic effect and cardiovascular protection have not been fully clarified. Therefore, we conducted this study to assess change in the levels of serum asprosin after treatment with SGLT2 inhibitors in patients with newly diagnosed T2DM.
This study was a randomized, double-blind, placebo-controlled trial. A total of 29 participants with newly diagnosed T2DM with body mass index (BMI) ≥ 23.0 kg/m and haemoglobin A1c (HbA1c) levels of 58-85 mmol/mol (7.5-10%) were randomized to SGLT2 inhibitors dapagliflozin 10 mg/d (n = 19) or placebo (n = 10) treatment for 24 weeks. We analyzed asprosin concentrations by an enzyme-linked immunosorbent assay. Besides, body weight, BMI, HbA1c, fasting plasma glucose (FPG), and lipid levels were measured at baseline and 24 weeks.
At 24 weeks, participants with SGLT2 inhibitors treatment exhibited lower levels of serum asprosin (22.87 vs 45.06 ng/ml in the placebo group; P < 0.001) after adjusting for baseline values. The levels of body weight, BMI, HbA1c, FPG, and triglyceride (TG) were decreased, while high density lipoprotein-cholesterol (HDL-C) was increased after SGLT2 inhibitors dapagliflozin treatment compared with placebo (P < 0.05 for all). Low density lipoprotein-cholesterol (LDL-C) and total cholesterol (TC) levels were unchanged in the SGLT2 inhibitors group and placebo group. No statistical correlation was found between the levels of serum asprosin and body weight, BMI, HbA1c, FPG, and lipid levels during the SGLT2 inhibitor dapagliflozin treatment.
These findings indicated that SGLT2 inhibitors can lower serum asprosin levels and improve glucolipid and weight in patients with newly diagnosed T2DM, which may benefit the cardiovascular system. Trial registration CTR20131268; Registered 20 March 2014 CTR20150102; Registered 03 March 2015. http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml .
阿扑脂蛋白是一种新型脂肪因子,可升高血糖水平并刺激食欲,已被证实在易患2型糖尿病(T2DM)、肥胖症和心血管疾病的人群中其病理水平会升高。钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂的降糖作用和心血管保护机制尚未完全阐明。因此,我们开展了这项研究,以评估新诊断的T2DM患者接受SGLT2抑制剂治疗后血清阿扑脂蛋白水平的变化。
本研究为一项随机、双盲、安慰剂对照试验。共有29例新诊断的T2DM患者,其体重指数(BMI)≥23.0kg/m²,糖化血红蛋白(HbA1c)水平为58 - 85mmol/mol(7.5 - 10%),被随机分为SGLT2抑制剂达格列净10mg/d治疗组(n = 19)或安慰剂组(n = 10),治疗24周。我们采用酶联免疫吸附测定法分析阿扑脂蛋白浓度。此外,在基线和24周时测量体重、BMI、HbA1c、空腹血糖(FPG)和血脂水平。
在24周时,校正基线值后,接受SGLT2抑制剂治疗的患者血清阿扑脂蛋白水平较低(安慰剂组为45.06ng/ml,治疗组为22.87ng/ml;P < 0.001)。与安慰剂相比,SGLT2抑制剂达格列净治疗后体重、BMI、HbA1c、FPG和甘油三酯(TG)水平降低,而高密度脂蛋白胆固醇(HDL-C)升高(所有P < 0.05)。SGLT2抑制剂组和安慰剂组的低密度脂蛋白胆固醇(LDL-C)和总胆固醇(TC)水平无变化。在SGLT2抑制剂达格列净治疗期间,血清阿扑脂蛋白水平与体重、BMI、HbA1c、FPG和血脂水平之间未发现统计学相关性。
这些发现表明,SGLT2抑制剂可降低新诊断的T2DM患者的血清阿扑脂蛋白水平,改善糖脂代谢和体重,这可能对心血管系统有益。试验注册号CTR20131268;于2014年3月20日注册CTR20150102;于2015年3月3日注册。http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml 。