达格列净对早期2 型糖尿病肾病患者肾小球和肾小管功能的影响*

Effects of dapagliflozin on glomerular and tubular function in patients with early type 2 diabetic nephropathy*

摘要:

目的 通过钠-葡萄糖共转运蛋白2抑制剂达格列净治疗早期2型糖尿病肾病患者的肾小球和肾小管 功能相关指标及炎症标志物的变化，探讨其改善肾功能的可能机制。方法 选取2017年12月—2018年12月就诊 于吉林大学第二医院内分泌科的2型糖尿病肾脏疾病患者160例。将患者随机分为二甲双胍组（MET组）和达格 列净组（DAP组）。患者均进行生活因素干预、调脂、降尿蛋白等基础治疗，MET组给予盐酸二甲双胍1 500 mg/d， DAP组给予达格列净10 mg/d降糖治疗，均治疗3个月。收集患者基线和治疗3个月后的临床资料及相关生化指 标。ELISA法检测炎症标志物TNF-α、IL-6及HMGB1的水平。结果 两组患者治疗前临床资料比较，差异无 统计学意义（P >0.05）。达格列净组治疗前后BUN、Scr、ACR、CysC、尿α1-MG、TNF-α、尿β2-MG、尿 NAG、IL-6及HMGB1的差值较二甲双胍组低（P <0.05），eGFR的差值较二甲双胍组高（P <0.05）。两组患者 均未发生低血糖事件。结论 钠-葡萄糖共转运蛋白2抑制剂达格列净可能通过抗炎作用改善早期2型糖尿病肾病 患者肾小球和肾小管功能。

Abstract:

Objective To observe the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin on glomerular and renal tubular function via the changes of related indicators and inflammatory markers in patients with early type 2 diabetic nephropathy, and to explore the possible mechanisms of dapagliflozin in improving renal function. Methods A total of 160 patients with type 2 diabetes who were admitted to our department were selected. The enrolled patients were randomly divided into the metformin group (MET group) and the dapagliflozin group (DAP group). All patients were given basic treatments such as intervening life factors, lowering the lipid, and reducing urinary protein. Besides, the MET group and the DAP group were treated with metformin hydrochloride tablets (1,500 mg per day) and dapagliflozin tablets (10 mg per day) respectively to control the blood glucose for 3 months. The clinical data and relevant biochemical indicators of patients at baseline and 3 months after treatment were collected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and high mobility group box protein 1 (HMGB1) were detected by enzyme-linked immunosorbent assay (ELISA). The data were statistically analyzed using SPSS 22.0 software. Results There was no statistical difference in the clinical data at baseline between the MET group and DAP group (P > 0.05). The differences in levels of blood urea nitrogen (BUN), creatinine (Cr), albumin-to-creatinine ratio (ACR), cystatin C (CysC), urinary α1-microglobulin (α1-MG), urinary β2-microglobulin (β2-MG), urinary N-acetyl-beta-D-glucosaminidase (NAG), TNF- α, IL-6, and HMGB1 before and after the treatment in the DAP group were lower than those in the MET group (P < 0.05). However, the difference in estimated glomerular filtration rate (eGFR) before and after the treatment in the DAP group was higher than that in the MET group (P < 0.05). None of the patients in both groups developed hypoglycemia during the treatment. Conclusions The SGLT2 inhibitor dapagliflozin may improve the glomerular and tubular function of patients with early type 2 diabetic nephropathy through anti-inflammatory effects.