Sodium-glucose cotransporter 2 (SGLT- 2) inhibitors exert cardiovascular and kidney-protective effects in people with diabetes. Attenuation of inflammation could be important for systemic protection. The lectin pathway of complement system activation is linked to diabetic nephropathy. We hypothesized that SGLT-2 inhibitors lower the circulating level of pattern-recognition molecules of the lectin cascade and attenuate systemic complement activation. Analysis of paired plasma samples from the DapKid crossover intervention study where patients with type 2 diabetes mellitus (T2DM) and albuminuria were treated with dapagliflozin and placebo for 12 weeks (10 mg/day, n=36). ELISA was used to determine concentrations of collectin kidney 1 (CL-K1), collectin liver 1 (CL-L1), mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), the anaphylatoxin complement factor 3a (C3a), the stable C3 split product C3dg and the membrane attack complex (sC5b-9). As published before, dapagliflozin treatment lowered Hba from 74 (14.9) mmol/mol to 66 (13.9) mmol/mol (p<0.0001), and the urine albumin/creatinine ratio from 167.8 mg/g to 122.5 mg/g (p<0.0001). Plasma concentrations of CL-K1, CL-L1, MBL, and MASP-2 did not change significantly after dapagliflozin treatment (P>0.05) compared to placebo treatment. The plasma levels of C3a (P<0.05) and C3dg (P<0.01) increased slightly but significantly, 0.6 [0.2] units/mL and 76 [52] units/mL respectively, after dapagliflozin treatment. The C9-associated neoepitope in C5b-9 did not change in plasma concentration by dapagliflozin (P>0.05). In patients with type 2 diabetes and albuminuria, SGLT-2 inhibition resulted in modest C3 activation in plasma, likely not driven by primary changes in circulating collectins and not resulting in changes in membrane attack complex. Based on systemic analyses, organ-specific local protective effects of gliflozins against complement activation cannot be excluded.

中文翻译：

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达格列净对 2 型糖尿病伴白蛋白尿患者血浆中集合素和补体激活的影响：来自 DapKid 队列的数据

钠-葡萄糖协同转运蛋白 2 (SGLT-2) 抑制剂对糖尿病患者具有心血管和肾脏保护作用。炎症的减弱对于系统保护可能很重要。补体系统激活的凝集素途径与糖尿病肾病有关。我们假设 SGLT-2 抑制剂会降低凝集素级联的模式识别分子的循环水平并减弱全身补体激活。对来自 DapKid 交叉干预研究的配对血浆样本进行分析，其中患有 2 型糖尿病 (T2DM) 和白蛋白尿的患者接受达格列净和安慰剂治疗 12 周（10 毫克/天，n=36）。使用 ELISA 测定肾集合素 1 (CL-K1)、肝集合素 1 (CL-L1)、甘露糖结合凝集素 (MBL)、MBL 相关丝氨酸蛋白酶 2 (MASP-2)、过敏毒素补体因子 3a 的浓度(C3a)、稳定的 C3 裂解产物 C3dg 和膜攻击复合物 (sC5b-9)。如之前发表的，达格列净治疗将 Hba 从 74 (14.9) mmol/mol 降低至 66 (13.9) mmol/mol (p<0.0001)，尿白蛋白/肌酐比值从 167.8 mg/g 降低至 122.5 mg/g (p< 0.0001）。与安慰剂治疗相比，达格列净治疗后CL-K1、CL-L1、MBL和MASP-2的血浆浓度没有显着变化（P>0.05）。达格列净治疗后，C3a（P<0.05）和C3dg（P<0.01）的血浆水平略有增加，但显着增加，分别为0.6[0.2]单位/mL和76[52]单位/mL。达格列净不会改变 C5b-9 中的 C9 相关新表位的血浆浓度（P>0.05）。在患有 2 型糖尿病和白蛋白尿的患者中，SGLT-2 抑制导致血浆中适度的 C3 激活，这可能不是由循环集合素的主要变化驱动的，也不会导致膜攻击复合物的变化。根据系统分析，不能排除格列净对补体激活的器官特异性局部保护作用。