达格列净抑制 SGLT-2 减少组织钠含量：一项随机对照试验。
SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial.
机构信息
Department of Nephrology and Hypertension, University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
Department for Diagnostic Radiology, University Hospital Erlangen, Erlangen, Germany.
出版信息
Cardiovasc Diabetol. 2018 Jan 4;17(1):5. doi: 10.1186/s12933-017-0654-z.
BACKGROUND AND AIMS
Sodium tissue content by Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes characterized by sodium retention leads to decreased tissue sodium content due to its pharmacological action.
MATERIALS AND METHODS
In a prospective double blind, placebo controlled, cross-over trial 59 patients (61 ± 7.6 years) with type 2 diabetes were randomized to either dapagliflozin 10 mg or placebo once daily for 6 weeks each. In addition to metabolic parameters and ambulatory blood pressure (BP) we analysed the sodium content in the skin and muscles of the lower leg by Na-MRI.
RESULTS
Compared to baseline 6 weeks treatment with the SGLT-2 inhibitor dapagliflozin decreased fasting (132 ± 28 vs. 114 ± 19 mg/dl, p < 0.001), postprandial blood glucose (178 ± 66 mg/dl vs. 153 ± 46 mg/dl, p < 0.001), body weight (87.6 vs. 86.6 kg, p < 0.001) and systolic (129 ± 12 vs. 126 ± 11 mmHg, p = 0.010), and diastolic (77.4 ± 9 vs. 75.6 ± 8 mmHg, p = 0.024), 24-h ambulatory BP. Tissue sodium content in the skin was reduced after 6 weeks treatment with dapagliflozin compared to baseline [24.1 ± 6.6 vs. 22.7 ± 6.4 A.U.(arbitrary unit) p = 0.013]. No significant reduction of tissue sodium content was observed in the muscle (M. triceps surae: 20.5 ± 3.5 vs. 20.4 ± 3.7 A.U. p = 0.801). No clear significant difference in tissue water content of muscle and skin was observed after 6 weeks of treatment with dapagliflozin, compared to baseline.
CONCLUSION
SGLT-2 inhibition with dapagliflozin resulted in a significant decrease in tissue sodium content of the skin after 6 weeks. This observation point to a decrease of total sodium content in patients with type 2 diabetes prone to cardiovascular complications, that might be mitigated by SGLT-2 inhibition. Trial registration The study was registered at http://www.clinicaltrials.gov (NCT02383238) retrospectively registered.
背景与目的
钠离子磁共振成像（Na-MRI）已在实验和人体研究中得到验证。SGLT-2 抑制剂以 1:1 的比例阻断葡萄糖和近端肾小管细胞中钠的重吸收。我们假设 SGLT-2 抑制剂在以钠潴留为特征的 2 型糖尿病患者中具有药理学作用，可导致组织钠含量降低。
材料和方法
在一项前瞻性、双盲、安慰剂对照、交叉试验中，59 名（61 ± 7.6 岁）2 型糖尿病患者随机分为达格列净 10mg 或安慰剂，每天一次，持续 6 周。除了代谢参数和动态血压（BP）外，我们还通过 Na-MRI 分析了小腿皮肤和肌肉中的钠含量。
结果
与基线相比，6 周的 SGLT-2 抑制剂达格列净治疗可降低空腹血糖（132 ± 28 与 114 ± 19mg/dl，p<0.001）、餐后血糖（178 ± 66 与 153 ± 46mg/dl，p<0.001）、体重（87.6 与 86.6kg，p<0.001）和收缩压（129 ± 12 与 126 ± 11mmHg，p=0.010）、舒张压（77.4 ± 9 与 75.6 ± 8mmHg，p=0.024）。24 小时动态血压。与基线相比，达格列净治疗 6 周后皮肤组织钠含量降低[24.1 ± 6.6 与 22.7 ± 6.4A.U.（任意单位），p=0.013]。达格列净治疗 6 周后，肌肉（三头肌）组织钠含量无明显降低[20.5 ± 3.5 与 20.4 ± 3.7A.U.，p=0.801]。与基线相比，达格列净治疗 6 周后，肌肉和皮肤的组织水含量无明显差异。
结论
达格列净抑制 SGLT-2 可导致皮肤组织钠含量在 6 周后显著降低。这一观察结果表明，易发生心血管并发症的 2 型糖尿病患者的总钠含量可能减少，而 SGLT-2 抑制可能减轻这种情况。试验注册：该研究在 http://www.clinicaltrials.gov（NCT02383238）上注册，为回顾性注册。
Zotero 插件