Yamada Tomoko, Sakaguchi Kazuhiko, Okada Yuko, Miura Hiroshi, Otowa-Suematsu Natsu, So Anna, Komada Hisako, Hirota Yushi, Ohara Takeshi, Kuroki Yasuo, Hara Kenta, Matsuda Tomokazu, Kishi Minoru, Takeda Akihiko, Yokota Kazuki, Tamori Yoshikazu, Ogawa Wataru
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017 Japan.
Division of General Internal Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Diabetol Int. 2020 Nov 10;12(2):197-206. doi: 10.1007/s13340-020-00474-2. eCollection 2021 Apr.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors often increase the hematocrit. It remains unclear whether this increase would be observed in all patients administered SGLT2 inhibitors, however. We therefore used the data from the previous study and investigated time-dependent alterations of various outcomes related to erythrocytes, erythropoiesis, and clinical outcome in type 2 diabetes subjects ( = 89) treated with ipragliflozin for 16 weeks. Among a total of 89 participants, 71 subjects (80.0% of total participants) showed the elevation of the hematocrit and 18 subjects (20.0% of total participants) did not at 16 weeks. Although the hematocrit levels at baseline were significantly lower in hematocrit-elevated group than non-elevated group, they reached the same levels 4 weeks after the onset of treatment. Binomial logistic regression analysis demonstrated that a lower baseline hematocrit level was related to the elevation of hematocrit at 16 weeks. Optimal cutoff hematocrit levels at baseline to predict hematocrit elevation were 46.9% (male) and 41.7% (female) in ROC analysis. Random intercept model analysis revealed the serum erythropoietin level increased in both hematocrit-elevated and non-elevated groups, whereas only the former group showed an increase in the percentage of reticulocytes during the first 4 weeks. These results suggest that the ipragliflozin-induced increase in hematocrit which is affected by the baseline hematocrit level is attributable to the responsiveness to, but not to the production of, erythropoietin. Collectively, Ht elevation observed in administration of SGLT2 inhibitors can result from erythropoietin-induced erythropoiesis, which is determined by the pre-treatment Ht level. Trial registration: This trial has been registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR no. 000015478).
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂常常会使血细胞比容升高。然而，目前尚不清楚在所有使用SGLT2抑制剂的患者中是否都会出现这种升高。因此，我们利用先前研究的数据，调查了89例接受依帕列净治疗16周的2型糖尿病患者中，与红细胞、红细胞生成及临床结局相关的各种指标随时间的变化情况。在总共89名参与者中，71名受试者（占总参与者的80.0%）在16周时血细胞比容升高，18名受试者（占总参与者的20.0%）未升高。虽然血细胞比容升高组的基线血细胞比容水平显著低于未升高组，但在治疗开始4周后两组达到相同水平。二项逻辑回归分析表明，较低的基线血细胞比容水平与16周时血细胞比容升高有关。ROC分析中预测血细胞比容升高的基线最佳临界血细胞比容水平，男性为46.9%，女性为41.7%。随机截距模型分析显示，血细胞比容升高组和未升高组的血清促红细胞生成素水平均升高，而只有前一组在最初4周内网织红细胞百分比增加。这些结果表明，依帕列净诱导的血细胞比容升高受基线血细胞比容水平影响，归因于对促红细胞生成素的反应性，而非促红细胞生成素的产生。总体而言，SGLT2抑制剂给药时观察到的血细胞比容升高可能是由促红细胞生成素诱导的红细胞生成所致，这由治疗前的血细胞比容水平决定。试验注册：本试验已在大学医院医学信息网络临床试验注册中心注册（UMIN-CTR编号000015478）。
