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钠-葡萄糖协同转运蛋白2选择性抑制剂依帕列净对2型糖尿病患者血糖昼夜变化的影响:一项使用连续血糖监测的研究

Effects of a sodium glucose co-transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring.

作者信息

Yamada Kentaro, Nakayama Hitomi, Yoshinobu Satoko, Kawano Seiko, Tsuruta Munehisa, Nohara Masayuki, Hasuo Rika, Akasu Shoko, Tokubuchi Ichiro, Wada Nobuhiko, Hirao Saori, Iwata Shinpei, Kaku Hiroo, Tajiri Yuji

机构信息

Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine Kurume, Japan.

出版信息

J Diabetes Investig. 2015 Nov;6(6):699-707. doi: 10.1111/jdi.12370. Epub 2015 Jun 20.

Abstract

AIMS/INTRODUCTION: To assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.

MATERIALS AND METHODS

We administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.

RESULTS

Continuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 ± 54 mg/dL to 141 ± 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of β-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 ± 0.5 vs 0.5 ± 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively.

CONCLUSIONS

The ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss.

摘要

目的/引言:评估钠-葡萄糖协同转运蛋白2抑制剂治疗对2型糖尿病病理生理学的影响。

材料与方法

我们对21例2型糖尿病住院患者给予依帕列净治疗7天,并分析血糖和3-羟基丁酸的昼夜变化情况。另外选取21例年龄、性别和体重指数相匹配的糖尿病患者作为对照。

结果

持续葡萄糖监测显示,给予依帕列净后,24小时血糖曲线下移且未发生低血糖。平均血糖水平从182±54mg/dL降至141±33mg/dL(P<0.0001)。血糖降低幅度与基线平均血糖水平高度相关。治疗期间,胰岛素抵抗的稳态模型评估值降低,β细胞功能的稳态模型评估值升高。0天和7天时,尿糖排泄均与平均血糖水平相关,不过7天时回归线更陡且左移。依帕列净治疗组患者体重减轻比对照组更多(1.4±0.5kg对0.5±0.6kg,P<0.0001)。3-羟基丁酸血浆水平显著升高,在早餐前和晚餐前达到峰值。患者年龄和体重减轻分别与7天时3-羟基丁酸的峰值水平呈负相关和正相关。

结论

依帕列净治疗改善了24小时血糖曲线且未引起低血糖。血糖降低幅度与基线血浆葡萄糖浓度密切相关,提示低血糖风险可能较低。对年轻患者和体重快速减轻的患者监测酮体水平可能较为谨慎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1842/4627548/63ac143b80bf/jdi0006-0699-f1.jpg

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