每日2次长效胰岛素方案转化为每日1次德谷胰岛素治疗成人1型糖尿病的有效性及安全性研究

Efficacy and safety of transitioning from twice-daily long-acting insulin to once-daily degludec in adult patients with type 1 diabetes mellitus

目的探讨每日2次长效胰岛素方案转化为每日1次德谷胰岛素治疗成人1型糖尿病的有效性及安全性。方法为单中心、开放、前瞻性、非随机对照研究。自2019年11月6日至2021年10月30日从北京协和医院内分泌科门诊招募T1DM患者作为受试者。将受试者降糖方案从基线每日2次长效胰岛素转化为每日1次的德谷胰岛素,干预时限为12周。收集受试者基线时年龄和糖尿病病程,以及基线和每日1次德谷胰岛素治疗12周后的CGM结果[包括平均血糖水平(MBG)、葡萄糖在目标范围内时间(TIR)、葡萄糖高于目标范围内时间(TAR)、葡萄糖低于目标范围内时间(TBR)、血糖水平标准差(SDBG)、平均血糖波动幅度(MAGE)],自我血糖监测(SMBG)情况(包括晚餐前、空腹、午餐前、睡前血糖),糖化血红蛋白(HbA_(1c))、空腹血糖(FPG)、低血糖事件、胰岛素剂量、体重。采用配对样本t检验或Wilcoxon符号秩检验对治疗前后相关资料进行比较。结果共纳入22例T1DM患者,年龄为(48.1±16.6)岁,糖尿病病程为12.00(6.75,18.25)年。与T1DM患者每日2次长效胰岛素相比,每日1次德谷胰岛素治疗12周后,在SMBG方面,晚餐前血糖差异无统计学意义(P>0.05),但有下降趋势,分别为(10.1±2.7)和(9.2±2.7)mmol/L,余SMBG指标(包括空腹、午餐前及睡前血糖)差异均无统计学意义(P>0.05)。CGM结果方面,MBG、TIR、TAR、TBR、SDBG、MAGE在转化治疗前后差异均无统计学意义(P>0.05),但TBR有下降趋势,分别为3.0%(0.5%,9.9%)和3.0%(0.5%,6.0%)。HbA1c、FPG、基础胰岛素剂量及每日总胰岛素剂量在转化治疗前后差异均无统计学意义(P>0.05),但是均有下降趋势,分别为(7.7±1.3)%和(7.5±1.1)%、(12.3±5.5)mmol/L和(10.3±4.6)mmol/L、(20.3±11.6)U和(18.6±7.7)U、(48.3±22.9)和(44.9±16.7)U。低血糖事件发生频率及体重在转化治疗前后差异均无统计学意义(P>0.05)。结论每日1次德谷胰岛素相对于每日2次长效胰岛素来说,对于成人T1DM患者疗效确切并具有良好的安全性,且减少了注射次数。

Objective To evaluate the efficacy and safety of transitioning from twice-daily long-acting insulin to once-daily degludec in adult patients with type 1 diabetes mellitus(T1DM).Methods This was a single-center,open,prospective,non-randomized controlled study.From November 6,2019 to October 30,2021,patients with T1DM were recruited from the Endocrinology Department outpatient clinic of Peking Union Medical College Hospital.T1DM patients receiving twice-daily long-acting insulin therapy were switched to once-daily degludec and the intervention period lasted for 12 weeks.Baseline demographic data including age and duration of diabetes were collected.Continuous glucose monitoring(CGM)[including mean blood glucose level(MBG),time in range(TIR),time above target glucose range(TAR),time below target glucose range(TBR),standard deviation of blood glucose(SDBG)and mean amplitude of glycemic excursion(MAGE)],self-monitoring of blood glucose(SMBG)(including pre-dinner blood glucose,fasting blood glucose,pre-lunch blood glucose and bedtime blood glucose),glycated hemoglobin A1c(HbA_(1c))levels,fasting plasma glucose(FPG),hypoglycemic events,insulin doses and weight were recorded at baseline and after 12 weeks of once-daily degludec insulin treatment.Paired-sample t-test or Wilcoxon signed-rank test was used to compare pre-and post-treatment data.Results A total of 22 T1DM patients were enrolled in the study,with an average age of(48.1±16.6)years and an average duration of diabetes of 12.00(6.75,18.25)years.Compared with T1DM patients receiving twice-daily long-acting insulin,after 12 weeks of once-daily degludec insulin treatment,there was no statistically significant difference in pre-dinner blood glucose levels as measured by SMBG(P>0.05),although a decreasing trend was observed with values of(10.1±2.7)mmol/L and(9.2±2.7)mmol/L,respectively.Other SMBG indices(including fasting,pre-lunch,and bedtime blood glucose)also showed no statistically significant differences(P>0.05).Regarding the CGM results,there were no statistically significant differences before and after the transition in MBG,TIR,TBR,TAR,SDBG,or MAGE(P>0.05).However,there was a decreasing trend in TBR with levels of 3.0%(0.5%,9.9%)and 3.0%(0.5%,6.0%),respectively.The differences in HbA1c,FPG,basal insulin dose,and total daily insulin dose before and after the transition therapy were not statistically significant(P>0.05);however,they all showed a decreasing trend,with values of(7.7±1.3)%and(7.5±1.1)%,(12.3±5.5)mmol/L and(10.3±4.6)mmol/L,(20.3±11.6)U and(18.6±7.7)U,(48.3±22.9)U and(44.9±16.7)U,respectively.There was no significant difference in the frequency of hypoglycemic events and the weight before and after the transition(P>0.05).Conclusion Compared to twice-daily long-acting insulin,once-daily degludec insulin has shown efficacy and safety in adult T1DM patients,and reduces the number of insulin injections.