英国剑桥大学代谢研究实验室Roman Hovorka团队研究了1型糖尿病幼儿的闭环控制的疗效。这一研究成果发表在2022年1月19日出版的《新英格兰医学杂志》上。

对于非常年幼的1型糖尿病儿童，混合闭环治疗（即人工胰腺）可能优于传感器增强泵治疗，但目前尚不清楚。

在这项多中心、随机、交叉试验中，研究组招募1-7岁的1型糖尿病儿童，他们在奥地利、德国、卢森堡和英国的七个中心接受胰岛素泵治疗。参与者在两个16周的周期内接受随机顺序的治疗，对闭环系统与传感器增强泵治疗（对照）进行比较。

主要终点为每个16周期间，传感器葡萄糖测量值在目标范围内（70-180 mg/dL）时间百分比的疗程间差异。根据意向治疗原则进行分析。关键次要终点包括高血糖状态时间百分比（葡萄糖水平>180 mg/dL）、糖化血红蛋白水平、平均传感器葡萄糖水平和低血糖状态时间百分比（葡萄糖水平<70 mg/dL）。并评估安全性。

共有74名参与者接受了随机分组。参与者的平均年龄为5.6±1.6岁，基线糖化血红蛋白水平为7.3±0.7%。闭环期间血糖水平在目标范围内的时间百分比比对照期间高8.7个百分点，组间差异显著。

闭环期间在高血糖状态下的时间百分比比对照期间低8.5个百分点，糖化血红蛋白水平比对照期间低0.4个百分点，平均传感器葡萄糖水平比对照期间低12.3 mg/dL，组间比较差异均显著。

两种治疗方法的低血糖状态时间百分比相似。在16周闭环期间，闭环模式的平均时间为95%。在闭环期间发生了一次严重低血糖的严重不良事件。还发生了一起被认为与治疗无关的严重不良事件。

研究结果表明，混合闭环系统显著改善了1型糖尿病幼儿的血糖控制，且不增加低血糖的时间。

附：英文原文

Title: Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes

Author: Julia Ware, M.D.,, Janet M. Allen, R.N.,, Charlotte K. Boughton, Ph.D.,, Malgorzata E. Wilinska, Ph.D.,, Sara Hartnell, B.Sc.,, Ajay Thankamony, M.Phil.,, Carine de Beaufort, Ph.D.,, Ulrike Schierloh, M.D.,, Elke Frhlich-Reiterer, M.D.,, Julia K. Mader, M.D.,, Thomas M. Kapellen, Ph.D.,, Birgit Rami-Merhar, M.D.,, Martin Tauschmann, Ph.D.,, Katrin Nagl, M.D.,, Sabine E. Hofer, M.D.,, Fiona M. Campbell, M.D.,, James Yong, M.D.,, Korey K. Hood, Ph.D.,, Julia Lawton, Ph.D.,, Stephane Roze, M.Sc.,, Judy Sibayan, M.P.H.,, Laura E. Bocchino, M.P.H.,, Craig Kollman, Ph.D.,, and Roman Hovorka, Ph.D.

Issue&Volume: 2022-01-19

Abstract:

Background

The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear.

Methods

In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level, <70 mg per deciliter). Safety was assessed.

Results

A total of 74 participants underwent randomization. The mean (±SD) age of the participants was 5.6±1.6 years, and the baseline glycated hemoglobin level was 7.3±0.7%. The percentage of time with the glucose level in the target range was 8.7 percentage points (95% confidence interval [CI], 7.4 to 9.9) higher during the closed-loop period than during the control period (P<0.001). The mean adjusted difference (closed-loop minus control) in the percentage of time spent in a hyperglycemic state was 8.5 percentage points (95% CI, 9.9 to 7.1), the difference in the glycated hemoglobin level was 0.4 percentage points (95% CI, 0.5 to 0.3), and the difference in the mean sensor glucose level was 12.3 mg per deciliter (95% CI, 14.8 to 9.8) (P<0.001 for all comparisons). The time spent in a hypoglycemic state was similar with the two treatments (P=0.74). The median time spent in the closed-loop mode was 95% (interquartile range, 92 to 97) over the 16-week closed-loop period. One serious adverse event of severe hypoglycemia occurred during the closed-loop period. One serious adverse event that was deemed to be unrelated to treatment occurred.

Conclusions

A hybrid closed-loop system significantly improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in hypoglycemia.

DOI: 10.1056/NEJMoa2111673

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2111673