小鼠持续葡萄糖监测技术的建立及其血糖时间序列的多尺度熵分析

doi:10.3969/j.issn.1674-8115.2021.02.002

上海交通大学学报(医学版) ›› 2021, Vol. 41 ›› Issue (2): 134-139.doi: 10.3969/j.issn.1674-8115.2021.02.002

小鼠持续葡萄糖监测技术的建立及其血糖时间序列的多尺度熵分析

李成¹(), 张明亮¹, 应令雯¹, 苏娇溶¹, 陶睿², 于霞², 包玉倩¹, 周健¹()

^1.上海交通大学附属第六人民医院内分泌代谢科，上海市糖尿病研究所，上海市糖尿病重点实验室，上海市糖尿病临床医学中心，上海 200233
^2.东北大学信息科学与工程学院，沈阳 110819

收稿日期:2020-04-22 出版日期:2021-02-28 发布日期:2021-02-28
通讯作者: 周健 E-mail:licheng_sjtu@sjtu.edu.cn;zhoujian@sjtu.edu.cn
作者简介:李成（1994—），女，博士生；电子信箱：licheng_sjtu@sjtu.edu.cn。
基金资助:
国家重点研发计划(2018YFC2001004);国家自然科学基金青年科学基金(61903071);上海市教育委员会高峰高原学科建设计划(20161430)

Establishment of continuous glucose monitoring in mice and multiscale entropy analysis of glucose time series

Cheng LI¹(), Ming-liang ZHANG¹, Ling-wen YING¹, Jiao-rong SU¹, Rui TAO², Xia YU², Yu-qian BAO¹, Jian ZHOU¹()

^1.Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Clinical Center for Diabetes, Shanghai 200233, China
^2.College of Information Science and Engineering, Northeastern University, Shenyang 110819, China

Received:2020-04-22 Online:2021-02-28 Published:2021-02-28
Contact: Jian ZHOU E-mail:licheng_sjtu@sjtu.edu.cn;zhoujian@sjtu.edu.cn
Supported by:
National Key Research and Development Program of China(2018YFC2001004);National Natural Science Foundation of China(61903071);Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20161430)

摘要/Abstract

摘要：

目的·建立小鼠持续葡萄糖监测（continuous glucose monitoring，CGM）技术，并对其血糖时间序列进行多尺度熵（multiscale entropy，MSE）分析。方法·选取饮食诱导肥胖型（diet-induced obesity，DIO）小鼠（n=3，DIO组）及对照组小鼠（n=3）为研究对象，利用全植入式血糖遥测系统分别收集2组小鼠的血糖及体温数据，取术后第10~14日数据进行分析，并统计系统的记录时间。利用MATLAB R2019b软件对2组小鼠术后第11~17日的血糖时间序列进行MSE分析，计算每个时间尺度上对应的熵值。结果·成功建立了以全植入式血糖遥测系统为基础的小鼠CGM技术。6只小鼠的平均记录时间为（27.3±9.3）d，共获得232 887个血糖数值。DIO组小鼠平均血糖水平为（7.04±0.71）mmol/L，平均体温为（33.34±0.18）℃。与对照组相比，DIO组小鼠血糖时间序列复杂度较低，但差异无统计学意义。结论·成功建立了小鼠CGM技术；MSE分析发现，DIO型小鼠血糖时间序列复杂度降低，可能是其早期糖代谢异常的表现之一。

关键词: 持续葡萄糖监测, 全植入式血糖遥测系统, 多尺度熵, 复杂度, 时间序列, 饮食诱导肥胖型小鼠

Abstract:

Objective·To establish continuous glucose monitoring (CGM) in mice and implement multiscale entropy (MSE) analysis of glucose time series. Methods·Diet-induced obesity (DIO) mice (n=3) and control mice (n=3) were selected as the research objects. The blood glucose and body temperature data of the two groups were collected by using the implantable glucose telemetry system. The data of 10?14 days after operation were analyzed, and the recording time of the system was counted. Using MATLAB R2019b software, MSE analysis was performed on glucose time series of the two groups from 11 to 17 days after operation, and the corresponding entropy value on each time scale was calculated. Results·The CGM technology based on the implantable glucose telemetry system in mice was successfully established. The average recording time of the 6 mice was (27.3±9.3) d, and 232 887 blood glucose values were obtained. The mean blood glucose level of the DIO mice was (7.04±0.71) mmol/L and the mean body temperature was (33.34±0.18) ℃. Compared with that of the control mice, the glucose time series complexity of the DIO mice was lower, and the difference between the two groups was not statistically significant. Conclusion·The CGM technology in mice is successfully established. MSE analysis shows that the complexity of glucose time series in the DIO mice decreases, which may be one of the manifestations of abnormal glucose metabolism in the early stage.

Key words: continuous glucose monitoring (CGM), implantable glucose telemetry system, multiscale entropy (MSE), complexity, time series, diet-induced obesity mouse

中图分类号:

R589.9

李成, 张明亮, 应令雯, 苏娇溶, 陶睿, 于霞, 包玉倩, 周健. 小鼠持续葡萄糖监测技术的建立及其血糖时间序列的多尺度熵分析[J]. 上海交通大学学报(医学版), 2021, 41(2): 134-139.

Cheng LI, Ming-liang ZHANG, Ling-wen YING, Jiao-rong SU, Rui TAO, Xia YU, Yu-qian BAO, Jian ZHOU. Establishment of continuous glucose monitoring in mice and multiscale entropy analysis of glucose time series[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(2): 134-139.

图/表 6

图1 HD-XG血糖遥测植入子植入小鼠的手术模式图Note:A. Surgical fields after left carotid artery separation. B. Placement of the sensor tip. C. Placement of the HD-XG glucose telemetry implant in subcutaneous tissue.

Fig 1 Operation pattern of HD-XG glucose telemetry implant in mice

表1 全植入式血糖遥测系统监测2组小鼠的记录时间及血糖值数量

Tab 1 Recording time and the number of glucose values of the two groups monitored by implantable glucose telemetry system

Index	DIO group (N=3)			Control group (N=3)
Index	1	2	3	1	2	3
Recording time/d	20	39	39	18	24	24
Total glucose number	27 192	55 906	55 799	25 007	34 455	34 528

表2 2组中每只小鼠第10~14日的平均血糖和体温

Tab 2 Mean blood glucose and body temperature of each mouse in the two groups from Day 10 to Day 14

Index	DIO group (N=3)			Control group (N=3)
Index	1	2	3	1	2	3
Mean blood glucose/(mmol·L^-1)	6.74±0.62	6.54±0.93	7.86±0.81	6.96±1.68	7.38±1.05	6.42±1.08
Mean body temperature/℃	33.15±1.77	33.37±0.61	33.50±0.74	33.02±0.93	34.29±0.84	34.06±0.89

图2 2组小鼠第10~14日的血糖图谱

Fig 2 Glucose profiles of mice in the two groups from Day 10 to Day 14

图3 2组小鼠第10~14日的体温水平图谱

Fig 3 Body temperature profiles of mice in the two groups from Day 10 to Day 14

图4 2组小鼠不同时间尺度下血糖时间序列的熵值

Fig 4 Entropy of glucose time series on different scales in the two groups

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小鼠持续葡萄糖监测技术的建立及其血糖时间序列的多尺度熵分析

Establishment of continuous glucose monitoring in mice and multiscale entropy analysis of glucose time series

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