基于持续扫描式葡萄糖监测系统探讨二甲双胍对青春期T1DM患儿的应用价值

doi:10.12372/jcp.2024.23e1198

摘要/Abstract

摘要：

目的基于持续扫描式葡萄糖监测系统探讨二甲双胍联合胰岛素注射液治疗青春期1型糖尿病（T1DM）儿童的疗效。方法 2018年1月至2023年5月门诊随访的青春期T1DM儿童99例，48例胰岛素联合盐酸二甲双胍片治疗为观察组，51例单用胰岛素治疗为对照组。比较两组儿童各项临床资料、监测指标及安全性。结果在3个月随访时观察组、对照组平均目标范围内时间（TIR）分别为76.6 %±9.1 %、65.9 %±15.0 %，中位高血糖时间（TAR）两组分别为7.0 %（3.0 %~14.3 %）、21.0 %（12.0 %~29.0 %），平均低血糖时间（TBR）两组分别为14.5 %±7.1 %、10.2 %±6.8 %，在6个月随访时观察组、对照组平均TIR两组分别为76.0 %±8.9 %、65.5 %±14.3 %，中位TAR两组分别为8.0 %（3.3 %~13.8 %）、24.0 %（15.0 %~29.0 %），平均TBR两组分别为14.4 %±5.9 %、10.0 %±6.8 %，以上变量两组间差异均有统计学意义（P均<0.05）。观察组两次随访中位胰岛素用量低于对照组。48例观察组患儿两次随访时中位胰岛素用量、中位BMI、平均TIR、平均TBR均高于其基线水平，中位TAR水平低于自身基线水平，以上变量差异均有统计学意义（P均<0.05）。观察组4例（8.33 %）出现胃肠道症状，无严重低血糖发生。结论二甲双胍联合胰岛素治疗方案，可以有效提高青春期T1DM儿童TIR。TBR水平增加，并不增加严重低血糖风险，安全性良好。二甲双胍联合胰岛素治疗对青春期T1DM儿童是一种可行的选择。

关键词: 1型糖尿病, 二甲双胍, 青春期, 持续扫描式葡萄糖监测系统

Abstract:

Objective To investigate the efficacy of metformin combined with insulin injection in the treatment of adolescents with type 1 diabetes mellitus (T1DM) based on the continuous scanning glucose monitoring system. Methods A total of 99 adolescents with T1DM were followed from January 2018 to May 2023. The observation group, comprising 48 adolescents, received a combination of insulin and metformin, while the control group of 51 patients was treated with insulin alone. The clinical data, monitoring indices and safety profiles of both groups, were compared. Results At the 3-month follow-up, the mean time in the target glucose range (TIR) was significantly higher in the observation group at 76.6%±9.1% compared to 65.9%±15.0% in the control group. The median time above target glucose range (TAR) in the two groups was 7.0% (3.0%-14.3%) and 21.0 % (12.0%-29.0%), respectively. The mean time below target glucose range (TBR) was 14.50%±7.13% in the observation group and 10.2%±6.8% in the control group. At the 6-month follow-up, the mean TIR in the observation group was 76.0 %±8.9 % compared to 65.5 %±14.3 % in the control group. The median TAR in the observation group was 8.0 %(3.3 %-13.8 %), while in the control group it was 24.0 %(15.0 %-29.0 %).The median TBR in the observation group was 14.4 %±5.9 % in contrast to 10.0 %±6.8 % in the control group. The differences in these variables between the two groups were statistically significant (all P<0.05). At the 3-month and 6-month follow-up, the median insulin dosage required by the observation group was lower than that of the control group (all P<0.05). At two follow-up visits, the median insulin dosage, median BMI, average TIR and average TBR of the patients in the observation group were all higher than their baseline level, and the median TAR level was lower than their baseline level, with statistical significance (all P<0.05). Gastrointestinal symptoms were reported in 4 cases (8.33 %) of the observation group, with no severe hypoglycemia observed. Conclusions The combination of metformin with insulin therapy significantly improved TIR in adolescents with T1DM. Although TBR level increases, this treatment regimen does not increase the risk of severe hypoglycemia. Metformin demonstrated a favorable safety profile, suggesting that the insulin-metformin combination is a viable treatment option for adolescents with T1DM.

Key words: type 1 diabetes, metformin, adolescent, continuous scanning glucose monitoring system

刘芳, 陈琼, 李杨世玉, 李园, 曹冰燕, 卫海燕, 张淼. 基于持续扫描式葡萄糖监测系统探讨二甲双胍对青春期T1DM患儿的应用价值[J]. 临床儿科杂志, 2024, 42(9): 774-781.

LIU Fang, CHEN Qiong, LI Yangshiyu, LI Yuan, CAO Bingyan, WEI Haiyan, ZHANG Miao. The application value of metformin in adolescents with T1DM based on continuous scanning glucose monitoring system[J]. Journal of Clinical Pediatrics, 2024, 42(9): 774-781.

图/表 3

表1

两组基线资料比较"

项目	观察组(n=48)	对照组(n=51)	统计量	P
男性[n(%)]	20（41.7）	18（35.3）	χ²=0.43	0.515
年龄[M(P₂₅~P₇₅)]/岁	11.3（10.7~12.1）	12.0（10.7~13.4）	Z=1.54	0.125
确诊年龄[M(P₂₅~P₇₅)]/岁	8.3（7.7~10.0）	8.3（7.7~10.0）	Z=1.33	0.183
病程[M(P₂₅~P₇₅)]/年	3.3（2.4~5.1）	3.1（2.0~4.9）	Z=0.56	0.573
BMI[M(P₂₅~P₇₅)]/kg·m^-2	17.5（15.8~19.4）	17.9（15.9~19.2）	Z=0.17	0.867
中心性肥胖[n(%)]	14（29.2）	10（19.6）	χ²=1.23	0.267
WHtR[M(P₂₅~P₇₅)]	0.43（0.40~0.46）	0.42（0.40~0.45）	Z=0.67	0.506
HtSDS[M(P₂₅~P₇₅)]	0.13（0.02~0.39）	0.15（0.02~0.34）	Z=0.49	0.621
Tanner分期[n(%)]			χ²=0.85	0.655
Ⅱ期	26（54.2）	23（45.1）
Ⅲ期	12（25.0）	16（31.4）
Ⅳ期	10（20.8）	12（23.5）
每周中等强度运动时间[n(%)]			χ²=2.19	0.335
≤150 min	6（12.5）	8（15.7）
150~300 min	20（41.7）	27（52.9）
≥300 min	22（45.8）	16（31.4）
胰岛素给药方式[n(%)]			χ²=2.59	0.108
皮下注射	15（31.3）	24（47.1）
胰岛素泵	33（68.8）	27（52.9）
胰岛素剂量[M(P₂₅~P₇₅)]/ U·kg^-1·d^-1	1.0（0.8~1.1）	1.0（0.9~1.2）	Z=0.84	0.399
糖尿病相关抗体[n(%)]
GADA阳性	35(72.9)	29(56.9)	χ²=2.79	0.095
ICA阳性	8（16.7）	8(15.7)	χ²=0.02	0.895
IAA阳性	11(22.9)	6(11.8)	χ²=2.16	0.141
联合检测阳性	40（83.3）	35(68.6)	χ²=2.91	0.088
空腹C肽[M(P₂₅~P₇₅))]/ng·mL^-1	0.04（0.04~0.14）	0.03（0.00~0.09）	Z=0.28	0.781
HbA1c[M(P₂₅~P₇₅)]/%	6.8（6.2~7.5）	6.7（6.2~7.5）	Z=0.12	0.902
维生素B₁₂[M(P₂₅~P₇₅)]/pg·mL^-1	456.0（345.0~546.0）	543.0（345.0~670.0）	Z=1.22	0.223
叶酸[M(P₂₅~P₇₅)]/ng·mL^-1	6.7（5.4~7.7）	6.4（4.9~8.7）	Z=0.47	0.641
RBC[M(P₂₅~P₇₅)]/×10¹²·L^-1	4.7（4.4~4.9）	4.8（4.6~4.9）	Z=0.83	0.408
Hb[M(P₂₅~P₇₅)]/g·L^-1	131.0（121.0~139.0）	132.0（127.0~140.0）	Z=0.70	0.483
AST[M(P₂₅~P₇₅)]/U·L^-1	23.0（18.0~28.0）	22.0（21.0~25.5）	Z=0.34	0.738
ALT[M(P₂₅~P₇₅)]/U·L^-1	14.5（12.0~20.0）	14.0（12.0~18.0）	Z=0.98	0.328
BUN[M(P₂₅~P₇₅)]/mmmol·L^-1	4.1（3.5~4.9）	4.2（3.8~4.9）	Z=0.47	0.638
SCr($\bar{x}±s$）/μmmol·L^-1	33.9±11.4	34.4±8.0	t=0.27	0.787
SUA[M(P₂₅~P₇₅)]/μmmol·L^-1	277.2（223.8~350.5）	293.3（250.8~393.3）	Z=0.60	0.552
TG[M(P₂₅~P₇₅)]/mmol·L^-1	0.8（0.6~1.04)	0.8（0.6~1.2）	Z=0.00	1.000
TCHO（$\bar{x}±s$）/mmol·L^-1	3.5±1.1	3.4±1.0	t=0.60	0.552
HDL[M(P₂₅~P₇₅)]/mmol·L^-1	1.7（1.5~1.9）	1.7（1.5~2.0）	Z=0.73	0.466
LDL[M(P₂₅~P₇₅)]/mmol·L^-1	2.2（1.8~2.6）	2.2（1.9~2.6）	Z=0.43	0.669
Lac[M(P₂₅~P₇₅)]/mmol·L^-1	1.2（0.5~1.5）	0.7（0.5~1.2)	Z=1.62	0.104
TIR($\bar{x}±s$）/%	67.2±13.9	67.0±14.2	t=0.08	0.936
TAR[M(P₂₅~P₇₅)]/%	23.0（12.5~34.8）	21.0（14.0~32.0）	Z=0.37	0.710
TBR($\bar{x}±s$）/%	8.5±4.3	9.8±4.3	t=1.46	0.147
MC[M(P₂₅~P₇₅)]/mmol·L^-1	7.3（6.6~7.7）	7.1（6.3~7.8）	Z=0.03	0.980

表1

表2

表3

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项目	访视时间	观察组(n=48)	对照组(n=51)	统计量	P
BMI[M(P₂₅~P₇₅)]/kg·m^-2	3个月	17.1（15.4~18.7）	18.0（15.8~19.5）	Z=1.50	0.134
BMI[M(P₂₅~P₇₅)]/kg·m^-2	6个月	17.0（15.2~18.4）	18.7（16.4~19.5）	Z=2.51	0.012
胰岛素用量[M(P₂₅~P₇₅)]/U·kg^-1·d^-1	3个月	0.8（0.7~0.8）	1.0（0.9~1.2）	Z=6.17	<0.001
胰岛素用量[M(P₂₅~P₇₅)]/U·kg^-1·d^-1	6个月	0.7（0.7~0.8）	1.0（0.9~1.2）	Z=6.50	<0.001
HtSDS[M(P₂₅~P₇₅)]/%	3个月	0.13（0.00~0.33）	0.13（0.01~0.33）	Z=0.45	0.656
HtSDS[M(P₂₅~P₇₅)]/%	6个月	0.13（0.01~0.33）	0.15（0.03~0.42）	Z=0.76	0.445
RBC[M(P₂₅~P₇₅)]/×10¹²·L^-1	3个月	4.7（4.4~4.9）	4.6(4.3~4.9)	Z=0.77	0.441
RBC[M(P₂₅~P₇₅)]/×10¹²·L^-1	6个月	4.6(4.4~4.9)	4.6(4.4~4.9)	Z=0.61	0.540
Hb[M(P₂₅~P₇₅)]/g·L^-1	3个月	130.0（123.0~139.0）	130.0（125.0~134.0）	Z=0.22	0.827
Hb[M(P₂₅~P₇₅)]/g·L^-1	6个月	130.0（126.0~134.0）	130.0（126.0~134.0）	Z=0.72	0.474
HbA1c[M(P₂₅~P₇₅)]/%	3个月	6.9（6.4~7.5）	6.7（6.1~7.5）	Z=0.41	0.679
HbA1c[M(P₂₅~P₇₅)]/%	6个月	7.0（6.2~7.4）	6.8（6.2~7.7）	Z=0.32	0.752
TIR($\bar{x}±s$）/%	3个月	76.6±9.1	65.9±15.0	t=4.29	<0.001
TIR($\bar{x}±s$）/%	6个月	76.0±8.9	65.5±14.3	t=4.41	<0.001
TAR[M(P₂₅~P₇₅)]/%	3个月	7.0（3.0~14.3）	21.0（12.0~29.0）	Z=5.75	<0.001
TAR[M(P₂₅~P₇₅)]/%	6个月	8.0（3.3~13.8）	24.0（15.0~29.0）	Z=5.88	<0.001
TBR($\bar{x}±s$）/%	3个月	14.5±7.1	10.2±6.8	Z=3.01	0.003
TBR($\bar{x}±s$）/%	6个月	14.4±5.9	10.0±6.8	t=3.32	0.001
MC[M(P₂₅~P₇₅)]/mmol·L^-1	3个月	7.1（6.3~8.1）	7.2（6.3~8.1）	t=0.16	0.875
MC[M(P₂₅~P₇₅)]/mmol·L^-1	6个月	7.4（6.5~7.9）	7.2（6.5~8.0）	Z=0.27	0.798

项目	3个月		6个月
项目	统计量	P	统计量	P
BMI[M(P₂₅~P₇₅)]/kg·m^-2	Z=5.45	<0.001	Z=5.26	<0.001
胰岛素用量[M(P₂₅~P₇₅)]/ U·kg^-1·d^-1	Z=6.03	<0.001	Z=6.03	<0.001
HtSDS[M(P₂₅~P₇₅)]	Z=0.14	0.889	Z=0.27	0.784
RBC[M(P₂₅~P₇₅)]/×10¹²·L^-1	Z=1.64	0.101	Z=0.50	0.616
Hb[M(P₂₅~P₇₅)]/g·L^-1	Z=1.18	0.238	Z=0.46	0.648
HbA1c[M(P₂₅~P₇₅)]/%	Z=1.21	0.225	Z=1.48	0.138
TIR($\bar{x}±s$）/%	t=4.09	<0.001	t=3.93	<0.001
TAR[M(P₂₅~P₇₅)]/%	Z=5.35	<0.001	Z=5.05	<0.001
TBR($\bar{x}±s$）/%	t=5.88	<0.001	t=6.22	<0.001
MC[M(P₂₅~P₇₅)]/mmol·L^-1	Z=1.49	0.134	Z=1.92	0.101