二甲双胍对喹硫平致精神分裂症患者糖脂代谢紊乱的疗效

doi:10.3969/j.issn.1674-8115.2021.06.012

摘要/Abstract

摘要：

目的·观察二甲双胍（metformin，MF）对喹硫平所致精神分裂症（schizophrenia，SZ）患者糖脂代谢紊乱的疗效。方法·纳入上海市虹口区精神卫生中心和上海市杨浦区精神卫生中心的83例SZ患者，随机分为治疗组（MF组）38例和对照组45例。对照组仅口服喹硫平治疗，MF组在喹硫平口服基础上，采用MF辅助治疗。于治疗前及治疗后第2、4、8周检测2组患者的葡萄糖（glucose，GLU）、总胆固醇（total cholesterol，TC）、三酰甘油（triacylglycerol，TAG）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol，HDL-C）、小而密低密度脂蛋白胆固醇（small density low-density lipoprotein cholesterol，sd-LDL-C）和同型半胱氨酸（homocysteine，HCY）。结果·治疗前对照组与MF组比较，患者的年龄、病程、体质量指数、GLU、TC、TAG、HDL-C、LDL-C、sd-LDL-C和HCY检测结果差异均无统计学意义。治疗8周后，对照组所有实验室指标检测结果较治疗前均升高；MF组GLU、TC、TAG、LDL-C、sd-LDL-C和HCY水平较治疗前均下降，但HDL-C水平较治疗前升高。治疗8周后2组HDL-C水平的差异无统计学意义（P=0.247），其他实验室指标的组间差异均有统计学意义（P<0.05），MF组的降糖、降脂效果显著优于对照组。方差分析结果显示，治疗4、8周后，对照组HDL-C水平与治疗前比较显著升高，差异有统计学意义（P=0.005，P=0.003）；对照组LDL-C水平在治疗2、4、8周后与治疗前比较显著升高（P=0.005，P=0.019，P=0.026）；对照组其他实验室指标与治疗前比较差异均无统计学意义。治疗2、4、8周后，MF组GLU、TC、TAG和sd-LDL-C水平与治疗前比较显著下降；治疗4、8周后，MF组LDL-C和HCY水平与治疗前比较显著降低；治疗2周后MF组HDL-C水平与治疗前比较显著升高，但治疗4、8周后检测结果与治疗前比较差异无统计学意义。结论·对喹硫平治疗后致糖脂代谢紊乱的SZ患者实施MF辅助治疗，可显著降低患者血糖水平，改善患者血脂代谢。

关键词: 喹硫平, 精神分裂症, 糖脂代谢紊乱, 二甲双胍

Abstract:

Objective·To investigate the therapeutic efficacy of metformin (MF) on glucose dysregulation and dyslipidaemia induced by quetiapine in patients with schizophrenia (SZ).

Methods·A total of 83 SZ patients from Shanghai Hongkou District Mental Health Center and Shanghai Yangpu District Mental Health Center were enrolled, and randomly divided into treatment group (MF group, n=38) and control group (n=45). The control group received oral quetiapine therapy, and the MF group additionally received metformin on the basis of oral quetiapine therapy. The serum levels of glucose (GLU), total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small density low-density lipoprotein cholesterol (sd-LDL-C) and homocysteine (HCY) were determined before treatment and 2, 4 and 8 weeks after treatment.

Results·There were no statistic differences in ages, courses, body mass index, the levels of GLU, TC, TAG, HDL-C, LDL-C, sd-LDL-C and HCY between the control and MF group before treatment (all P>0.05). After 8 weeks of treatment, levels of all biomarkers elevated in the control group. The levels of GLU, TC, TAG, LDL-C, sd-LDL-C and HCY were lower after treatment, and the level of HDL-C elevated higher in the MF group. The variations of levels of HDL-C after treatment showed statistically no significant difference between the two groups (P=0.247), while statistical differences existed in other biomarkers, which indicated that the glucose-lowering and lipid-lowering efficacies in the MF group were significantly better than those in the control group. The analysis of variance suggested that, in the control group, the level of HDL-C elevated significantly after 4 and 8 weeks′ treatment, having statistical differences (P=0.005 and P=0.003). The level of LDL-C elevated significantly after 2, 4 and 8 weeks′ treatment (P=0.005, P=0.019 and P=0.026), and no statistical differences were observed in other biomarkers. In the MF group, the levels of GLU, TC, TAG and sd-LDL-C were lower 2, 4 and 8 weeks after treatment, the levels of LDL-C and HCY descended 4 and 8 weeks after treatment, and no statistical differences were observed in other biomarkers. The level of HDL-C was higher after 2 weeks, treatment, but showed statistically no significant differences 4 and 8 weeks after treatment, compared to the level determined before treatment.

Conclusion·Administration of MF in the SZ patients having glucose dysregulation and dyslipidaemia induced by quetiapine can significantly lower serum level of GLU, and improve the serum lipid profiles.

Key words: quetiapine, schizophrenia (SZ), glucosedysregulation and dyslipidaemia, metformin (MF)

中图分类号:

R749.3

宋兵福, 丁彬彬, 张晓丽, 姚莉韵. 二甲双胍对喹硫平致精神分裂症患者糖脂代谢紊乱的疗效[J]. 上海交通大学学报(医学版), 2021, 41(6): 776-780.

Bing-fu SONG, Bin-bin Ding, Xiao-li ZHANG, Li-yun YAO. Observation of therapeutic efficacy of metformin on glucose dysregulation and dyslipidaemia induced by quetiapine in patients with schizophrenia[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(6): 776-780.

图/表 4

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Indicator	Control group (n=45)	MF group (n=38)	P value
Male/female/n	27/18	26/12	-
Age/year	55.18±16.04	61.00 （57.75, 65.00）	0.249
Course/month	14.63±0.47	14.53±0.77	0.698
BMI/(kg·m^-2)	22.07±4.67	21.43±3.61	0.194
GLU/(mmol·L^-1)	6.68±1.89	6.55 （5.15, 9.19）	0.370
TC/(mmol·L^-1)	4.91±0.94	5.21±0.87	0.135
TAG/(mmol·L^-1)	2.31 （1.87, 3.32）	1.93 （1.51, 2.41）	0.134
HDL-C/(mmol·L^-1)	1.02 （0.87, 1.13）	1.01±0.26	0.766
LDL-C/(mmol·L^-1)	2.46 （2.12, 3.41）	2.89±0.73	0.104
sd-LDL-C/(mmol·L^-1)	1.08±0.44	1.22±0.46	0.167
HCY/(μmol·L^-1)	25.82±12.81	26.87±13.39	0.718

Indicator	Control group (n=45)	MF group (n=38)	P value
Male/female/n	27/18	26/12	-
Age/year	55.18±16.04	61.00 （57.75, 65.00）	0.249
Course/month	14.63±0.47	14.53±0.77	0.698
BMI/(kg·m^-2)	22.07±4.67	21.43±3.61	0.194
GLU/(mmol·L^-1)	6.68±1.89	6.55 （5.15, 9.19）	0.370
TC/(mmol·L^-1)	4.91±0.94	5.21±0.87	0.135
TAG/(mmol·L^-1)	2.31 （1.87, 3.32）	1.93 （1.51, 2.41）	0.134
HDL-C/(mmol·L^-1)	1.02 （0.87, 1.13）	1.01±0.26	0.766
LDL-C/(mmol·L^-1)	2.46 （2.12, 3.41）	2.89±0.73	0.104
sd-LDL-C/(mmol·L^-1)	1.08±0.44	1.22±0.46	0.167
HCY/(μmol·L^-1)	25.82±12.81	26.87±13.39	0.718

Biomarker	Control group （n=45）	MF group （n=38）	P value
GLU/(mmol·L^-1)	0.002±0.923	-0.955 （-3.445, 0.155）	0.001
TC/(mmol·L^-1)	0.122±1.111	-1.082±1.016	0.000
TAG/(mmol·L^-1)	0.055±1.205	-0.675 （-1.273, -0.080）	0.000
HDL-C/(mmol·L^-1)	0.163±0.394	0.071±0.316	0.247
LDL-C/(mmol·L^-1)	0.314±1.081	-0.491±0.715	0.000
sd-LDL-C/(mmol·L^-1)	0.123±0.475	-0.320 （-0.595, -0.105）	0.000
HCY/(μmol·L^-1)	0.949±16.297	-8.037±16.825	0.016

Biomarker	Control group （n=45）	MF group （n=38）	P value
GLU/(mmol·L^-1)	0.002±0.923	-0.955 （-3.445, 0.155）	0.001
TC/(mmol·L^-1)	0.122±1.111	-1.082±1.016	0.000
TAG/(mmol·L^-1)	0.055±1.205	-0.675 （-1.273, -0.080）	0.000
HDL-C/(mmol·L^-1)	0.163±0.394	0.071±0.316	0.247
LDL-C/(mmol·L^-1)	0.314±1.081	-0.491±0.715	0.000
sd-LDL-C/(mmol·L^-1)	0.123±0.475	-0.320 （-0.595, -0.105）	0.000
HCY/(μmol·L^-1)	0.949±16.297	-8.037±16.825	0.016

Biomarker	Control group （n=45）			MF group （n=38）
Biomarker	2 week	4 week	8 week	2 week	4 week	8 week
GLU/(mmol·L^-1)	6.22 （5.11, 7.74）	6.17 （5.04, 8.28）	5.98 （5.29, 8.13）	6.24 （5.05, 9.52）^①	5.59 （4.96, 6.35）^②	5.59 （4.92, 6.02）^②
TC/(mmol·L^-1)	5.05±1.06	5.13±0.94	5.03±1.11	4.59±1.04^②	4.28±0.87^②	4.13±0.92^②
TAG/(mmol·L^-1)	2.13 （1.52, 2.89）	2.67±1.64	2.37 （1.58, 3.60）	1.44 （1.16, 2.21）^③	1.33 （1.12, 1.88）^③	1.18 （0.93, 1.68）^②
HDL-C/(mmol·L^-1)	1.11±0.22	1.20±0.32^④	1.13 （1.00, 1.31）^⑤	1.19±0.25^③	1.13±0.26	1.08±0.27
LDL-C/(mmol·L^-1)	2.94±0.80^④	2.96±0.81^⑥	2.98±0.99^⑦	2.70±0.86	2.56±0.77^⑧	2.18 （1.79, 3.01）^①
sd-LDL-C/(mmol·L^-1)	1.14±0.53	1.19±0.50	1.10 （0.92, 1.64）	1.06±0.55^⑨	0.94±0.35^②	0.94±0.41^③
HCY/(μmol·L^-1)	23.90 （18.53, 33.25）	26.57±11.23	23.60 （15.75, 34.05）	19.15 （15.48, 29.40）	16.91±7.83^②	17.20（12.90, 22.03）^⑩