APP下载

首发精神分裂症患者治疗前后血脂、血糖水平变化的研究

2021-12-20张怡邱聪龙周东升陈赞陈寿林刘灵江徐永明吴向平

中国现代医生 2021年27期
关键词:精神分裂症血脂血糖

张怡 邱聪龙 周东升 陈赞 陈寿林 刘灵江 徐永明 吴向平

[關键词] 首发;精神分裂症;血脂;血糖;停药

[中图分类号] R749.3          [文献标识码] A          [文章编号] 1673-9701(2021)27-0025-05

Study on the changes of blood lipid and blood glucose levels before and after treatment of patients with first-episode schizophrenia

ZHANG Yi   QIU Conglong   ZHOU Dongsheng   CHEN Zan   CHEN Shoulin   LIU Lingjiang   XU Yongming

WU Xiangping

Department of Psychiatry, Ningbo Kangning Hospital, Ningbo   315201, China

[Abstract] Objective To observe the changes of blood lipid and blood glucose levels in patients with first-episode schizophrenia before and after treatment. Methods A total of 109 patients with first-episode schizophrenia (the observation group) and 113 healthy check-ups (the control group) from the Department of Psychiatry of Ningbo Kangning Hospital from January 2017 to June 2018 were selected as the study subjects. Their blood lipid and blood glucose levels in peripheral blood before treatment and at 1 month, 12 months and 18 months after treatment were observed. Based on the presence or absence of medicine-taking after discharge, the observation group was divided into a medicated group (with 55 cases) and an unmedicated group (with 54 cases), and the levels of blood lipid and blood glucose before and after treatment were compared between the two groups. Results Before treatment, the levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), apolipoprotein B (apoB), Lipoproteins (LPa), phospholipids (PLIP) and lipase (LPS) in the observation group were lower than those in the control group, and apolipoprotein A1 (apoA1) level was higher than that in the control group. After treatment, the levels of TC, HDL, apoB, LPa, PLIP, LPS and glucose (Glu) in the observation group were lower than those in the control group, and apoA1 level was higher than that in the control group. The observation group was compared before and after treatment, the levels of HDL, apoA1 and Glu decreased compared with those before treatment, and TG level increased compared with those before treatment. All the above-mentioned differences were statistically significant(P<0.05). In the unmedicated group, TG and apoB levels after treatment were higher than those before treatment, while apoA1 and apolipoprotein E (APOE) levels were lower than those before treatment. At 18 months after treatment, the levels of HDL, LDL, apoA1 and Glu were lower than those before treatment, while apoB and LPa levels were higher than those before treatment in the medicated group. In the un medicated group, the levels of HDL, apoA1, LPS and Glu after treatment were lower than those before treatment, while the levels of TG, apoB and LPa were higher than those before treatment. All the above-mentioned differences were statistically significant(P<0.05). Conclusion The levels of TC, TG, HDL, apoB, LPa, PLIP and LPS are low in patients with schizophrenia. The increase of TG level predicts the improvement of disease condition. Short-term medicine-taking can cause HDL, apoA1 and Glu levels to decrease, TG level to increase. Long-term medicine-taking can cause apoA1 level to decrease. Interruption of medicine-taking can cause apoA1 and LPS levels to decrease. After drug withdrawal, TG and apoB levels may increase, while apoA1 and APOE levels may decrease, and HDL and Glu levels may return to unmedicated levels.

[Key words] First episode; Schizophrenia; Blood lipid; Blood glucose; Drug withdrawal

精神分裂症临床表现为一系列的幻觉妄想综合征,对患者的社会功能、劳动能力造成极大的损害,有研究显示,该疾病是心血管疾病的高危因素,继而影响患者寿命[1]。代谢综合征是心血管疾病危险因素,主要表现为脂肪、蛋白质等代谢紊乱导致的一种病理状态,血脂、血糖(Blood glucose,Glu)水平的紊乱是其一重要标志。精神分裂症可能会影响患者的血脂[2]、血糖[3]水平,服用抗精神病药物更会引起血脂、血糖代谢异常,诱发代谢综合征[4-5]。但是,抗精神病药物是当前治疗精神分裂症的主要药物,使用率高[6]。所以,明确精神分裂症及抗精神病药物与血脂、血糖之间的关系有较大意义。虽然此类研究较多,但结论不一[7-8],且关于长期服药、中断服药、精神分裂症本身对血脂、血糖水平的影响,尤其是外周血中载脂蛋白A1(Apolipoprotein A1,apoA1)、载脂蛋白B(Apolipoprotein B,apoB)、脂蛋白(Lipoproteins,LPa)、磷脂(Phospholipid,PLIP)、血清脂肪酶(Lipase,LPS)、载脂蛋白E(Apolipoprotein E,APOE)水平的影响阐述较少,本研究就此展开观察与进一步研究,现报道如下。

1 资料与方法

1.1 一般资料

选取2017年1月至2018年6月在宁波市康宁医院精神科住院的109例首发精神分裂症患者(观察组)和113名健康体检者(对照组)作为研究对象。观察组在接受抗精神病药物前、接受药物后1个月及第12、18个月出院后在门诊随访时检测外周血中血脂、血糖水平。首次住院周期不大于2个月,治疗效果均为好转;出院后第12、18个月至门诊随访,根据第12个月随访时有无服药,将观察组分为服药组55例和未服药组54例。观察组109例,男50例,女59例;年龄13~65岁,平均(39.08±14.97)岁;对照组113名,男51名,女62名;年龄9~79岁,平均(42.56±15.64)岁。两组性别构成、年龄、收缩压、舒张压、腰围、体重、BMI、空腹血糖、吸烟情况、高血压家族史、高脂血症家族史、糖尿病家族史比较,差异无统计学意义(P>0.05),具有可比性。见表1。本研究符合医院医学伦理要求,且所有患者均签订知情同意书。

所有受试者均为宁波本地户口居民,一日三餐,主食为米饭,进食规律,饮食结构基本相同。观察组诊断需符合国际疾病分类第10版(International classification of diseases,ICD-10)精神与行为障碍分类中的F20“精神分裂症”诊断标准,且均为首发患者。服药组为18个月研究期间,连续足量、按时服药的观察组受试者。未服药组为第12个月随访时发现未连续服药,且第12个月前已至少连续6个月未服用抗精神病药物,并在第12个月后继续给予原抗精神病药物种类、剂量治疗的观察组受试者。

排除标准:①既往有癫痫、惊厥、脑肿瘤等中枢神经器质性疾病史者;②既往有酒精、鸦片类、大麻类等及其他精神活性物质依赖史者;③患有严重心血管、肝、肾、血液、内分泌等疾病者;④怀孕或处于哺乳期者;⑤既往有高脂血症、糖尿病、痛风等内分泌代谢性疾病史者;⑥近期服用影响血脂、血糖水平药物者,如肾上腺皮质激素、性激素、甲状腺激素类药物,利尿剂等。

1.2 方法

所有研究对象前3 d清淡饮食,以素食为主,并于检查前保证空腹12~14 h,入院次日,抽取晨起安静状态下静脉血3 mL,离心10 min,2500 r/min,分离血清标本,放置于-20℃下保存待测。

三酰甘油(Triglyceride,TG)、Glu采用氧化酶法测定,总胆固醇(Total cholesterol,TC)采用CHOD-PAP法测定,血清高密度脂蛋白(Serum high-density lipoprotein,HDL)、血清低密度脂蛋白(Serum low-density lipoprotein,LDL)采用一步酶法测定,apoA1、apoB、LPa、LPS、APOE采用免疫比浊法测定,PLIP采用胆碱氧化酶法测定。所有标本均在AU5800全自动生化分析仪器上测定,操作过程严格按照说明书要求进行。在接受抗精神病药物前、接受药物后1个月及第12、18个月出院后检测血脂、血糖水平。

1.3 观察指标

观察血脂、血糖水平,包括TC、TG、HDL、LDL、apoA1、apoB、LPa、PLIP、LPS、APOE及Glu。

1.4 统计学方法

采用 SPSS 25.0统计学软件对数据进行分析,符合正态分布及方差齐性的计量资料以均数±标准差(x±s)表示,组间比较采用独立样本t检验,组内比较采用配对样本t检验;计数资料以[n(%)]表示,组间比较采用χ2检驗,P<0.05为差异有统计学意义

2 结果

2.1 观察组治疗前后血脂、血糖水平与对照组的比较

治疗前观察组TC、TG、HDL、apoB、LPa、PLIP、LPS水平低于对照组,apoA1水平高于对照组;治疗后,观察组TC、HDL、apoB、LPa、PLIP、LPS、Glu水平低于对照组,apoA1水平高于对照组;观察组治疗前后比较,HDL、apoA1、Glu水平较前下降,TG水平较前升高,差异均有统计学意义(P<0.05)。见表2。

2.2 未服药组治疗前与治疗后12个月时血脂、血糖水平比较

未服药组TG、apoB水平较治疗前升高;apoA1、APOE水平较治疗前下降,差异有统计学意义(P<0.05)。见表3。

2.3 服藥组、未服药组治疗前与治疗后18个月时血脂、血糖水平比较

服药组治疗后18个月时HDL、LDL、apoA1、Glu水平低于治疗前,apoB、LPa水平高于治疗前;未服药组18个月时HDL、apoA1、LPS、Glu水平低于治疗前,TG、apoB、LPa水平高于治疗前,差异有统计学意义(P<0.05)。见表4。

3 讨论

多项流行病学调查、临床研究显示,精神分裂症患者在服用抗精神病药物前,就已经存在血脂、血糖水平的代谢紊乱[9-10]。一项横断面调查显示,超过半数的首发精神分裂症患者血脂水平存在异常[11]。

本研究发现首发精神分裂症患者TC、TG、HDL、apoB、LPa、PLIP、LPS水平低于健康对照组,apoA1水平高于健康对照组,与朱文标等[12]研究结果一致。薛永等[13]发现,精神分裂症患者TC、LDL、apoA1、apoB、HDL水平均低于健康对照组。万凤等[14]也发现,首发精神分裂症患者的血脂异常,主要表现为HDL水平降低。故HDL水平降低,是被发现较多的结论之一,推测原因可能是HDL水平在体内主要起到逆向转运胆固醇,抑制血栓、氧化应激、抗动脉硬化、抑制炎症的作用,低HDL水平是代谢综合征的高危因素[15],而精神分裂症患者是代谢综合征的易感人群。另外,本研究发现患者的Glu水平在服药前与正常人群没有差异,可能与胰岛素抵抗[4]有关,由于精神分裂症等原因导致体内的胰岛素对葡萄糖的摄取、转化、利用障碍,从而分泌过量的胰岛素[16],以达到控制血糖至正常水平,是一种代偿机制。

患者服药1个月后,病情好转,TG水平由低于正常上升至与对照组无差异,表明TG水平升高,是病情好转的信号,与薛永等[13]研究结果一致。有人认为精神分裂症患者在未治疗时思维紊乱增多,行为忙碌,是增加体脂代谢加快的缘故,随着病情控制,体能活动减少,思维紊乱得到控制,血脂水平逐步恢复正常。本研究发现,长期服用抗精神病药物与短期服药的患者,其血脂、血糖水平变化呈现不同的趋势。短期连续服用抗精神病药物会使患者的HDL、apoA1、Glu水平下降,TG水平升高,与朱文标等[12]研究结果基本一致;长期连续服用抗精神病药物会使患者的apoA1水平下降,apoB、LPa水平升高,与薛永等[13]研究部分一致,较为明确的是短期服药,会使TG水平升高,HDL水平下降,长期表现则显示apoB水平升高明显。

另外,中断服药6个月以上的患者,其apoA1、LPS水平下降,apoB水平升高;该结果与18个月内连续服药患者数据相仿;比对未服药组12个月时与治疗前发现,患者的TG、apoB水平升高,apoA1、APOE水平降低,HDL、Glu水平恢复至未服药水平;表明抗精神病药物对患者的血脂水平影响较为持久,长期停药后,短期再服药对血脂影响并不大。与郭红中[17]的研究结果相仿,其原因可能是精神分裂症患者随着疾病的进展,阴性症状不断加重[18],药物及疾病导致的认知功能损伤加深,病耻感强烈,导致其不愿接触社会,退缩家中并少活动,继而形成不健康的饮食及生活方式,引起患者肥胖,引发血脂、血糖水平异常[19-20]。

综上所述,首发精神分裂症患者的血脂、血糖水平受多因素影响,其中的机制涉及多种神经递质的改变,多种传导通路的变化,服用抗精神病药物无论短期、长期,或是停药,都会对血脂、血糖水平产生不同影响,需进一步探索与展开临床研究。

[参考文献]

[1] Mamakou V,Thanopoulou A,Gonidakis F,et al. Schizophrenia and type 2 diabetes mellitus[J]. Psychiatrike=Psychiatriki,2018,29(1):64-73.

[2] Veru-lesmes F,Rho A,Joober R,et al. Socioeconomic deprivation and blood lipids in first-episode psychosis patients with minimal antipsychotic exposure:Implications for cardiovascular risk[J]. Schizophrenia Research,2020,216(2):111-117.

[3] Turangan DR,Loebis B,Husada SM,et al. Differences of fasting blood glucose level in people with schizophrenia between before and after getting aripiprazole treatment[J]. Open Access Macedonian Journal of Medical Sciences,2019,7(16):2607-2611.

[4] Guest PC. Insulin resistance in schizophrenia[J]. Advances in Experimental Medicine and Biology,2019,1134(2):1-16.

[5] Li S,Gao Y,Lv H,et al. T(4)and waist:Hip ratio as biomarkers of antipsychotic-induced weight gain in Han Chinese inpatients with schizophrenia[J]. Psychoneuroendocrinology,2018,88(3):54-60.

[6] Górska N,S?覥upski J,Cuba?覥aw J. Antipsychotic drugs in epilepsy[J]. Neurologia I neurochirurgia Polska,2019,53(6):408-412.

[7] 邓顺顺,平军娇,杨建明. 精神分裂症伴高同型半胱氨酸血症患者治疗前后尿酸与糖脂代谢变化的研究[J]. 检验医学与临床,2020,17(3):347-349,353.

[8] 朱意平,李春阳,陈红红,等. 住院精神分裂症患者合并代谢综合征的影响因素[J]. 四川精神卫生,2018,31(6):540-543.

[9] Chen CH,Shyue SK,Hsu CP,et al. Atypical antipsychotic drug olanzapine deregulates hepatic lipid metabolism and aortic inflammation and aggravates atherosclerosis[J]. Cellular Physiology and Biochemistry:International Journal of Experimental Cellular Physiology,Biochemistry,and Pharmacology,2018,50(4):1216-1229.

[10] Grajales D,Ferreira V,Valverde ■M. Second-generation antipsychotics and dysregulation of glucose metabolism:Beyond weight gain[J]. Cells,2019,8(11):1136.

[11] Penninx B,Lange SMM. Metabolic syndrome in psychiatric patients:Overview,mechanisms,and implications[J].Dialogues in Clinical Neuroscience,2018,20(1):63-73.

[12] 朱文标,朱弈璇,陈策,等. 首发精神分裂症患者血糖和血脂代谢情况及奥氮平治疗的影响[J]. 中华全科医学,2016,14(11):1832-1834,1954.

[13] 薛永,程险峰,沈冲,等. 首发精神分裂症患者治疗前后血清游离脂肪酸和血脂水平变化及临床意义[J]. 中国医药导报,2014,11(31):56-60.

[14] 萬凤,陈周文,戎笛声,等. 首发未服药精神分裂症患者糖脂代谢研究[J]. 精神医学杂志,2015,28(3):190-191.

[15] Roever L,Resende ES,Diniz ALD,et al. High-density lipoprotein-cholesterol functionality and metabolic syndrome:Protocol for review and meta-analysis[J]. Medicine,2018,97(24):e11 094.

[16] Soontornniyomkij V,Lee EE,Jin H,et al. Clinical correlates of insulin resistance in chronic schizophrenia:Relationship to negative symptoms[J]. Frontiers in Psychiatry,2019,23(10):251.

[17] 郭红中. 长期服用抗精神病药治疗对精神分裂症患者肝脏及血脂水平的影响[J]. 人人健康,2019,10(20):218.

[18] Galderisi S,Mucci A,Buchanan RW,et al. Negative symptoms of schizophrenia:New developments and unanswered research questions[J]. The Lancet Psychiatry,2018, 5(8):664-677.

[19] Porcelli S,Van der wee N,Van der werff S,et al. Social brain,social dysfunction and social withdrawal[J]. Neuroscience and Biobehavioral Reviews,2019,97(2):10-33.

[20] 蒋庆,曹亚琴. 巩固维持期精神分裂症患者血脂异常的影响因素[J]. 中国民康医学,2018,30(13):97-99.

(收稿日期:2020-11-30)

猜你喜欢

精神分裂症血脂血糖
细嚼慢咽,对减肥和控血糖有用么
一吃饺子血糖就飙升,怎么办?
食品防腐剂治疗精神分裂症,靠谱吗
血脂常见问题解读
你了解“血脂”吗
妊娠期血糖问题:轻视我后果严重!
猪的血糖与健康
五行音乐疗法对慢性精神分裂症治疗作用的对照研究
脑尔新胶嚢治疗精神分裂症的初步临床观察
氨磺必利治疗精神分裂症