氯氮平和经典抗精神病药的长期治疗对患者体重、糖代谢及血脂的影响

The effects of long duration treatment of clozapine and typical antipsychotics on patients' body weight,metabolism of glucose and lipids

目的探讨长期应用氯氮平和经典类抗精神病药(APS)对精神分裂症患者体重、血糖和血脂等代谢指标的影响及其可能的相关因素。方法共调查使用APS≥5年的精神分裂症患者271例,分别测量其身高和体重,检测空腹和餐后2h血糖、空腹血清游离脂肪酸、血清胰岛素和瘦素水平。按药物使用情况将患者分为氯氮平组、经典APS单一治疗组(经典组)或联合用药组进行比较。结果①联合用药组体质量指数、空腹血糖、血甘油三酯和血游离脂肪酸水平均显著高于经典组(P<0·05);血胰岛素和胰岛素抵抗指数也均显著高于经典组和氯氮平组(P<0·05)。②氯氮平组和联合用药组糖耐量降低和2型糖尿病发生率均明显高于经典组(P<0·05)。③患者体质量指数与其空腹血糖、血清瘦素、血甘油三酯、胆固醇水平以及与胰岛素抵抗指数均呈正相关(P均小于0·05);患者血清瘦素水平与其血胰岛素水平也呈正相关(P=0·008)。④多元逐步线型回归分析表明,进入影响空腹血糖水平方程的因素分别为胰岛素抵抗指数、血胰岛素、胆固醇和体质量指数(P<0·05)。结论单用氯氮平及其与经典抗精神病药联用,均易导致患者肥胖,且易导致患者血糖、血脂、血游离脂肪酸水平升高,并与胰岛素抵抗和糖耐量降低发生相关,可能增加2型糖尿病的发生。

Objective To explore how the long duration treatment of clozapine and typical antipsychotics （APS） impacted on body weight, fasting blood glucose and serum lipids in schizophrenic patients. Methods 271 cases of schizophrenic patients with more than 5 year treatment were investigated. The height and body weight, fasting and 2-hour after meal blood glucose, fasting serum free fatty acids（ FFA）, serum insulin and leptin level of all patients were measured re- spectively. All patients were divided into three groups： single-use clozapine group （SCG）, single-use typical APS group （SAPSG） and co-use of colzapine and typical APS group （CUG）. Results ①The body weight, fasting blood glucose, blood glyceride, and serum FFA levels in the patients of CUG were markedly higher than those in patients of SAPSG （ All P 〈0.05 ）. Serum insulin levels and Homeostasis model of assessment of insulin resistance （HOMA-IR） in patients of CUG were also remarkably higher than those in patients of SAPSG and SCG （ P 〈 O.05 ）. ②The incidence rates of impaired glucose tolerance （IGT） and type 2 diabetes mellitus in patients of SCG and CUG were significantly higher than those in patients of SAPSG （ P 〈 0.05 ）. ③The body mass index of patients were positively correlated with fasting blood glucose, serum leptin levels, blood glyceride, cholesterol, and HOMA-IR, respectively （ r = 0.154, 0.557,0. 436, 0.199, and 0.144, respectively;P 〈0.05）. Serum leptin levels were also positively correlated with insulin （r =0.194, P =0.008）.④Multiple stepwise linear regression analysis indicated that all variables enterin~ into the fourth multivariate model at the0.05 significance level were HOMA-IR, serum insulin, serum cholesterol, and body mass index; （ R^2 = 0.829）. Conclusions Long duration of clozapine either alone or in combination with typical antipsychoties both easily induced elevations of body weight, fasting blood glucose, serum lipids, and serum FFA. These elevations might relate to insulin resistance and IGT, and increase the incidence of type 2 diabetes mellitus.