Palik E, Birkás K D, Faludi G, Karádi I, Cseh K
Semmelweis University Third Department of Internal Medicine, Budapest, Hungary.
Diabetes Res Clin Pract. 2005 Jun;68 Suppl1:S60-4. doi: 10.1016/j.diabres.2005.03.008. Epub 2005 Apr 7.
The prevalence of diabetes mellitus and metabolic syndrome is higher in patients with schizophrenia than in the normal population. Atypical antipsychotic drugs are used in psychiatry since the beginning of 1990. These drugs differ from the "typical" antipsychotics used previously, as they have less extrapyramidal side effects, and because of this they are tolerated better, but are associated with weight-gain and disturbances in carbohydrate metabolism. Ghrelin is an orexigen hormone partaking in body weight regulation. It is produced in the enteroendocrine P/D1 cells of the gastric mucosa and secreted to the circulation. The aim of our study was to determine ghrelin levels of atypical antipsychotic-treated patients in relationship with their body mass index (BMI) and carbohydrate metabolism. We measured the fasting serum ghrelin levels in 56 patients (male/female: 16/40, age mean+/-S.D.: 50.6+/-5.6 years) treated with atypical antipsychotics (clozapine, olanzapine, risperidon and quetiapine), and in 75 healthy control subjects, age and gender matched (RIA Linco, USA) in relationship with their BMI and their fasting and 75 g OGTT 120 min blood glucose values. The serum ghrelin levels of the patient group were notably higher (1333+/-659 pg/ml) than in the control group (368+/-103, p<0.0001; Mann-Whitney). We found no difference among the four antipsychotics in weight-gain, diabetes prevalence and the serum ghrelin levels. The BMI of the patient group was significantly higher (29.3+/-7.2 kg/m2 versus 24.3+/-3.7 kg/m2, p<0.0001; Mann-Whitney); 32% of them had blood glucose abnormality (18/56). There was no difference between the ghrelin levels in diabetic and non-diabetic patients. We found a significant negative linear correlation between the serum ghrelin and BMI (r=-0.35, p=0.0078; Spearman), the ghrelin and fasting blood glucose (r=-0.32, p=0.015) and OGTT 75 g 120 min blood glucose levels (r=-0.27, p=0.036). The orexigen effect of elevated serum ghrelin levels can contribute to the weight-gain and high diabetes prevalence associated with atypical antipsychotic treatment. The link between atypical antipsychotic treatment and elevated serum ghrelin levels is unknown so far, but a dysregulation of the central feedback mechanism can be hypothesised.
精神分裂症患者中糖尿病和代谢综合征的患病率高于正常人群。自20世纪90年代初以来，非典型抗精神病药物开始用于精神病学领域。这些药物与先前使用的“典型”抗精神病药物不同，因为它们的锥体外系副作用较少，因此耐受性更好，但与体重增加和碳水化合物代谢紊乱有关。胃饥饿素是一种参与体重调节的促食欲激素。它由胃黏膜的肠内分泌P/D1细胞产生并分泌到循环中。我们研究的目的是确定接受非典型抗精神病药物治疗的患者的胃饥饿素水平与其体重指数（BMI）和碳水化合物代谢之间的关系。我们测量了56例接受非典型抗精神病药物（氯氮平、奥氮平、利培酮和喹硫平）治疗的患者（男/女：16/40，年龄均值±标准差：50.6±5.6岁）以及75名年龄和性别匹配的健康对照者（美国RIA Linco公司）的空腹血清胃饥饿素水平，同时测量了他们的BMI、空腹血糖以及75g口服葡萄糖耐量试验（OGTT）120分钟时的血糖值。患者组的血清胃饥饿素水平显著高于对照组（1333±659 pg/ml比368±103，p<0.0001；曼-惠特尼检验）。我们发现四种抗精神病药物在体重增加、糖尿病患病率和血清胃饥饿素水平方面没有差异。患者组的BMI显著更高（29.3±7.2 kg/m² 对 24.3±3.7 kg/m²，p<0.0001；曼-惠特尼检验）；其中32%的患者有血糖异常（18/56）。糖尿病患者和非糖尿病患者的胃饥饿素水平没有差异。我们发现血清胃饥饿素与BMI之间存在显著的负线性相关（r=-0.35，p=0.0078；斯皮尔曼检验），与空腹血糖之间也存在显著负线性相关（r=-0.32，p=0.015），与OGTT 75g 120分钟血糖水平之间同样存在显著负线性相关（r=-0.27，p=0.036）。血清胃饥饿素水平升高的促食欲作用可能导致与非典型抗精神病药物治疗相关的体重增加和高糖尿病患病率。到目前为止，非典型抗精神病药物治疗与血清胃饥饿素水平升高之间的联系尚不清楚，但可以推测中枢反馈机制存在失调。
