Melkersson Kristina, Berinder Katarina, Hulting Anna-Lena
Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
Neuro Endocrinol Lett. 2011;32(4):428-36.
This study consisting of two subprojects was undertaken to evaluate the effects of hyperprolactinemia on cardiovascular disease (CVD) risk parameters such as anthropometric measures, insulin sensitivity and blood lipids in patients with schizophrenia or related psychoses on long term treatment with antipsychotics.
In subproject Ι, 45 patients receiving the 2nd generation antipsychotics risperidone, clozapine or olanzapine were compared regarding prolactin (PRL), body mass index (BMI), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood lipids. In subproject Π, 24 patients receiving 1st or 2nd generation antipsychotics were investigated with diurnal profile of PRL and oral glucose tolerance test (OGTT).
Elevated PRL levels were found in about 45% of the patients and occurred more often in patients receiving risperidone or haloperidol, compared to patients receiving clozapine or olanzapine. In contrast, in subproject Ι, insulin and HOMA-IR were higher and high density lipoprotein cholesterol was lower in patients receiving clozapine or olanzapine, compared with patients receiving risperidone. However, PRL levels did not correlate to BMI, insulin, HOMA-IR or lipids in any of these three treatment groups. In subproject Π, OGTT showed impaired glucose tolerance in 25% and new-onset diabetes in 4% of the 24 patients investigated. Additionally, the PRL (median 24 h) levels correlated positively to the 2 h glucose level at OGTT (rs=0.42, p=0.04).
Our findings point to that hyperprolactinemia due to 1st and 2nd generation antipsychotics may decrease insulin sensitivity, whereas other mechanisms probably underlie insulin resistance induced by PRL-sparing antipsychotics such as clozapine and olanzapine.
本研究由两个子项目组成,旨在评估高催乳素血症对长期接受抗精神病药物治疗的精神分裂症或相关精神病患者心血管疾病(CVD)风险参数的影响,这些参数包括人体测量指标、胰岛素敏感性和血脂。
在子项目Ⅰ中,比较了45例接受第二代抗精神病药物利培酮、氯氮平或奥氮平治疗的患者的催乳素(PRL)、体重指数(BMI)、胰岛素、胰岛素抵抗稳态模型评估(HOMA-IR)和血脂。在子项目Ⅱ中,对24例接受第一代或第二代抗精神病药物治疗的患者进行了PRL昼夜变化曲线和口服葡萄糖耐量试验(OGTT)。
约45%的患者PRL水平升高,与接受氯氮平或奥氮平治疗的患者相比,接受利培酮或氟哌啶醇治疗的患者中更常出现PRL水平升高。相反,在子项目Ⅰ中,与接受利培酮治疗的患者相比,接受氯氮平或奥氮平治疗的患者胰岛素和HOMA-IR更高,高密度脂蛋白胆固醇更低。然而,在这三个治疗组中的任何一组中,PRL水平均与BMI、胰岛素、HOMA-IR或血脂无关。在子项目Ⅱ中,OGTT显示,在24例接受调查的患者中,25%的患者糖耐量受损,4%的患者新发糖尿病。此外,PRL(24小时中位数)水平与OGTT时的2小时血糖水平呈正相关(rs=0.42,p=0.04)。
我们的研究结果表明,第一代和第二代抗精神病药物所致的高催乳素血症可能会降低胰岛素敏感性,而其他机制可能是氯氮平和奥氮平等不引起高催乳素血症的抗精神病药物所致胰岛素抵抗的基础。