Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
J Clin Endocrinol Metab. 2010 Jan;95(1):118-25. doi: 10.1210/jc.2008-1815. Epub 2009 Nov 11.
A large body of evidence suggests that antipsychotic drugs cause body weight gain and type 2 diabetes mellitus, and atypical (new generation) drugs appear to be most harmful. The aim of this study was to determine the effect of short-term olanzapine (atypical antipsychotic drug) and haloperidol (conventional antipsychotic drug) treatment on glucose and lipid metabolism.
Healthy normal-weight men were treated with olanzapine (10 mg/d; n = 7) or haloperidol (3 mg/d, n = 7) for 8 d. Endogenous glucose production, whole body glucose disposal (by [6,6-(2)H(2)]glucose dilution), lipolysis (by [(2)H(5)]glycerol dilution), and substrate oxidation rates (by indirect calorimetry) were measured before and after intervention in basal and hyperinsulinemic condition.
Olanzapine hampered insulin-mediated glucose disposal (by 1.3 mg x kg(-1) x min(-1)), whereas haloperidol did not have a significant effect. Endogenous glucose production was not affected by either drug. Also, the glycerol rate of appearance (a measure of lipolysis rate) was not affected by either drug. Olanzapine, but not haloperidol, blunted the insulin-induced decline of plasma free fatty acid and triglyceride concentrations. Fasting free fatty acid concentrations declined during olanzapine treatment, whereas they did not during treatment with haloperidol.
Short-term treatment with olanzapine reduces fasting plasma free fatty acid concentrations and hampers insulin action on glucose disposal in healthy men, whereas haloperidol has less clear effects. Moreover, olanzapine, but not haloperidol, blunts the insulin-induced decline of plasma free fatty acids and triglyceride concentrations. Notably, these effects come about without a measurable change of body fat mass.
大量证据表明，抗精神病药物会导致体重增加和 2 型糖尿病，而非典型（新一代）药物的危害似乎更大。本研究旨在确定短期奥氮平（非典型抗精神病药）和氟哌啶醇（传统抗精神病药）治疗对葡萄糖和脂质代谢的影响。
健康正常体重男性接受奥氮平（10mg/d；n=7）或氟哌啶醇（3mg/d，n=7）治疗 8 天。在基础和高胰岛素状态下，分别在干预前后测量内源性葡萄糖生成、全身葡萄糖处置（通过 [6,6-(2)H(2)]葡萄糖稀释）、脂肪分解（通过 [(2)H(5)]甘油稀释）和底物氧化率（通过间接测热法）。
奥氮平阻碍了胰岛素介导的葡萄糖处置（减少 1.3mg x kg(-1) x min(-1)），而氟哌啶醇则没有显著影响。两种药物均不影响内源性葡萄糖生成。此外，甘油的出现率（脂肪分解率的一种衡量标准）也不受任何一种药物的影响。奥氮平而非氟哌啶醇可减弱胰岛素诱导的血浆游离脂肪酸和甘油三酯浓度下降。奥氮平治疗期间空腹游离脂肪酸浓度下降，而氟哌啶醇治疗期间则未下降。
短期奥氮平治疗可降低健康男性的空腹血浆游离脂肪酸浓度，并阻碍胰岛素对葡萄糖处置的作用，而氟哌啶醇的作用则不那么明显。此外，奥氮平而非氟哌啶醇可减弱胰岛素诱导的血浆游离脂肪酸和甘油三酯浓度下降。值得注意的是，这些作用是在没有可测量的体脂质量变化的情况下产生的。
