Lilly Research Laboratories, Indianapolis, IN, USA.
Diabetes Obes Metab. 2011 Aug;13(8):726-35. doi: 10.1111/j.1463-1326.2011.01398.x.
To assess changes in insulin sensitivity in non-diabetic adults with schizophrenia or schizoaffective disorder treated with olanzapine or risperidone.
One hundred and thirty patients were randomly assigned to 12 weeks double-blind treatment with olanzapine or risperidone. Insulin sensitivity was measured using a two-step euglycaemic, hyperinsulinaemic clamp procedure. Whole-body adiposity was measured using dual-energy X-ray absorptiometry. The primary endpoint was the within-group change from baseline in insulin sensitivity normalized to fat-free mass (M(ffm) /I) during the clamp procedure's low-insulin phase, using an analysis of covariance model including the covariate weight change.
Forty-one olanzapine-treated and 33 risperidone-treated patients completed baseline and endpoint clamp measurements. Mean M(ffm) /I during the low-insulin phase declined 9.0% (p = 0.226) in olanzapine-treated patients and 13.2% (p = 0.047) in risperidone-treated patients (between-group difference p = 0.354). During the high-insulin phase, M(ffm) /I declined 10.4% (p = 0.036) in olanzapine-treated patients and 2.1% (p = 0.698) in risperidone-treated patients (between-group difference p = 0.664). Changes in M(ffm) /I correlated inversely with changes in body weight and adiposity, which were generally higher in olanzapine-treated patients. Significant within-group increases in fasting glucose, but not haemoglobin A1c (HbA1c), were observed during olanzapine treatment. The fasting glucose change was not correlated with M(ffm) /I changes.
Small, but statistically significant, decrements in insulin sensitivity were observed in olanzapine- and risperidone-treated patients at 1 of 2 insulin doses tested. Significant increases in fasting glucose and insulin and total fat mass were observed only in olanzapine-treated patients. Changes in insulin sensitivity correlated significantly with changes in weight or adiposity, but not with changes in glucose.
评估非糖尿病精神分裂症或分裂情感障碍患者在使用奥氮平或利培酮治疗后的胰岛素敏感性变化。
130 名患者被随机分配接受 12 周的奥氮平或利培酮双盲治疗。使用两步法血糖正常、高胰岛素钳夹程序测量胰岛素敏感性。使用双能 X 射线吸收法测量全身脂肪量。主要终点是钳夹程序低胰岛素期内，根据协变量体重变化，用协方差模型分析，对正常化到去脂体重的胰岛素敏感性（M（ffm）/I）的组内基线变化。
41 名奥氮平治疗和 33 名利培酮治疗的患者完成了基线和终点钳夹测量。奥氮平治疗组低胰岛素期内 M（ffm）/I 平均下降 9.0%（p=0.226），利培酮治疗组下降 13.2%（p=0.047）（组间差异 p=0.354）。在高胰岛素期，奥氮平治疗组 M（ffm）/I 下降 10.4%（p=0.036），利培酮治疗组下降 2.1%（p=0.698）（组间差异 p=0.664）。M（ffm）/I 的变化与体重和脂肪量的变化呈负相关，而这些变化在奥氮平治疗组中通常更高。在奥氮平治疗期间，观察到空腹血糖显著升高，但血红蛋白 A1c（HbA1c）无显著升高。空腹血糖的变化与 M（ffm）/I 的变化无关。
在 2 种胰岛素剂量测试中，奥氮平和利培酮治疗的患者均出现胰岛素敏感性的微小但具有统计学意义的降低。仅在奥氮平治疗组观察到空腹血糖和胰岛素以及总脂肪量的显著增加。胰岛素敏感性的变化与体重或脂肪量的变化显著相关，但与血糖的变化无关。
