氯氮平治疗精神分裂症血糖控制异常危险增大
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英国的一项新研究说，服用氯氮平的精神分裂症病人血糖控制异常的危险增大见（Am J Psychiatry 2004 Feb;161:2:361-3）。
以前的研究发现，氯氮平增加了胰岛素水平，表明此药可能引起胰岛素耐受性，但还缺乏此药影响葡萄糖-胰岛素内环境稳定性的资料。为此，伦敦精神病学研究所的豪伊斯（Oliver D. Howes）和同事检查了20名单用氯氮平治疗的精神分裂症病人的血糖控制和胰岛素敏感性。
研究开始时，病人都没有糖尿病或在接受控制血糖的治疗，也没有其它与葡萄糖不耐受有关的疾病。在基线评估后，根据每位病人的临床反应调整了氯氮平的用量。研究初、2-4月间按ＷＨＯ的规定在禁食后9小时用标准的葡萄糖耐量试验测量了血糖水平，用内环境稳定模型评估法评估了胰岛素耐性，用高效液相层析测量了氯氮平水平。
结果表明，55%的病人糖耐量开始出现异常，其中1人发展为糖尿病，2人空腹血糖受损，8人血糖耐量异常。治疗后血糖控制异常的病人比例比治疗前显著增加（P = .006）。平均空腹血糖水平（0.55 mmol/L）和平均2小时血糖水平（1.4 mmol/L）也显著增高，但胰岛素水平、胰岛素耐性和平均身体质量指数无显著变化。
“就我们所知，这是第一个表明氯氮平治疗4个月内血浆血糖浓度增加而胰岛素耐性或身体质量指数没变的研究”，作者写道，因此，医生在决定给予氯氮平治疗时，需要考虑多糖症和糖尿病的危险。
A Prospective Study of Impairment in Glucose Control Caused by Clozapine Without Changes in Insulin Resistance
OBJECTIVE: This prospective study examines the effect of clozapine on glucose control and insulin sensitivity.
METHOD: Glucose homeostasis was measured in nine female and 11 male patients with schizophrenia (mean age=30.5 years, SD=7.4) before clozapine treatment and after a mean of 2.5 months (SD=0.95) of clozapine treatment. Oral glucose tolerance and insulin levels were measured. Insulin resistance level was measured by the homeostasis model assessment.
RESULTS: Eleven (55%) of the patients developed abnormal glucose control; the mean age of these patients was 30.2 (SD=7.1), and five were women. Patients’ insulin resistance at baseline (mean insulin resistance level=3.88, SD=2.93) was unaffected by clozapine. Mean fasting and 2-hour glucose levels significantly increased by 0.55 mmol/liter and 1.4 mmol/liter, respectively. There was no correlation between change in body mass index and change in fasting glucose levels.
CONCLUSIONS: Clozapine impairs glucose control within 4 months of treatment, independent of changes in insulin sensitivity and body mass index.
Am J Psychiatry 2004 Feb;161:2:361-3
原文！！
以前的研究发现，氯氮平增加了胰岛素水平，表明此药可能引起胰岛素耐受性，但还缺乏此药影响葡萄糖-胰岛素内环境稳定性的资料。为此，伦敦精神病学研究所的豪伊斯（Oliver D. Howes）和同事检查了20名单用氯氮平治疗的精神分裂症病人的血糖控制和胰岛素敏感性。
研究开始时，病人都没有糖尿病或在接受控制血糖的治疗，也没有其它与葡萄糖不耐受有关的疾病。在基线评估后，根据每位病人的临床反应调整了氯氮平的用量。研究初、2-4月间按ＷＨＯ的规定在禁食后9小时用标准的葡萄糖耐量试验测量了血糖水平，用内环境稳定模型评估法评估了胰岛素耐性，用高效液相层析测量了氯氮平水平。
结果表明，55%的病人糖耐量开始出现异常，其中1人发展为糖尿病，2人空腹血糖受损，8人血糖耐量异常。治疗后血糖控制异常的病人比例比治疗前显著增加（P = .006）。平均空腹血糖水平（0.55 mmol/L）和平均2小时血糖水平（1.4 mmol/L）也显著增高，但胰岛素水平、胰岛素耐性和平均身体质量指数无显著变化。
“就我们所知，这是第一个表明氯氮平治疗4个月内血浆血糖浓度增加而胰岛素耐性或身体质量指数没变的研究”，作者写道，因此，医生在决定给予氯氮平治疗时，需要考虑多糖症和糖尿病的危险。
A Prospective Study of Impairment in Glucose Control Caused by Clozapine Without Changes in Insulin Resistance
OBJECTIVE: This prospective study examines the effect of clozapine on glucose control and insulin sensitivity.
METHOD: Glucose homeostasis was measured in nine female and 11 male patients with schizophrenia (mean age=30.5 years, SD=7.4) before clozapine treatment and after a mean of 2.5 months (SD=0.95) of clozapine treatment. Oral glucose tolerance and insulin levels were measured. Insulin resistance level was measured by the homeostasis model assessment.
RESULTS: Eleven (55%) of the patients developed abnormal glucose control; the mean age of these patients was 30.2 (SD=7.1), and five were women. Patients’ insulin resistance at baseline (mean insulin resistance level=3.88, SD=2.93) was unaffected by clozapine. Mean fasting and 2-hour glucose levels significantly increased by 0.55 mmol/liter and 1.4 mmol/liter, respectively. There was no correlation between change in body mass index and change in fasting glucose levels.
CONCLUSIONS: Clozapine impairs glucose control within 4 months of treatment, independent of changes in insulin sensitivity and body mass index.
Am J Psychiatry 2004 Feb;161:2:361-3
原文！！
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