氯氮平治疗精神分裂症血糖控制异常危险增大
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【据Docguide.com2004年3月2日讯】据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《美国精神病学杂志》（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。
原文：Am J Psychiatry 2004 Feb;161:2:361-3 附摘要：
A prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance.
Howes OD, Bhatnagar A, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS.
Division of Psychological Medicine, Insitute of Psychiatry, London, UK. sphaoah@iop.kcl.ac.uk
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.
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。
原文：Am J Psychiatry 2004 Feb;161:2:361-3 附摘要：
A prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance.
Howes OD, Bhatnagar A, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS.
Division of Psychological Medicine, Insitute of Psychiatry, London, UK. sphaoah@iop.kcl.ac.uk
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.
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