详细记录  
题名:Insulin secretion in patients receiving clozapine, olanzapine, quetiapine and risperidone.
作者:MANU P; CORRELL CU; WAMPERS M; VAN WINKEL R; YU W; SHIFFELDRIM D; KANE JM; DE HERT M;
来源:Schizophr Res. 2013 Feb;143(2-3):358-62. doi: 10.1016/j.schres.2012.11.016. Epub [ IF= 0.00 ] ]
URL :10.1016/j.schres.2012.11.016
日期:20130228
摘要:BACKGROUND: Second-generation antipsychotics (SGAs) increase the risk of type 2
diabetes. The mechanism is thought to center on drug-induced weight gain, which
starts the dysmetabolic cascade of insulin resistance, increased insulin
production and pancreatic beta-cell failure. An independent effect of SGAs on
insulin secretion has been suggested in animal models, but has not been
demonstrated in clinical samples. OBJECTIVE: To determine the post-challenge
insulin secretion in patients treated with SGAs. METHOD: We identified 520
non-diabetic individuals treated with clozapine (N=73), olanzapine (N=190),
quetiapine (N=91) or risperidone (N=166) in a consecutive, single-site cohort of
783 adult psychiatric inpatients who underwent a comprehensive metabolic
assessment. Insulin secretion was measured as the area under the curve
(AUC(insulin)) generated by levels recorded at baseline, 30, 60 and 120 min after
the intake of 75 g of glucose. The independent predictors of insulin secretion
were determined with regression analysis in the entire sample and separately in
patients with normal glucose tolerance (NGT) and prediabetes. RESULTS: The
post-challenge AUC(insulin) was independently predicted by AUC(glucose), waist
circumference, triglyceride levels and younger age (p<0.0001); non-smoking status
(p=0.0012); and treatment with clozapine (p=0.021). The model explained 33.5% of
the variance in insulin secretion (p<0.0001). The clozapine effect was present in
the NGT group, but not in prediabetics. CONCLUSIONS: Clozapine, but not
olanzapine, quetiapine and risperidone, is an independent predictor of
post-challenge insulin secretion in non-diabetics, particularly in those with
normal glucose tolerance. The findings suggest that the diabetogenic risk of
clozapine may persist even after weight reduction.

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