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Insulin secretion in patients receiving clozapine, olanzapine, quetiapine and risperidone.

Abstract：

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.

journal_name

Schizophr Res

journal_title

Schizophrenia research

authors

Manu P,Correll CU,Wampers M,van Winkel R,Yu W,Shiffeldrim D,Kane JM,De Hert M

doi

10.1016/j.schres.2012.11.016

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

358-62

issue

2-3

eissn

0920-9964

issn

1573-2509

pii

S0920-9964(12)00651-2

journal_volume

143

pub_type

杂志文章

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