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.

• Authors: Peter Manu, Christoph U Correll, Martien Wampers, Ruud van Winkel, Weiping Yu, Daphna Shiffeldrim, John M Kane, Marc De Hert
• Journal: Schizophrenia research (Schizophr Res) Vol. 143 Issue 2-3 Pg. 358-62 (Feb 2013) ISSN: 1573-2509 [Electronic] Netherlands
• PMID: 23231880 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antipsychotic Agents
• Dibenzothiazepines
• Insulin
• Benzodiazepines
• Quetiapine Fumarate
• Clozapine
• Risperidone
• Olanzapine

Topics

• Adult
• Antipsychotic Agents (adverse effects, pharmacology)
• Area Under Curve
• Benzodiazepines (adverse effects, pharmacology)
• Clozapine (adverse effects, pharmacology)
• Diabetes Mellitus, Type 2 (chemically induced, diagnosis)
• Dibenzothiazepines (adverse effects, pharmacology)
• Female
• Humans
• Insulin (metabolism)
• Insulin Secretion
• Male
• Middle Aged
• Olanzapine
• Predictive Value of Tests
• Quetiapine Fumarate
• Regression Analysis
• Risperidone (adverse effects, pharmacology)